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Here, the authors quantify the effect of cryo-EM data acquisition with stage-tilt on the global resolution of reconstructions and present a tool for predicting an optimal stage-tilt angle to ameliorate the effects of preferred specimen orientation.

Toll-like receptors (TLRs) play a key role in the innate immune system. Here, Kornilov et al. resolve the 3D structures of the membrane-associated parts of four TLRs to reveal properties of the juxta-membrane domain.

Porous graphene integrated into graphene oxide membranes yields smart molecular sieves that switch separation based on the solvent. This allows for graded separations of different-sized molecules.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Alkaline hydrogen production needs stable catalysts, but the electrical double layer is overlooked. Here, the authors report a dense epitaxial hydroxide layer that strengthens the double layer, prevents catalyst leaching, and enhances material stability for 1,400 h in an industrial electrolyzer.

The suppressed Cl^- transport under micropore confinement is a critical challenge. Here, authors report tailoring the pore chemistry of framework polymer membranes, which alters the interaction between Cl^- and membranes and speeds Cl^- transport, improving flow battery performance.

ABC transporters are mobile and adaptative molecular machines. Here, Gobet et al characterize how substrate-binding influences the ABC transporter BmrA and triggers cooperativity in ATP-binding, utilizing an integrative structural enzymology approach.

URAT1 is the target for gout drugs that block urate reuptake in the kidneys, however current treatments have limitations. Here, authors show how urate-lowering drugs inhibit URAT1, facilitating antigout drug development.

In this work, the authors report that tetrameric tip-link complex, pivotal for force transmission, forms slip-ideal-slip bonds under tension, serving as efficient force-filters in the auditory process.

Bacterial cell division depends on the dynamic assembly of FtsZ proteins, forming the Z-ring. Here, the authors show that the N-terminal intrinsically disordered region of FtsZ functions as a cis-acting disassembly element and is essential for Z-ring condensation at midcell in E. coli cells.

During transport by the Na⁺/K⁺-ATPase, Na⁺ and K⁺ ions become occluded between intra- and extracellular gates. Here Castillo et al. measure transient electrical signals arising from K⁺ occlusion and use molecular simulations to describe a K⁺ gating mechanism fundamentally different to that of Na⁺.

This study reports the preparation of degradable poly(β-amino ester) microparticles as a promising replacement for nondegradable microplastics in cleansing products and food fortification, demonstrating effective cleansing, toxic element removal and robust nutrient protection with efficient release.

Systematic base-editing and computational screens identify specific cysteine residues on VPS35 in the retromer complex as key sensors that decrease mitochondrial translation in response to reactive oxygen species signals.

A study reports the development of a structural derivative of amphotericin B with broad antifungal activity in mice but without the renal toxicity associated with amphotericin B.

Energy–structure–function maps that describe the possible structures and properties of molecular crystals are developed, and these maps are used to guide the experimental discovery of porous materials with specific functions.

Aqueous zinc batteries offer a safe and low-cost energy storage option but have a limited lifespan. Here, authors develop a multi-halogen mediated high entropy electrolyte that restructures ion interactions, enabling high energy batteries with extended cycle life and low electrolyte cost.

STING is a promising drug target, but selective activation is necessary for safety and efficacy. Researchers have developed a two-component prodrug system for potent pharmacological activation of STING that offers excellent tumour targeting.

The authors investigate the X-ray-induced electron dynamics, on the sub-femtosecond timescale, of hydrated Na⁺, Mg²⁺, and Al³⁺ ions providing insights into the ultrafast charge-transfer processes in aqueous environments.

Intense, coherent X-ray pulses from a free-electron laser can be used to obtain high-resolution morphology of individual sub-micrometre particles in their native state, while at the same time their composition is analysed by mass spectrometry.

Filamin C is a key actin-binding protein involved in cardiomyopathies and musculoskeletal disorders. Here, Wang et al reveal that it interacts with the heat shock protein HSPB7 under biomechanical stress, forming a stable hetero-dimer which is regulated by phosphorylation.

The ground state of yttrium-doped lithium holmium fluoride, a realisation of dilute magnetic dipoles, has been the subject of much debate. Biltmo and Henelius demonstrate theoretically that the system freezes and exhibits extremely slow and unusual glassy dynamics.

The delta opioid receptor (δOR) is key in modulating sensation and emotion with a lower risk of drug dependence. Here, authors report cryo-EM structure of δOR and design probes to explore its signaling bias, with insights for drug discovery.

Species differences in innate immune sensing could impact nanomedicine development. Here the authors examine phagocyte recognition and show the defined molecular patterns on polymer-coated nanoparticles in different species are driven by ficolin and complement opsonisation.

Safe electrolytes for wide temperature applications of lithium metal batteries are highly demanded. Here, authors develop an ether-based electrolyte with 1,3,5-trioxane additive which renders thermoresponsivity, enabling lithium metal batteries in the range of −60 to 60 °C.

The rational design of carbon-supported transition metal single atom catalysts with precise coordination tailoring remains challenging. Here, the authors develop a topological heteroatom-transfer strategy to precisely control the P coordination in Co single atoms for hydrogen evolution.

Group IV–VI materials often exist in a state near an electronic or structural phase transition. Here, the authors use ultrafast X-ray scattering to show that coupling of band-edge electrons and phonons causes the ferroelectric instability observed in lead telluride.

Bacterial resistance to sulfonamide antibiotics (sulfas) is mediated by acquisition of sul genes, which encode sulfa-insensitive versions of the target enzyme, dihydropteroate synthase. Here, Venkatesan et al. study Sul enzymes using biochemical, structural, mutational and functional analyses, revealing the molecular basis for Sul-mediated drug resistance.

NMDA receptors are glutamate-gated ion channels that regulate fast signaling in the brain. Here, the authors show that the opening and closing patterns of the channel derive from the action of two gates that are regulated by distinct subunits.

Innate and adaptive immunity are equally important for the anti-tumor response and immunotherapy simultaneously activating both arms could have therapeutic benefits. Here authors show that a composite nanoparticle platform that immobilizes monoclonal antibodies targeting PD-L1, 4- 1BB and NKG2A or TIGIT recruits and activates both NK and CD8 + T cells.

Path-integral Monte Carlo (PIMC) techniques are used to simulate thermodynamic properties of warm dense matter but currently suffer from uncontrolled approximations and exponentially scaling computational costs. Here, the authors provide a way to overcome these issues, developing PIMC simulations of warm dense beryllium in agreement with x-ray Thomson scattering.

Identifying determinants of broadly neutralizing antibodies against hepatitis C virus (HCV) may guide HCV vaccine design. Here, the authors discover new anti-HCV antibodies using computational screening and analyze the amino acid composition and sequence-structure relationships in this antibody family.

Glycine receptors (GlyRs) mediate motor control and pain perception. Here, Kumar et al. present structures of GlyR bound to Δ9 -tetrahydrocannabinol (THC) using cryo-electron microscopy, providing insight into the therapeutic effects of cannabinoids.

Here the authors identify distinct mechanisms by which domain-specific p53 mutations activate cancer cell growth via the epidermal growth factor receptor (EGFR). These mechanisms affect sensitivity to EGFR inhibitors, opening avenues for targeted therapy.

Nanopores of porous electrodes have key roles in enhancing supercapacitor performance, but little is known at the atomic level. Merlet et al. perform molecular dynamics simulations and report the effects of confinement of electrolyte ions inside the pores on charge storage efficiency.

A newly discovered negative allosteric modulator of the µ-opioid receptor works together with naloxone to potently block opioid agonist signalling with reduced adverse effects.

There is a need to design soft robots for rapid movement in extreme environments, though it is a challenge to balance electronic and mechanical properties while being stable in extreme conditions. Here the authors design an ethylene glycol gel which balances stability with its electronic and mechanical performance.

A biocatalytic approach to enantioselective nucleophilic aromatic substitution (S_NAr) was achieved through laboratory evolution of highly efficient and selective S_NArase biocatalysts.

Using cryo-EM, Kendrick et al. reveal multiple dynein conformations during dynein’s mechanochemical cycle and Lis1 binding that represent intermediate states of dynein’s activation.

Adherens junctions mediate force transmission and connect the cytoskeleton of adjacent cells. This study demonstrates that force transmission can be achieved through direct and functional β-catenin/vinculin interaction in the absence of α-catenin.

Torrens-Spence et al. reveal how plants in the cabbage family uniquely accelerate production of salicylic acid, a key defense hormone, through evolution of a specialized enzyme called EPS1. This finding could help enhance disease resistance in other crops.

Here, the authors identify a conformational switch in the amino-terminal transactivation domain of c-MYC, termed coreMYC, which cycles between a closed, inactive state and an open, active conformation. Polyphenol epigallocatechin gallate (EGCG) is used to modulate the conformational landscape of coreMYC, stabilizing the closed and inactive conformation.

H₂O₂-dependent haem-peroxygenase-catalysed C–H bond oxyfunctionalization reactions have attracted much attention, but elevated concentrations of H₂O₂ are detrimental to the enzyme. Now, it is reported that this biocatalyst can operate via an alternative pathway using O₂ and small-molecule reductants.

Hybrid QM/MM molecular dynamics simulations reveal that the kinetics and thermodynamics of the first splicing step are regulated by a K⁺ ion that facilitates optimal positioning of reactive moieties.

Oxides with a face-centred cubic anion sublattice are generally not considered as solid-state electrolytes. Li superionic conductivity in face-centred cubic oxides with face-sharing Li configurations have now been created through cation over-stoichiometry in rocksalt-type lattices via excess Li.

Codon 158 gain-of-function mutant p53 (158-mutp53) promotes tumourigenesis in lung cancer. Here, the authors show that 158-mutp53 render cancers sensitive to cisplatin and p53 acetylation agents through a mechanism where acetylated mutant p53 upregulates TRAIP and inhibits NF-ĸB signaling.

The mechanism of Complex I remains to be fully determined. Here, the authors used an integrative approach to show that the dissected antiporter modules of Complex I have all the essential elements required to transport protons across the membrane.

Electrolyte interactions critically govern battery performance yet lack precise design principles. The authors introduce interaction motif descriptors to design an electrolyte enabling 99.7% Li-metal Coulombic efficiency for 4.5 V batteries.

Implant-associated infections with Staphylococcus aureus pose serious clinical challenges. Here, the authors develop a biosensor based on toxin-responsive liposomes encapsulating gold nanoclusters, providing a non-invasive, colourimetric diagnostic tool for bacterial infection detection with urinary readout.

CYSLTR2 and P2RY6 are identified as endogenous ceramide receptors, and inhibition of these ameliorates atherosclerosis, particularly in chronic-kidney-disease-associated cardiovascular disease.