Nature Communications最新文献

The topological Hall effect, driven by the exchange interaction between conduction electrons and topological magnetic textures such as skyrmions, is a powerful probe for investigating the topological properties of magnetic materials. Typically, this phenomenon arises in systems with broken global inversion symmetry, where Dzyaloshinskii-Moriya interactions stabilize such textures. Here, we report the discovery of an emergent giant topological Hall effect in the twisted Fe₃GeTe₂ metallic system, which notably preserves the general global inversion symmetry. This effect manifests exclusively within a narrow window of "magic" twist angles ranging from 0.45° to 0.75°, while it is absent outside of that range, highlighting its unique and emergent nature. Micromagnetic simulations reveal that this topological Hall effect originates from a skyrmion lattice induced by alternating in-plane and layer-contrasting Dzyaloshinskii-Moriya interactions that result from local inversion symmetry breaking. Our findings underscore twisted Fe₃GeTe₂ as a versatile platform for engineering and controlling topological magnetic textures in metallic twisted van der Waals magnets, thereby opening up new avenues for next-generation spintronic devices.

The arcuate nucleus of the hypothalamus plays a central role in sensing and integrating nutritional, hormonal, and neural signals that regulate feeding, energy homeostasis, growth, and reproduction, all of which show pronounced sex differences. However, the cellular mechanisms underlying these responses remain poorly understood. We performed snRNA-seq of the mediobasal hypothalamus, focusing on the arcuate nucleus, in female and male mice under different nutritional states. Analysis of 42 cell types revealed that Agrp neurons were most sensitive to nutritional changes, dopaminergic neurons showed strong sex-specific differences, and KNDy neurons were highly responsive to both sex and nutrition. Pomc neurons displayed moderate nutritional sensitivity. Most glial populations were stable, although microglia and oligodendrocytes showed moderate variation. Cell-cell communication analysis identified neurotrophic factor signaling as a key pathway regulated by sex and nutrition. This study represents a major effort to comprehensively characterize sex-specific differences in arcuate nucleus response across nutritional conditions.

Fungal inositol phosphorylceramide (IPC) synthase is an essential enzyme complex that catalyzes a critical step in sphingolipid biosynthesis. It is the molecular target of potent antifungal aureobasidin A (AbA). Despite its therapeutic relevance, the lack of structural and mechanistic insights into IPC synthase function and inhibition has impeded rational antifungal drug development. Here, we present cryo-EM structures of Saccharomyces cerevisiae IPC synthase in two distinct functional states: a ceramide-bound form and an AbA-inhibited complex. Our study reveals a conserved heterodimeric architecture formed by Aur1 and Kei1, stabilized through extensive protein-protein and lipid-mediated interactions. Within catalytic Aur1, we identify a membrane-embedded reaction chamber harboring a conserved H-H-D catalytic triad (H255, H294, and D298) essential for IPC synthesis. Structural comparisons illuminate the mechanism of ceramide recognition and reveal how AbA acts as a competitive inhibitor by occupying the substrate-binding pocket. Further analyses identify key residues involved in AbA binding and explain the molecular basis of drug resistance. Together, these findings advance the mechanistic understanding of fungal IPC biosynthesis and inhibition, and establish a foundation for developing new antifungal drugs targeting IPC synthase.

Organic scintillators are promising for X-ray imaging due to low cost, sustainability, and tunable structures, but their commercial use is limited by poor understanding of charge transfer design for balancing light yield, decay, and bandwidth. Here, we propose a spatially decoupled heavy atom antenna strategy, integrating alkyl bromides into a hybridized local and charge-transfer scaffold to create a scintillator. This architecture leverages the moderate charge-transfer state to deliver an optimal combination of a short radiative lifetime (3.74 ns), a narrow radioluminescence bandwidth (56 nm), a large Stokes shift (110 nm) and a high photoluminescence quantum yield of 100%. As a result, this scintillator exhibits excellent radioluminescence properties, rendering it suitable for highly sensitive X-ray detections. In this work, we elucidate a general design principle for creating high-performance scintillators that meet the stringent multi-property demands of advanced X-ray imaging applications.

Initiation and sustainment of oncogenic signaling is a hallmark of cancer evolution and progression. In renal clear cell carcinoma, loss of von Hippel-Lindau protein causes stabilization of hypoxia-inducible transcription factors (HIF) evoking a pseudo-hypoxic response, perturbing epithelial homeostasis and leading to cancer development. Although genetic polymorphisms link the EPAS1 oncogene (coding for HIF-2α) to renal cancer and anti-HIF-2 compounds emerge as renal tumor therapies, little is known about transcriptional dysregulation of this factor in renal malignancies. We use genetic, epigenetic and transcriptomic data from large patient cohorts and cell models to dissect mechanisms of augmented EPAS1 transcription in clear cell renal cell carcinoma. We define an oncogenic enhancer of EPAS1 which operates depending on the presence of HIF and renal lineage-specific factors, thereby providing evidence for an auto-regulatory feed-forward circuit of HIF-2α regulation which promotes renal cancer growth.

Nonsense-mediated mRNA decay (NMD) relies on the coordinated assembly and action of multiple protein factors. Degradation of target mRNAs begins with endonucleolytic cleavage near premature stop codons, but the mechanisms of endonuclease activation and regulation remain unclear. Using structural predictions, biochemical in vitro assays, and cell-based NMD analysis, we show that SMG5 and SMG6 interact via their PIN domains to form a composite interface (cPIN) with full endonuclease activity. In vitro reconstituted SMG5-SMG6 cPIN heterodimers show high activity, as SMG5 completes the SMG6 active site and substrate binding site. Mutations in residues at their predicted interaction surfaces, RNA-binding sites, or active site attenuate or abolish cPIN activity in vitro and impair cellular NMD. Our findings demonstrate how paralogous PIN domains complement each other to assemble a highly active endonuclease in NMD, providing a structural and mechanistic explanation for efficient NMD substrate degradation.

We report a scalable and sustainable method for synthesizing graphene oxide (GO) via a non-thermal atmospheric nano-second pulsed plasma (NSPP) process, using methane as the carbon source and water as the substrate. Unlike conventional chemical vapor deposition (CVD), which demands high temperatures, low pressures, and inert gases, this approach operates at ambient conditions without additional gas inputs. The plasma decomposes methane directly on or near the water surface, producing high-purity, single-layer GO with tunable oxygen content and flake size. Gas chromatography confirms substantial hydrogen generation and minimal greenhouse gas emissions. Atomic Force Microscopy (AFM) analysis verifies single-layer morphology. Scaling the process with a four-gap reactor yields 5 g of GO per day, exceeding conventional CVD output while reducing cost and environmental impact. This plasma-driven strategy provides an energy-efficient route for large-scale GO production, with potential applications in electronics, energy storage, coatings, and concrete composites.

Thermoelectric generators offer a promising approach for harvesting waste heat from both natural and human-made sources, enabling sustainable electricity generation. While geometric design plays a crucial role in optimizing device performance, conventional approaches remain confined to simple configurations, limiting efficiency improvements. This constraint arises from the complex interplay of multiphysical interactions and diverse thermal environments, which complicates structural optimization. Here, we introduce a universal design framework that integrates topology optimization (TO) with additive manufacturing to systematically derive high-efficiency thermoelectric 3D architectures. By formulating an optimization problem to maximize power generation efficiency, our approach explores an unprecedentedly large design space, optimizing the geometries of thermoelectric materials across diverse thermal boundary conditions and material properties. The resulting TO-derived geometries consistently outperform conventional cuboids, demonstrating significant efficiency gains. Beyond in-silico studies, we provide theoretical insights and experimental validation, confirming the feasibility of our design approach. Our study offers a transformative way for enhancing thermoelectric power generation, with broad implications for next-generation sustainable energy technologies.

Polymer matrix has been extensively explored for decades to achieve efficient room-temperature phosphorescence from dispersed chromophores. However, the impact of the polymer matrix on the optical characteristics of chromophores remains elusive. Herein, we report that different asymmetric environments of polymer matrix delicately regulate the thermally stimulated phosphorescence property (estimated maximum total Φ_PL: 92% at 298 K) of the molecularly dispersed chromophores. It essentially controls the degree of exo- and endothermic transition of excited states with the same and different multiplicity. The excited-state calculations demonstrate a significant influence of matrix environment on the dynamic phosphorescence property. Furthermore, we have investigated the impact of matrix-assisted conformers on dynamic phosphorescence for BANHPh and BANMePh in contrast to the completely locked geometry of BANH2. These matrix-induced, tunable phosphorescent emitters have been found to be highly competent in applications such as information encryption and afterglow display.