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Homogeneous catalytic hydroboration represents a valuable strategy for the synthesis of alcohols but reports which employ iron-based catalysts are somewhat limited. Here, the authors report an iron metalloborane complex as an efficient pre-catalyst for hydroboration of ketones, cyclic esters and CO₂ with mild conditions.

Spatiotemporal insight into photoactivation of the prototypical B₁₂ photoreceptor CarH is revealed across nine orders of magnitude in time, identifying a transient adduct that distinguishes it from thermally activated B₁₂ enzymes.

The selective dissociation and formation of different functional groups in a single organic molecule may prove useful for making nanoscale devices and offer new opportunities for studying changes in electronic structure. It has now been shown that bond-selective chemistry can be induced and visualized at the submolecular level in a complex thiol-based molecule using a scanning tunnelling microscope.

The authors describe the discovery of a series of potent non-competitive allosteric inhibitors of the ZIKV NS2B-NS3 protease, which exhibit antiviral activity in vitro and robust oral efficacy against ZIKV infections in a mouse model.

The chemical recycling of polyurethane through catalytic hydrogenation to recover anilines and polyols has attracted increasing attention. Here, the authors demonstrate that polyurethane can be broken down into aniline monomers using CeO₂ nanoparticles as a catalyst to cleave carbamate bonds.

Understanding metal-metal bonding involving f-block elements has been challenging. Here, the authors report a series of mixed-valence di-metallofullerenes which feature single electron actinide-lanthanide metal-metal bonds.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Biocatalytic methods to access thioesters, such as acyl-coenzyme A, from carboxylic acids are underdeveloped. Now, it is shown that the adenylation domain of a carboxylic acid reductase enzyme can be exploited as a promiscuous thioester synthetase and combination with acyltransferases facilitates the synthesis of amides and peptide labelling.

Catch bonds where lifetime increases with force applied can form when T cell receptors (TCR) interact with agonist peptide-MHC (pMHC) complexes. Here the authors use a modelling and experimental approach to analyse 55 TCR–pMHC bond lifetime curves measured under force to further characterise the structural bases and functional relevance of catch bonds.

Oxygen capture is attractive for catalysis, sensing, and separations, but engineering stable and selective adsorbents is challenging. Here the authors combine metal-based electron transfer with secondary coordination sphere effects in a metal-organic framework, leading to strong and reversible O₂ adsorption that also exhibits negative cooperativity.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Diatomic actinide molecules are ideal models for studying rare multiple-bond motifs. Here, the authors report host-guest structures of metastable charged U≡N diatoms confined in fullerene cages and stabilized by coordinative electron transfer.

Annunziato, Quan and Donckele et al. identify G3BP2 (Ras–GAP SH3 domain-binding protein 2) as a molecular glue-induced neosubstrate of the CRL4^CRBN E3 ubiquitin ligase. The CRBN–glue neosurface uses a molecular surface mimicry mechanism to recruit and degrade G3BP2 in a compound-dependent manner.

The A3 adenosine receptor is a promising drug target for cancer, inflammation, and glaucoma. Here, authors determine atomic structures of the human A3 receptor, identifying a previously hidden binding pocket that will aid in the development of more effective A3 receptor-targeted medicines.

Anti-tumor functions of low-avidity T cells are often suboptimal. Here the authors show that genetic disruption of TIGIT in TCR-engineered T cells enhances their anti-tumor activity against pancreatic and other gastrointestinal cancers by increasing TCR signal strength.

It remains elusive whether the T cell repertoire will cover all point mutations of a major epitope. The authors here show that COVID vaccine–induced CD8⁺ T cells detect most YLQ peptide variants except R5, but naïve T cells fill this gap by responding to R5 despite abundant WT-specific cells, ensuring broad coverage to prevent viral immune-escape.

Nature's approach to biosynthesis often involves the rapid generation of advanced, enantiopure intermediates from simple starting materials. A new, highly efficient strategy adapts this approach, using organocascade catalysis to quickly construct a key intermediate that can be converted into several complex natural products.

The cool sub-Neptune LP 791-18 c, with an equilibrium temperature of 355 K, was found to host a hazy atmosphere, distinct from any other temperate sub-Neptune studied so far. The discovery demonstrates the intrinsic diversity of these worlds.

The mechanisms that impact tumorigenesis during aging are incompletely understood. Here Shuldiner et al. show that in mice, aging represses KRAS-driven lung tumorigenesis and dampens the impact of inactivating many tumor suppressor genes, which may contribute to the deceleration in cancer incidence with extreme age in humans.

Our annual survey highlights startups tackling intractable viruses with new vaccine design, engineering a reliable source of platelets, universalizing cell therapies, improving cancer screening, developing RNA-editing platforms and targeting protein–RNA interactions. Michael Eisenstein, Ken Garber, Caroline Seydel and Laura DeFrancesco report.

Emerging materials between molecules and materials demand new modeling approaches. Here, the authors present a localized active space approach that enables accurate and efficient band structure calculations to capture long-range charge and energy transfer in correlated materials.

Moral-Sanz, Fernández-Carrasco and colleagues identify senolytic properties of sea anemone-derived pore-forming toxins, with selectivity mediated by senescence-associated lipid profiles. An optimized senotoxin improves the efficacy of chemotherapy in mouse models.

Actinide-ligand bonds with high multiplicities remain poorly understood. Here, the authors investigate covalency in actinide complexes and identify terminal O and N ligands that are triply to quadruply bonded to the actinide, facilitated by electrostatic, steric, and covalent interactions.

Structural, pharmacological and computational studies reveal how different classes of positive allosteric modulators bind to distinct allosteric sites and use noncanonical mechanisms to activate the free-fatty acid receptor FFA2.

G protein-coupled receptors are a major class of drug targets. Here, the authors demonstrate that these receptors may induce a reaction reverse to canonical GTP binding, namely- the release of GTP from G protein, through unique functional activation of the receptor. Further, the reverse reaction is agonist specific.

CNS toxicity was unexpectedly observed for anti-miR-17 RGLS4326 in nonclinical studies. Here, authors identify AMPA receptor inhibition as the likely culprit. Replacement of 3’-terminus guanine to adenine leads to discovery of farabursen (RGLS8429) that is devoid of CNS toxicity.

Acrylics and acrylates have become important building blocks for the chemical industry, but their efficient synthesis remains a challenge. Here, the authors report the first example of the catalytic aerobic partial oxidation of allyl ether to its acrylate ester derivative using a Li ion promoted mesoporous manganese oxide under mild conditions.

The tasks of the cytoskeleton depend on the fine-tuned interplay between the three filamentous components: actin filaments, microtubules, and intermediate filaments. Here, the authors show in a reconstituted in vitro system that vimentin intermediate filaments stabilize microtubules against depolymerization and support microtubule rescue by direct interactions.

Metal–sulfur motifs are commonly found in enzymatic active sites and heterogeneous catalysis, but they remain underexplored in porous solids. Now, sulfur-based ligands have been incorporated into metal–organic frameworks through post-synthetic modifications. The resulting sulfide MOFs exhibit enhanced catalytic performance in the selective hydrogenation of nitroarenes compared with their parent MOFs containing terminal or bridging chloride and hydroxyl groups.

Nature Biotechnology’s annual survey highlights university startups that are, among other things, rethinking how to deliver gene-editing therapy and tackling various metabolic conditions, immune disorders and cancer with microbiome treatments or immunotherapy. Michael Eisenstein, Ken Garber, Esther Landhuis, Caroline Seydel and Laura DeFrancesco report.

Crystal structures of human CB₁ bound to two cannabinoid agonists reveal key features, including a twin toggle switch and binding pocket reduction, advancing understanding of receptor dynamics and guiding cannabinoid drug design.

Using proximity-based screening, protein engineering, and structural analysis, this study describes the development of a p62-based biodegrader for the clearance of organelles and aggregated proteins by autophagy-targeted degradation.

The synthesis of uranium- and thorium-containing metallabiphenylenes demonstrates the ability of the actinides to stabilize aromatic/antiaromatic structures where transition metals have failed.

Nitrogen oxides are major air pollutants; capture and abatement technologies exist but they typically involve toxic species or precious-metal catalysts. Now, a metal–organic framework has been shown to store NO₂ dimers selectively, and to separate NO₂ from other gases under wet conditions. Treatment with water in air leads to conversion of NO₂ into HNO₃—an important feedstock for fertilizer production—with full recovery of the host.

Two-dimensional (2D) crystals offer exciting opportunities to study dislocations, including their migration dynamics. Here, the authors show the local strain field at the dislocation core and dislocation motion leading to grain boundary migration in a monolayer of tungsten disulphide.

The authors identify a Cys→Ser transformation (C19S) in insulin leading to neoepitope presentation and CD4⁺ T cell autoreactivity in type 1 diabetes. Inflammation and oxidative stress enhanced C19S transformation in β cells and antigen-presenting cells, resulting in C19S-specific CD4⁺ T cells with an activated memory phenotype linked to disease progression.

The pathogen Staphylococcus aureus can invade and replicate within human cells. Here, Rodrigues Lopes et al. use an image-based screening approach to identify S. aureus factors important for invasion, intracellular replication, persistence, and host toxicity in non-professional phagocytic cells.

The first steps of charge transfer in molecules after their interaction with light occur on an ultrafast timescale. Now, by combining attosecond pump/few-femtosecond probe spectroscopy with quantum chemistry calculations, it has been shown that a concerted nuclear and electronic motion drives electron transfer in donor–π–acceptor molecules on a sub-10-fs timescale.

Ground state destabilization is often evoked as a possible explanation of orotidine-5′-phosphate decarboxylase catalysis. Now, high-resolution structures of this enzyme provide time-resolved snapshots along its reaction coordinate revealing that transition-state stabilization by electrostatic interactions drives its reactivity.

The SARS-CoV-2 spike glycoprotein is flexible, and its receptor-binding domain (RBD) fluctuates between open and closed conformations. Disulfide bonds are engineered into the spike ectodomain to lock the RBD in the closed state, leading to a construct with high thermostability.

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

Ribosomes convert chemical energy to mechanical work. Here, the authors monitor ribosome binding to the GTPase EF-G and the ensuing mechanical work on mRNA in real time, uncovering a major energetic contribution from EF-G binding, rather than GTP hydrolysis, to the mechanical work.

Tessellation of self-assembling molecular building blocks is attractive for accessing metal-organic materials with geometric frustration, however such motifs are rare. Here the authors use ytterbium(II) as a five-vertex node to assemble an Archimedean tessellation in a bulk, molecule-based material.

Nature Biotechnology’s annual survey highlights academic start ups that are, among other things, correcting misfolded or disordered proteins, creating second-generation GPCR agonists, building a new gene delivery platform and mining cancer genomes for novel targets.

Chronic Kidney Disease affects 1 in 10 people worldwide with prevalence continuing to rise, thus there is a need to identify novel biomarkers that can add value to existing clinical and biochemical risk predictors. Here the authors identify miR190a-5p as potential indicator of kidney health and disease progression in patients with chronic kidney disease.