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Enzyme substrates and products often diffuse too rapidly to assess the catalytic implications of these movements. Here, the authors characterise the structural basis of product and substrate diffusion for an exo-hydrolase and discover a substrate-product assisted processive catalytic mechanism.

Using a histone focused multi-omics approach, here the authors show that increased H3K4 methylation drives triple-negative breast cancer phenotypes, revealing potential novel therapeutic avenues.

Jun N-terminal kinase (JNK) is necessary for development in tumours, indicating it may play tumour-promoting roles; however, the experimental analysis of the role of JNK in proliferation is hindered by its pro-apoptotic activity. Here the authors carry out experiments in Drosophila with genetic backgrounds that make cells refractory to apoptosis to definitely prove the JNK pathway contribution to tumorigenesis.

In a double-blind, randomized, placebo-controlled trial, dapagliflozin, as an adjunct to insulin, resulted in significant reductions in glomerular filtration rate and measures of glycemia when compared to placebo in youth with type 1 diabetes.

The tunability of covalently bound cationic and anionic moieties of zwitterionic materials makes them attractive for potential applications. A family of zwitterions exhibiting molecular disorder and plasticity allows their use as a solid-state conductive matrix.

Aminated heteroaromatics are usually synthesized from heteroaromatic substrates. Now, a general photochemical approach that exploits non-aromatic N-heterocyclic ketones as starting materials for the coupling with amines under desaturative catalysis is reported as an alternative.

Genetic and Structural analysis of COVID patients cohort reveals a correlation between mitochondrial haplogroup and SARS-CoV-2 severity.

The creation of biomaterials which are resorbable and have biomimetic mechanical properties is key to successful tissue engineering. Here the authors report on the creation of a new biopolymer where the mechanical properties can be tuned by changing the ratios of cis:trans double bonds in the backbone.

The source of highly oxidized arc magmas may rely on the infiltration of sediment-derived fluids that contain oxidized aqueous species—notably sulfate—into deserpentinization fluids, according to thermodynamic modelling.

The construction of a synthetic cell will be contingent on the development of an evolvable genetic replicator. Here, authors create a Darwinian protocell that supports protein synthesis, DNA self-replication, and adaptive evolution.

Misfolding of transthyretin can cause amyloid aggregation disorders that can be treated by stabilizing the tetrameric form with tafamidis. Here the authors show that tolcapone, a drug already FDA-approved for Parkinson disease, has strong transthyretin stabilizing function and might be a superior therapeutic option for CNS amyloidosis as it can cross the blood brain barrier.

A three-dimensional metal–organic framework reversibly binds ammonia by cooperative insertion into its metal–linker bonds to form a dense, one-dimensional coordination polymer, enabling high-capacity ammonia uptake with intrinsic thermal management.

A design pipeline is presented whereby binding proteins can be designed de novo without the need for prior information on binding hotspots or fragments from structures of complexes with binding partners.

A metalloenzyme capable of oxidatively cleaving cellulose, found in a microbial community specialized in lignocellulose degradation, could enable sustainable biofuel production.

Glycosyl cations are universally accepted as key intermediates in the mechanism of glycosylation—the reaction that covalently links carbohydrates to other molecules—but their high reactivity makes them difficult to characterize. Using HF/SbF₅ superacid, two glucosyl cations have been generated and stabilized, then characterized by NMR spectroscopy aided by computation and their conformation elucidated.

Most cases of craniofacial microsomia are sporadic but familial cases have been reported. Here the authors report that variants in FOXI3 can cause a small fraction of cases with different modes of inheritance including autosomal dominant with reduced penetrance.

During cell adhesion, integrins are typically thought to require immobilized ligands for spreading. Here, the authors demonstrate that cells can spread and form mature integrin adhesions on fluid substrates by interacting with high-affinity Invasin ligands.

Dual photo- and metal-catalysis is generally not well-understood when the metal catalyst is a gold complex. Here the authors show that a variation of a known metallaphotoredox annulation is possible without an added photocatalyst, proceeding putatively through a gold–intermediate photosensitization by the aggregate of a potassium amide reactant, and yielding indole derivatives.

Schneeberger, Kim, Geesdorf, Rajewsky, Heppner et al. tease IL-12 and IL-23 signaling apart in mouse models and human brain tissue to define a role for oligodendroglial and neuronal IL-12 signaling in neuroimmune crosstalk in Alzheimer’s disease.

Promoter recognition is a critical step in the initiation of transcription of DNA to RNA. Here, the authors describe a novel mechanism by which a phage-encoded RNA polymerase recognizes viral promoters containing deoxyuridines instead of thymidines.

A synergistic dopant-additive combination strategy using methylammonium chloride as the dopant and a Lewis-basic ionic-liquid additive is shown to enable the fabrication of perovskite solar modules achieving record certified performance and long-term operational stability.

Tsuji–Trost allylation is a traditional method for selective C-C bond formation that involves the use of palladium-based catalysts. Here, the authors report a metal-free, photocatalytic allylation of several heterocycles, amines and alcohols, which can be easily tuned towards the Z- or E- allylated product.

Microbes and viruses inhabit the subseafloor crust beneath hydrothermal vents. Here the authors show that vent endemic animals such as giant tubeworms also live in vent subseafloor cavities, implicating subseafloor dispersal of vent larvae and the need to protect seafloor and subseafloor vent habitats.

Single-atom metal catalysts offer maximized material efficiency, but there is large room to improve the intrinsic activity per metal atom for many reactions. Here, the authors demonstrate that the solution for CO oxidation is to tackle the issue of lacking neighboring Pt atoms in the single-atom Pt1/CeO2 system.

A comparison of copper and zinc isotopic measurements between the Ryugu samples and various carbonaceous chondrites excludes any genetic link between the two except for the CI (Ivuna-type) chondrites. Ryugu-like material might have accounted for ~5% of Earth’s mass.

Effective treatments for myelin repair are currently lacking. Here, the authors show that two FDA-approved drugs, leucovorin and dyclonine, identified through pharmacogenomic screening, promote oligodendrocyte formation and brain repair in myelin injury models.

Sluggish Zn²⁺-dominated Faradic reactions lead to suboptimal charge-storage capacity and durability of aqueous zinc battery cathodes. Here, the authors present a proton-selective interfacial coating strategy that enables high-performance cathodes with fast-kinetics proton-dominated Faradic reactions.

Bacillus anthracis causes the infectious disease anthrax. Here, the authors synthesized deoxy glycosides that are effective against B. anthracis and related bacteria and found that these amphiphilic compounds kill bacteria via an unusual mechanism of action.

In this study, the authors report a mutation that increases the production of recombinant SARS-CoV-2 Spike and exposure of the RBD. In animal models, a Spike-based vaccine containing the mutation induces strong immunogenicity, provides protection from disease and results in faster tissue viral clearance.

Wilcox et al. (2022) show that NMDA receptor channel blockers, some of which are clinically important drugs, can access their binding site via 2 routes: a well-known path from the extracellular solution, and another path through the plasma membrane.

GPCR dynamics are critical for signal transmission into the cell. Here, the authors probe receptor plasticity using molecular dynamics simulations, enabling the detection of allosteric sites and drug entry gateways for a broad range of GPCR types.