Endowing synthetic materials with adaptability and responsiveness to dynamically optimize their states represents a premier frontier in biomimetic science. However, achieving life-like, rapid yet reversible adaptation under benign triggers remains hindered by high reconfiguration energy or delayed structural recovery. In this work, we present dynamic supercooled crystal-gels that achieve ultrafast, reversible stiffening without requiring continuous energy input. Inspired by the tactile-triggered stiffening of starfish tissues, it utilizes non-equilibrium energy of internal supercooled liquid to realize templated crystallization upon a benign tactile stimulus trigger. Meanwhile, the crystalline structure is reversible under appropriate temperature and humidity perturbations. This synchronously achieves a 2596-fold adjustment in compressive modulus, circumventing the conventional trade-off between energy demands for mechanical reinforcement and structural stability. As a functional validation, microneedles based on supercooled crystal-gels fulfill the divergent requirements for skin adaptation and seconds-scale drug release through their mechanical adaptation, achieving rapid cumulative drug release of ≈37.76% at 10 s and 88.12% within 5 min. This work delineates a strategy for endowing materials with autonomous mechanical adaptation and opens new opportunities for life-like functional evolution in soft robotics and bio-integrated electronics.
Doc2s modulate neurotransmitter release through interactions with Munc13-1, SNAREs, lipids, and Ca2+, which involve the Doc2 C2 domains and Munc13-interacting domain (MID). However, it is unclear how these interactions are coupled, how Doc2s bind to Munc13-1, and how they bind to the SNAREs. Here we determined the cryo-electron microscopy structure of a Doc2B-Munc13-1 complex aided by an AI-designed Munc13-1 binder, revealing how Doc2B MID binds to a Munc13-1 hydrophobic pocket essential for opening syntaxin-1 and explaining why Doc2B inhibits SNARE assembly. NMR and fluorescence spectroscopy show that Doc2B MID binds lipids and that MID-lipid and MID-Munc13-1 interactions are mutually exclusive, suggesting that membrane binding helps release the inhibition of Munc13-1. NMR shows that Doc2B binds to the SNARE complex via two helices of C2B. Based on these results and liposome fusion assays, we propose a working model whereby: 1. Doc2B MID-Munc13-1 interactions facilitate synergistic binding of both proteins to the plasma membrane, with the MID inhibiting Munc13-1. 2. Membrane binding facilitates MID-lipid interactions that transiently relieve the inhibition of Munc13-1, allowing SNARE complex assembly. 3. Doc2B binding to the SNARE complex inhibits neurotransmitter release but generates a primed state that mediates neurotransmitter release by an as-yet-unknown mechanism.
ABSTRACT Sulfide‐based all‐solid‐state lithium‐ion batteries (ASSLIBs) employing fully active, carbon‐free micro‐silicon (µSi) anodes present significant potential for high energy density, enhanced safety, and reduced cost. However, their practical application is challenged by inherent issues such as sluggish reaction kinetics, substantial volume expansion, and low Coulombic efficiency, which collectively degrade overall electrochemical performance. Herein, an interfacial engineering strategy is developed to construct an active interface layer on µSi particles via a mechanochemical cold‐pressing method. The resulting Li─Si alloy layer acts as an active lithium reservoir, which enables active lithium reservoir. Furthermore, this spontaneously formed active layer exhibits high ionic/electronic conductivities and accommodates volume changes due to its favorable mechanical properties, thereby improving electrode reaction kinetics and structural stability. ASSLIBs fabricated with LiNi 0.83 Co 0.12 Mn 0.05 O 2 cathode and modified µSi anode deliver a high initial specific capacity of 182.55 mAh g −1 and retain a capacity retention of 89.2% after 200 cycles at 0.1 C. This work offers a facile interfacial engineering technique for constructing self‐compensating lithium reservoirs and promotes the development of high‐energy‐density silicon‐based solid‐state batteries.
ABSTRACT Neurogenic bone regeneration is essential for the effective restoration of bone tissue functionality, while the mechanisms and new strategies underlying neurogenic bone regeneration remain to be further explored. Here, single‐cell transcriptomic analysis revealed enhanced mesenchymal‐Schwann cell crosstalk during bone regeneration. Functionally, we verify that Schwann cells are indispensable for bone regeneration via paracrine exosome‐mediated crosstalk with MSCs, a process promoted by Reelin. Mechanistically, Reelin enhances Schwann cell‐derived exosome internalization by MSCs via regulating exosomal proteins, especially UBE2K, which promotes MSC osteogenic differentiation through the ERK pathway, associated with Lys63‐linked polyubiquitination. For effective neurogenic bone regeneration, we engineered mesoporous silica nanoparticles (MSNs) as a CRISPRa delivery system for local Reln gene activation at the defect area. This mRNA delivery system could promote bone regeneration in both calvarial defect and tibial fracture models by constructing a pro‐osteogenic neurogenic microenvironment. Collectively, our findings uncover a Reelin‐Schwann cell exosomes‐ERK regulatory axis in bone regeneration with translational potential, highlighting the therapeutic value of targeting neural‐osteogenic crosstalk in bone regeneration.
ABSTRACT Microplastic pollution may influence neurodevelopment, yet its relationship with attention‐deficit/hyperactivity disorder (ADHD) remains unclear. We integrated a pediatric cohort, multi‐omics analyses, network toxicology, and animal experiments to investigate polyethylene (PE) microplastic exposure in ADHD vulnerability. Among 90 children, PE was the predominant polymer detected in blood and was more abundant in children with ADHD. Higher PE burden was associated with greater symptom severity, increased IL‐6, and reduced antioxidant capacity. Multi‐omics and network analyses converged on PI3K/AKT1/Nrf2 signaling. In a perinatal nicotine mouse model, developmental PE co‐exposure exacerbated ADHD‐like behaviors, dopaminergic dysfunction, and oxidative injury. Melatonin partially alleviated these abnormalities by restoring PI3K/AKT1/GSK3β and Nrf2 signaling, whereas AAV‐mediated PI3K knockdown weakened its protective effects. Collectively, the human findings identify circulating PE burden as an environmental correlate of ADHD‐related neurodevelopmental vulnerability, while the animal experiments provide evidence that developmental PE co‐exposure can aggravate ADHD‐like abnormalities in a susceptible background.
