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The ryanodine receptor (RyR2) is an intracellular Ca2+ release channel which mediates numerous cellular functions across different tissues. Dysregulation of RyR2 channel activity leads to pathological Ca2+ release, which often underlies disrupted cellular signaling in disease states. In the heart, RyR2 channels forms discrete clusters and calcium release units (CRUs) which control channel activity. These structures demonstrate nanoscale remodeling in disease states associated with pathological Ca2+ release activity in the heart. Hence, these nanoscale structures are critical in regulating Ca2+ release in health and disease. RyR2 is also expressed in brain; however, whether analogous clusters and CRUs form in neurons remains unexplored. Using super-resolution imaging, we assessed RyR2 organization in CA1 pyramidal neurons of wild-type mice. Furthermore, we used the APP/PS1 mouse model of Alzheimer's disease (AD) to assess whether there is nanoscale remodeling of RyR2 in a setting associated with pathological Ca2+ release in neurons. Here, we provide the first identification and detailed characterization of RyR2 clusters in central nervous system neurons, which are comparable to those reported in the heart. Moreover, we observed a decrease in RyR2 cluster size and reduced CRU organization in AD mice at an age associated with high plaque burden and cognitive deficits. This remodeling is analogous to that reported in pathological states in the heart. Together, these findings implicate the nanoscale remodeling of RyR2 clusters and CRUs as a novel mechanism underlying Ca2+ channel dysregulation and neuronal dysfunction in AD.

Three-dimensional metastructures with nanoscale feature sizes exhibit unique properties compared with structures with larger feature sizes, but are difficult to fabricate. Here we introduce implosion carving (ImpCarv), a method for photopatterning vacancies of complex geometry throughout materials, followed by isotropic shrinkage (>10-fold). ImpCarv works by photoactivating sensitizers to generate reactive oxygen species that cleave a swollen hydrogel at defined points, followed by controlled shrinkage via dehydration. ImpCarv creates three-dimensional metastructures where the refractive index of each point throughout a material can be specified with nanoscale precision via material presence or absence. By leveraging refractive index programmability for precise phase control, we demonstrate an all-optical machine learning device with nanoscale neuron sizes operating at visible wavelengths. ImpCarv may thus support diverse applications in nanophotonics and nanotechnology.

Architected metamaterials derive their exceptional mechanical performance from their precisely-tailored underlying topologies, enabling access to regions of materials selection charts unattainable by conventional materials. While substantial advances have been achieved at micro-, meso-, and macroscales, further improvements are increasingly constrained, motivating exploration of nanoscale architected materials where surface and size effects dominate the overall multiphysics performance. Here, we resort to molecular dynamics simulations to systematically explore the mechanical response of nickel-based nano-architected metamaterials. By varying topology, relative density, crystallinity, and grain size, we demonstrate the broad tunability of elastic moduli, strength, and Poisson's ratio enabled by the rational design of underlying nano-architecture. Notably, the proposed nano-architected metamaterials outperform most previously reported architected materials at comparable densities, highlighting the effectiveness of nanoscale topology-driven designs. Atomistic analyses reveal that nanoscale free surfaces promote dislocation nucleation while inhibiting dislocation propagation, leading to flow stresses exceeding those of bulk counterparts. To bridge length scales and draw inspiration from crystallography, we design and 3D print hierarchical polymeric metamaterials and experimentally characterize their mechanical behavior. Despite being fabricated from an intrinsically brittle polymer, these structures exhibit topology-dependent stiffness and strength, alongside ductile plastic deformation and enhanced toughness, attributable to their hierarchical architectures. Together, this work introduces a crystallography-inspired architectural design paradigm for mechanical metamaterials and imparts scalable guidelines for achieving lightweight, mechanically efficient structures across multiple length scales.

Ice fall incidents, such as detached ice chunks from bridge stay cables, pose not only serious safety hazards to pedestrians and vehicles below but also significant serviceability issues, as bridge closures required for inspection or ice removal can lead to costly disruptions. The current trend of climate change exacerbates this kind of hazard. The availability of a reliable engineering tool, such as an accurate numerical model grounded in nanoscale melt-front physics, is imperative to provide a clear insight into the ice detachment mechanism and develop effective de-icing solutions. Classical molecular dynamics simulations are conducted in the current study to investigate the melting of an ice cube in an atomically flat silver slab. The TIP4P/ice water model is adopted and the simulation is conducted in canonical ensemble with a layer-resolved Langevin thermostat. The phase evolution is tracked via the averaged tetrahedral order parameter, while systematically varying five controls: the depth of heated layers, the silver substrate thickness, the ice thickness, the lateral confinement, and the ice crystal contact orientation (basal vs prism). Results show that melting is controlled primarily by the substrate temperature; variations in heat-conducting-layer count had a minor influence and converged to similar end states. Doubling the ice thickness increases the melt time approximately by three times, whereas relaxing periodic boundaries reshapes the melt into domes or spreading films. Presenting the basal plane instead of a prism plane accelerates loss of crystalline order. Collectively, the simulations yield a numerically consistent set of parameters that not only advances the existing knowledge of nanoscale ice melting simulation but can also be transferred to continuum-scale de-icing simulations, enabling accurate modeling of melt-induced ice detachment from structural components, such as bridge stay cables.

Plasmonic nanostructures enable light-driven chemical transformations through localized electromagnetic fields and hot-carrier generation. Here, we demonstrate that amide bond formation between carboxylic acids and amines, which is thermodynamically unfavorable under ambient conditions, can be directly driven in plasmonic nanogaps without coupling agents or thermal activation. Under resonant excitation, hot electrons generated in the nanogap activate the carbonyl group within a spatially confined environment, enabling a nucleophilic attack and subsequent bond formation. In situ surface-enhanced Raman spectroscopy reveals the emergence of amide vibrational modes, supported by density functional theory calculations. The reaction exhibits a clear excitation power threshold, is suppressed under off-resonant conditions, and is not induced by thermal heating alone, confirming its nonthermal origin. Furthermore, plasmon-induced nanoparticle aggregation provides independent evidence of covalent bond formation at the nanoscale. These findings establish plasmonic nanogaps as functional reaction environments that enable reactions without coupling agents and demonstrate that nanoscale confinement and localized electronic excitation can drive thermodynamically challenging transformations.

Morphology is a critical determinant of the photovoltaic performance of organic solar cells (OSCs), as it governs charge generation, separation, and transport by regulating nanoscale phase separation and molecular packing within the active layer. Among the various strategies developed to control morphology, solid additives (SAs) have emerged as a particularly promising approach. Offering advantages such as low cost and ease of incorporation, SAs enable precise tuning of active layer morphology without the need for complex synthetic modification. By promotion of favorable nanoscale phase separation, SAs can facilitate the formation of well-organized domains that enhance charge transport pathways while reducing charge recombination losses. Recent advances have underscored the significant potential of SA engineering in advancing OSCs toward large-scale commercial deployment. This review provides a comprehensive summary of recent progress in SA development with a particular emphasis on their roles in regulating film formation dynamics and optimizing morphologies. Finally, we highlight the remaining challenges and propose future research directions to further exploit SA engineering in the realization of high-efficiency, stable organic photovoltaic devices.

This work developed and evaluated a crocin-coated zinc-sodium alginate-polyethylene glycol (Zn/SAG/PEG/Cr) nanocomposite as a potential therapeutic against bladder cancer using T24 human carcinoma and Vero kidney epithelial cells. Systematic characterization confirmed successful zinc incorporation, a crystalline inorganic phase, and nanoscale particle size with high compositional purity. MTT assay demonstrated that the nanocomposite exerts selective, concentration-dependent cytotoxicity against T24 cells while maintaining biocompatibility with normal Vero cells. Mechanistic analysis revealed that treatment of the nanocomposite significantly enhanced intracellular reactive oxygen species (ROS) generation, disrupted mitochondrial membrane potential, and compromised plasma membrane integrity. Furthermore, the nanocomposite suppressed pro-inflammatory mediators (TNF-α, NF-κB, COX-2, and IL-6) and induced apoptosis, evidenced by elevated Bax, caspase-3, and caspase-9 levels alongside reduced Bcl-2 expression. Crucially, the formulated nanocomposite attenuated the PI3K/Akt/mTOR signaling pathway, a key regulator of bladder cancer progression. Despite these potent anti-oncogenic effects, challenges remain regarding the precise control of crocin release kinetics and the long-term metabolic clearance of the metallic zinc component. Future prospects involve validating these findings in orthotopic animal models to assess systemic toxicity and optimizing the formulation for targeted intravesical delivery to improve clinical translation.

Thermal management has emerged as a materials bottleneck for three-dimensional integrated circuits, which are being actively explored to enable dense vertical connectivity and mitigate interconnect delay and energy consumption. Unlike 2D-structure chips, stacked tiers confine dissipation within a boundary-rich back-end-of-line (BEOL) heterostructure. Heat must cross ultrathin dielectrics, porous interlayers, and numerous metal/dielectric and bonding interfaces. Consequently, interfacial resistance and thin-film size effects often determine temperature increase and reliability margins. This perspective highlights the materials physics underlying thermal limits and relates it to integration and design considerations. First, lattice heating is described by a carrier-phonon relaxation pathway in which the optical phonon bath serves as a transient energy reservoir and modulates ultrafast thermal responses. Second, heat transport in nanoscale BEOL multilayer stacks is discussed with emphasis on thickness-dependent conduction and finite thermal penetration that filters temperature transients across tiers. Then, vertical heat removal is governed by interfacial thermal boundary conductance (TBC) and via-network electrothermal coupling with parasitic Joule heating. Finally, thermal pathways are discussed, including thermally conductive insulating dielectrics and heat spreaders, TBC enhancing interlayers, low-temperature bonding and alternative metallization, and functional via architectures consistent with the BEOL thermal budget.

Inadequate control over aggregation and morphology evolution remains a major constraint in ternary organic solar cells (TOSCs). To address this, two small-molecule donors, C1 and C2, were designed with identical backbones but distinct aromatic connecting units: a phenyl linkage in C1 and a thiophene linkage in C2. It is revealed that steric torsion is utilized by the phenyl linkage in C1 to suppress excessive self-aggregation and induce balanced, mixed-orientation molecular packing. In contrast, the thiophene linkage in C2 promotes a coplanar backbone with tighter, predominantly face-on π-π stacking, leading to over-crystallization. Consequently, C1 facilitates finer interpenetrating networks with redistributed π-π interactions, supporting efficient in-plane charge transport. Benefiting from this optimized morphology and favorable energy alignment, the PM6:Y6:C1 device achieves an outstanding Fill Factor (FF) of 77.90% and a Power Conversion Efficiency (PCE) of 17.98%, significantly outperforming binary devices and the C2-based ternary devices. This work establishes aromatic connecting unit modulation as a pivotal strategy for precisely controlling aggregation and nanoscale morphology in high-performance TOSCs.

Microelectrode arrays are an essential tool for interfacing with nerve tissue to better understand brain functioning, as well as for therapeutic applications. Yet, the structural customizability of microelectrode arrays and the integration of specific materials into electrode designs remain challenging. Two-photon polymerization (2PP) is a high-resolution additive fabrication technique capable of producing micro- and nanoscale architectures, thus offering design flexibility for microelectrode arrays. However, due to the limited electrical conductivity of photo-cross-linkable polymers, 2PP three-dimensional (3D) printing is not widely adopted for the fabrication of microelectrode arrays yet. In this work, we present the millimeter-scaled integration of the conductive polymer poly(3,4-ethylenedioxythiophene):tetrafluoroborate (PEDOT:BF4) into 2PP 3D-printed neural probe architectures via electrochemical deposition. Unlike state-of-the-art thin-film PEDOT coatings, this approach enables the formation of vertically extended, entirely polymer-based electrodes with a length in the millimeter range. These all-polymer electrode arrays exhibit low impedance, excellent electrochemical and mechanical stability, and enable neural recordings in freely moving rats. This fabrication process may thus provide a platform technology for customizable microelectrode arrays, demonstrating the effective integration of a conductive polymer into 2PP 3D-printed microneedle arrays. This platform could be leveraged for a wide range of applications in the broader field of bioelectronics.

Cardiometabolic diseases (CMDs) represent a growing global health burden, with chronic inflammation and gut microbiota dysbiosis emerging as central contributors to their pathogenesis. Among the diverse microbial products influencing host physiology, bacterial extracellular vesicles (BEVs) have gained attention as potent mediators of interkingdom communication. These nanoscale vesicles, secreted by both gram-positive and gram-negative bacteria, carry a complex cargo of proteins, lipids, nucleic acids, and pathogen-associated molecular patterns (PAMPs) that interact with host pattern recognition receptors (PRRs) to modulate immune and metabolic responses. BEVs can traverse intestinal barriers, disseminate systemically, and accumulate in cardiometabolic tissues, where they influence inflammation, insulin sensitivity, and organ function. This review synthesizes current evidence linking BEVs to CMDs, explores mechanisms of BEV-host crosstalk, and highlights their potential as diagnostic biomarkers and therapeutic vectors. We also discuss emerging technologies for BEV characterization and propose future research directions to better understand their role in CMD pathophysiology.

Transcription of eukaryotic genes by RNA Polymerase II occurs in temporal bursts and spatial clusters. It is regulated by dozens of transcription factor and coactivator proteins and guided by epigenetic histone marks. Colocalization of transcription machinery in dense foci suggests that cooperative effects orchestrate the process. Factory or condensate models provide a framework for the spatial assembly of the transcription machinery at highly active chromatin loci. But conventional methods lack the resolution to determine how chromatin regulatory elements interact with spatial clusters of the transcription machinery, and whether chromatin structural features modulate functional output. Here, we use super-resolution microscopy to elucidate nanoscale organization of regulatory chromatin at Pol II clusters across scales. We find that Pol II clusters exist on a continuous spectrum of sizes and represent promoter chromatin hubs. We uncover a layered organization of regulatory chromatin, where Pol II clusters form at H3K27ac and H3K4me3-rich domains while H3K4me1 positions peripherally at the surface of large Pol II clusters. Perturbation experiments are consistent with a model in which cohesin loop extrusion forms the active chromatin scaffold underlying transcription assemblies while condensate-driven interactions play only a minor role in genome organization at these sites. Importantly, the number and size of transcriptional burst size increases with Pol II cluster size, revealing directly the cooperative benefits of transcription organization in promoter hubs and a functional consequence of local chromatin structure.

Terahertz (THz) radiation provides an effective means to probe and manipulate collective molecular dynamics in confined water. In this work, nonequilibrium molecular dynamics simulations are employed to investigate the frequency-dependent thermal response and microscopic structure of water confined in armchair-type double-walled carbon nanotubes (DWCNTs). Water encapsulated in (3, 3)@(13, 13), (3, 3)@(18, 18), and (3, 3)@(23, 23) DWCNTs is subjected to linearly polarized THz electric fields applied either parallel or perpendicular to the nanotube axis, and the resulting temperature jump, ΔT, is analyzed over a broad THz frequency range. In comparison with bulk water, confined water exhibits substantially enhanced and highly frequency-selective heating, with a pronounced dependence on field polarization. Under axial polarization, water confined in the narrowest (3, 3)@(13, 13) DWCNT shows a strong resonant response, yielding a maximum temperature increase of ΔT ∼ 370 K, approximately 3.3 times that of bulk water. This enhancement weakens systematically with increasing outer nanotube diameter and higher initial temperature. Analyses of oxygen-oxygen radial distribution functions and transverse density profiles reveal that nanoscale confinement induces pronounced molecular ordering and spatial localization, characterized by ring-like density distributions within the nanotube cross section. These confinement-induced structural features indicate a strong coupling between collective molecular motions and external THz fields, demonstrating that geometric confinement and field polarization jointly regulate resonant energy absorption in nanoscale aqueous systems.