The electronic passivation of small-form-factor devices requires a fundamental change in electromagnetic interference (EMI) shielding, transitioning from bulky metal cans to conformal thin films1-4. However, reducing the thickness induces poor shielding performance associated with the skin depth of shielding materials5,6. To overcome the performance limitations of thin-film shields, absorption during multiple internal reflections should be driven7. For absorption during multiple internal reflections, pores have been intentionally introduced into shielding materials such as metals8-12 and two-dimensional (2D) titanium carbides/nitrides (MXenes)13-19. However, these approaches involve insufficient thinness, non-uniformity and/or processing incompatibility. Here we propose embedding non-porous MXene film into metal thin films to achieve unprecedented shielding performance at a thickness of just 1 μm (about 70 decibels; about 80 decibels at 1.9-μm thickness) without the limitations associated with porous structures. This exceptional performance in simple-stacked metal/MXene/metal structures, which deviates from the typical thickness dependency, arises from the formation of electromagnetic wave confinement walls at the interfaces, driven by the conductivity mismatch between the metal and MXene. The confined electromagnetic waves within the MXene 'well' are effectively attenuated through polarization loss, primarily driven by dipoles at the metal-MXene interfaces. Our embedded-MXene-in-metal shields provide conformal EMI protection for portable USB (Universal Serial Bus) 3.0 flash drives and flexible Schottky diodes. Our embedded-MXene-in-metal shields may open new avenues in packaging technologies, enabling EMI-free ubiquitous electronics.

Ion-channel activity reflects a combination of open probability and unitary conductance1. Many channels display subconductance states that modulate signalling strength2,3, yet the structural mechanisms governing conductance levels remain incompletely understood. Here we report that conductance levels are controlled by the bending patterns of pore-forming transmembrane helices in the heterotetrameric neuronal channel GluN1a-2B N-methyl-D-aspartate receptor (NMDAR). Our single-particle electron cryomicroscopy (cryo-EM) analyses demonstrate that an endogenous neurosteroid and synthetic positive allosteric modulator (PAM), 24S-hydroxycholesterol (24S-HC), binds to a juxtamembrane pocket in the GluN2B subunit and stabilizes the fully open-gate conformation, where GluN1a M3 and GluN2B M3' pore-forming helices are bent to dilate the channel pore. By contrast, EU1622-240 binds to the same GluN2B juxtamembrane pocket and a distinct juxtamembrane pocket in GluN1a to stabilize a sub-open state whereby only the GluN2B M3' helix is bent. Consistent with the varying extents of gate opening, the single-channel recordings predominantly show full-conductance and subconductance states in the presence of 24S-HC and EU1622-240, respectively. Another class of neurosteroid, pregnenolone sulfate, engages a similar GluN2B pocket, but two molecules bind simultaneously, revealing a diverse neurosteroid recognition pattern. Our study identifies that the juxtamembrane pockets are critical structural hubs for modulating conductance levels in NMDAR.

Infection by yellow fever virus (YFV), the prototype Orthoflavivirus, induces a febrile syndrome in humans that can progress to liver failure, haemorrhage and death1. Despite decades of study, the entry receptors for YFV remain unclear. Here, using a surface protein-targeted CRISPR-Cas9 screen, we identified LRP4, a low-density lipoprotein receptor (LDLR) family member, as a candidate entry receptor for YFV. Genetic ablation of LRP4 impaired YFV infection of cells and, reciprocally, complementation or ectopic expression of LRP4 increased infection. Related viruses in the YFV antigenic complex also showed LRP4-dependent infection. LRP4 promoted YFV entry into cells through LDLR type A (LA) domain binding to domain III of the YFV envelope protein. Soluble LRP4-Fc decoy receptors neutralized YFV infection in cell culture and reduced viral burden in vivo. As we observed residual YFV infection in LRP4-deficient cells, we evaluated whether other LDLR family members promote YFV entry. This approach identified LRP1 and VLDLR as additional receptors for YFV infection in cell culture. LRP1-Fc, LRP4-Fc and VLDLR-Fc decoys protected mice from YFV challenge, and LRP1-Fc decoys inhibited YFV infection and liver pathogenesis in mice engrafted with human hepatocytes. A genetic deficiency of LRP1 in primary human hepatocyte cultures also resulted in reduced YFV infection. Our findings establish a role for multiple LDLR family members in YFV entry, infection and pathogenesis, which has implications for receptor use and countermeasure development for multiple emerging orthoflaviviruses.

Somatic chromosome instability results in widespread structural and numerical chromosomal abnormalities (CAs) during cancer evolution1-3. Although CAs have been linked to mitotic errors resulting in the emergence of nuclear atypia4-7, the underlying processes and rates of spontaneous CA formation in human cells are underexplored. Here we introduce machine-learning-assisted genomics and imaging convergence (MAGIC)-an autonomously operated platform that integrates live-cell imaging of micronucleated cells, machine learning on-the-fly and single-cell genomics to systematically investigate CA formation. Applying MAGIC to near-diploid, non-transformed cell lines, we track de novo CAs over successive cell cycles, highlighting the common role of dicentric chromosomes as initiating events. We determine the baseline CA mutation rate, which approximately doubles in TP53-deficient cells, and observe that chromosome losses arise more frequently than gains. The targeted induction of DNA double-strand breaks along chromosome arms triggers distinct CA processes, revealing stable isochromosomes, coordinated segregation and amplification of isoacentric segments in multiples of two, as well as complex CA outcomes, influenced by the chromosomal break location. Our data contrast de novo CA spectra from somatic mutational landscapes after selection occurred. The experimentation enabled by MAGIC advances the dissection of DNA rearrangement processes, shedding light on fundamental determinants of chromosomal instability.

The generation and maintenance of immunity is a dynamic process that is dependent on age1-3. Here, to better understand its progression, we profiled peripheral immunity in more than 300 healthy adults (25 to 90 years of age) using single-cell RNA sequencing, proteomics and flow cytometry, following 96 adults longitudinally across 2 years with seasonal influenza vaccination. The resulting resource generated a single-cell RNA-sequencing dataset of more than 16 million peripheral blood mononuclear cells with 71 immune cell subsets from our Human Immune Health Atlas and enabled us to interrogate how immune cell composition and states shift with age, chronic viral infection and vaccination. From these data, we demonstrate robust, non-linear transcriptional reprogramming in T cell subsets with age that is not driven by systemic inflammation or chronic cytomegalovirus infection. This age-related reprogramming led to a functional T helper 2 (TH2) cell bias in memory T cells that is linked to dysregulated B cell responses against highly boosted antigens in influenza vaccines. Collectively, this study reveals unique features of the immune ageing process that occur prior to advanced age and provides novel targets for age-related immune modulation. We provide interactive tools for exploring this extensive human immune health resource at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ .

We previously identified an embryonic shift in the corticospinal motor neuronal transcriptome after spinal cord injury associated with successful axonal regeneration1. Exploiting this transcriptional regenerative 'signature', here we used in silico screens to identify small molecules that generate similar shifts in the transcriptome, and identified thiorphan-a neutral endopeptidase inhibitor-as a lead candidate. In a new adult motor cortex neuronal in vitro screen2, thiorphan increased neurite outgrowth 1.8-fold (P < 0.001). We then infused thiorphan into the central nervous system beginning 2 weeks after severe C5 spinal cord contusions and, when combined with a neural stem cell graft, thiorphan elicited significant improvements in forelimb function (P < 0.005) and corticospinal regeneration (P < 0.05). Extending clinical relevance, thiorphan significantly increased neurite outgrowth in primary cortical neuronal cultures from a 56-year-old human. These findings represent a new path for drug discovery, starting from in silico screens to proof-of-concept in adult human brain cultures.

The iron and steel sector is central to national net-zero efforts but remains hard to abate1,2. Existing decarbonization roadmaps fail to guide technology choices for individual plants, given their heterogeneity and economic constraints3-5. Here, by integrating two global plant-level datasets and forecasted technology costs, we develop a model to identify the least-cost technology pathway for each plant worldwide in alignment with national carbon-neutrality targets. In the short term (pre-2030), energy efficiency improvements and scrap reuse are the cheapest decarbonization strategies, reducing cumulative global carbon dioxide (CO2) emissions by 7.8 Gt and 7.2 Gt at average costs of -US$8.5 tCO2-1 and US$0.3 tCO2-1, respectively. In the long term (after 2030), smelt reduction with carbon capture is expected to become technically mature and economically viable, achieving approximately 6.0 Gt of CO2 reductions at costs of US$7-15 tCO2-1 in Chinese plants and US$26-75 tCO2-1 in plants across Japan, Korea and Europe. After 2040, green-hydrogen-based steelmaking is estimated to contribute an additional 0.3 Gt of CO2 abatement in European plants at costs of US$27-44 tCO2-1. This study tailors plant-specific least-cost technology pathways that reconcile stakeholders' economic interests with climate objectives, enabling actionable decarbonization strategies and supporting global net-zero targets.

The disappearance of ice shelves, the floating margins of the Antarctic ice sheet that restrain the ice flow into the ocean1-3, would strongly accelerate the Antarctic contribution to sea-level rise4-6. Their viability in a warming world has motivated substantial work that focuses on the influence of the warming atmosphere7-10. Here we revisit the concept of ice-shelf viability in a holistic manner, taking into account mass loss due to both the atmosphere and the ocean to estimate when it becomes almost impossible for the ice shelves to maintain their present-day shape. We show that for a scenario in which global warming remains largely below 2 °C, only 1 out of 64 ice shelves will become likely non-viable by 2300. For a scenario in which global warming reaches nearly 12 °C by 2300, many ice shelves become non-viable once global warming exceeds 4.5 °C, loss that is mainly due to an increase in ocean-induced melt. By 2150 and 2300, 26 and 38 ice shelves, respectively, become likely non-viable. Loss of ice-sheet regions restrained by these 38 ice shelves represent a sea-level rise potential of 10 m. Our estimates are latest bounds for reaching non-viability, and ice-shelf collapse could occur even earlier, in particular owing to the synergy with hydrofracturing.

Solid-state lithium metal batteries are facing huge challenges under practical working conditions1,2. Even when the ionic conductivity of composite solid-state electrolytes is increased to 1 mS cm-1, it is still difficult to realize long-life cycling of solid-state batteries above a current density of 1 mA cm-2 and an areal capacity of 1 mAh cm-2 (ref. 3). The fundamental cause is the brittle nature of the solid-electrolyte interphase (SEI) with sluggish lithium-ion transport and the resulting lithium dendrites and severe side reactions. Here we report a ductile inorganic-rich SEI that retains its structural integrity while allowing easy ion diffusion at high current densities and areal capacities. The ductility of the SEI is ascribed to the Ag2S and AgF components, which are formed by a substitution reaction between Li2S/LiF in the SEI and AgNO3 in the dielectric composite electrolytes. Even at a high current density of 15 mA cm-2 and an areal capacity of 15 mAh cm-2, a symmetrical lithium cell with such an SEI has a long cycle life of over 4,500 hours. Furthermore, the ductile SEI also works over 7,000 hours at -30 °C, even under practical conditions of 5 mA cm-2 and 5 mAh cm-2.

Each year, snakebite envenoming claims thousands of lives and causes severe injury to victims across sub-Saharan Africa, many of whom depend on antivenoms derived from animal plasma as their sole treatment option1. Traditional antivenoms are expensive, can cause adverse immunological reactions, offer limited efficacy against local tissue damage and are often ineffective against all medically relevant snake species2. There is thus an urgent unmet medical need for innovation in snakebite envenoming therapy. However, developing broad-spectrum treatments is highly challenging owing to the vast diversity of venomous snakes and the complex and variable composition of their venoms3. Here we addressed this challenge by immunizing an alpaca and a llama with the venoms of 18 different snakes, including mambas, cobras and a rinkhals, constructing phage display libraries, and identifying high-affinity broadly neutralizing nanobodies. We combined eight of these nanobodies into a defined oligoclonal mixture, resulting in an experimental polyvalent recombinant antivenom that was capable of neutralizing seven toxin families or subfamilies. This antivenom effectively prevented venom-induced lethality in vivo across 17 African elapid snake species and markedly reduced venom-induced dermonecrosis for all tested cytotoxic venoms. The recombinant antivenom performed better than a currently used plasma-derived antivenom and therefore shows considerable promise for comprehensive, continent-wide protection against snakebites by all medically relevant African elapids.

At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth1, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto's paradox2. Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale primary fibroblasts. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic hits to undergo malignant transformation than human fibroblasts. However, bowhead whale cells exhibited enhanced DNA double-strand break repair capacity and fidelity, and lower mutation rates than cells of other mammals. We found the cold-inducible RNA-binding protein CIRBP to be highly expressed in bowhead fibroblasts and tissues. Bowhead whale CIRBP enhanced both non-homologous end joining and homologous recombination repair in human cells, reduced micronuclei formation, promoted DNA end protection, and stimulated end joining in vitro. CIRBP overexpression in Drosophila extended lifespan and improved resistance to irradiation. These findings provide evidence supporting the hypothesis that, rather than relying on additional tumour suppressor genes to prevent oncogenesis3-5, the bowhead whale maintains genome integrity through enhanced DNA repair. This strategy, which does not eliminate damaged cells but faithfully repairs them, may be contributing to the exceptional longevity and low cancer incidence in the bowhead whale.