Search

Cryo-electron microscopy structures of the bile acid transporter OSTα–OSTβ, which has a key role in bile acid homeostasis, provide insight into its distinct architecture and mechanism of substrate translocation.

Hepatocyte-specific GPR110 mediates metabolic dysfunction-associated steatohepatitis progression by regulating hepatic oestrogen sensitivity in a sex-specific manner, specifically in female mice.

This is a Protocol for fluorescent intrabody localization microscopy imaging, which enables single-particle tracking of proteins in living cells, using unique nanobodies to capture protein conformer subpopulations. This is followed by nanoclustering analysis using spatiotemporal indexing to analyze their spatiotemporal clustering.

The perceived toxicity of organometallic reagents has limited their use in living systems. Now it has been shown that balancing flexible chelation with biocompatible ligands without precluding chemical reactivity enables organonickel-mediated S-arylation inside cells. This reaction enables deep chemical surveys of reactive proteins and covalent tracking of intracellular viral and bacterial pathogens.

Alphaherpesvirus infections pose a health challenge due to the lack of effective broad-spectrum antiviral strategies. Here, the authors identify a broadly neutralizing antibody, 16F9, which targets glycoprotein B, offering cross-protection against multiple viruses and demonstrating robust efficacy in mouse models, paving the way for antiviral interventions.

Staphylococcus aureus can aggregate within human synovial fluid and lead to joint infections. Here, the authors reveal that the fatty acid kinase system and its downstream saeRS regulator control S. aureus aggregation within synovial fluid.

Frequent recalibration poses a challenge to the reliability of cuffless blood pressure monitoring devices. Here, the authors introduce a conformal and stretchable piezoelectric microsystem combined with a demographic-adaptive model, enabling calibration-free, continuous BP tracking.

Yang et al. uncover the molecular details of how mitochondrial proteins cross the outer and inner mitochondrial membranes, with hydrophobicity guiding them into distinct pathways toward specific destinations.

ANPELA is a software package to compare and assess the performance of different workflows for processing single-cell proteomic data, ensuring the user selects the most appropriate processing workflow for their experimental design question.

Analyzing the massive and heterogenous datasets from genome-wide chromatin immunoprecipitation (ChIP) datasets presents several computational and statistical challenges. Ji et al. present a software suite that integrates all steps in ChIP-chip and ChIP-seq data analyses and illustrate the use of these tools by comparing the ability of the two platforms to identify transcription factor binding sites.

High-throughput electron tomography has been challenging due to time-consuming alignment and reconstruction. Here, the authors demonstrate real-time tomography with dynamic 3D tomographic visualization integrated in tomviz, an open-source 3D data analysis tool.

He, Teng and Yang et al. report how metformin, the widely used antidiabetic drug, inhibit its target, the respiratory complex I, through a distinct state-dependent, inhibitor trapping mechanism, thus providing the molecular basis for its superior clinical tolerance.

This work presents a portable nanofiber-based imaging technique that uses luminescent nanofibers to achieve high-resolution replication of human skin textures, such as fingerprints, with fine morphological details, including sweat pores, ridges, and scars.

The vasopressin V2 receptor (V2R) is a key regulator of water balance, and its antagonists are promising therapeutics for hyponatremia. Here, the authors offer structural insights into antagonist recognition and antagonism of V2R.

Obstructive sleep apnea can be ameliorated through accurate detection and localization of airway obstructions. Here, the authors present a flexible, catheter-based pressure sensor array that enables continuous high-sensitivity upper airway pressure assessment and obstructions localization.

The phosphoethanolamine transferase modifies lipopolysaccharide structure and confers antibiotic resistance on Gram-negative bacteria. Here the authors reveal how the membrane lipid modulates the conformational transition of this important enzyme.

Carbohydrates are essential for regulating various biological processes. Here, the authors developed DeepGlycanSite, a deep learning model that accurately predicts carbohydrate-binding sites on proteins, offering insights into carbohydrate regulation of therapeutically important proteins.

NADPH oxidase 5 (NOX5) is activated by Ca²⁺ signaling, catalyzing superoxide production by transferring electrons from intracellular NADPH to extracellular oxygen. Here the authors uncover the molecular basis of NOX5 activation and electron transfer.

Follicle stimulating hormone (FSH) is a glycoprotein hormone the functions of which are mediated by a G protein-coupled receptor, FSHR. Here, Duan et al. report cryo-EM structures of FSHR in active and inactive states, suggesting the molecular basis of FSH and small allosteric agonist-mediated FSHR activation.

PCBP2 is elevated in AD and forms condensates that sequester mitochondrial proteins and RBPs, disrupting mitochondrial function and the NMD of BACE1 mRNA, alongside amyloid deposition. The small molecule, CN-0928 mitigates AD pathology by inhibiting PCBP2 condensation.

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

Some thiamine diphosphate-dependent enzymes are powerful biocatalysts, forming carbon–carbon bonds between two α-keto acids, but their catalytic properties have been poorly understood. Now the substrate selectivity and catalytic stereoselectivity of two representative enzymes, CsmA and BbmA, have been fully characterized. Enzymatic total synthesis using these enzymes generates diverse carboligation products.

The authors report a molecular ferroelectric (TMCM)[FeCl₄], which shows strong magnetostrictive and magnetoelectric effects at room temperature. The spin-lattice coupling of FeCl₄ and flexible structure of organic cations are responsible for these effects.

The Neuro-stack is a wearable platform for recording from single neurons in freely moving humans. It also allows for personalized stimulation during real-time decoding of neural activity.

Renal cell carcinoma consists of several subtypes, and recurrence is highly dependent on subtype. Here, the authors develop a multi-classifier using imaging, lncRNA and clinical data to predict recurrence in papillary renal cell carcinoma.

In this technical report Ma et al. present scMORE, a polygenic method integrating single-cell multiomics and GWAS to prioritize cell-type-specific, trait-relevant eRegulons. scMORE revealed regulators underlying 31 immune and aging traits, including Parkinson’s disease.

It is difficult to detect low abundance RNAs in sequencing experiments, and biochemical methods to enrich or deplete specific RNAs are time-consuming, costly and can damage RNA. Here, authors develop a biochemical-free technology to enrich or deplete RNA classes in real-time during direct RNA sequencing.

Receptor tyrosine kinases play a key role in the regulation of intracellular signal transduction revealing their potential for targeted therapy. Here this group reports an aptamer-directed phosphatase recruiting chimeras for direct dephosphorylation of tyrosine residues on the receptor targets thereby inhibiting transmission of phosphorylation signals both in vitro/vivo.

Authors demonstrate coherence of the K⁺ ions confined in potassium-selective channels, which determines transport. The coherent oscillation state of confined K⁺ ions in the channel dominates each transport event, serving as the physical basis for the high flux of channel.

Thyroid-stimulating hormone and autoantibody M22 push the extracellular domain of the thyrotropin receptor into an upright active conformation, revealing a universal activation mechanism of glycoprotein hormone receptors and providing the molecular basis of Graves’ disease, hypothyroidism and Hashimoto’s disease.

Chiral alkyne motifs bearing an α stereocentre are often found in many bioactive compounds, chemical probes, and functional materials. Here the authors show NiH-catalysed reductive migratory hydroalkynylation of olefins with bromoalkynes that form benzylic alkynylation products in high yield and with excellent regioselectivity.

Organic electrode materials offer a versatile and sustainable route for lithium-ion batteries, but their application is hindered by low working voltages and poor cycling stability. Now, it has been shown that dissolving halide electrolytes into organic electrodes effectively tunes the working voltage and enhances the electrochemical performance of all-solid-state batteries.

This paper presents an Adaptive Learning PHysics-Assisted Light-Field Microscopy (Alpha-LFM) approach, which relies on a physics-assisted deep-learning framework and adaptive-tuning strategy capable of light-field reconstruction at sub-diffraction-limit resolution. This approach enables rapid and gentle 3D imaging of subcellular dynamics.

The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac Na_V1.5 channels. Here authors reveal the cryo-EM structure of LqhIII bound to Na_V1.5 which shows that LqhIII traps the gating charges of the S4 segment in a unique intermediate-activated state and explains why LqhIII slows inactivation of Na_V channels but does not open them.

Relaxin family peptide receptor 4 (RXFP4) regulates pleiotropic biological processes. Here, authors report cryo-EM structures revealing the ligand-binding modes and key determinants of peptidomimetic agonism and subtype selectivity

The high dimensionality of ion mobility (IM)-resolved metabolomics data presents a great challenge to data processing. Here, authors develop a mass spectrum-oriented bottom-up assembly algorithm and the end-to-end computational framework Met4DX for IM-resolved metabolomics.

Emerging high-plex imaging technologies are limited in resolving subcellular biomolecular features. Here, the authors propose a spatial histopathology tool that allows for high-plex protein staining and physical expansion, while retaining the lateral tissue expansion.

The orphan GPR84 plays important roles in inflammation, fibrosis, and metabolism. Here, authors report cryo-EM structures of the receptor bound to two ligands, with insights into ligand binding and entry from the extracellular milieu.

Inspired by class II aldolases found in nature, the authors report a biomimetic copper/squaramide cooperative catalysis strategy for asymmetric Mannich reactions between challenging acyclic ketimines and α-substituted β-keto esters.

Ductal lavage represents a treatment option for idiopathic granulomatous mastitis. Here, the authors report the results of a randomized clinical trial, indicating that ductal lavage followed by observation is non-inferior to oral corticosteroids

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.

The commercialization of organic solar cells has been hindered by the limited device stability. Here, authors show that the connectivity of electron transport network is a key factor determining electron transport and device stability, with polymeric acceptors likely to establish such a network.

We report on the structures of the TAAR1–G-protein complex when bound to methamphetamine and other amines.

In this clinical trial, the authors demonstrate that recombinant gE-Fc Fusion Protein Vaccine LZ901 for herpes zoster induces superior cellular immunogenicity and exhibits a better safety profile than HZ/su in adults ≥50 years, supporting its potential as vaccine candidate.