Science Advances最新文献

Tuberous sclerosis complex (TSC) is targeted to the lysosomal membrane, where it hydrolyzes RAS homolog-mTORC1 binding (RHEB) from its GTP-bound to GDP-bound state, inhibiting mechanistic target of rapamycin complex 1 (mTORC1). Loss-of-function mutations in TSC cause TSC disease, marked by excessive tumor growth. Here, we overcome a high degree of continuous conformational heterogeneity to determine the 2.8-Å cryo-electron microscopy (cryo-EM) structure of the complete human TSC in complex with the lysosomal recruitment factor WD repeat domain phosphoinositide-interacting protein 3 (WIPI3). We discover a previously undetected amino-terminal TSC1 HEAT repeat dimer that clamps onto a single TSC wing and forms a phosphatidylinositol phosphate (PIP)-binding pocket, which specifically binds monophosphorylated PIPs. These structural advances provide a model by which WIPI3 and PIP-signaling networks coordinate to recruit TSC to the lysosomal membrane to inhibit mTORC1. The high-resolution TSC structure reveals previously unrecognized mutational hotspots and uncovers crucial insights into the mechanisms of TSC dysregulation in disease.

Nature uses discrete molecular building blocks to form polymers that assemble into multicomponent, multi-dynamic networks, inside (cytoskeleton) and outside (extracellular matrix) the cell. Both the intra-fibrous molecular dynamics and interactions between fibers dictate (non)linear mechanics, such as stress stiffening and relaxation, and ultimately biological function. Current synthetic systems capture only one dynamic process. Here, we present multi-dynamic hydrogels by uniting a stress-stiffening polymer with supramolecular polymers. Crucial is the molecular dynamics of the supramolecular polymers: They dictate the interaction strength with the stress-stiffening polymer and the subsequent dynamic mechanical properties of the mixed networks. The biological relevance of our multi-dynamic hydrogels is demonstrated by their ability to support fibroblast cell spreading. Future work may address the display of various dynamically presented bioactive cues to cells.

Dendrite growth in solid-state sodium batteries (SSBs) is one of the most concerned issues that critically affect the battery efficiency and cycling performance. Here, by designing a fluorescent Eu³⁺-doped Na₃Zr₂Si₂PO₁₂ solid electrolyte (SE) to facilitate three-dimensional (3D) optical imaging on a confocal laser scanning microscopy, a fluorescence tomography (FT) method is developed for observing the sodium dendrite growth during charge/discharge cycles of the SSBs in a 3D view. It is quantitatively revealed that small-size sodium islands appear after several cycles, and with the cycles increasing, large-size dendrites in tens of micrometers gradually form until a critical sodium dendrite volume arrives where a short circuit or severe performance deterioration occurs. Furthermore, by regulating the Eu³⁺ doping ratio, a record-high sodium plating/stripping cycling stability for more than 1 year (487.5 days) is achieved at 25°C. This work demonstrates an FT method observing sodium dendrite growth in SSBs and will promote the functional design of high-performance SEs.

The overexpression and misfolding of viral proteins in the endoplasmic reticulum (ER) may cause cellular stress, thereby inducing a cytoprotective, proteostatic host response involving phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α). Here, we show that hepatitis A virus, a positive-strand RNA virus responsible for infectious hepatitis, adopts a stress-resistant, eIF2α-independent mechanism of translation to ensure the synthesis of viral proteins within the infected liver. Cap-independent translation directed by the hepatovirus internal ribosome entry site and productive hepatovirus infection of mice both require platelet-derived growth factor subunit A (PDGFA)-associated protein 1 (PDAP1), a small phosphoprotein of unknown function with eIF4E-binding activity. PDAP1 also interacts with eIF1A and is essential for translating stress-resistant host messenger RNAs that evade the proteostatic response to ER stress and that encode proteins promoting the survival of stressed cells.

Considering the characteristics and operating environment of remotely controlled miniature soft robots, achieving delicate adhesion control over various target surfaces is a substantial challenge. In particular, the ability to delicately grasp wrinkled and soft biological and nonbiological surfaces with low preload without causing damage is essential. The proposed adhesive robotic system, inspired by the secretions from a velvet worm, uses a structured magnetorheological material that exhibits precise adhesion control with stability and repeatability by the rapid stiffness change controlled by an external magnetic field. The proposed adhesion protocol involves controlling soft-state adhesion, maintaining a large contact area, and enhancing the elastic modulus, and the mechanical structure enhances the effectiveness of this protocol. Demonstrations of the remote adhesive robot include stable transportation in soft and wet organs, unscrewing a nut from a bolt, and supporting mouse tumor removal surgery. These results indicate the potential applicability of the soft adhesive robot in biomedical engineering, especially for targeting small-scale biological tissues and organisms.

Plasmon resonance represents the collective oscillation of free electron gas density and enables enhanced light-matter interactions in nanoscale dimensions. Traditionally, the classical Drude model describes plasmonic excitation, wherein plasma frequency exhibits no spatial dispersion. Here, we show conclusive experimental evidence of the breakdown of plasmon resonance and a consequent metal-insulator transition in an ultrathin refractory plasmonic material, hafnium nitride (HfN). Epitaxial HfN thick films exhibit a low-loss and high-quality Drude-like plasmon resonance in the visible spectral range. However, as the film thickness is reduced to nanoscale dimensions, Coulomb interaction among electrons increases because of electron confinement, leading to the spatial dispersion of plasma frequency. With a further decrease in thickness, electrons lose their ability to shield the incident electric field, turning the medium into a dielectric. The observed metal-insulator transition might carry some signatures of Wigner crystallization and indicates that such transdimensional, between 2D and 3D, films can serve as a promising playground to study strongly correlated electron systems.

Through first-principles calculations based on density functional theory, we investigate the crystal and electronic structures of twisted bilayer BaTiO₃. Our findings reveal that large stacking fault energy leads to a chiral in-plane vortex pattern that was recently observed in experiments. We also found nonzero out-of-plane local dipole moments, indicating that the strong interlayer interaction might offer a promising strategy to stabilize ferroelectric order in the two-dimensional limit. The vortex pattern in the twisted BaTiO₃ bilayer supports localized electronic states with quasi-flat bands, associated with the interlayer hybridization of oxygen p_z orbitals. We found that the associated bandwidth reaches a minimum at ∼19^∘ twisting, configuring the largest magic angle in moiré systems reported so far. Further, the moiré vortex pattern bears a notable resemblance to two interpenetrating Lieb lattices and the corresponding tight-binding model provides a comprehensive description of the evolution the moiré bands with twist angle and reveals the topological nature.

Nickel-based catalysts are widely studied for water-gas shift (WGS), a key intermediate step in hydrogen production from carbon-based feedstocks. Their viability under practical conditions is limited at high temperatures when Ni aggregates and converts CO to methane, an undesirable side product. Because experimental and computational studies identify undercoordinated Ni step sites as most active toward CH₄ formation, we eliminate Ni step sites by atomically dispersing Ni into networked, nanoparticulate CeO₂ aerogels. The mesoporous catalyst with 2.5 atomic % Ni in CeO₂ is highly active for WGS, converting near-equilibrium levels of CO at 350°C, while no CH₄ is detected at the limit of detection (<2 parts per million). In contrast, supporting low weight percentages of Ni clusters or nanoparticles on CeO₂ aerogels leads to methanation. The CH₄ yield produced by the atomically dispersed Ni-substituted CeO₂ aerogel is over an order of magnitude lower than previously reported Ni-based catalysts claiming methane suppression, marking an important advance in the development of WGS catalysts.

The timing, tempo, and causative mechanisms of Ocean Anoxic Event 1a (OAE1a), one of several such abrupt perturbations of the Mesozoic global carbon cycle, remain uncertain. Mudstones interbedded with tuffs in Hokkaido, Japan preserve carbon and osmium isotope shifts recording OAE1a. U-Pb zircon ages of tuffs constrain the OAE1a onset to 119.55 +0.072/-0.079 million years ago (Ma) and its duration to 1116 +87/-93 thousand years (kyr). Isotopic excursions of osmium followed by carbon that mark the rapid onset of OAE1a each lasted ~115 kyr. Critically, the occurrence of index fossil Leupoldina cabri in the Hokkaido OAE1a section, which also caps and thus postdate Ontong Java Plateau (OJP) basalts, has a U-Pb zircon age of ~118.7 to 118.4 Ma. Therefore, OJP volcanism remains a probable source of unradiogenic osmium and light carbon and a causative mechanism of OAE1a.

Optical-resolution fluorescence imaging through and within complex samples presents a major challenge due to random light scattering, with substantial implications across multiple fields. While considerable advancements in coherent imaging through severe multiple scattering have been recently introduced by reflection matrix processing, approaches that tackle scattering in incoherent fluorescence imaging have been limited to sparse targets, require high-resolution control of the illumination or detection wavefronts, or require a very large number of measurements. Here, we present an approach that allows the adaptation of well-established reflection matrix techniques to scattering compensation in incoherent fluorescence imaging. We experimentally demonstrate that a small number of conventional wide-field fluorescence microscope images acquired under unknown random illuminations can effectively be used to construct a virtual fluorescence-based reflection matrix. Processing this matrix by an adapted matrix-based scattering compensation algorithm allows reconstructing megapixel-scale images from <150 acquired frames, without any spatial light modulators or computationally intensive processing.