Advanced Science最新文献

Hypertrophic scars (HS) are fibroproliferative lesions arising from aberrant wound healing, their high incidence is countered by a lack of effective interventions owing to an incomplete understanding of pathogenesis. Here, we identify dysregulated mitochondrial dynamics as a key driver of HS and develop a new targeted therapy. Specifically, excessive mitochondrial fission was observed in macrophages derived from both human and murine HS tissues. In vitro and in vivo experiments revealed that this imbalance is governed by AURKB-mediated phosphorylation of DRP1 at Ser616 site. Through machine-learning coupled with biological validation, we identified the natural small-molecule Asiaticoside (AS) as a potent AURKB inhibitor. However, AS has limited targeting accuracy and poor bioavailability. To overcome these challenges, we developed cRGD-decorated extracellular vesicles (EVs) loaded with AS (AS@cRGD-EVs), enabling targeted delivery of AS to macrophages within wound tissue. In vitro and in vivo studies showed that AS@cRGD-EVs effectively restrained macrophage mitochondrial fission, rebalanced the inflammatory milieu, and conferred significant anti-scarring efficacy in murine HS models. This work establishes mitochondrial dynamics as a therapeutic axis for HS and delivers a targeted nanotherapeutic ready for translational evaluation.

The growing demand for distributed sustainable energy solutions has driven innovations in atmospheric moisture and droplet-enabled electricity generation. This study introduces a dual-mode moisture-droplet energy-harvesting coating (MDEC) that integrates a moisture electricity generator (MEG) and a triboelectric droplet electricity generator (DEG) into a single scalable coating system. By employing hybrid MXene-bridged graphene oxide (GO) microspheres as the hybrid ink electrode and a fluorocarbon resin dielectric layer, the developed MDEC overcomes the limitations of traditional metal-based electrodes that cannot be scaled for manufacturing and the inefficiency of single-energy harvesting schemes in moisture environments. The MEG component achieves a voltage output of 0.85 V at 25% relative humidity through ion concentration gradient diffusion, whereas the DEG component has a peak power density of 36 W m^-2 with a short-circuit current of 301 µA and an open-circuit voltage of 36.5 V. Modular integration of 360 units enables linear voltage scaling up to 301 V, successfully powering commercial LEDs and charging capacitor devices. This design offers a promising pathway for scalable low-power electronics and Internet of Things (IoT) applications.

Optical tweezers have revolutionized the manipulation of micro- and nano-scale particles, with impacts across biophysics, materials science, and quantum optics. However, their miniaturization for lab-on-a-chip applications is hindered by bulky optical components. While metasurface-based optical tweezers offer an ultracompact alternative, they suffer from laser-induced thermal effects, which degrade their performance, stability, and durability. Here, we overcome this challenge with diamond metasurfaces, leveraging the material's exceptional thermal conductivity, low thermal expansion, and high optical damage threshold to ensure structural integrity under high-power illumination. We experimentally demonstrate versatile particle manipulations using diamond metasurface optical tweezers, including 2D trapping, precise translocation, and controlled rotation via angular momentum transfer. This work not only resolves the critical thermal limitations of conventional metasurface optical tweezers but also establishes a robust platform for high-power, miniaturized optomechanical systems, paving the way for their scalable integration into demanding photonic applications.

Minimizing the footprint of individual cells in a memristor array is crucial for increasing packing density, reducing power consumption and boosting computational performance. However, the downscaling of memristive devices incorporating halide perovskites has been challenging due to the polycrystalline nature of the active layer. In this work, we employed monocrystalline nanoplates of the all-inorganic perovskite CsPbBr₃, and combined nanofabrication and conductive atomic force microscopy to progressively downsize the memristors to the micrometer and nanometer scale. We report an ion crowding effect in these micro- and nano- devices with unilaterally downscaled electrodes. The ion crowding effect is analogous to the current crowding effect in bipolar junction transistors, and originates from the substantially enhanced electric field in the peripheral of downsized electrodes. This effect fundamentally alters the microscopic ionic transport and distribution, leading to distinct switching behaviors and morphological deformation including protrusions and indentations. Further downsizing the critical dimension of memristors to 30 nm intensifies the crowding effect, resulting in anisotropic switching characteristics and unique "hole-in-a-bump" surface feature. This study offers insight into the field-induced ionic behaviors at microscale, and lays the groundwork for miniaturized perovskite memristors.

Mitochondrial dysfunction plays a key role in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). As is known to play a key role in mitochondria, ECSIT, in relation to oxidized mitochondrial DNA is still unclear. This study examines mitochondrial ECSIT expression in MASH mouse models. Mitochondria-targeted ECSIT transgenic (ECSIT^MTG) mice and wild-type (WT) controls are fed a high-fat, high-cholesterol (HFHC) diet for 16 weeks or a methionine- and choline-deficient (MCD) diet for 8 weeks. Results demonstrate that mitochondrial ECSIT overexpression alleviates diet-induced MASH phenotypes. Mechanistically, we demonstrate that mitochondrial ECSIT promotes the localization of the deubiquitinase OTUD3 to mitochondria. OTUD3 then stabilizes SIRT3 via deubiquitination, thereby inhibiting mtDNA oxidation and alleviating steatosis-induced metabolic disorders. Overall, these findings indicate that mitochondrial ECSIT protects against MASH progression by stabilizing SIRT3, suggesting its potential as a therapeutic target.

Superlattices composed of nanometer-thick constituent layers with smooth interfaces exhibit a minimum in their cross-plane thermal conductivity as the period thickness is increased, marking a transition from coherent to incoherent phonon transport. Previous attempts to explain this minimum using the phonon Boltzmann transport equation (BTE) required an ad hoc diffuse interface scattering model due to the BTE's inherent particle-based framework. We apply the phonon Wigner transport equation (WTE) to study superlattices with smooth interfaces, a framework that inherently includes both the particle-like (i.e., population-channel) and wave-like (i.e., coherence-channel) contributions to thermal conductivity. Our results reveal that the WTE coherence channel is responsible for the thermal conductivity increase in the incoherent regime. The two distinct phonon wave effects in superlattices-the coherent transport induced by wave interference at the interfaces and the WTE coherence-channel transport enabled by tunneling between phonon modes-are examined in detail, along with their connection to the interfacial vibrational modes.

Bone metastasis is a devastating consequence of lung cancer. However, the key metabolic factors that determine the risk of bone metastasis remain unclear. Here, we show that glucose transporter type 3 (SLC2A3) is notably overexpressed by lung cancer bone metastatic cells and tissues, as a facilitator of lung cancer bone metastasis. Additionally, SLC2A3 promotes glucose metabolism, which promotes tumor cell proliferation and metastasis via lactate-mediated p53 lactylation. Within the tumor microenvironment, cancer cells serve as the primary source of secreted lactate, which induces protumor bone metastasis via osteoclast differentiation and suppresses the antitumor activity of CD8⁺ T cells. Subsequently, we developed Paris saponin VII, a SLC2A3 inhibitor that effectively suppressed bone metastasis in lung cancer bone metastasis mouse models and patient organoids. Notably, either inhibition of SLC2A3 or lactate limitation improved the tumor response and increased the sensitivity of lung cancer bone metastases to PD-1 treatment. Collectively, our findings highlight that targeting SLC2A3-mediated lactate metabolism, either alone or in combination with PD-1 inhibition, is a potential strategy for treating lung cancer bone metastasis.

Organ size homeostasis plays vital roles in maintaining the normal growth and development in both animals and plants. Grain size is an important agronomic trait for stable yield, quality, domestication, and breeding in crops, but the molecular mechanism underlying final size homeostasis remains unclear. Here, we identified three genes, OsGRX8, OsbZIP47 and OsbZIP08, underlying grain-length variation by genome-wide association study (GWAS) in rice. We confirmed that OsGRX8, OsbZIP47 and OsbZIP08 interact with each other and transcription factors OsbZIP47 negatively and OsbZIP08 positively regulate the expression of the downstream glutaredoxin-encoding gene OsGRX8. The binding ability of OsbZIP08 on the promoter of OsGRX8 in indica is higher than that in japonica, leading the differential expression of OsGRX8 between two subspecies. We further revealed a natural negative feedback regulatory mechanism for grain size homeostasis: OsGRX8 controls the reduction modification of OsbZIP47 thereby increasing OsbZIP47-OsbZIP08 interaction in a redox-dependent way or directly interacts with OsbZIP08 in a redox-independent way to inhibit the transcriptional activity of OsbZIP08 on OsGRX8. Finally, we revealed that two self-regulatory haplotypes (SRHs), caused by co-selected variations of the three genetically unlinked genes which formed the negative feedback loops, showed distinctive indica-japonica differentiation and large genetic contribution to key yield traits. Our findings provided the evolutional OsGRX8-(OsbZIP47)-OsbZIP08-OsGRX8 regulatory loops for synergistically controlling grain size homeostasis by fine-tuning OsGRX8 self-expression, offering a novel case for uncovering QTL interactions underlying genetic diversity of important traits in crops.

CuCrP₂S₆ is a van der Waals multiferroic where the tunable Cu⁺ sublattice underpins its exceptional ferroelectric and electronic switching properties. Yet, the microscopic mechanism governing Cu⁺ ordering has remained elusive. Here, we combine single-crystal X-ray and neutron diffraction with pair distribution function analysis to uncover a temperature-driven evolution of Cu⁺ ordering, giving rise to an incommensurate quasi-antipolar phase between the paraelectric and antiferroelectric states. The modulation originates from correlated Cu⁺ occupancy redistribution coupled to breathing distortion of surrounding S₃ triangles, establishing a symmetry-adapted lattice distortion mode. Diffuse scattering persisting over 35 K above the transition confirms that the structural instability follows an order-disorder mechanism. The spontaneous off-centering of Cu⁺ positions CuCrP₂S₆ as a model platform for correlated order-disorder phenomena in 2D layered ferroics, and provides design principles for next-generation memory and logic devices.

Liquid-liquid phase separation (LLPS) of polymers underlies the formation of biomolecular condensates and offers a versatile route to functional soft materials. Traditionally, LLPS is attributed to changes in solvent quality or associative coacervation, but here a purely entropic connectivity-driven mechanism is demonstrated: reversible crosslinking. Using coarse-grained simulations of a minimal bead-spring model in good solvent, it is shown that transient, pairwise crosslinks alone can drive phase separation at ultralow polymer densities, yielding highly swollen, water-rich condensates. The phase behavior exhibits closed-loop coexistence and re-entrant percolation. This is captured quantitatively by a mean-field Semenov-Rubinstein theory with a single fit parameter, the effective repulsion parameter. Notably, phase boundaries are largely robust to rearrangements of crosslinkable domains along the sequence; only highly blocky sequences appreciably reduce the phase separation region and can even convert condensates into micelles or connected micelle networks. These results establish an entropy-enabled mechanism for mesoscale organization and suggest routes to programmable, membraneless materials in synthetic and RNA-protein contexts.