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Designing a fit-for-purpose global health architecture requires regional coordination and global alignment.

Bennu samples have abundant supernova stardust and clasts that are richer in presolar silicates and organics than other chondritic samples, suggesting that the protolith sampled material with a unique mixture of primordial components before undergoing heterogeneous aqueous alteration.

Structures of the growing peptide chain on and off the ribosome reveal that the ribosome destabilizes the unfolded nascent chain, promoting the formation of partially folded intermediate states.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

BamA is the catalytic core of the BAM complex, which inserts proteins into bacterial outer membranes. Here, the authors show that hinge flexibility between BamA’s β-barrel and POTRA domains is vital, demonstrating how evolution has fine-tuned the BamA sequence and structure for function.

The clinical efficacy of the antidiabetic drug acarbose is hampered by degradation by acarbose-preferred glucosidase (Apg) from the intestinal bacterium K. grimontii. Here the authors decipher the mechanism of Apg-mediated acarbose degradation and provide avenues towards the design of next-generation diabetes drugs.

Here, the authors report that combining Army Liposome Formulation with QS21 saponin (ALFQ) and Alum to formulate the ΔV1gp120 boost decreases the risk of simian immunodeficiency virus (SIV) mac251 acquisition in female macaques.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

BK channels regulate potassium flow but lack clear steric gates. Here, authors show that lipid tails enter the pore in the closed state, triggering dewetting and blocking ion flow-revealing a lipid-mediated hydrophobic gating mechanism.

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.

In this work, Beyer and colleagues have utilized display screening technologies to comprehensively chart RAS proteins “druggability” and in doing so unravel a targetable ligand-induced pocket in RAS opening unprecedented anti-RAS targeted opportunities.

The vaginal microbiome is a critical determinant of health. Here, the authors present VIRGO2, a gene catalog describing these microbial communities and analyze vaginal metagenomes and metatranscriptomes to derive insights into their function and ecology.

Rocha-Roa et al. identify TMEM170 proteins as endoplasmic reticulum lipid scramblases that partner with bridge-like lipid transfer proteins BLTP1/Csf1 proteins to enable bulk lipid transport between organelles.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

Amyloid fibrils are ordered protein assemblies implicated in neurodegenerative disease. Here the authors show that hairpin trimers can be transition states of fibril nucleation, explaining how different fibril isoforms may arise from alternative nucleation sites.

This study shows how Escherichia coli ApaH hydrolyzes enigmatic Np₄N alarmones and decaps Np₄-capped RNAs, thereby impacting their lifetimes. Key features enable ApaH to bind RNA substrates in two orientations, depending on the cap and the first RNA nucleotide.

Adriaenssens et al. show that unlike soluble cargo receptors, transmembrane cargo receptors initiate autophagosome biogenesis by recruiting the FIP200/ULK1 or WIPI–ATG13 complex, revealing unexpected flexibility in the selective autophagy machinery.

Published sequencing data sets of cancer samples could be used to identify genetic variants associated with the risk of developing cancer. Here, Luet al. analyse over 4,000 tumour-normal pairs to reveal variable frequencies of inherited susceptibilities across 12 cancer types and find enrichment of functionally validated missense variants of unknown significance.

The authors here present a high-resolution structure of riluzole bound to a voltage-gated sodium channel. This identifies an intramembranous drug-binding site allowing the potent riluzole-induced enhancement of channel inactivation, normalising the hyperexcitable cellular states found in ALS models. This supports riluzole repurposing and aids future drug design efforts.

The DNA-dependent protease SPRTN cleaves toxic DNA-protein crosslinks (DPCs). Here, the authors show that SPRTN is activated by DPC-ubiquitylation through an allosteric ubiquitin binding interface. This regulatory mechanism enables precise control of SPRTN activity during DNA repair.

Antimicrobial resistance continues to be a critical One Health challenge, despite research and policy progress. Building on the past decade of research, this Perspective provides an integrative roadmap for addressing antimicrobial resistance by leveraging the complexities of human and environment interactions.

Efficient and accurate constant potential simulation is essential for electrochemical modeling. Here, authors propose a constant potential framework by combining the machine learning force field with the charge equilibration method to study the dendrites nucleation at the Li metal battery interface.

Patients with kidney failure undergoing maintenance hemodialysis have poor long-term survival. Here the authors use affinity-based proteomics to identify circulating risk factors for mortality in patients with kidney failure on hemodialysis.

Description of the cryo-EM structures of the parathyroid hormone type 1 receptor associated with G_q reveals two distinct extracellular conformations with N-glycans stabilizing a ligand-tilted conformation.

Using an electrolyte micro-emulsion strategy, a lithium anode and high-voltage cathode can be simultaneously stabilized by liquid–liquid interfacial tension to achieve high-energy-density lithium-metal batteries.

DNA can be folded into rationally designed, unique, and functional materials. Here the authors analyse an archetypal DNA nanoarchitecture with single particle cryo-electron microscopy and molecular dynamics simulations.

Subtle changes in solvent composition control peptide crystal polymorphism, enabling the formation of distinct structures and offering new insights for designing advanced bio-inspired materials.

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.

The prevalence of mutations that can predispose to pancreatic adenocarcinoma (PDAC) remains unclear, especially in underrepresented populations. Here, the authors create a germline mutation map of 1,123 Chinese PDAC patients and compare them to cohorts from other populations, finding CFTR as a potential driver.

Energy coupling factor (ECF) transporters are responsible for the uptake of micronutrients and consist of an integral membrane unit, the S-component, which confers substrate specificity. Here, authors present multi-scale molecular dynamics simulations and in vitro experiments to study the molecular toppling mechanism of the S-component of a folate-specific ECF transporter.

Potential ligand class-dependent differences in STING activation have both evolutionary and therapeutic implications. Here, the authors observe a unique oligomerization state of STING with an open-LBD ligand, suggesting additional regulatory mechanisms involved in activation by this ligand class.