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Scattering‐Enhanced Light Extraction for Radiative Thermal Load Mitigation in Fluorescent Films

Scattering‐enhanced light extraction overcomes total internal reflection limitations in fluorescent films, expanding the sub‐ambient cooling color range from 26.7% to 64.9% in CIE 1931 space. Optimal TiO2 nanoparticle doping (0.5 wt.%) achieves 85.9% light extraction efficiency and 89.5% visible reflectance. Outdoor experiments demonstrate 4.1 °C temperature reduction compared to undoped films, offering scalable colored cooling solutions. Abstract To mitigate solar heating in colored objects, fluorescent coloration has been proposed as an alternative to traditional absorptive pigments. However, the Stokes‐shifted photons generated by fluorophores predominantly remain trapped by total internal reflection (TIR), increasing the parasitic solar absorption and the radiative thermal load. This work introduces a scattering‐enhanced light extraction strategy that overcomes the TIR limit in fluorescent films. A sequential quadratic programming‐driven optimization model establishes the theoretical minimum radiative thermal load for both traditional and fluorescent‐colored surfaces. Results reveal that while traditional absorption‐based color achieves only 19.3% sub‐ambient cooling chromaticity in the CIE 1931 color space, light extraction technology expands the range from 26.7% to 64.9% for fluorescent color. TiO2 nanoparticles enhance light extraction through multiple Mie‐scattering, with Monte Carlo ray‐tracing simulation identifying an optimal 0.5 wt% TiO2 nanoparticle concentration yielding 85.9% light extraction efficiency, significantly outperforming the TiO2‐free fluorescent film (25.3%) and a higher 15 wt.% concentration (66.6%). Outdoor experiments confirm the optimal 0.5 wt% sample exhibits a 4.1 °C temperature decrease compared to the control (0 wt.%) sample. This approach offers cost‐effective scalability advantages over microtexture‐based light extraction methods. Scattering-enhanced light extraction overcomes total internal reflection limitations in fluorescent films, expanding the sub-ambient cooling color range from 26.7% to 64.9% in CIE 1931 space. Optimal TiO 2 nanoparticle doping (0.5 wt.%) achieves 85.9% light extraction efficiency and 89.5% visible reflectance. Outdoor experiments demonstrate 4.1 °C temperature reduction compared to undoped films, offering scalable colored cooling solutions. Abstract To mitigate solar heating in colored objects, fluorescent coloration has been proposed as an alternative to traditional absorptive pigments. However, the Stokes-shifted photons generated by fluorophores predominantly remain trapped by total internal reflection (TIR), increasing the parasitic solar absorption and the radiative thermal load. This work introduces a scattering-enhanced light extraction strategy that overcomes the TIR limit in fluorescent films. A sequential quadratic programming-driven optimization model establishes the theoretical minimum radiative thermal load for both traditional and fluorescent-colored surfaces. Results reveal that while traditional absorption-based color achieves only 19.3% sub-ambient cooling chromaticity in the CIE 1931 color space, light extraction technology expands the range from 26.7% to 64.9% for fluorescent color. TiO 2 nanoparticles enhance light extraction through multiple Mie-scattering, with Monte Carlo ray-tracing simulation identifying an optimal 0.5 wt% TiO 2 nanoparticle concentration yielding 85.9% light extraction efficiency, significantly outperforming the TiO 2 -free fluorescent film (25.3%) and a higher 15 wt.% concentration (66.6%). Outdoor experiments confirm the optimal 0.5 wt% sample exhibits a 4.1 °C temperature decrease compared to the control (0 wt.%) sample. This approach offers cost-effective scalability advantages over microtexture-based light extraction methods. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Enhanced Single‐Particle Upconversion Imaging via Energy Migration Boosting

A core‐shell‐shell Yb3⁺/Er3⁺ UCNP architecture is engineered to balance energy migration and back energy transfer, yielding more than a tenfold enhancement in single‐particle brightness. Leveraging these optimized probes, it achieves long‐term, high‐resolution single‐particle tracking in live neurons, uncovering coordinated transport mechanisms of motor proteins. Abstract Lanthanide‐doped upconversion nanoparticles (UCNPs) are promising bioimaging probes due to their exceptional photostability and minimal background interference. However, their limited single‐particle brightness has hindered broader applications. The study addresses this challenge by enhancing energy migration (EM) between sensitizer Yb3+ to improve energy transfer efficiency to emitter Er3+. Nanoparticles are designed with a sensitizer/emitter‐segregated core‐shell‐shell architecture (NaLu0.9Er0.1F4@NaYbF4@NaLuF4) to inhibit back energy transfer (BET) and then increased Yb3+ doping levels (NaLu0.9‐xYbxEr0.1F4@NaYbF4@NaLuF4) to enhance EM into the core. UCNPs with an alloy‐core of NaYb0.9Er0.1F4 exhibited the brightest upconversion luminescence, achieving over a tenfold enhancement compared to NaLu0.9Er0.1F4‐core counterparts, highlighting the importance of EM. Further optimization of the Yb3+/Er3+ ratio and inert shell thickness (NaLuF4) maximized single‐particle brightness. These optimized UCNPs enabled long‐term tracking of axonal transport in live dorsal root ganglion (DRG) neurons. Using a Bayesian Hidden Markov Model, it quantitatively characterized resolved heterogeneous motion states and annotated trajectories with local spatiotemporal dynamics of retrograde, anterograde, and diffusive motions. The analysis revealed a kinesin‐dynein coordination mechanism, where anterograde motion facilitates retrograde activation. It also examined the effects of inhibitors and stimulants on transport behavior. These findings establish upconversion single‐particle tracking (uSPT) as a powerful tool for long‐term, real‐time monitoring of neuronal activities. A core-shell-shell Yb 3 ⁺/Er 3 ⁺ UCNP architecture is engineered to balance energy migration and back energy transfer, yielding more than a tenfold enhancement in single-particle brightness. Leveraging these optimized probes, it achieves long-term, high-resolution single-particle tracking in live neurons, uncovering coordinated transport mechanisms of motor proteins. Abstract Lanthanide-doped upconversion nanoparticles (UCNPs) are promising bioimaging probes due to their exceptional photostability and minimal background interference. However, their limited single-particle brightness has hindered broader applications. The study addresses this challenge by enhancing energy migration (EM) between sensitizer Yb 3+ to improve energy transfer efficiency to emitter Er 3+. Nanoparticles are designed with a sensitizer/emitter-segregated core-shell-shell architecture (NaLu 0.9 Er 0.1 F 4 @NaYbF 4 @NaLuF 4 ) to inhibit back energy transfer (BET) and then increased Yb 3+ doping levels (NaLu 0.9-x Yb x Er 0.1 F 4 @NaYbF 4 @NaLuF 4 ) to enhance EM into the core. UCNPs with an alloy-core of NaYb 0.9 Er 0.1 F 4 exhibited the brightest upconversion luminescence, achieving over a tenfold enhancement compared to NaLu 0.9 Er 0.1 F 4 -core counterparts, highlighting the importance of EM. Further optimization of the Yb 3+ /Er 3+ ratio and inert shell thickness (NaLuF 4 ) maximized single-particle brightness. These optimized UCNPs enabled long-term tracking of axonal transport in live dorsal root ganglion (DRG) neurons. Using a Bayesian Hidden Markov Model, it quantitatively characterized resolved heterogeneous motion states and annotated trajectories with local spatiotemporal dynamics of retrograde, anterograde, and diffusive motions. The analysis revealed a kinesin-dynein coordination mechanism, where anterograde motion facilitates retrograde activation. It also examined the effects of inhibitors and stimulants on transport behavior. These findings establish upconversion single-particle tracking (uSPT) as a powerful tool for long-term, real-time monitoring of neuronal activities. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Beyond Density: Unveiling the Trade‐Off in Catalytic Site Optimization Using Defect‐Engineered UiO‐66

A well‐designed experimental model reveals a trade‐off between intrinsic activity and catalytic site density in performance optimization, due to inherent diffusion resistance arising from substrate adsorption at catalytic sites. Abstract Enhancing intrinsic activity and increasing catalytic site density are two widely employed strategies to improve catalytic performance. Although typically considered independently, their interplay remains poorly understood. Here, two UiO‐66 metal–organic frameworks (MOFs) with distinct catalytic site densities—linker‐defective UiO‐66L and cluster‐defective UiO‐66C—are synthesized and systematically compared. Despite a higher density of open Zr catalytic sites, UiO‐66L exhibited lower catalytic activity than UiO‐66C across four model reactions, performing similarly to defect‐free UiO‐66. Although defect engineering is expected to enlarge pore connectivity, diffusion‐ordered spectroscopy (DOSY) and molecular dynamics (MD) simulations surprisingly reveal that UiO‐66C exhibits similar diffusion rates to defect‐free UiO‐66, while UiO‐66L shows significantly slower diffusion. This discrepancy is attributed to self‐adsorption of reactants at the high‐density catalytic sites, which induces local diffusion resistance even in the presence of expanded channels. These findings reveal a performance trade‐off between catalytic site density and intrinsic activity, establishing a critical threshold beyond which further increases in site density can hinder rather than enhance catalysis. A well-designed experimental model reveals a trade-off between intrinsic activity and catalytic site density in performance optimization, due to inherent diffusion resistance arising from substrate adsorption at catalytic sites. Abstract Enhancing intrinsic activity and increasing catalytic site density are two widely employed strategies to improve catalytic performance. Although typically considered independently, their interplay remains poorly understood. Here, two UiO-66 metal–organic frameworks (MOFs) with distinct catalytic site densities—linker-defective UiO-66L and cluster-defective UiO-66C—are synthesized and systematically compared. Despite a higher density of open Zr catalytic sites, UiO-66L exhibited lower catalytic activity than UiO-66C across four model reactions, performing similarly to defect-free UiO-66. Although defect engineering is expected to enlarge pore connectivity, diffusion-ordered spectroscopy (DOSY) and molecular dynamics (MD) simulations surprisingly reveal that UiO-66C exhibits similar diffusion rates to defect-free UiO-66, while UiO-66L shows significantly slower diffusion. This discrepancy is attributed to self-adsorption of reactants at the high-density catalytic sites, which induces local diffusion resistance even in the presence of expanded channels. These findings reveal a performance trade-off between catalytic site density and intrinsic activity, establishing a critical threshold beyond which further increases in site density can hinder rather than enhance catalysis. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Hepatocyte‐Specific GSDMD Deficiency Aggravates Sepsis by Disrupting Non‐Canonical Secretion of Anti‐Inflammatory Factors

This study proposes for the first time that hepatic GSDMD plays a key protective role in sepsis. Hepatic GSDMD may release inflammatory inhibitory factors including VEGF‐B and Gremlin‐1 through pore‐forming activity to inhibit the production of inflammatory factors from macrophages, thereby alleviating the inflammatory response of septic mice. Abstract Gasdermin D (GSDMD)‐mediated pyroptosis in macrophages plays a clear role in promoting inflammation and mortality in sepsis. The liver is a commonly damaged organ during sepsis and also an important organ for releasing acute response proteins. However, whether pyroptosis occurs and the function of GSDMD in hepatocytes remains unclear. It is surprising to find that hepatocyte‐specific GSDMD knockout (GSDMDhep‐/‐) mice have significantly reduced survival rates, markedly elevated systemic inflammation, and increased inflammation in the peritoneal cavity and lungs, suggesting that the absence of GSDMD in hepatocytes promotes systemic inflammatory responses. Serum proteomic analysis shows that anti‐inflammatory factors such as VEGF‐B and Gremlin‐1 are significantly reduced in GSDMDhep‐/‐ mice. Through in vitro and in vivo experiments combined with a constructed full‐length GSDMD and a mutant GSDMD plasmid (GSDMD‐c.D276A) that cannot be cleaved, VEGF‐B and Gremlin‐1 are verified to be released from hepatocytes through the pore‐forming activity of GSDMD, thus inhibiting the production of inflammatory factors by macrophages. More importantly, hepatocyte‐specific replenishment of full‐length GSDMD can reverse the exacerbated inflammatory response in GSDMDhep‐/‐ mice. These findings together establish that hepatic GSDMD plays a key protective role in sepsis by promoting the release of anti‐inflammatory factors through pore formation in hepatocytes. This study proposes for the first time that hepatic GSDMD plays a key protective role in sepsis. Hepatic GSDMD may release inflammatory inhibitory factors including VEGF-B and Gremlin-1 through pore-forming activity to inhibit the production of inflammatory factors from macrophages, thereby alleviating the inflammatory response of septic mice. Abstract Gasdermin D (GSDMD)-mediated pyroptosis in macrophages plays a clear role in promoting inflammation and mortality in sepsis. The liver is a commonly damaged organ during sepsis and also an important organ for releasing acute response proteins. However, whether pyroptosis occurs and the function of GSDMD in hepatocytes remains unclear. It is surprising to find that hepatocyte-specific GSDMD knockout (GSDMD hep-/- ) mice have significantly reduced survival rates, markedly elevated systemic inflammation, and increased inflammation in the peritoneal cavity and lungs, suggesting that the absence of GSDMD in hepatocytes promotes systemic inflammatory responses. Serum proteomic analysis shows that anti-inflammatory factors such as VEGF-B and Gremlin-1 are significantly reduced in GSDMD hep-/- mice. Through in vitro and in vivo experiments combined with a constructed full-length GSDMD and a mutant GSDMD plasmid (GSDMD-c.D276A) that cannot be cleaved, VEGF-B and Gremlin-1 are verified to be released from hepatocytes through the pore-forming activity of GSDMD, thus inhibiting the production of inflammatory factors by macrophages. More importantly, hepatocyte-specific replenishment of full-length GSDMD can reverse the exacerbated inflammatory response in GSDMD hep-/- mice. These findings together establish that hepatic GSDMD plays a key protective role in sepsis by promoting the release of anti-inflammatory factors through pore formation in hepatocytes. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Identifying Beneficial and Adverse Co4+ Species in Cobalt‐Based Oxygen Evolution Catalysts via Precursor Polymorphism Engineering

This study resolves conflicting roles of Co⁴⁺ species in cobalt‐based oxygen evolution reaction (OER) catalysts by engineering precursor polymorphism. Through controlled annealing of cobalt oxysulfide, researchers selectively stabilize γ‐CoO2 (enabling oxygen pathway mechanism) and β‐CoO2 (following conventional mechanism). γ‐CoO2 demonstrates superior performance, highlighting micro‐environment design for efficient catalysis. Abstract The oxygen evolution reaction (OER) is a critical bottleneck in water electrolysis for hydrogen production, necessitating catalysts that optimize both efficiency and cost. Cobalt‐based materials offer a viable alternative to noble metals, but their development is complicated by uncertainties regarding the role of Co⁴⁺ species formed during operation. Conflicting studies debate whether CoO2 acts as the active phase or if Co⁴⁺ species may suppress reactivity. To address this, the Co⁴⁺ impact on OER activity is systematically investigated by tailoring the reconstruction of polymorphic cobalt oxysulfide. Through thermal annealing, crystallinity and local coordination are controlled to selectively stabilize γ‐CoO2 and β‐CoO2 phases under OER conditions, respectively. Structural analysis reveals that H2O/OH− intercalation drives lattice expansion, favoring γ‐CoO2 formation, while rigid Co─O bonds limit flexibility, yielding β‐CoO2. Mechanistic studies show γ‐CoO2 promotes superoxide (Co─O─O─Co) intermediates via the oxygen pathway mechanism (OPM), whereas β‐CoO2 follows the conventional adsorbate evolution mechanism (AEM). As a result, γ‐CoO2 exhibits superior catalytic performance, with lower overpotentials and enhanced long‐term stability. These insights highlight the pivotal role of Co⁴⁺ micro‐environments in OER performance, offering a rational framework for optimizing transition‐metal catalysts. This study resolves conflicting roles of Co⁴⁺ species in cobalt-based oxygen evolution reaction (OER) catalysts by engineering precursor polymorphism. Through controlled annealing of cobalt oxysulfide, researchers selectively stabilize γ-CoO 2 (enabling oxygen pathway mechanism) and β-CoO 2 (following conventional mechanism). γ-CoO 2 demonstrates superior performance, highlighting micro-environment design for efficient catalysis. Abstract The oxygen evolution reaction (OER) is a critical bottleneck in water electrolysis for hydrogen production, necessitating catalysts that optimize both efficiency and cost. Cobalt-based materials offer a viable alternative to noble metals, but their development is complicated by uncertainties regarding the role of Co⁴⁺ species formed during operation. Conflicting studies debate whether CoO 2 acts as the active phase or if Co⁴⁺ species may suppress reactivity. To address this, the Co⁴⁺ impact on OER activity is systematically investigated by tailoring the reconstruction of polymorphic cobalt oxysulfide. Through thermal annealing, crystallinity and local coordination are controlled to selectively stabilize γ-CoO 2 and β-CoO 2 phases under OER conditions, respectively. Structural analysis reveals that H 2 O/OH − intercalation drives lattice expansion, favoring γ-CoO 2 formation, while rigid Co─O bonds limit flexibility, yielding β-CoO 2. Mechanistic studies show γ-CoO 2 promotes superoxide (Co─O─O─Co) intermediates via the oxygen pathway mechanism (OPM), whereas β-CoO 2 follows the conventional adsorbate evolution mechanism (AEM). As a result, γ-CoO 2 exhibits superior catalytic performance, with lower overpotentials and enhanced long-term stability. These insights highlight the pivotal role of Co⁴⁺ micro-environments in OER performance, offering a rational framework for optimizing transition-metal catalysts. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Laser‐Induced 3D Graphene Enabled Polymer Composites with Improved Mechanical and Electrical Properties Toward Multifunctional Performance

In this study, the utilization of 3D printing driven by laser‐induced graphene and a conventional infiltration process for assembling kinds of graphene‐based polymer composites is described. The synergistic integration of polymers and the interconnected 3D‐LIG frameworks has endowed the composites with remarkable mechanical, electrical, and tunable properties for applications in de‐icing, microwave absorption, and flexible sensors. Abstract Conductive graphene‐based composites are attracting substantial interest due to their excellent mechanical and electrical properties for potential applications in electronics. Typically, such composites are fabricated by infiltrating the 3D graphene framework with the polymer matrix. However, the production of 3D graphene foams is limited by the challenges in preparing graphene dispersions, while 3D printing presents a significant breakthrough in the fabrication of desired 3D graphene‐based structures. Here, the utilization of the 3D printing technique driven by laser‐induced graphene (LIG) and a conventional penetration process for assembling graphene‐based conductive polymer composites is described. The synergistic integration endowed the proposed 3D‐LIG/epoxy composites with an electrical conductivity of 3.54 S m−1 in through‐plane, and a tensile strength of ≈5.4 MPa by a 7606% improvement with a high specific strength of 6.8 × 103 (N m) kg−1. Meanwhile, the flexible composites exhibited an outstanding ductility reaching a 230% tensile‐failure strain and a 50% high linear elastic strain. The prepared 3D‐LIG/polymer composites thus demonstrated the functionalized behaviors for applications in de‐icing, microwave absorption, and flexible sensors. In this study, the utilization of 3D printing driven by laser-induced graphene and a conventional infiltration process for assembling kinds of graphene-based polymer composites is described. The synergistic integration of polymers and the interconnected 3D-LIG frameworks has endowed the composites with remarkable mechanical, electrical, and tunable properties for applications in de-icing, microwave absorption, and flexible sensors. Abstract Conductive graphene-based composites are attracting substantial interest due to their excellent mechanical and electrical properties for potential applications in electronics. Typically, such composites are fabricated by infiltrating the 3D graphene framework with the polymer matrix. However, the production of 3D graphene foams is limited by the challenges in preparing graphene dispersions, while 3D printing presents a significant breakthrough in the fabrication of desired 3D graphene-based structures. Here, the utilization of the 3D printing technique driven by laser-induced graphene (LIG) and a conventional penetration process for assembling graphene-based conductive polymer composites is described. The synergistic integration endowed the proposed 3D-LIG/epoxy composites with an electrical conductivity of 3.54 S m −1 in through-plane, and a tensile strength of ≈5.4 MPa by a 7606% improvement with a high specific strength of 6.8 × 10 3 (N m) kg −1. Meanwhile, the flexible composites exhibited an outstanding ductility reaching a 230% tensile-failure strain and a 50% high linear elastic strain. The prepared 3D-LIG/polymer composites thus demonstrated the functionalized behaviors for applications in de-icing, microwave absorption, and flexible sensors. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Autologous Organoid‐T Cell Co‐Culture Platform for Modeling of Immune‐Mediated Drug‐Induced Liver Injury

A matrix‐free human liver organoid–T cell co‐culture platform enables modeling of immune‐mediated drug‐induced liver injury (iDILI). Using flucloxacillin and patient‐matched cells, this system recapitulates HLA‐B*57:01–restricted CD8⁺ T cell activation and hepatocyte damage. By linking genetic risk to immune function, this approach enables mechanistic dissection and functional prediction of idiosyncratic hepatotoxicity in vitro. Abstract Modeling adaptive immune responses in induced pluripotent stem cell (iPSC)‐derived liver systems remains a critical barrier for studying immune‐mediated hepatic diseases, including idiosyncratic drug‐induced liver injury (iDILI). Conventional hepatotoxicity models lack the components required to capture patient‐specific, T cell‐mediated injury. Here, a scalable and matrix‐free human liver organoid (HLO) microarray platform is presented that enables controlled co‐culture of Human Leukocyte Antigen (HLA)‐genotyped, iPSC‐derived HLOs with autologous CD8⁺ T cells. This immune‐competent system supports antigen‐specific T cell activation and reproduces cytotoxic effector responses in a genetically defined context. As a proof‐of‐concept, the platform models clinically relevant iDILI caused by flucloxacillin in HLA‐B*57:01 carriers, recapitulating CD8⁺ T cell proliferation, hepatocyte apoptosis, and variability in immune responses across donors. The system captures hallmark features of adaptive immune‐mediated hepatotoxicity, including secretion of tumor necrosis factor‐alpha and Granzyme B, and cytokeratin‐18 release from injured hepatocytes. By linking genetic susceptibility with functional immune outcomes, this platform provides a modular and scalable approach for evaluating immune‐mediated toxicities. The method offers broad utility for mechanistic studies of drug hypersensitivity, immune‐related adverse events, and preclinical safety assessment in support of precision medicine. A matrix-free human liver organoid–T cell co-culture platform enables modeling of immune-mediated drug-induced liver injury (iDILI). Using flucloxacillin and patient-matched cells, this system recapitulates HLA-B*57:01–restricted CD8⁺ T cell activation and hepatocyte damage. By linking genetic risk to immune function, this approach enables mechanistic dissection and functional prediction of idiosyncratic hepatotoxicity in vitro. Abstract Modeling adaptive immune responses in induced pluripotent stem cell (iPSC)-derived liver systems remains a critical barrier for studying immune-mediated hepatic diseases, including idiosyncratic drug-induced liver injury (iDILI). Conventional hepatotoxicity models lack the components required to capture patient-specific, T cell-mediated injury. Here, a scalable and matrix-free human liver organoid (HLO) microarray platform is presented that enables controlled co-culture of Human Leukocyte Antigen (HLA)-genotyped, iPSC-derived HLOs with autologous CD8⁺ T cells. This immune-competent system supports antigen-specific T cell activation and reproduces cytotoxic effector responses in a genetically defined context. As a proof-of-concept, the platform models clinically relevant iDILI caused by flucloxacillin in HLA-B*57:01 carriers, recapitulating CD8⁺ T cell proliferation, hepatocyte apoptosis, and variability in immune responses across donors. The system captures hallmark features of adaptive immune-mediated hepatotoxicity, including secretion of tumor necrosis factor-alpha and Granzyme B, and cytokeratin-18 release from injured hepatocytes. By linking genetic susceptibility with functional immune outcomes, this platform provides a modular and scalable approach for evaluating immune-mediated toxicities. The method offers broad utility for mechanistic studies of drug hypersensitivity, immune-related adverse events, and preclinical safety assessment in support of precision medicine. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Material‐to‐Application Integration: Rapid Fabrication of Field‐Deployable Hydrogel‐SiO2 DNA Separator for Low‐Resource Point‐of‐Care Diagnostics

A rapidly fabricated hydrogel‐SiO2 composite enables ultralow‐cost, equipment‐minimized DNA extraction, outperforming commercial kits. Hierarchical microstructures enhance hydrophobic/salt‐bridge‐driven adsorption. Integrated with visual LAMP, this field‐deployable system detects Vibrio parahaemolyticus at 10 CFU mL−1 in <40 min, offering transformative point‐of‐care diagnostics for resource‐limited settings. Abstract Current nucleic acid (NA) diagnostics are hindered in resource‐limited settings by equipment needs and high costs. S(PAA‐SiO2) is developed, a hydrogel‐SiO2 composite deoxyribonucleic acid (DNA) separator addressing these challenges through rapid (<10 min), simple, and skill‐free preparation, ultralow cost ($0.028 per unit), and equipment‐minimized mass production capacity (96 units per batch). Further systematic investigation of SiO2 particle surface modification revealed critical enhancements in DNA adsorption properties. With maintaining structural thermal stability, SiO2 integration significantly improved the surface roughness, specific surface area, and hydrophobicity, leading to hydrophobic and salt bridge effect‐enhanced DNA adsorption. Especially, SiO2 modification with mixed particle size formed a hierarchical microstructure to promote turbulence and interface interaction. Device S(PAA‐SiO2‐Mix) achieved a higher DNA extraction yield than the commercial kits. It possesses potential value for Polymerase Chain Reaction (PCR) diagnosis of bacterial, viral, parasitic, and fungal pathogens. By orchestrating three technological progresses ‐ rapid S(PAA‐SiO2‐Mix) fabrication, high‐throughput DNA extraction, and visual loop‐mediated isothermal amplification (LAMP) ‐ a field‐deployable diagnostic workflow is established for Vibrio parahaemolyticus (v. parahaemolyticus, Vpa). This platform achieves equipment‐minimized point‐of‐care detection in <40 min with a sensitivity of 10 CFU mL−1. Its simplicity, speed, and accuracy offer a transformative solution for resource‐limited diagnostics. This work advances separation interface design and presents a novel vision for integrated, equipment‐free molecular detection systems. A rapidly fabricated hydrogel-SiO 2 composite enables ultralow-cost, equipment-minimized DNA extraction, outperforming commercial kits. Hierarchical microstructures enhance hydrophobic/salt-bridge-driven adsorption. Integrated with visual LAMP, this field-deployable system detects Vibrio parahaemolyticus at 10 CFU mL −1 in <40 min, offering transformative point-of-care diagnostics for resource-limited settings. Abstract Current nucleic acid (NA) diagnostics are hindered in resource-limited settings by equipment needs and high costs. S(PAA-SiO 2 ) is developed, a hydrogel-SiO 2 composite deoxyribonucleic acid (DNA) separator addressing these challenges through rapid (<10 min), simple, and skill-free preparation, ultralow cost ($0.028 per unit), and equipment-minimized mass production capacity (96 units per batch). Further systematic investigation of SiO 2 particle surface modification revealed critical enhancements in DNA adsorption properties. With maintaining structural thermal stability, SiO 2 integration significantly improved the surface roughness, specific surface area, and hydrophobicity, leading to hydrophobic and salt bridge effect-enhanced DNA adsorption. Especially, SiO 2 modification with mixed particle size formed a hierarchical microstructure to promote turbulence and interface interaction. Device S(PAA-SiO 2 -Mix) achieved a higher DNA extraction yield than the commercial kits. It possesses potential value for Polymerase Chain Reaction (PCR) diagnosis of bacterial, viral, parasitic, and fungal pathogens. By orchestrating three technological progresses - rapid S(PAA-SiO 2 -Mix) fabrication, high-throughput DNA extraction, and visual loop-mediated isothermal amplification (LAMP) - a field-deployable diagnostic workflow is established for Vibrio parahaemolyticus (v. parahaemolyticus, Vpa). This platform achieves equipment-minimized point-of-care detection in <40 min with a sensitivity of 10 CFU mL −1. Its simplicity, speed, and accuracy offer a transformative solution for resource-limited diagnostics. This work advances separation interface design and presents a novel vision for integrated, equipment-free molecular detection systems. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Smart Gated Hollow Mesoporous Silica Hydrogel for Targeting Endoplasmic Reticulum Stress and Promoting Periodontal Tissue Regeneration

The hollow mesoporous silica loaded with quercetin (HM‐QU@PEG) is combined with a thermosensitive anti‐bacterial matrix (TF127) to prepare HQUP@TF127. HQUP@TF127 effectively eliminates excessive ROS, alleviates endoplasmic reticulum stress, relieves mitochondrial calcium overload, and blocks the p53‐dependent apoptotic cascade. Furthermore, it enhances the osteogenic differentiation capability of PDLSCs, thereby creating a favorable microenvironment for periodontal tissue regeneration. Abstract Periodontitis is a multifactorial inflammatory disease involving pathogenic biofilm formation, amplified oxidative stress, and impaired tissue regeneration. In addition to its complicated pathology, effective treatment of periodontitis is challenged by a dynamic oral microenvironment that prevents drug retention. To overcome these issues, an anti‐bacterial, ROS‐scavenging, and tissue‐regenerative hydrogel system (HQUP@TF127) is developed. In this triple‐functional HQUP@TF127, a ROS‐responsive gatekeeper on hollow mesoporous silica nanoparticles enabled the spatiotemporally controlled release of quercetin, a naturally occurring anti‐inflammatory and osteogenic ingredient. The covalent attachment of the antibacterial, 4‐terpineol with thermosensitive Pluronic F127 prolonged retention time, thereby ensuring deep penetration and eradication of subgingival pathogens. HQUP@TF127 restored endoplasmic reticulum homeostasis and, maximized the osteogenic potential of periodontal ligament stem cells. In a rat model of periodontitis, HQUP@TF127 effectively suppressed osteoclast activation by inhibiting inflammatory infiltration and collagen degradation. Micro‐computed tomography analysis confirmed an increase in bone mineral density and periodontal tissue regeneration. HQUP@TF127, addressed the multifactorial pathology and obstacles to local drug administration and, requires further translational research by virtue of its triple synergistic mechanisms of action and advantages in local drug delivery. The hollow mesoporous silica loaded with quercetin (HM-QU@PEG) is combined with a thermosensitive anti-bacterial matrix (TF127) to prepare HQUP@TF127. HQUP@TF127 effectively eliminates excessive ROS, alleviates endoplasmic reticulum stress, relieves mitochondrial calcium overload, and blocks the p53-dependent apoptotic cascade. Furthermore, it enhances the osteogenic differentiation capability of PDLSCs, thereby creating a favorable microenvironment for periodontal tissue regeneration. Abstract Periodontitis is a multifactorial inflammatory disease involving pathogenic biofilm formation, amplified oxidative stress, and impaired tissue regeneration. In addition to its complicated pathology, effective treatment of periodontitis is challenged by a dynamic oral microenvironment that prevents drug retention. To overcome these issues, an anti-bacterial, ROS-scavenging, and tissue-regenerative hydrogel system (HQUP@TF127) is developed. In this triple-functional HQUP@TF127, a ROS-responsive gatekeeper on hollow mesoporous silica nanoparticles enabled the spatiotemporally controlled release of quercetin, a naturally occurring anti-inflammatory and osteogenic ingredient. The covalent attachment of the antibacterial, 4-terpineol with thermosensitive Pluronic F127 prolonged retention time, thereby ensuring deep penetration and eradication of subgingival pathogens. HQUP@TF127 restored endoplasmic reticulum homeostasis and, maximized the osteogenic potential of periodontal ligament stem cells. In a rat model of periodontitis, HQUP@TF127 effectively suppressed osteoclast activation by inhibiting inflammatory infiltration and collagen degradation. Micro-computed tomography analysis confirmed an increase in bone mineral density and periodontal tissue regeneration. HQUP@TF127, addressed the multifactorial pathology and obstacles to local drug administration and, requires further translational research by virtue of its triple synergistic mechanisms of action and advantages in local drug delivery. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Interpretable Multimodal Fusion Model Enhances Postoperative Recurrence Prediction in Gastric Cancer

An interpretable multimodal fusion model (RSA) integrating clinical, radiomic, and pathomic features is developed and validated to predict early postoperative recurrence in gastric cancer. The RSA model demonstrates superior predictive performance and holds potential for guiding adjuvant chemotherapy decisions and improving individualized patient management. Abstract Accurate prediction of early postoperative recurrence in locally advanced gastric cancer (LAGC) remains challenging due to tumor heterogeneity and limitations of traditional clinicopathological factors. This study aims to develop and validate an interpretable multimodal model for precise recurrence prediction. 1580 LAGC patients are enrolled from six Chinese medical centers and a multimodal fusion Risk Stratification Assessment (RSA) model integrating clinical, radiomic, and pathomic data is developed. Model performance is evaluated using internal, external, prospective, and public dataset validations. Transcriptome sequencing is conducted to elucidate biological mechanisms underlying recurrence. The RSA model significantly outperforms clinical‐only, radiomic‐only, and pathomic‐only models in predicting early recurrence, achieving area under the curve (AUC) values of 0.903 in the training cohort, 0.902 in internal validation, and ranging from 0.884 to 0.889 in external validations. Stratification by the RSA model consistently identifies high‐risk patients with significantly poorer five‐year survival across all cohorts (all P<0.001). Transcriptomic analysis reveals that high‐risk patients exhibit significant immune cell infiltration, increased expression of immune checkpoint molecules, and activation of immune‐related pathways, including interferon signaling and the IL‐6/JAK/STAT3 pathway. The integrated multimodal RSA model effectively predicts recurrence risk and prognosis in LAGC, enabling precise patient stratification and individualized postoperative management. An interpretable multimodal fusion model (RSA) integrating clinical, radiomic, and pathomic features is developed and validated to predict early postoperative recurrence in gastric cancer. The RSA model demonstrates superior predictive performance and holds potential for guiding adjuvant chemotherapy decisions and improving individualized patient management. Abstract Accurate prediction of early postoperative recurrence in locally advanced gastric cancer (LAGC) remains challenging due to tumor heterogeneity and limitations of traditional clinicopathological factors. This study aims to develop and validate an interpretable multimodal model for precise recurrence prediction. 1580 LAGC patients are enrolled from six Chinese medical centers and a multimodal fusion Risk Stratification Assessment (RSA) model integrating clinical, radiomic, and pathomic data is developed. Model performance is evaluated using internal, external, prospective, and public dataset validations. Transcriptome sequencing is conducted to elucidate biological mechanisms underlying recurrence. The RSA model significantly outperforms clinical-only, radiomic-only, and pathomic-only models in predicting early recurrence, achieving area under the curve (AUC) values of 0.903 in the training cohort, 0.902 in internal validation, and ranging from 0.884 to 0.889 in external validations. Stratification by the RSA model consistently identifies high-risk patients with significantly poorer five-year survival across all cohorts (all P<0.001). Transcriptomic analysis reveals that high-risk patients exhibit significant immune cell infiltration, increased expression of immune checkpoint molecules, and activation of immune-related pathways, including interferon signaling and the IL-6/JAK/STAT3 pathway. The integrated multimodal RSA model effectively predicts recurrence risk and prognosis in LAGC, enabling precise patient stratification and individualized postoperative management. Advanced Science, Volume 12, Issue 43, November 20, 2025.

A Novel Self‐Regulated, Non‐Directional Magnetic Thermos‐Brachytherapy 125I Seed Enhances Anticancer Efficacy by Rescuing Immune Escape

This work constructs magnetic nanoparticles (MNPs) and incorporates them with silver rods coated with 125I to form a novel composite seed, which exhibits direction‐independent and self‐regulated heating efficiency, as well as the capacity of preventing MNPs leakage and enabling repeated hyperthermia. Mechanistically, the composite seed‐relied combination therapy enhances anti‐cancer efficacy through rescuing PD‐L1+ neutrophil‐mediated immune escape. Abstract Integrating mild hyperthermia (MH) with 125I brachytherapy holds potential for overcoming treatment resistance and improving anticancer efficacy. Here, magnetic nanoparticles (MNPs) with a suitable Curie temperature are constructed and incorporated with silver rods coated with 125I to form composite seeds. In vitro simulations and in vivo validations demonstrated their effective performance in radiation dose and temperature control. Compared with traditional thermoseeds and previously reported MNPs, this composite seed exhibits direction‐independent and self‐regulated heating efficiency. Additionally, the titanium shell prevented MNPs leakage and enabled its repeated hyperthermia treatment capacity. Subsequently, the enhanced pancancer anticancer efficacy of the composite seed‐relied 125I@MH therapy is confirmed through cellular and animal experiments involving liver cancer and prostate cancer. Further tumor microenvironment investigations based on a subcutaneous liver cancer mouse model identified that 125I therapy recruited Cd274/Pd‐l1+ neutrophils and induced T‐cell exhaustion, leading to immune evasion and brachytherapy resistance. The addition of MH significantly reversed this effect, restoring the function of effector T cells (IFN‐γ+ T cells) and activating T‐cell immunity. In conclusion, this study developed a novel composite seed with superior anticancer efficacy, which holds promising therapeutic potential for the treatment of malignancies, particularly solid tumors, in future clinical practice. This work constructs magnetic nanoparticles (MNPs) and incorporates them with silver rods coated with 125 I to form a novel composite seed, which exhibits direction-independent and self-regulated heating efficiency, as well as the capacity of preventing MNPs leakage and enabling repeated hyperthermia. Mechanistically, the composite seed-relied combination therapy enhances anti-cancer efficacy through rescuing PD-L1 + neutrophil-mediated immune escape. Abstract Integrating mild hyperthermia (MH) with 125 I brachytherapy holds potential for overcoming treatment resistance and improving anticancer efficacy. Here, magnetic nanoparticles (MNPs) with a suitable Curie temperature are constructed and incorporated with silver rods coated with 125 I to form composite seeds. In vitro simulations and in vivo validations demonstrated their effective performance in radiation dose and temperature control. Compared with traditional thermoseeds and previously reported MNPs, this composite seed exhibits direction-independent and self-regulated heating efficiency. Additionally, the titanium shell prevented MNPs leakage and enabled its repeated hyperthermia treatment capacity. Subsequently, the enhanced pancancer anticancer efficacy of the composite seed-relied 125 I@MH therapy is confirmed through cellular and animal experiments involving liver cancer and prostate cancer. Further tumor microenvironment investigations based on a subcutaneous liver cancer mouse model identified that 125 I therapy recruited Cd274/Pd-l1 + neutrophils and induced T-cell exhaustion, leading to immune evasion and brachytherapy resistance. The addition of MH significantly reversed this effect, restoring the function of effector T cells (IFN-γ + T cells) and activating T-cell immunity. In conclusion, this study developed a novel composite seed with superior anticancer efficacy, which holds promising therapeutic potential for the treatment of malignancies, particularly solid tumors, in future clinical practice. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Jigsaw Puzzle Inspired Patterning of Gas Diffusion Layers for Enhanced Water Management in Polymer Electrolyte Fuel Cells

A novel jigsaw‐inspired method introduces patterned hydrophilic domains into gas diffusion layers (GDLs) to enhance water management in polymer electrolyte fuel cells (PEFCs). This scalable technique improves high‐current performance by separating water and gas pathways, offering a promising advance for hydrogen‐based energy systems. Abstract Under high current density operation, water generation at the cathode of polymer electrolyte fuel cells (PEFCs) floods the electrode, resulting in severe mass transport limitation and an associated voltage drop. Water management is thus of crucial importance in improving the overall performance of fuel cell systems. Gas diffusion layers (GDLs) with independent pathways for either gaseous oxygen or liquid water transport present a potential solution to this issue. Here a novel, simple, and scalable method is presented for inducing patterned hydrophobicity into GDLs. Hydrophilic GDLs are prepared by immersion of commercial hydrophobic GDLs in hydrogen peroxide. Circular disks are then punched from these using a precision die‐cutter. Meanwhile, an array of corresponding holes is punched into conventional hydrophobic GDLs. The hydrophilic disks are then pressed into the holes of the hydrophobic GDL and held in place via friction locking, analogous to completing a jigsaw puzzle. This Jigsaw Puzzle Inspired Patterning (JPIP) technique creates precisely patterned hydrophilic domains to act as dedicated water channels, with separate hydrophobic domains for unhindered gas transport. The use of JPIP GDLs dramatically improves fuel cell performance under high current density operation, with important implications for decarbonization via the hydrogen economy. A novel jigsaw-inspired method introduces patterned hydrophilic domains into gas diffusion layers (GDLs) to enhance water management in polymer electrolyte fuel cells (PEFCs). This scalable technique improves high-current performance by separating water and gas pathways, offering a promising advance for hydrogen-based energy systems. Abstract Under high current density operation, water generation at the cathode of polymer electrolyte fuel cells (PEFCs) floods the electrode, resulting in severe mass transport limitation and an associated voltage drop. Water management is thus of crucial importance in improving the overall performance of fuel cell systems. Gas diffusion layers (GDLs) with independent pathways for either gaseous oxygen or liquid water transport present a potential solution to this issue. Here a novel, simple, and scalable method is presented for inducing patterned hydrophobicity into GDLs. Hydrophilic GDLs are prepared by immersion of commercial hydrophobic GDLs in hydrogen peroxide. Circular disks are then punched from these using a precision die-cutter. Meanwhile, an array of corresponding holes is punched into conventional hydrophobic GDLs. The hydrophilic disks are then pressed into the holes of the hydrophobic GDL and held in place via friction locking, analogous to completing a jigsaw puzzle. This Jigsaw Puzzle Inspired Patterning (JPIP) technique creates precisely patterned hydrophilic domains to act as dedicated water channels, with separate hydrophobic domains for unhindered gas transport. The use of JPIP GDLs dramatically improves fuel cell performance under high current density operation, with important implications for decarbonization via the hydrogen economy. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Loss of Hepatic Angiotensinogen Attenuates Diastolic Dysfunction in Heart Failure with Preserved Ejection Fraction

Increased hepatic angiotensinogen (AGT) abundance leads to cardiac diastolic dysfunction via the AngII‐independent pathway. Liver‐derived AGT is internalized by LRP2 in cardiac endothelial cells, subsequently contributing to myocardial diastolic dysfunction by suppressing microvascular angiogenesis via inhibiting the GATA2/Pim3 pathway. In vivo 18β‐glycyrrhetinic acid infusion may be a promising approach targeting hepatic AGT for heart failure with preserved ejection fraction (HFpEF) therapy. Abstract Heart failure with preserved ejection fraction (HFpEF) is a prevalent complex syndrome characterized by diastolic dysfunction with limited therapeutic options. While the renin‐angiotensin system (RAS) is implicated in heart failure pathogenesis, the causal contribution of angiotensinogen (AGT), the unique precursor of the RAS, to HFpEF remains undefined. Using a two‐hits mouse HFpEF model (high‐fat diet + L‐NAME), consistent upregulation of hepatic and plasma AGT is identified in wild‐type mice of both sexes. Critically, hepatocyte‐specific AGT deletion directly ameliorated diastolic dysfunction in male and female HFpEF mice, whereas systemic angiotensin II blockade (losartan) failed to improve cardiac diastolic function. Mechanistically, hepatic AGT drove HFpEF through LRP2‐mediated internalization in cardiac endothelial cells, suppressing the GATA2/Pim3 signaling axis, which inhibited microvascular angiogenesis and ultimately exacerbated diastolic dysfunction. To validate therapeutic potential, it is demonstrated that 18β‐glycyrrhetinic acid – identified as a potent hepatic AGT inhibitor – significantly improved cardiac diastolic function in HFpEF mice. These findings establish hepatic AGT as a causal contributor to HFpEF pathogenesis and reveal its therapeutic targeting as a promising strategy. Increased hepatic angiotensinogen (AGT) abundance leads to cardiac diastolic dysfunction via the AngII-independent pathway. Liver-derived AGT is internalized by LRP2 in cardiac endothelial cells, subsequently contributing to myocardial diastolic dysfunction by suppressing microvascular angiogenesis via inhibiting the GATA2/Pim3 pathway. In vivo 18β-glycyrrhetinic acid infusion may be a promising approach targeting hepatic AGT for heart failure with preserved ejection fraction (HFpEF) therapy. Abstract Heart failure with preserved ejection fraction (HFpEF) is a prevalent complex syndrome characterized by diastolic dysfunction with limited therapeutic options. While the renin-angiotensin system (RAS) is implicated in heart failure pathogenesis, the causal contribution of angiotensinogen (AGT), the unique precursor of the RAS, to HFpEF remains undefined. Using a two-hits mouse HFpEF model (high-fat diet + L-NAME), consistent upregulation of hepatic and plasma AGT is identified in wild-type mice of both sexes. Critically, hepatocyte-specific AGT deletion directly ameliorated diastolic dysfunction in male and female HFpEF mice, whereas systemic angiotensin II blockade (losartan) failed to improve cardiac diastolic function. Mechanistically, hepatic AGT drove HFpEF through LRP2-mediated internalization in cardiac endothelial cells, suppressing the GATA2/Pim3 signaling axis, which inhibited microvascular angiogenesis and ultimately exacerbated diastolic dysfunction. To validate therapeutic potential, it is demonstrated that 18β-glycyrrhetinic acid – identified as a potent hepatic AGT inhibitor – significantly improved cardiac diastolic function in HFpEF mice. These findings establish hepatic AGT as a causal contributor to HFpEF pathogenesis and reveal its therapeutic targeting as a promising strategy. Advanced Science, Volume 12, Issue 43, November 20, 2025.

A Lipid with Lewis Pair‐Mediated Targeting and Multiple Stimuli‐Responsive Delivery of Antibiotics for Bacterial Infections

Lewis pair‐integrated lipids (Lp‐lipids), combining targeted delivery and stimuli‐responsive are developed for antibiotic delivery. These lipids form nanoparticles that bind biofilms via boronate ester bonds and respond to acidic pH, H2O2, and ATP, enabling controlled drug release. Lp‐lipids effectively eradicate bacteria, showing promise for clinical translation. Abstract Integrating both targeted delivery and stimulus‐responsive release into a single small molecule for drug delivery presents challenges related to synthesis, stability, and efficacy. In this study, single‐molecular lipids incorporating a Lewis pair (Lp‐lipids) are described, composed of a Lewis acid (phenylboronic acid) and a Lewis base (amine) within a single small molecular structure, to formulate lipid nanoparticles for antibiotic delivery. For targeted delivery to bacterial biofilms, the phenylboronic acid selectively binds to bacteria or biofilms by forming boronate ester bonds with diols in the microbial dextran or peptidoglycan. Additionally, the amine group responds to the acidic microenvironment, enhancing electrostatic interactions with bacteria and biofilms. Regarding stimulus‐responsive drug release, the Lewis base reacts to low pH, while the Lewis acid responds to H2O2 and ATP, triggering changes in the hydrophobicity and structural integrity of the lipid nanoparticles. These changes facilitate the release of encapsulated antibiotics, effectively eradicating both Gram‐positive and Gram‐negative bacteria in vitro and in vivo. The combined targeting and stimuli‐responsive release properties of Lp‐lipids significantly enhance their potential for biomedical applications and clinical translation. Lewis pair-integrated lipids ( Lp -lipids), combining targeted delivery and stimuli-responsive are developed for antibiotic delivery. These lipids form nanoparticles that bind biofilms via boronate ester bonds and respond to acidic pH, H 2 O 2, and ATP, enabling controlled drug release. Lp -lipids effectively eradicate bacteria, showing promise for clinical translation. Abstract Integrating both targeted delivery and stimulus-responsive release into a single small molecule for drug delivery presents challenges related to synthesis, stability, and efficacy. In this study, single-molecular lipids incorporating a Lewis pair ( Lp -lipids) are described, composed of a Lewis acid (phenylboronic acid) and a Lewis base (amine) within a single small molecular structure, to formulate lipid nanoparticles for antibiotic delivery. For targeted delivery to bacterial biofilms, the phenylboronic acid selectively binds to bacteria or biofilms by forming boronate ester bonds with diols in the microbial dextran or peptidoglycan. Additionally, the amine group responds to the acidic microenvironment, enhancing electrostatic interactions with bacteria and biofilms. Regarding stimulus-responsive drug release, the Lewis base reacts to low pH, while the Lewis acid responds to H 2 O 2 and ATP, triggering changes in the hydrophobicity and structural integrity of the lipid nanoparticles. These changes facilitate the release of encapsulated antibiotics, effectively eradicating both Gram-positive and Gram-negative bacteria in vitro and in vivo. The combined targeting and stimuli-responsive release properties of Lp -lipids significantly enhance their potential for biomedical applications and clinical translation. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Dynamic Neural Deactivation Bridges Direct and Competitive Inhibition Processes

Dynamic neural deactivation bridges traditionally distinct inhibitory mechanisms—direct inhibition and competition‐induced inhibition—revealing a common neural signature across modalities. Multimodal neuroimaging and behavioral experiments demonstrate a temporal dynamic characterized by progressive frontoparietal activation decay and enhanced sensory‐region deactivation, crucially linked to inhibition efficacy. This universal neural deactivation mechanism, confirmed through causal manipulation, reshapes understanding of cognitive control processes. Abstract Inhibition is an important concept in cognitive neuroscience. Direct inhibition, characterized by the active suppression of stimuli, and competition‐induced inhibition, which involves ignoring irrelevant stimuli by prioritizing relevant ones, have traditionally been considered distinct and studied separately. Although their spatial neural overlap has been highlighted, the temporal dimension—the development of neural activities over time—remains largely unexplored. Using multimodal neuroimaging and behavioral experiments in the auditory and visual domains, in addition to conjunction analyses that capture their neural commonalities, we observed that both inhibition types exhibit a shared deactivation temporal dynamic. It is characterized by a progressive reduction in frontoparietal activation and increased deactivation in sensory regions, a pattern that is positively correlated with improved inhibition performance and whose causal disruption contributes to reduced inhibitory effect. Furthermore, this deactivation‐dominant pattern is consistent across different sensory modalities and generalizes to various low‐processing demand scenarios, whether actively induced or passively experienced. In addition, functional blurring in information clarity during inhibition is found. Overall, the findings reveal that diverse inhibitory processes for modulating information input converge on a shared neural substrate characterized by dynamic feedforward signal attenuation, thereby bridging previously disconnected domains of inhibition research and offering new perspectives of neural deactivation. Dynamic neural deactivation bridges traditionally distinct inhibitory mechanisms—direct inhibition and competition-induced inhibition—revealing a common neural signature across modalities. Multimodal neuroimaging and behavioral experiments demonstrate a temporal dynamic characterized by progressive frontoparietal activation decay and enhanced sensory-region deactivation, crucially linked to inhibition efficacy. This universal neural deactivation mechanism, confirmed through causal manipulation, reshapes understanding of cognitive control processes. Abstract Inhibition is an important concept in cognitive neuroscience. Direct inhibition, characterized by the active suppression of stimuli, and competition-induced inhibition, which involves ignoring irrelevant stimuli by prioritizing relevant ones, have traditionally been considered distinct and studied separately. Although their spatial neural overlap has been highlighted, the temporal dimension—the development of neural activities over time—remains largely unexplored. Using multimodal neuroimaging and behavioral experiments in the auditory and visual domains, in addition to conjunction analyses that capture their neural commonalities, we observed that both inhibition types exhibit a shared deactivation temporal dynamic. It is characterized by a progressive reduction in frontoparietal activation and increased deactivation in sensory regions, a pattern that is positively correlated with improved inhibition performance and whose causal disruption contributes to reduced inhibitory effect. Furthermore, this deactivation-dominant pattern is consistent across different sensory modalities and generalizes to various low-processing demand scenarios, whether actively induced or passively experienced. In addition, functional blurring in information clarity during inhibition is found. Overall, the findings reveal that diverse inhibitory processes for modulating information input converge on a shared neural substrate characterized by dynamic feedforward signal attenuation, thereby bridging previously disconnected domains of inhibition research and offering new perspectives of neural deactivation. Advanced Science, Volume 12, Issue 43, November 20, 2025.