Nature Communications最新文献

Cilia assembly and function rely on the bidirectional transport of components between the cell body and ciliary tip via Intraflagellar Transport (IFT) trains. Anterograde and retrograde IFT trains travel along the B- and A-tubules of microtubule doublets, respectively, ensuring smooth traffic flow. However, the mechanism underlying this segregation remains unclear. Here, we test whether tubulin detyrosination (enriched on B-tubules) and tyrosination (enriched on A-tubules) have a role in IFT logistics. We report that knockout of tubulin detyrosinase VashL in Chlamydomonas reinhardtii causes frequent IFT train stoppages and impaired ciliary growth. By reconstituting IFT train motility on de-membranated axonemes and synthetic microtubules, we show that anterograde and retrograde trains preferentially associate with detyrosinated and tyrosinated microtubules, respectively. We propose that tubulin tyrosination/detyrosination is crucial for spatial segregation and collision-free IFT train motion, highlighting the significance of the tubulin code in ciliary transport.

Modulation of electronic spin states in cobalt-based catalysts is an effective strategy for molecule activations. Crystalline-amorphous interfaces often exhibit unique catalytic properties due to disruptions of long-range order and alterations in electronic structure. However, the mechanisms of molecule activation and spin states at interfaces remain elusive. Herein, we present a Co₃O₄ spinel-based catalyst featuring crystalline-amorphous interfaces. Characterization analyses confirm that tetrahedral Co²⁺ is selectively etched from bulk spinel, forming amorphous CoO islands on the surface. The resultant symmetry breaking in the coordination field induces a reconstruction of the Co³⁺ 3 d orbitals, leading to high-spin states. In CO oxidation, the interface serves as novel active sites with a lower energy barrier, facilitated by lattice oxygen activation. In N₂O decomposition, the interface promotes reassociation of dissociated oxygen through quantum spin exchange interactions. This work provides a straightforward approach to modulating the spin state of interfaces and elucidates their role in molecule activations.

Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria. This diagnostic approach executes the significant guiding missions of screening a customized host-guest drug delivery system by disclosing the rationale behind the discrimination. We design eight azocalix[4]arenes with differential active targeting, cellular internalization, and hypoxia responsiveness to penetrate cells and interact with bacteria. Loaded with fluorescent indicators, these azocalix[4]arenes form a sensor array capable of discriminating eight intracellular bacterial species without cell lysis or separation. By fingerprinting specimens collected from bacteria-infected mice, the facilitated accurate diagnosis offers valuable guidance for selecting appropriate antibiotics. Moreover, mannose-modified azocalix[4]arene (ManAC4A) is screened as a drug carrier efficiently taken up by macrophages. Doxycycline loaded with ManAC4A exhibits improved efficacy against methicillin-resistant Staphylococcus aureus-infected peritonitis. This study introduces an emerging paradigm to intracellular bacterial diagnosis and treatment, offering broad potential in combating bacterial infectious diseases.

Wearable and implantable bioelectronics that can interface for extended periods with highly mobile organs and tissues across a broad pH range would be useful for various applications in basic biomedical research and clinical medicine. The encapsulation of these systems, however, presents a major challenge, as such devices require superior barrier performance against water and ion penetration in challenging pH environments while also maintaining flexibility and stretchability to match the physical properties of the surrounding tissue. Current encapsulation materials are often limited to near-neutral pH conditions, restricting their application range. In this work, we report a liquid-based encapsulation approach for bioelectronics under extreme pH environments. This approach achieves high optical transparency, stretchability, and mechanical durability. When applied to implantable wireless optoelectronic devices, our encapsulation method demonstrates outstanding water resistance in vitro, ranging from extremely acidic environments (pH = 1.5 and 4.5) to alkaline conditions (pH = 9). We also demonstrate the in vivo biocompatibility of our encapsulation approach and show that encapsulated wireless optoelectronics maintain robust operation throughout 3 months of implantation in freely moving mice. These results indicate that our encapsulation strategy has the potential to protect implantable bioelectronic devices in a wide range of research and clinical applications.

How macrophages in the tissue environment integrate multiple stimuli depends on the genetic background of the host, but this is still poorly understood. We investigate IL-4 activation of male C57BL/6 and BALB/c strain specific in vivo tissue-resident macrophages (TRMs) from the peritoneal cavity. C57BL/6 TRMs are more transcriptionally responsive to IL-4 stimulation, with induced genes associated with more super enhancers, induced enhancers, and topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling reveals C57BL/6 specific enrichment of NF-κB, IRF, and STAT motifs. Additionally, IL-4-activated C57BL/6 TRMs demonstrate an augmented synergistic response upon in vitro lipopolysaccharide (LPS) exposure, despite naïve BALB/c TRMs displaying a more robust transcriptional response to LPS. Single-cell RNA sequencing (scRNA-seq) analysis of mixed bone marrow chimeras indicates that transcriptional differences and synergy are cell intrinsic within the same tissue environment. Hence, genetic variation alters IL-4-induced cell intrinsic epigenetic reprogramming resulting in strain specific synergistic responses to LPS exposure.

Compute-in-memory based on resistive random-access memory has emerged as a promising technology for accelerating neural networks on edge devices. It can reduce frequent data transfers and improve energy efficiency. However, the nonvolatile nature of resistive memory raises concerns that stored weights can be easily extracted during computation. To address this challenge, we propose RePACK, a threefold data protection scheme that safeguards neural network input, weight, and structural information. It utilizes a bipartite-sort coding scheme to store data with a fully on-chip physical unclonable function. Experimental results demonstrate the effectiveness of increasing enumeration complexity to 5.77 × 10⁷⁵ for a 128-column compute-in-memory core. We further implement and evaluate a RePACK computing system on a 40 nm resistive memory compute-in-memory chip. This work represents a step towards developing safe, robust, and efficient edge neural network accelerators. It potentially serves as the hardware infrastructure for edge devices in federated learning or other systems.

Regulator of cell death-1 (RCD-1) governs the heteroallelic expression of RCD-1-1 and RCD-1-2, a pair of fungal gasdermin (GSDM)-like proteins, which prevent cytoplasmic mixing during allorecognition and safeguard against mycoparasitism, genome exploitation, and deleterious cytoplasmic elements (e.g., senescence plasmids) by effecting a form of cytolytic cell death. However, the underlying mechanisms by which RCD-1 acts on the cell membrane remain elusive. Here, we demonstrate that RCD-1 binds acidic lipid membranes, forms pores, and induces membrane bending. Using atomic force microscopy (AFM) and AlphaFold, we show that RCD-1-1 and RCD-1-2 form heterodimers that further self-assemble into ~14.5 nm-wide transmembrane pores (~10 heterodimers). Moreover, through AFM force spectroscopy and micropipette aspiration, we reveal that RCD-1 proteins bend membranes with low bending moduli. This combined action of pore formation and membrane deformation may constitute a conserved mechanism within the broader GSDM family.

Lactate produced during ischemia-reperfusion injury is known to promote lactylation of proteins, which play controversial roles. By analyzing the lactylomes and proteomes of mouse myocardium during ischemia-reperfusion injury using mass spectrometry, we show that both Serpina3k protein expression and its lactylation at lysine 351 are increased upon reperfusion. Both Serpina3k and its human homolog, SERPINA3, are abundantly expressed in cardiac fibroblasts, but not in cardiomyocytes. Biochemically, lactylation of Serpina3k enhances protein stability. Using Serpina3k knockout mice and mice overexpressing its lactylation-deficient mutant, we find that Serpina3k protects from cardiac injury in a lysine 351 lactylation-dependent manner. Mechanistically, ischemia-reperfusion-stimulated fibroblasts secrete Serpina3k/SERPINA3, and protect cardiomyocytes from reperfusion-induced apoptosis in a paracrine fashion, partially through the activation of cardioprotective reperfusion injury salvage kinase and survivor activating factor enhancement pathways. Our results demonstrate the pivotal role of protein lactylation in cardiac ischemia-reperfusion injury, which may hold therapeutic value.

Hybrid superconductor-semiconductor Josephson field-effect transistors (JoFETs) function as Josephson junctions with gate-tunable critical current. Additionally, they can feature a non-sinusoidal current-phase relation (CPR) containing multiple harmonics of the superconducting phase difference, a so-far underutilized property. Here we exploit this multi-harmonicity to create a Josephson circuit element with an almost perfectly π-periodic CPR, indicative of a largely dominant charge-4e supercurrent transport. We realize such a Josephson element, recently proposed as building block of a protected superconducting qubit, using a superconducting quantum interference device (SQUID) with low-inductance aluminum arms and two nominally identical JoFETs. The latter are fabricated from a SiGe/Ge/SiGe quantum-well heterostructure embedding a high-mobility two-dimensional hole gas. By carefully adjusting the JoFET gate voltages and finely tuning the magnetic flux through the SQUID close to half a flux quantum, we achieve a regime where the (sin (2varphi )) component accounts for more than 95% of the total supercurrent. This result demonstrates a new promising route towards parity-protected superconducting qubits.

Silicon-based all-solid-state batteries offer high energy density and safety but face significant application challenges due to the requirement of high external pressure. In this study, a Li₂₁Si₅/Si–Li₂₁Si₅ double-layered anode is developed for all-solid-state batteries operating free from external pressure. Under the cold-pressed sintering of Li₂₁Si₅ alloys, the anode forms a top layer (Li₂₁Si₅ layer) with mixed ionic/electronic conduction and a bottom layer (Si–Li₂₁Si₅ layer) containing a three-dimensional continuous conductive network. The resultant uniform electric field at the anode|SSE interface eliminates the need for high external pressure and simultaneously enables a twofold enhancement of the lithium-ion flux at the anode interface. Such an efficient ionic/electronic transport system also facilitates the uniform release of cycling expansion stresses from the Si particles and stabilizes bulk-phase and interfacial structure of anode. Consequently, the Li₂₁Si₅/Si–Li₂₁Si₅ anode exhibited a critical current density of 10 mA cm⁻² at 45 °C with a capacity of 10 mAh cm⁻². And the Li₂₁Si₅/Si–Li₂₁Si₅|Li₆PS₅Cl|Li₃InCl₆|LCO cell achieve an high initial Coulombic efficiency of (97 ± 0.7)% with areal capacity of 2.8 mAh cm⁻² at 0.25 mA cm⁻², as well as a low expansion rate of 14.5% after 1000 cycles at 2.5 mA cm⁻².