Spatiotemporally controlled, tumor-selective activation of N-oxide prodrugs within tumors remains a longstanding challenge in cancer therapy. Herein, we report a broadly applicable strategy driven by clinical ultrasound for the reductive deoxygenation of N-oxides, enabling externally controlled prodrug activation via a riboflavin tetrabutyrate (TBR)/NADPH redox-relay system. Under mild, clinically translatable ultrasound (1 MHz, 2.0 W/cm2, 50% duty cycle), this platform promotes efficient N-O bond cleavage through single-electron transfer and hydrogen-atom transfer. Density functional theory calculations support that all ground-state steps are thermodynamically favorable with negative Gibbs free-energy changes (ΔG), supporting the feasibility of sonochemical N-oxide reduction. This method exhibits broad substrate generality toward diverse N-oxide compounds, including the clinically investigated hypoxia-activated prodrug banoxantrone (AQ4N), quinoline N-oxide, 8-hydroxyquinoline N-oxide, clozapine N-oxide, and olanzapine N-oxide. In hypoxic tumor cells, the ultrasound/TBR system enhances intracellular AQ4 formation significantly and reduces the IC50 of AQ4N from 35.0 to 2.8 mg/L. In vivo, the combination of AQ4N, TBR, and ultrasound increased intratumoral AQ4 formation by approximately 24.1-fold and achieved a tumor inhibition rate of 113.7%, outperforming AQ4N monotherapy (82.3%). This sonochemically triggered activation platform bypasses the heterogeneity of tumor-microenvironment stimuli and offers a versatile, externally controlled framework for precision prodrug chemotherapy with deep tissue penetration and clinical translatability.

Metal-ceramic composites often face an inherent trade-off between strength and toughness, limiting their potential in advanced structural applications. This study introduces a novel strategy for fabricating Al/Al2O3 composites with multi-scale hierarchical architectures, leveraging digital light processing (DLP), confined freeze-casting, and pressure infiltration to create interpenetrating metallic networks within discrete ceramic scaffolds. By optimizing sintering temperatures and printing parameters, the resulting composites, with 33.2-37.0 vol% ceramic content, achieve bending strengths of 576-605 MPa, crack-initiation toughness (KIc) of 12.8-13.4 MPa & sdot;m1/2, and crack-growth toughness (KJc) of 48-51 MPa & sdot;m1/2, surpassing the performance of most conventional Al/Al2O3 composites. These remarkable properties stem from synergistic strengthening-toughening mechanisms across millimeter, micrometer, and submicron/nanoscale structural levels, including crack deflection, bridging, blunting, and interfacial sliding. This work not only addresses the strength-toughness dilemma but also opens a new avenue for the design of high-performance composites with enhanced damage tolerance and mechanical reliability.

Hydrogels derived from biomacromolecules offer excellent biocompatibility for biomedical applications, yet their limited mechanical strength often restricts broader use. Aramid nanofibers (ANFs) have emerged as high-performance building blocks for nanocomposites, but the influence of their surface states on nodal connectivity and reinforcement efficiency remains insufficiently understood. In this work, we utilize ANFs as a fibrous scaffold to construct composite hydrogels with gelatin. Gelatin coats ANF surfaces through interfacial hydrogen bonding, promoting inter-fiber connections, as confirmed by graph-theoretical analysis of average nodal connectivity. The resulting composite hydrogels can be further cross-linked with tannic acid to form a hierarchical network with markedly enhanced strength and modulus. The incorporation of tannic acid also enables in situ formation of monodisperse silver nanoparticles, imparting antimicrobial functionality. Moreover, the hydrogels exhibit sustained tannic-acid release while maintaining mechanical integrity. This synergistic integration of synthetic ANFs with natural biomolecules provides a robust platform for developing multifunctional hydrogels for biomedical applications.

Multimodal nanotherapeutic systems capable of integrating photothermal, catalytic, and gas-mediated strategies offer powerful opportunities to overcome the limitations of single-mode cancer therapies. Here, we develop a near-infrared (NIR) light-activated biomimetic nanomotor for targeted nitric oxide (NO) delivery and synergistic cancer therapy. The nanomotor is constructed from bowl-shaped mesoporous polydopamine nanoparticles loaded with Fe(II) as a Fenton catalyst and BNN6 as a thermally responsive NO donor (denoted as PFB). To endow tumor specificity, the nanomotor is further camouflaged with MCF-7 cancer cell membrane (PFB@CM), enabling homologous recognition and enhanced intratumoral accumulation. Upon NIR irradiation, PFB@CM exhibits strong photothermal conversion efficiency that initiates 3 synergistic processes: (a) self-thermophoretic propulsion that promotes cellular internalization; (b) heat-triggered decomposition of BNN6 for precise NO release; and (c) heat-accelerated Fe(II) release from the polydopamine matrix. The liberated Fe(II) catalyzes endogenous H2O2 via a Fenton-like reaction to generate reactive oxygen species, which subsequently react with NO to yield highly cytotoxic reactive nitrogen species. This cascade amplifies oxidative and nitrosative stress within tumor cells, enabling photothermal, chemodynamic, and NO-mediated synergistic therapy. The design of PFB@CM integrates homologous targeting, autonomous motility, and NIR-responsive multimechanism activation, demonstrating a versatile strategy for precision nanomedicine and highlighting the potential of light-activated nanomotors for safe and effective multimodal cancer therapy.

Structural gradients are prevalent in biological hard tissues such as nacre, bones, tooth enamel, and eggshells, where they play a crucial role in optimizing load-bearing performance. While biomineralization naturally creates elegant gradations using a diverse range of anisotropic minerals, replicating this concept in synthetic materials with 1D building blocks is challenging due to the lack of mechanisms for controlling axial alignment at the microand nanoscale. In this work, a layer-by-layer, self-regulated growth of fluorapatite crystallites is used to synthesize columnar nanocomposites with structural gradients that closely resemble the architecture of eggshells. As fluorapatite layers stack, the crystallographic alignment gradually improves due to spatial restrictions imposed by radially growing crystallites. Epoxy infiltration results in columnar nanocomposites with surface modulus and hardness comparable to tooth enamel, decreasing gradually toward the interior. The variation in crystallite orientation also governs the gradient in strain rate sensitivity and resistance to creep deformation, as confirmed by finite element simulations. These gradient mechanical properties can be tailored by adjusting the growth kinetics of fluorapatite crystallites, which control lateral growth cessation and the magnitude of alignment gradients. Eggshell-like columnar nanocomposites provide a promising biomimetic prototype for designing structural materials with intricate features.

Biomimetic mineralization of iron oxide on cellulose nanocrystals creates chiral nanowhiskers with an anisotropy-dependent g -factor, altering the response of helical photonic films to magnetic fields.

Osmotic energy from mixing seawater and river water offers a promising alternative to traditional nonrenewable resources. Harvesting osmotic energy requires the design of ultrathin membranes with high ion selectivity for high ionic conductance. However, lab-scale membranes suffer from high-cost, low mechanical properties, and limited membrane area. Here, we demonstrate the fabrication of large-scale self-standing aramid nanofiber (ANF) membranes with thickness of several micrometers through a simple blade-coating method. The properties of fabricated ANF membranes were investigated in detail, which showed great mechanical chemical stability, high mechanical properties, and surface charge density. The application for osmotic energy conversion was further explored, and the ANF membrane with intact structure gave an output power density of 0.83 W m-2 for 50-fold NaCl. Moreover, the power density can reach up to 7.63 W m-2 when the concentration gradient increased to 500-fold. The ANF energy generator maintained the output capacity for 15 days. This scalable and low-cost ANF membrane provides a promising opportunity to harvest osmotic energy for practical energy plants.

Heterogenous and gradient structures are common in biological materials and essential for achieving exceptional mechanical properties from cost-effective components. Integrating glass flakes into this design concept holds great potential for enhancing the performance of bioinspired transparent materials, particularly through a synthesis approach that allows for precise control over their structural properties. In this study, we demonstrate that glass flakes modified with silane agents can spontaneously form a surface layer at the air-liquid interface. This interfacial assembly enables the layer-by-layer embedding of highly aligned glass flakes within the polymer matrix. By varying the aspect ratios of the glass flakes during film construction, we can create a controllable gradient, nacre-like architecture that offers an enhanced balance of strength and toughness, while maintaining transparency and haze comparable to the homogeneous structures. Lamination of both homogeneous and heterogeneous composite films further enables the evaluation of bending properties. The heterogeneous structure results in a superior combination of flexural strength, bending energy, fracture toughness, and work of fracture. Finite element simulations highlight the critical role of gradient structures and repeated sequences in redistributing stress and mitigating crack propagation. The interfacial assembly of glass flakes offers a versatile platform for optimizing the performance of bioinspired transparent materials by enabling precise and flexible manipulation of microstructures.

Aramid nanofibers (ANFs) have emerged as promising building blocks for bioinspired materials due to their exceptional mechanical strength and chemical stability. However, their widespread application has been hindered by the limitations of conventional top-down synthesis from Kevlar, which is costly, inefficient, and offers limited control over molecular structure. Addressing this challenge, a cost-effective, bottom-up strategy is reported to fabricate limpet-inspired composite fibers by combining the self-assembly of ANFs from poly(paraphenylene terephthalamide) polyanions with in situ iron oxide mineralization. This approach enables spontaneous co-alignment of ANFs and β-FeOOH nanowhiskers, emulating the hierarchical architecture of limpet teeth. Guided by hydrogen bonding and π-π stacking, self-assembly regulates nanoscale ordering, crystallinity, and interfacial interactions-critical for enhancing mechanical performance. The resulting fibers exhibit an ultimate strength of 1.8 GPa, modulus of 42.7 GPa, and toughness of 336 MJ m- 3, surpassing spider silk and many high-performance synthetic fibers. Multiscale toughening mechanisms, including crystallographic slip, melt-recrystallization, and micro-crazing, are enabled by the semicrystalline structure of the ANFs. Beyond mechanical properties, the fibers display paramagnetic behavior and UV resistance. This work introduces a scalable platform for multifunctional composite fibers, integrating molecular-level control with structural biomimicry and advanced functionality.

Resistance to DNA damage is one of the primary mechanisms by which tumor cells evade the effects of standard chemotherapeutic agents and radiotherapy. Dynamic and complex interactions between the tumor microenvironment (TME) and tumor cells critically influence the DNA damage response. Interleukin-33 (IL-33) is a multifunctional cytokine secreted at high levels in response to cellular damage and stress. Recently, increasing evidence has suggested that IL-33 plays a key role in promoting the therapeutic resistance of tumors. However, the actual source of IL-33 during cancer therapy and how IL-33 contributes to a resistant TME remain incompletely understood. In this study, we found that both cancer-associated fibroblasts (CAFs) and tumor cells treated with DNA damage-inducing agents expressed and secreted high levels of IL-33, subsequently leading to enhanced DNA damage repair efficacy. Mechanistically, nuclear IL-33 primarily functions as a transcriptional co-activator of homologous recombination repair (HRR) genes, whereas the active form of IL-33 can drive the non-homologous end joining (NHEJ) pathway via the canonical IL-33/ST2 axis. Overall, we demonstrated that IL-33 plays a key role in mediating a DNA damage-resistant TME, which could represent a potential therapeutic vulnerability in chemoresistant cancer cells.

Designing and developing multifunctional wound dressings with sustained drug-release capability is a promising strategy for minimizing the risks of wound infection and promoting wound healing. Collagen composite aerogels have been widely employed as a medical device building block, although they still fail to display competitive mechanical properties and sustained drug-release capability. Thus, we solve this challenge by pursuing a multi-scale design method, which utilizes glutamic acid (Glu) to regulate the collagen self-assembly behavior to obtain a network-structured collagen/glutamate composite aerogel with sustained drug release, biocompatibility, and hemostatic ability. Through structural and performance analysis, the Glu endows collagen composite aerogels with excellent structural stability and superior mechanical properties by regulating the intermolecular interaction between collagen molecules, which made the aerogels achieve a supramolecular network structure through the entanglement of high-density collagen fibrils and showed excellent sustained drug-release characteristics. Moreover, collagen/Glu composite aerogels also exhibited outstanding biocompatibility and hemostatic capability. This self-assembly strategy provides new insight aimed at collagen composite aerogels with supramolecular network structures and sustained drug-release capability, making them a promising candidate for wound dressings in future clinical applications.

The development of robust and active oxygen evolution reaction (OER) electrocatalysts is urgently desirable for the widespread implementation of proton exchange membrane water electrolyzers (PEMWE), yet remains a critical challenge. We propose a catalyst named U-IrRuOx@IrRu (where "U" denotes "ultrathin"), which features a spontaneously formed amorphous oxide shell that synergistically optimizes the electronic structure and corrosion resistance. Combined experimental and theoretical studies reveal that the oxyphilic Ru-induced electronic modulation weakens Ir-O binding strength, thereby accelerating the rate-determining step of *OOH formation. In addition, the metallic alloy core functions as an electron reservoir, suppressing excessive oxidation of active sites while ensuring high conductivity. Due to these attributes, the U-IrRuOx@IrRu demonstrates a low overpotential of 230 mV at 10 mA cm-2 , outperforming commercial IrO2 (CM) by 65 mV. When integrated into a PEMWE with an ultra-low Ir loading of 0.25 mgIr cm-2 , it delivers an industrial current density of 2 A cm-2 at 1.74 V and 3 A cm-2 at 1.836 V, surpassing the U.S. Department of Energy (DOE) 2025 target. More impressively, the U-IrRuOx@IrRubased electrolyzer can stably operate for over 550 h, with an extremely low decay rate of 7.52 lV h-1 , corresponding to a predicted lifespan of 23,000 h with 90 % performance retention. (c) 2025 Science Press and Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. and Science Press. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) selectively arrest malignant cells in the G1 phase of cell cycle by inhibiting CDK4/6-mediated phosphorylation of retinoblastoma protein. However, CDK4/6i therapy is often ineffective against triple-negative breast cancer (TNBC) due to the high lysosomal content in TNBC cells, which sequesters the drugs and prevents them from reaching their nuclear target. To address this challenge, three pH- and glutathione-responsive poly(amino acid) nanogels composed of methoxy poly(ethylene glycol) of various lengths and poly(L-glutamic acid-co-L-cystine) (mPEG- P(Glu10-co-Cys25)) were developed to efficiently deliver the CDK4/6i abemaciclib (ABE) to TNBC cells. These nanogels bypassed lysosomal sequestration, thereby enhancing the efficacy of molecularly targeted immunotherapy. Among the nanogels, the formulation with mPEG2000 (NG2000) exhibited the highest efficiency in delivering ABE, resulting in increased cell apoptosis, activation of an anti-cancer immune response, reduction of immunosuppression, and improved therapeutic outcomes against TNBC. Furthermore, NG2000/ABE enhanced immune checkpoint therapy for TNBC, achieving a tumor inhibition rate of 89.66%. These findings demonstrate the potential of poly(amino acid) nanoformulations for delivering CDK4/6 inhibitors as molecularly targeted immunotherapy for TNBC in clinical applications.

Nickel (Ni) foil current collectors exhibit high stability, making them promising candidate materials for next-generation high-performance anode-free lithium metal batteries (AFLMBs). However, the inherent lithiophobicity of Ni foil results in compromised reversibility of lithium deposition and stripping on its surface, significantly limiting its practical application. Herein, a ZnNi alloy layer (ZnNi@Ni) is fabricated on Ni foil via thermal evaporation and an in situ alloying method. Uniform ZnNi nanoarrays with strong adhesion to the substrate are constructed, providing abundant lithiophilic nucleation sites while maintaining electrochemical inertness toward metallic Li. In contrast, the lithiophilic Zn coating used as a control sample suffers mechanical failure due to alloying-induced volume expansion during lithium deposition, ultimately compromising its lithiophilicity. Density functional theory (DFT) calculations confirm ZnNi's enhanced lithiophilicity and strong adsorption of TFSI- anions, which synergistically reduce Li nucleation barriers, guide uniform Li deposition, and promote LiF-rich SEI formation. Consequently, Li deposition with a high areal capacity (10 mAh cm-2) and low volume expansion is achieved on ZnNi@Ni. In ZnNi@Ni||Li half-cells, and significant reversibility is demonstrated, sustaining 800 cycles at 1 mA cm-2, 1 mAh cm-2 with 99.21% average Coulombic efficiency (CE), and 250 cycles under more rigorous conditions (3 mA cm-2, 6 mAh cm-2) with 99.40% CE. When assembled into AFLMB with a Ni-rich ternary cathode (LiNi0.94Co0.03Mn0.03O2, NCM-Ni94) and Li3N prelithiation, the battery retains 89.6% capacity after 100 cycles and delivers an energy density exceeding 400 Wh kg-1. This work demonstrates a high-performance lithiophilic material design strategy, offering a promising route toward practical high-energy-density AFLMBs.

Polyphosphate (polyP), a biocompatible and biodegradable polymer, holds significant promise for drug delivery applications. Recent studies reveal that polyP and Mn2+ ions can self-assemble into nanosheets, with cetrimonium (CTA) acting as a templating agent. However, the underlying molecular mechanism remains poorly understood. Using coarse-grained molecular dynamics simulations, we reveal that polyP and CTA form a stable, sandwich-like nanostructure, with polyP positioned at the center. Self-assembly is driven by hydrophobic interactions, with curvature controlled by surface tension, which is determined by the interplay of electrostatic and hydrophobic interactions at the polyP/CTA interface. The addition of Mn2+ and oleate ions into the solution flattens the structure, while higher polyP-to-CTA ratios promote Mn2+ penetration. These findings highlight the power of simulations in uncovering self-assembly mechanisms and advancing applications in drug delivery.

Polymer fibers that combine high toughness and heat resistance are hard to achieve, which, however, hold tremendous promise in demanding applications such as aerospace and military. This prohibitive design task exists due to the opposing property dependencies on chain dynamics because traditional heat-resistant materials with rigid molecular structures typically lack the mechanism of energy dissipation. Aramid nanofibers have received great attention as high-performance nanoscale building units due to their intriguing mechanical and thermal properties, but their distinct structural features are yet to be fully captured. We show that aramid nanofibers form nanoscale crimps during the removal of water, which primarily resides at the defect planes of pleated sheets, where the folding can occur. The precise control of such a structural relaxation can be realized by exerting axial loadings on hydrogel fibers, which allows the emergence of aramid fibers with varying angles of crimps. These crimped fibers integrate high toughness with heat resistance, thanks to the extensible nature of nanoscale crimps with rigid molecular structures of poly(p-phenylene terephthalamide), promising as a template for stable stretchable electronics. The tensile strength/modulus (392-944 MPa/11-29 GPa), stretchability (25-163%), and toughness (154-445 MJ/cm(3)) are achieved according to the degree of crimping. Intriguingly, a toughness of around 430 MJ/m(3) can be maintained after calcination below the relaxation temperature (259 degrees C) for 50 h. Even after calcination at 300 degrees C for 10 h, a toughness of 310 MJ/m3 is kept, outperforming existing polymer materials. Our multiscale design strategy based on water-bearing aramid nanofibers provides a potent pathway for tackling the challenge for achieving conflicting property combinations.

Functions such as biocompatibility, degradability, therapeutics, and imaging are critical for use of microrobots in clinical scenarios; however, incorporation of these functions into a single microrobotic entity is still challenging. Herein, we report multifunctional Ti3C2 MXene-based magnetically actuated microrobots (MXBOTs), which are prepared by sequentially electrostatic coating of Ti3C2 nanosheets and Fe3O4 nanoparticles on the surface of biodegradable gelatin methacryloyl (GelMA)-based helical microstructures. These MXBOTs can move along predefined paths under a rotating magnetic field. The incorporation of Ti3C2 nanosheets provides MXBOTs with an advantageous photothermal effect and photoacoustic (PA) imaging capability. Additionally, MXBOTs can be loaded with fluorescent molecules, enabling fluorescence imaging. After loading the chemotherapeutic drug DOX, the MXBOTs@DOX were able to accelerate the release of DOX under the stimulation of temperature and acidic pH. This work presents a viable approach for developing biodegradable and functional microrobots for targeted delivery and synergistic chemo-photothermal therapy.

Living organisms employ a key strategy to construct resilient load-bearing structures: the strategic layering of anisotropic elements. Natural biomineralized tissues showcase a remarkable attribute-an exact alignment of multiple building units, a quality notably absent in contemporary biomimetic reproductions. We demonstrate the fabrication of artificial shells by integrating vertically aligned TiO2 nanorods into a polymer matrix atop clay multilayers. This approach combines chemical synthesis with molecular assembly to mimic the bilayer structure of mollusk shells, which consists of polygonal prismatic units on a brick-and-mortar architecture. Our study reveals a critical design principle for artificial shells through a combination of nanoindentation and finite element analysis. This design minimizes stress concentration factors at the interface and enhances penetration resistance, mainly attributed to the properties of the bottom layer. In comparing our artificial shells with their natural counterparts, we uncover additional design principles, such as hierarchical architecture and microscale prism size. These artificial shells possess the intriguing ability to partially self-heal due to a dynamic hydrogen bonding network. Furthermore, they can serve as humidity-sensitive actuators, with bending direction controlled by the aspect ratios of clay nanosheets. Our work offers valuable insights for the rational design of multifunctional, multilayer materials with enhanced impact resistance.

Aramid nanofibers (ANFs), with attractive mechanical and thermal properties, have attracted much attention as key building units for the design of high-performance composite materials. Although great progress has been made, the potential of ANFs as fibrous protein mimetics for controlling the growth of inorganic materials has not been fully revealed, which is critical for avoiding phase separation associated with typical solution blending. In this work, we show that ANFs could template the oriented growth of beta-FeOOH nanowhiskers, which enables the synthesis of ANFs/beta-FeOOH hybrids as composite coatings for polypropylene (PP) separators in Li-S batteries. The modified PP separator exhibits enhanced mechanical properties, heightened thermal performance, optimized electrolyte wettability, and improved ion conductivity, leading to superior electrochemical properties, including high initial specific capacity, better rate capability, and long cycling stability, which are superior to those of the commercial PP separators. Importantly, the addition of beta-FeOOH to ANFs could further contribute to the suppression of lithium polysulfide shuttling by chemical immobilization, inhibition of the growth of lithium dendrites because of the intrinsic high modulus and hardness, and promotion of reaction dynamics due to the catalytic effect. We believe that our work may provide a potent biomimetic pathway for the development of advanced battery separators based on ANFs.

Lung cancer remains the leading cause of cancer-related death worldwide, and drug resistance represents the main obstacle responsible for the poor mortality and prognosis. Here, to identify a novel gene signature for predicting survival and drug response, we jointly investigated RNA sequencing data of lung adenocarcinoma patients from TCGA and GEO databases, and identified a ferroptosis-related gene signature. The signature was validated in the validation set and two external cohorts. The high-risk group had a reduced survival than the low-risk group (P < 0.05). Moreover, the established gene signature was associated with tumor mutation burden, microsatellite instability, and response to immune checkpoint blockade. In addition, four candidate oncogenes (RRM2, SLC2A1, DDIT4, and VDAC2) were identified to be candidate oncogenes using in silico and wet experiments, which could serve as potential therapeutic targets. Collectively, this study developed a novel ferroptosis-related gene signature for predicting prognosis and drug response, and identified four candidate oncogenes for lung adenocarcinoma.