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Producing isolated single-photon emitters in hexagonal boron nitride with predefined spin transitions is challenging. Oxygen annealing enables the controlled fabrication of narrowband quantum emitters with optically active spin for quantum applications.

Organochlorides are widespread in natural products, therefore the methods for site-selective chlorination at specific C–H bonds are of great interest. Here, the authors report a copper(I)-catalysed synthetic method for the efficient site-selective C(sp³)–H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T at room temperature.

Identification of embryo's sticky molecules could aid IVF.

Multidrug efflux pumps help bacteria survive stress and promote antibiotic resistance. Here, authors define the molecular detail of an anaerobic-connected pump MdtF uncovering acid-responsive activity which may enable toxin control in certain niches.

An aromatic hydrogen bond—an interaction between the π-electron cloud of an aromatic ring and a hydrogen-bond donor—can substitute for a conventional hydrogen bond in sequence-specific protein—DNA interactions and can contribute 0.5–1 kcal mol⁻¹ to binding and 1–2 kcal mol⁻¹ to specificity.

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.

Amide bond formation is a hugely important reaction in organic synthesis. This Perspective examines the factors that influence the choice of reaction conditions for this process, comparing widely used stoichiometric reagents with catalysts. The authors draw on both academic and industrial data and focus on the efficiency, scope and sustainability of the various approaches.

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

Although the conformations of highly populated protein metastable states have been studied in detail, capturing the transitions between those states has remained challenging. Here, the authors present an algorithm that generates trajectories in torsion angle space by minimising the kinetic energy required for a transition between experimentally determined end states, demonstrating its application to three membrane transporter superfamilies.

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.

M. tuberculosis cytochrome bd oxidase is of interest as a TB drug target. Here, the authors present the 2.5 Å cryo-EM structure of M. tuberculosis cytochrome bd oxidase and identify a disulfide bond within the canonical quinol binding and oxidation domain (Q-loop) and a menaquinone-9 binding site at heme b₅₉₅.

Structures of USP1−UAF complexes, including a cryo-EM structure of USP−UAF1 bound to its substrate FANCI−FANCD2, reveal molecular details of USP1−UAF1 regulation and substrate recognition.

Here, the authors present a method that enables time-resolved serial protein crystallography over a wide temperature range (10–70 °C). This 5D crystallography approach can be implemented to illuminate protein function at physiologically relevant conditions.

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.

Visualizing single-molecule reactions using electron microscopy can be difficult because of potential radiation damage from the electron beam. Now, however, it has been shown that a high-energy electron beam can be used to synthesize metallo-azafullerenes. Atomic-resolution, time-resolved transmission electron microscopy, with the help of computational calculations, is used to monitor the metal-encapsulation dynamics.

In this work, protein-metal complexes implicated in the pathogenesis of amyotrophic lateral sclerosis were mapped by mass spectrometry imaging. Metal-deficient hSOD1G93A complexes were revealed to be localised with disease pathology in the spinal cord and brain.

Metal-mediated activation of CO for C-C coupling reactions is a valuable approach to carbon monoxide valorization. Here, the authors use low-coordinate iron(II) complexes for the selective scission and homologation of CO affording unusual squaraines and iron carboxylates under mild conditions.

Photoinduced electron transfer through, and between, pyrrole moieties is an important process both in the natural world and emerging technologies. Here, the authors use both experiment and theoretical calculation to investigate a previously undiscovered relaxation pathway arising in pyrrole dimers.

The efficacy of cancer immunotherapy relies on the sufficient functional immune cells recruited. Here this group designs an abemaciclib-loaded supramolecular peptide hydrogel achieving sustained release after intratumoral injection to effectively induce cancer cell death and increase IL-2 secretion, thereby exerting immunotherapy for triple-negative breast cancer.

Cryo-electron microscopy was used to study human mechanistic target of rapamycin complex 1 (mTORC1) activation on lysosomal membranes, showing progressive recruitment by RAG–Ragulator, RHEB and RAPTOR, culminating in mTOR–membrane engagement and full enzyme activation.

Khawaja et al. show sex-specific differences in neuronal-activity regulation by chaperone-mediated autophagy and that loss of chaperone-mediated autophagy leads to defective neuronal physiology and increased seizure susceptibility, linking chaperone-mediated autophagy to neuronal excitability.

The crystal structure of FANCL, the catalytic subunit of the Fanconi Anemia core complex, reveals an unexpected domain architecture. The molecule comprises an N-terminal E2-like fold, a novel double-RWD domain, which is found to be responsible for substrate binding, and a C-terminal RING domain that is predicted to facilitate E2 binding.

This work advances multimodal structural refinements to generate 3D polarization maps for relaxor ferroelectrics, revealing continuous textures with vortex meron features tied to chemical disorder and deepening understanding of relaxor phenomena.

Mutations in RAS and PI3Kα drive cancer by activating the PI3K-AKT-mTOR pathway. The authors present RAS-PI3Kα structures, revealing interaction interfaces, isoform-specific differences, and a framework for designing PI3Kα-specific inhibitors.

JAK inhibitors display very good clinical responses in patients with myeloproliferative neoplasms, irrespective of JAK2 mutational status. Here, the authors discover that JAK inhibitors exert their anti-tumorigenic effects by targeting the bone marrow stroma and non-malignant hematopoietic cells instead of the oncogenic signaling in myeloproliferative neoplasms.

The combination of the brain-permeable mTOR inhibitor RapaLink-1 and the brain-impermeable FKBP12 ligand RapaBlock enable brain-specific inhibition of mTOR.

Jansen et al. determined the cryo-electron microscopy structure of human GTPase-activating protein complex GATOR2 bound to CASTOR1 in the absence of arginine, providing insight into how CASTOR1 binds to GATOR2 to disinhibit GATOR1 when arginine levels are low, promoting mechanistic target of rapamycin complex 1 inactivation.

Three new red-excitable monomeric fluorescent proteins obtained by structure-guided mutagenesis of mNeptune are described in this work. The authors show the use of one of them, mCardinal, to visualize the differentiation of myoblasts into myocytes in living mice.

This study uncovers a distinct mechanistic pathway for bio-olefin production from industrial feedstocks by fatty acid peroxygenases through unconventional decarboxylation, paving the way for sustainable bio-based hydrocarbon production.

To celebrate the first anniversary of Nature Reviews Earth & Environment, we asked five researchers investigating solid Earth processes to outline notable developments within their discipline and provide thoughts on important work yet to be done.

The eukaryotic RNA Polymerase III transcribes tRNAs, some ribosomal and spliceosomal RNAs. Here, the authors resolve a cryo-EM structure of human RNA Polymerase III in its apo form and complemented it with crystal structures and SAXS analysis of RPC5, revealing insights into the molecular mechanisms of Pol III transcription.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

The insecticidal protein Mpf2Ba1 shows potent control against corn rootworm. Here, the authors present detailed structural analyses revealing transitions between its three main stages of pore formation. These findings uncover molecular mechanisms of bacterial pore assembly and advance both crop biotechnology and food security.

The structure of the formate channel FocA from Vibrio cholerae reveals a pentamer, with each monomer possessing its own substrate translocation pore. The selectivity filter consists of a central constriction ring and a cytoplasmic slit, which binds two formate ions. Surprisingly, FocA shares many similarities with aquaporin and glycerol channels.

Serial femtosecond crystallography and the use of X-ray free-electron lasers (XFEL) promise to revolutionize structural biology. Here, the authors describe refinements that reduce the redundancy required to obtain quality XFEL data and report a 1.75-Å structure—not obtainable by synchrotron radiation—using less than 6,000 crystals.