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Kosmotrope-Promoted Proton Hopping in Supramolecular Conductors
Structural mechanism of SAM-AMP and SAM-AMP2 synthesis by the type III-D2 CRISPR effector complex
Advancing global genomic equity: making a case for national genome projects in Africa
Dichography: two-frame ultrafast imaging from a single diffraction pattern
Abstract We experimentally demonstrate that pairs of time-delayed ultrabright and ultrashort X-ray pulses of two different colors, delivered by modern X-ray Free Electron Lasers, can provide two time-delayed snapshots of a sample. We introduce Dichography, a method that algorithmically separates the diffraction signals overlapping on the detector and independently retrieves the two images of the specimen. We employ Dichography to reconstruct two views of individual xenon-doped helium nanodroplets with 20 nm spatial resolution. The consistency of structures observed in both images at delays up to 750 fs provides evidence that, under these illumination conditions, significant structural damage only occurs at longer timescales. We further validate the method by imaging pairs of silver nanoparticles intercepted by the same light pulse. Dichography enables a new class of experiments across physics, chemistry, and materials science, making a significant step toward the original promise of X-ray free-electron lasers to capture ultrafast movies of nanomatter.
Neutrophil-derived S100A8/A9 impairs megakaryocyte maturation in immune thrombocytopenia
Divergent responses of soil organic and inorganic carbon driven by land use during coastal reclamation
Assembly-Line Biosynthesis in Living-Cell Emulsions via Tunable Supramolecular Surface Chemistry
Abstract Nature organizes enzymes in micro-compartments to enable efficient biosynthesis, inspiring multienzyme cascades for producing complex molecules. However, practical implementation is often limited by enzyme incompatibility, poor substrate transfer, and inefficient catalyst recycling. Here, we report a living biocatalytic platform that operates as a factory-like assembly line within Pickering emulsions. Tunable supramolecular chemistry is used to graft an oil-derived photocatalyst onto enzyme-overexpressing Escherichia coli ( E. coli ) cells, generating amphiphilic “suprabacteria” that self-assemble at water–oil interfaces and stabilize emulsions. These interfacial suprabacteria accelerate chemoenzymatic and multienzyme cascades, achieving reaction rates up to 45-fold higher than conventional biphasic systems. The platform supports single-step, sequential, and one-pot cascade reactions, including gram-scale benzoin synthesis. Importantly, the dynamic supramolecular linkage enables on-demand dual recycling: either the living-cell conjugate is reused, or the synthetic catalyst is selectively recovered and reattached to fresh cells. This strategy integrates chemical and biological catalysis in a sustainable, scalable platform for future greener industrial biosynthesis.
Small-molecule modulation of β-arrestins
Abstract β-Arrestins are multifunctional regulators of G-protein-coupled receptor (GPCR) signalling and orchestrate diverse downstream signalling events and physiological responses across the GPCR superfamily 1–3 . Although GPCR pharmacology has advanced to target orthosteric and allosteric sites, as well as G proteins and GPCR kinases, direct chemical tools to modulate β-arrestin activities have remained conspicuously absent. Here we report the identification of small-molecule inhibitors that selectively target β-arrestins and delineate their mechanism of action through integrated pharmacological, biochemical, biophysical and structural analyses. These inhibitors disrupt β-arrestin engagement with agonist-activated GPCRs, impairing desensitization, internalization and β-arrestin-dependent physiological functions while sparing G protein–receptor coupling. Cryo-electron microscopy, molecular dynamics simulations and structure-guided mutagenesis reveal that one modulator, Cmpd-5, engages a pocket within the central crest of β-arrestin1 formed by the middle, C and lariat loops, a critical receptor-binding interface, stabilizing a distinct conformation that is incompatible with full β-arrestin–receptor engagement. Together, these findings establish a mechanistic framework for β-arrestin modulation, reveal a novel allosteric site for structure-based drug design, and open new avenues for transducer-targeted, pathway-specific GPCR therapeutic agents.
Generic generation and manipulation of high-dimensional spin-orbit states in Hilbert space
Abstract Light carries both spin (polarization) and orbital angular momentum. Combining these degrees of freedom produces hybrid spin–orbit states that live in a high-dimensional Hilbert space, offering greater information capacity and robustness for optical communication, quantum technologies, and metrology. However, generating arbitrary states in these spaces and characterizing them efficiently has remained difficult. Here we show a compact metasurface that generates arbitrary spin–orbit states in a four-dimensional Hilbert space, visualized on a Poincaré hypersphere, with straightforward scalability to higher dimensions. Using a tetratomic unit cell, the single-layer device precisely controls complex amplitude, phase, and polarization. We further introduce an efficient interferometric scheme that reconstructs the full density matrix of any N -dimensional spin–orbit state using only three interferograms. This approach uncovers an intrinsic spin–orbit parity order that governs the symmetry of projected intensity patterns, independent of the weighting of the eigenmodes, and enables controlled mode transformations through higher-order geometric phases. These advances establish a versatile platform for high-dimensional photonic technologies.
Garbage collection
Site-controlled quantum dot arrays edge-coupled to integrated silicon nitride waveguides and devices
Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload
Abstract The small molecule Necrocide 1 (NC1) constitutively activates human TRPM4, triggering Na⁺ influx and leading to necrotic cell death, a process termed Necrosis by Sodium Overload (NECSO). NC1 activation is specific to human TRPM4 and does not affect most of the other mammalian TRPM4 orthologs. Here, we elucidate the molecular mechanism underlying NC1 activation and its species-specific selectivity for human TRPM4 using a combination of single-particle cryo-EM, electrophysiology, and cell death assays. We identify the NC1-binding site and the key molecular determinants responsible for channel activation. In addition, we explain the insensitivity of mouse TRPM4 to NC1 and pinpoint specific residues that define NC1 specificity for human TRPM4. Given the upregulation of TRPM4 in various human cancers, our mechanistic insights into NC1 activation and specificity provide a framework for the potential development of cancer therapeutics targeting TRPM4-mediated necrosis.