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A Comprehensive Lateral Flow Strip Assay for On‐Site mRNA Vaccine Quality Control in Decentralized Manufacturing

A rapid, portable lateral flow strip assay for on‐site mRNA quality control is developed, enabling sequence‐independent analysis of 5' capping, integrity, and LNPs encapsulation efficiency. This cost‐effective method offers real‐time stability monitoring, reduced sample requirements, and comparable accuracy to standard techniques, enhancing manufacturing workflows and ensuring mRNA therapeutic efficacy in decentralized settings. Abstract The rapid adoption of mRNA‐based vaccines highlights the critical need for on‐site quality control (QC) methods, particularly in low‐income countries with decentralized manufacturing. Existing techniques, such as liquid chromatography‐mass spectrometry (LC‐MS) and capillary electrophoresis (CE), are resource‐intensive, requiring specialized equipment and expertise. To address this, a comprehensive lateral flow strip assay (LFSA) has been developed to evaluate key mRNA quality attributes—5' capping efficiency, integrity, and lipid nanoparticles (LNPs) encapsulation efficiency. Leveraging antibody‐labeled fluorescence nanoparticles and polydeoxythymidine oligonucleotide to simultaneously probe both 5' cap and poly(A) tail, the LFSA offers sequence‐independent, rapid (15 min), and sensitive mRNA analysis. Validation against standard methods demonstrates comparable accuracy while significantly reducing sample requirements and operational complexity. Moreover, the LFSA enables real‐time monitoring of mRNA stability under varying storage conditions and provides precise encapsulation assessments, distinguishing between intact and degraded mRNA in LNPs. This portable and cost‐effective platform bridges critical gaps in mRNA QC, streamlines manufacturing workflows, and ensures mRNA therapeutic efficacy in diverse applications. A rapid, portable lateral flow strip assay for on-site mRNA quality control is developed, enabling sequence-independent analysis of 5' capping, integrity, and LNPs encapsulation efficiency. This cost-effective method offers real-time stability monitoring, reduced sample requirements, and comparable accuracy to standard techniques, enhancing manufacturing workflows and ensuring mRNA therapeutic efficacy in decentralized settings. Abstract The rapid adoption of mRNA-based vaccines highlights the critical need for on-site quality control (QC) methods, particularly in low-income countries with decentralized manufacturing. Existing techniques, such as liquid chromatography-mass spectrometry (LC-MS) and capillary electrophoresis (CE), are resource-intensive, requiring specialized equipment and expertise. To address this, a comprehensive lateral flow strip assay (LFSA) has been developed to evaluate key mRNA quality attributes—5' capping efficiency, integrity, and lipid nanoparticles (LNPs) encapsulation efficiency. Leveraging antibody-labeled fluorescence nanoparticles and polydeoxythymidine oligonucleotide to simultaneously probe both 5' cap and poly(A) tail, the LFSA offers sequence-independent, rapid (15 min), and sensitive mRNA analysis. Validation against standard methods demonstrates comparable accuracy while significantly reducing sample requirements and operational complexity. Moreover, the LFSA enables real-time monitoring of mRNA stability under varying storage conditions and provides precise encapsulation assessments, distinguishing between intact and degraded mRNA in LNPs. This portable and cost-effective platform bridges critical gaps in mRNA QC, streamlines manufacturing workflows, and ensures mRNA therapeutic efficacy in diverse applications. Advanced Science, Volume 12, Issue 43, November 20, 2025.

TBC1D22B Regulates ER‐to‐Golgi Trafficking via RAB1B Inactivation and Promotes Oncogenic Programs in Breast Cancer

TBC1D22B, a Golgi‐localized RabGAP linked to poor prognosis in breast cancer, inhibits ER‐to‐Golgi transport via RAB1B inactivation. This disrupts secretion, drives oncogenic transcriptional reprogramming, and promotes tumor growth. These findings indicate that TBC1D22B connects membrane trafficking to transcriptional control and cancer progression. Abstract TBC1D22B is a GTPase‐activating protein (GAP) associated with poor prognosis in breast cancer (BC). Using complementary proximity‐labeling and co‐immunoprecipitation proteomics, the TBC1D22B interactome in BC cells is defined, revealing strong enrichment in components of the ER‐to‐Golgi trafficking machinery, endosomal transport, and adhesion‐related pathways. Functional assays, using the Retention Using Selective Hooks (RUSH) system, demonstrate that TBC1D22B inhibits ER‐to‐Golgi transport in a GAP‐dependent manner. Mechanistic studies identify RAB1B as a direct target of TBC1D22B, and RAB1B silencing phenocopies the trafficking defects caused by TBC1D22B overexpression. In 3D culture, TBC1D22B promotes spheroid growth in a manner dependent on its GAP activity and not replicated by its paralog TBC1D22A. Transcriptomic profiling reveals that TBC1D22B overexpression triggers repression of a core module of extracellular matrix and adhesion‐related genes, consistent with altered secretory activity. Importantly, this transcriptional program is also evident in primary Luminal BC with high TBC1D22B expression, highlighting a conserved and functionally relevant signature. Together, these findings establish TBC1D22B as a regulator of ER‐to‐Golgi trafficking via RAB1B and implicate it in oncogenic transcriptional remodeling and tumor growth. TBC1D22B, a Golgi-localized RabGAP linked to poor prognosis in breast cancer, inhibits ER-to-Golgi transport via RAB1B inactivation. This disrupts secretion, drives oncogenic transcriptional reprogramming, and promotes tumor growth. These findings indicate that TBC1D22B connects membrane trafficking to transcriptional control and cancer progression. Abstract TBC1D22B is a GTPase-activating protein (GAP) associated with poor prognosis in breast cancer (BC). Using complementary proximity-labeling and co-immunoprecipitation proteomics, the TBC1D22B interactome in BC cells is defined, revealing strong enrichment in components of the ER-to-Golgi trafficking machinery, endosomal transport, and adhesion-related pathways. Functional assays, using the Retention Using Selective Hooks (RUSH) system, demonstrate that TBC1D22B inhibits ER-to-Golgi transport in a GAP-dependent manner. Mechanistic studies identify RAB1B as a direct target of TBC1D22B, and RAB1B silencing phenocopies the trafficking defects caused by TBC1D22B overexpression. In 3D culture, TBC1D22B promotes spheroid growth in a manner dependent on its GAP activity and not replicated by its paralog TBC1D22A. Transcriptomic profiling reveals that TBC1D22B overexpression triggers repression of a core module of extracellular matrix and adhesion-related genes, consistent with altered secretory activity. Importantly, this transcriptional program is also evident in primary Luminal BC with high TBC1D22B expression, highlighting a conserved and functionally relevant signature. Together, these findings establish TBC1D22B as a regulator of ER-to-Golgi trafficking via RAB1B and implicate it in oncogenic transcriptional remodeling and tumor growth. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Sleep Deprivation Aggravates Periodontitis Through Trigeminal‐Periodontal Neuroimmune Pathway Mediated by the AChE‐ACh‐α7nAChR Axis

Sleep deprivation (SD) exacerbates ligature‐induced periodontitis (LIP) through the trigeminal nerve‐periodontal neuroimmune pathway mediated by the acetylcholinesterase (AChE)‐acetylcholine (ACh)‐α7 nicotinic receptor (α7nAChR) axis. While electroacupuncture (EA) alleviates the condition of LIP combined with SD by activating the α7nAChR. Abstract Continuous sleep deprivation (SD) triggers systemic inflammatory storm and immune dysregulation, yet its specific impact on periodontitis and the corresponding therapeutic interventions remains unclear. Consequently, this study elucidates the neuroimmune mechanisms linking SD to ligature‐induced periodontitis (LIP) in mice and evaluates electroacupuncture (EA) as a novel adjunctive therapy. Screening analyses (ELISA, public databases, flow cytometry, immunofluorescence, etc.) identified pivotal roles of acetylcholine (ACh), α7 nicotinic acetylcholine receptor (α7nAChR), and acetylcholinesterase (AChE) in SD‐aggravated periodontitis with a decrease in ACh levels, down‐regulation of α7nAChR on macrophages, and an increase in trigeminal ganglion‐derived AChE. Clinical validation in periodontitis patients with poor sleep (PSQI ≥ 5) confirmed this tripartite cholinergic imbalance. Ultimately, both in vivo and in vitro data demonstrated that EA inhibits M1 polarization while promoting M2 polarization of macrophages through α7nAChR activation. Therefore, SD exacerbates periodontitis via the AChE‐ACh‐α7nAChR axis‐mediated trigeminal‐periodontal neuroimmune pathway, whereas EA partially reverses this pathology by targeting macrophage α7nAChR. These findings reveal new insights into the “oral‐brain axis” in oral disease pathogenesis and provide novel therapeutic strategies for periodontitis patients with comorbid sleep disorders. Sleep deprivation (SD) exacerbates ligature-induced periodontitis (LIP) through the trigeminal nerve-periodontal neuroimmune pathway mediated by the acetylcholinesterase (AChE)-acetylcholine (ACh)-α7 nicotinic receptor (α7nAChR) axis. While electroacupuncture (EA) alleviates the condition of LIP combined with SD by activating the α7nAChR. Abstract Continuous sleep deprivation (SD) triggers systemic inflammatory storm and immune dysregulation, yet its specific impact on periodontitis and the corresponding therapeutic interventions remains unclear. Consequently, this study elucidates the neuroimmune mechanisms linking SD to ligature-induced periodontitis (LIP) in mice and evaluates electroacupuncture (EA) as a novel adjunctive therapy. Screening analyses (ELISA, public databases, flow cytometry, immunofluorescence, etc.) identified pivotal roles of acetylcholine (ACh), α7 nicotinic acetylcholine receptor (α7nAChR), and acetylcholinesterase (AChE) in SD-aggravated periodontitis with a decrease in ACh levels, down-regulation of α7nAChR on macrophages, and an increase in trigeminal ganglion-derived AChE. Clinical validation in periodontitis patients with poor sleep (PSQI ≥ 5) confirmed this tripartite cholinergic imbalance. Ultimately, both in vivo and in vitro data demonstrated that EA inhibits M1 polarization while promoting M2 polarization of macrophages through α7nAChR activation. Therefore, SD exacerbates periodontitis via the AChE-ACh-α7nAChR axis-mediated trigeminal-periodontal neuroimmune pathway, whereas EA partially reverses this pathology by targeting macrophage α7nAChR. These findings reveal new insights into the “oral-brain axis” in oral disease pathogenesis and provide novel therapeutic strategies for periodontitis patients with comorbid sleep disorders. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Lifespan‐Regulated CAR‐Macrophages from Myeloid Progenitors for Enhanced Colorectal Cancer Therapy

Using a tamoxifen‐inducible Hoxb8 system, proliferative bone marrow progenitors can be generated, which are subsequently engineered with an anti‐CEA CAR construct containing a suicide gene (iCas9) and differentiated into CAR‐macrophages. This method facilitates scale up the production of CAR‐macrophages. Meanwhile, lifespan‐regulated CAR‐macrophages from myeloid progenitors enhance solid tumor immunotherapy, overcoming gene transduction efficiency and scalability for advanced cancer therapy. Abstract Adoptive cell therapies for solid tumors face persistent challenges from poor tumor infiltration and immunosuppressive microenvironment. To overcome these limitations, a clinically scalable platform is developed to generate chimeric antigen receptor macrophages (CAR‐HMs) from tamoxifen‐regulated immortalized Hoxb8‐transduced myeloid progenitors, achieving >95% CAR transduction efficiency and 60‐fold expansion within 10 days. Engineered with a colorectal cancer‐specific anti‐carcinoembryonic antigen (CEA) CAR, these FcγRI‐CAR‐HMs demonstrated potent tumoricidal activity (>80% CRC cell lysis in vitro), deep tissue penetration (>100 µm in 3D tumor spheroids), and significant therapeutic efficacy (≈89% tumor regression in vivo). Mechanistic studies demonstrated that FcγRI‐CAR‐HMs remodeled the tumor microenvironment through direct tumor phagocytosis, T cells recruitment and activation, and synergistic enhancement of anti‐PD‐1 therapy in colorectal cancer models, while an integrated inducible caspase‐9 (iCas9) suicide switch ensured safety without compromising long‐term persistence. This progenitors‐based platform not only addresses critical manufacturing challenges but also unlocks the full therapeutic potential of CAR‐macrophages, whose unique ability to synergize with checkpoint inhibitors provides a transformative approach for treatment‐refractory solid tumors. Using a tamoxifen-inducible Hoxb8 system, proliferative bone marrow progenitors can be generated, which are subsequently engineered with an anti-CEA CAR construct containing a suicide gene (iCas9) and differentiated into CAR-macrophages. This method facilitates scale up the production of CAR-macrophages. Meanwhile, lifespan-regulated CAR-macrophages from myeloid progenitors enhance solid tumor immunotherapy, overcoming gene transduction efficiency and scalability for advanced cancer therapy. Abstract Adoptive cell therapies for solid tumors face persistent challenges from poor tumor infiltration and immunosuppressive microenvironment. To overcome these limitations, a clinically scalable platform is developed to generate chimeric antigen receptor macrophages (CAR-HMs) from tamoxifen-regulated immortalized Hoxb8-transduced myeloid progenitors, achieving >95% CAR transduction efficiency and 60-fold expansion within 10 days. Engineered with a colorectal cancer-specific anti-carcinoembryonic antigen (CEA) CAR, these FcγRI-CAR-HMs demonstrated potent tumoricidal activity (>80% CRC cell lysis in vitro), deep tissue penetration (>100 µm in 3D tumor spheroids), and significant therapeutic efficacy (≈89% tumor regression in vivo). Mechanistic studies demonstrated that FcγRI-CAR-HMs remodeled the tumor microenvironment through direct tumor phagocytosis, T cells recruitment and activation, and synergistic enhancement of anti-PD-1 therapy in colorectal cancer models, while an integrated inducible caspase-9 (iCas9) suicide switch ensured safety without compromising long-term persistence. This progenitors-based platform not only addresses critical manufacturing challenges but also unlocks the full therapeutic potential of CAR-macrophages, whose unique ability to synergize with checkpoint inhibitors provides a transformative approach for treatment-refractory solid tumors. Advanced Science, Volume 12, Issue 43, November 20, 2025.

UCP2 Upregulates ACSL3 to Enhance Lipid Droplet Release from Acinar Cells and Modulates the Sirt1/Smad3 Pathway to Promote Macrophage‐to‐Myofibroblast Transition in Chronic Pancreatitis

These findings suggest that UCP2 promotes LD formation and release in acinar cells by upregulating ACSL3 expression. This alteration in the local lipid metabolic environment indirectly drives the MMT process. Additionally, UCP2 may regulate the acetylation of Smad3 through Sirt1, enhancing its nuclear activity and activating the TGF‐β/ Smad3 signaling pathway. This, in turn, promotes fatty acid metabolism, providing energy for macrophage MMT and synergistically inducing pancreatic fibrosis. Abstract Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by pancreatic fibrosis and functional decline. Here, we identify macrophage‐to‐myofibroblast transition (MMT) as a novel feature of CP and investigate the role of mitochondrial uncoupling protein 2 (UCP2) in this process. Using mouse models, human pancreatic specimens, and cell lines, we show that UCP2 is markedly upregulated in CP, primarily in acinar cells. UCP2 knockout reduces MMT and alleviates fibrosis, whereas macrophage depletion reverses this protective effect, confirming the central role of MMT. Metabolomic profiling reveals that UCP2 knockout alters lipid metabolism by downregulating acyl‐CoA synthetase long‐chain family member 3 (ACSL3) and reducing lipid droplet (LD) release in acinar cells. Mechanistically, UCP2 upregulation increases silent information regulator 1 (Sirt1) expression, enhances Smad3 phosphorylation and nuclear translocation, and activates transforming growth factor‐β (TGF‐β)/Smad3 signaling to promote macrophage MMT. Macrophage‐specific Sirt1 knockout suppresses both fibrosis and MMT. In conclusion, UCP2 drives CP progression by regulating ACSL3‐mediated LD release in acinar cells and modulating macrophage function through the Sirt1/Smad3 pathway. Targeting UCP2 may represent a promising therapeutic strategy for CP. These findings suggest that UCP2 promotes LD formation and release in acinar cells by upregulating ACSL3 expression. This alteration in the local lipid metabolic environment indirectly drives the MMT process. Additionally, UCP2 may regulate the acetylation of Smad3 through Sirt1, enhancing its nuclear activity and activating the TGF-β/ Smad3 signaling pathway. This, in turn, promotes fatty acid metabolism, providing energy for macrophage MMT and synergistically inducing pancreatic fibrosis. Abstract Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by pancreatic fibrosis and functional decline. Here, we identify macrophage-to-myofibroblast transition (MMT) as a novel feature of CP and investigate the role of mitochondrial uncoupling protein 2 (UCP2) in this process. Using mouse models, human pancreatic specimens, and cell lines, we show that UCP2 is markedly upregulated in CP, primarily in acinar cells. UCP2 knockout reduces MMT and alleviates fibrosis, whereas macrophage depletion reverses this protective effect, confirming the central role of MMT. Metabolomic profiling reveals that UCP2 knockout alters lipid metabolism by downregulating acyl-CoA synthetase long-chain family member 3 (ACSL3) and reducing lipid droplet (LD) release in acinar cells. Mechanistically, UCP2 upregulation increases silent information regulator 1 (Sirt1) expression, enhances Smad3 phosphorylation and nuclear translocation, and activates transforming growth factor-β (TGF-β)/Smad3 signaling to promote macrophage MMT. Macrophage-specific Sirt1 knockout suppresses both fibrosis and MMT. In conclusion, UCP2 drives CP progression by regulating ACSL3-mediated LD release in acinar cells and modulating macrophage function through the Sirt1/Smad3 pathway. Targeting UCP2 may represent a promising therapeutic strategy for CP. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Solid Additives for Spontaneously Spreading‐Processed Organic Photovoltaics

This work developed a spontaneous spreading process with solid additives for the fabrication of organic photovoltaics (OPVs). By regulating interfacial tension, the solid additives enable the formation of uniform films on the water surface. A remarkable power conversion efficiency of 16.4% is recorded in the OPVs using phenanthrene (PAT) as the additive. Abstract The spontaneous spreading (SS) process offers a unique solution‐processed platform for fabricating organic photovoltaics (OPVs) under open‐air conditions. Yet its development is hindered by limited strategies to achieve uniform film thickness and homogeneous phase morphology. In this work, an SS process is developed using the green solvent o‐xylene and mediated by solid additives to regulate interfacial tension, enabling the formation of uniform SS‐films on the water surface. The aromatic solid additive phenanthrene (PAT) extended the drying time of the wet film, effectively suppressed excessive acceptor aggregation, enhanced molecular packing order, and optimized phase‐separated morphology for the SS‐film. The OPV device with SS‐film as the active layer achieved a champion efficiency of 16.4%. To the best of current knowledge, this is the first attempt to introduce solid additives in SS‐processed OPVs, offering a versatile strategy to simultaneously adjust film‐forming kinetics and phase morphology. This study presents a simple approach to fabricating solution OPVs with solution processability and reproducibility. This work developed a spontaneous spreading process with solid additives for the fabrication of organic photovoltaics (OPVs). By regulating interfacial tension, the solid additives enable the formation of uniform films on the water surface. A remarkable power conversion efficiency of 16.4% is recorded in the OPVs using phenanthrene (PAT) as the additive. Abstract The spontaneous spreading (SS) process offers a unique solution-processed platform for fabricating organic photovoltaics (OPVs) under open-air conditions. Yet its development is hindered by limited strategies to achieve uniform film thickness and homogeneous phase morphology. In this work, an SS process is developed using the green solvent o-xylene and mediated by solid additives to regulate interfacial tension, enabling the formation of uniform SS-films on the water surface. The aromatic solid additive phenanthrene (PAT) extended the drying time of the wet film, effectively suppressed excessive acceptor aggregation, enhanced molecular packing order, and optimized phase-separated morphology for the SS-film. The OPV device with SS-film as the active layer achieved a champion efficiency of 16.4%. To the best of current knowledge, this is the first attempt to introduce solid additives in SS-processed OPVs, offering a versatile strategy to simultaneously adjust film-forming kinetics and phase morphology. This study presents a simple approach to fabricating solution OPVs with solution processability and reproducibility. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Reaction Suppression Between a High‐Ni Cathode Material (NMC622) and Li7La3Zr2O12 on Co‐Sintering for Manufacturing Bulk‐Type All‐Solid‐State Batteries: A New Method and Its Mechanism

A bulk‐type all‐solid‐state battery is produced by co‐sintering the proprietary NMC622 and LLZ. This proprietary NMC622 can avoid the formation of impurity phases under co‐sintering. The reduced Ni2+ fraction in NMC622 and the presence of a self‐formed Li2CO3 surface layer result in this outcome. It is possible to realize a rechargeable all‐solid‐state battery. Abstract Co‐sintering cathode materials with Li7La3Zr2O12 (LLZ) is a promising strategy for fabricating bulk‐type all‐solid‐state batteries (ASSBs). However, preventing reactions between different materials, which is difficult with high‐capacity cathode materials such as LiNi0.6Mn0.2Co0.2O2 (NMC622), is a pre‐requisite for applying this strategy. To overcome this issue, Li1+xNi0.6Mn0.2Co0.2O2 (x = 0.01–0.2), which intentionally deviates from the stoichiometric NMC622 composition, is synthesized here. The formation of impurity phases in the co‐sintering process can be controlled by adjusting the co‐sintering temperature and x. Impurity phases are not formed on co‐sintering with x = 0.075 at 800 °C because reduced cation mixing in NMC622 and the presence of a self‐formed Li2CO3 layer on the particle surface, ensured by adjusting x, effectively suppresses reactions. Furthermore, good results are observed at sintering temperatures where the proportions of Ni2+ and Co2+, which promote cation mixing, are low. This study clarifies relevant reaction mechanisms using various analytical methods (such as temperature‐rise X‐ray absorption fine structure analysis and scanning transmission electron microscopy‐electron energy loss spectroscopy), and confirms the repetitive operation of bulk‐type ASSBs assembled using co‐sintered Li1+xNi0.6Mn0.2Co0.2O2 (x = 0.075)/LLZ electrolyte systems. The method reported herein can be potentially adopted for cost‐effective and high‐energy‐capacity ASSB production. A bulk-type all-solid-state battery is produced by co-sintering the proprietary NMC622 and LLZ. This proprietary NMC622 can avoid the formation of impurity phases under co-sintering. The reduced Ni 2+ fraction in NMC622 and the presence of a self-formed Li 2 CO 3 surface layer result in this outcome. It is possible to realize a rechargeable all-solid-state battery. Abstract Co-sintering cathode materials with Li 7 La 3 Zr 2 O 12 (LLZ) is a promising strategy for fabricating bulk-type all-solid-state batteries (ASSBs). However, preventing reactions between different materials, which is difficult with high-capacity cathode materials such as LiNi 0.6 Mn 0.2 Co 0.2 O 2 (NMC622), is a pre-requisite for applying this strategy. To overcome this issue, Li 1+ x Ni 0.6 Mn 0.2 Co 0.2 O 2 ( x = 0.01–0.2), which intentionally deviates from the stoichiometric NMC622 composition, is synthesized here. The formation of impurity phases in the co-sintering process can be controlled by adjusting the co-sintering temperature and x. Impurity phases are not formed on co-sintering with x = 0.075 at 800 °C because reduced cation mixing in NMC622 and the presence of a self-formed Li 2 CO 3 layer on the particle surface, ensured by adjusting x, effectively suppresses reactions. Furthermore, good results are observed at sintering temperatures where the proportions of Ni 2+ and Co 2+, which promote cation mixing, are low. This study clarifies relevant reaction mechanisms using various analytical methods (such as temperature-rise X-ray absorption fine structure analysis and scanning transmission electron microscopy-electron energy loss spectroscopy), and confirms the repetitive operation of bulk-type ASSBs assembled using co-sintered Li 1+ x Ni 0.6 Mn 0.2 Co 0.2 O 2 ( x = 0.075)/LLZ electrolyte systems. The method reported herein can be potentially adopted for cost-effective and high-energy-capacity ASSB production. Advanced Science, Volume 12, Issue 43, November 20, 2025.

A Biomimetic Fiber‐Entangled Permeable Electronic Skin for Strain‐Insensitive and High‐Resolution Tactile Sensing

A biomimetic fiber‐entangled island architecture is proposed to address the stress concentration issues commonly observed in conventional island arrays. Based on this architecture, a pressure‐sensing e‐skin with simultaneously high spatial resolution, low strain interference, and excellent permeability is developed, which is further applied to wearable pressure imaging. Abstract Electronic skins (e‐skins) incorporating island architectures represent a promising platform for strain‐insensitive tactile sensing by mechanically decoupling sensing units from deformations. However, conventional island designs encounter stress concentration issues caused by inherent modulus mismatches, critically limiting achievable island densities. This limitation forces a stubborn trade‐off between strain‐insensitivity and sensing resolution. Here, inspired by the entangled elastin networks surrounding human tactile receptors, a biomimetic fiber‐entangled island architecture is proposed that addresses the stress concentration issue, providing a viable solution for strain‐insensitive and high‐resolution tactile sensing. The mechanism by which the fiber‐entangled architecture mitigates stress concentration is based on the strain‐dependent reorientation of its constituent fibers. As a demonstration of this solution, a pressure sensing e‐skin exhibiting simultaneous high resolution (100 unit cm−2) and low strain interference (gauge factor < 0.03) is developed. Implemented with artificial neural networks, the e‐skin demonstrates proof‐of‐concept functionality as a wearable Braille point‐to‐read system. The fiber‐entangled architecture proposed here will emerge as a versatile platform for next‐generation humanoid sensing. A biomimetic fiber-entangled island architecture is proposed to address the stress concentration issues commonly observed in conventional island arrays. Based on this architecture, a pressure-sensing e-skin with simultaneously high spatial resolution, low strain interference, and excellent permeability is developed, which is further applied to wearable pressure imaging. Abstract Electronic skins (e-skins) incorporating island architectures represent a promising platform for strain-insensitive tactile sensing by mechanically decoupling sensing units from deformations. However, conventional island designs encounter stress concentration issues caused by inherent modulus mismatches, critically limiting achievable island densities. This limitation forces a stubborn trade-off between strain-insensitivity and sensing resolution. Here, inspired by the entangled elastin networks surrounding human tactile receptors, a biomimetic fiber-entangled island architecture is proposed that addresses the stress concentration issue, providing a viable solution for strain-insensitive and high-resolution tactile sensing. The mechanism by which the fiber-entangled architecture mitigates stress concentration is based on the strain-dependent reorientation of its constituent fibers. As a demonstration of this solution, a pressure sensing e-skin exhibiting simultaneous high resolution (100 unit cm −2 ) and low strain interference (gauge factor < 0.03) is developed. Implemented with artificial neural networks, the e-skin demonstrates proof-of-concept functionality as a wearable Braille point-to-read system. The fiber-entangled architecture proposed here will emerge as a versatile platform for next-generation humanoid sensing. Advanced Science, Volume 12, Issue 43, November 20, 2025.

All‐In‐One Iontronic Sensing Aligner for High‐Precision 3D Orthodontic Force Monitoring

A wireless, battery‐free orthodontic sensing system is developed by integrating a cross‐shaped iontronic sensor and an origami‐inspired NFC circuit into clear aligners. This all‐in‐one device enables real‐time, in vivo 3D force monitoring with high precision and long‐term stability, providing clinicians with quantitative biomechanical feedback to optimize treatment efficacy and personalize orthodontic care. Abstract Clear aligners offer aesthetic and comfort advantages in orthodontics, yet their ability to deliver effective forces relies heavily on empirical judgment or large‐scale optical scanning, lacking real‐time quantitative evaluation. Integrating pressure sensors into aligners is a promising solution, but challenges in miniaturization, multi‐dimensional sensing, measurement accuracy, and biocompatibility hinder clinical application. Here, an all‐in‐one Orthodontic Force Acquisition System (OFAS) is presented that enables real‐time, 3D force monitoring using a cross‐shaped iontronic sensing array and an origami‐inspired, wireless battery‐free readout circuit miniaturized for single‐tooth placement. The system employs a cross‐linked polyelectrolyte with low creep and high repeatability, achieving 1.14% measurement accuracy. A 15‐day in vivo study demonstrates that OFAS accurately captured dynamic force profiles with strong correlation to tooth displacement (R2 > 0.99), confirming its feasibility for real‐time, quantitative orthodontic force measurement and enabling timely treatment adjustments. A wireless, battery-free orthodontic sensing system is developed by integrating a cross-shaped iontronic sensor and an origami-inspired NFC circuit into clear aligners. This all-in-one device enables real-time, in vivo 3D force monitoring with high precision and long-term stability, providing clinicians with quantitative biomechanical feedback to optimize treatment efficacy and personalize orthodontic care. Abstract Clear aligners offer aesthetic and comfort advantages in orthodontics, yet their ability to deliver effective forces relies heavily on empirical judgment or large-scale optical scanning, lacking real-time quantitative evaluation. Integrating pressure sensors into aligners is a promising solution, but challenges in miniaturization, multi-dimensional sensing, measurement accuracy, and biocompatibility hinder clinical application. Here, an all-in-one Orthodontic Force Acquisition System (OFAS) is presented that enables real-time, 3D force monitoring using a cross-shaped iontronic sensing array and an origami-inspired, wireless battery-free readout circuit miniaturized for single-tooth placement. The system employs a cross-linked polyelectrolyte with low creep and high repeatability, achieving 1.14% measurement accuracy. A 15-day in vivo study demonstrates that OFAS accurately captured dynamic force profiles with strong correlation to tooth displacement (R 2 > 0.99), confirming its feasibility for real-time, quantitative orthodontic force measurement and enabling timely treatment adjustments. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Root Meristem Maintenance Mechanisms are Key to Plant Defense Against Nanoplastics

Small nanoplastics can disrupt cell integrity and inhibit cell division in meristem zone of plant root. The plants can counteract the cell damage by upregulating genes associated with root meristem maintenance and increasing auxin accumulation by PIN2 transport inhibition. The defense strategies enhance stress tolerance but impair the gravitropic growth of plants. Abstract The pervasive prevalence of nanoplastics in environment poses a challenge that threatens ecosystem and agricultural production. Despite their ubiquity, the determinants of nanoplastics phytotoxicity and the mechanisms through which plants defend against this phytotoxicity remain poorly understand. In this study, it is demonstrated that the phytotoxicity of nanoplastics is inversely correlated with particle size. Specifically, polystyrene‐nanoplastics sized at 20 nm dramatically inhibit root growth in Arabidopsis, while larger particles (100 to 1000 nm) have minimal effects. Mechanistically, these small nanoplastics primarily target the root meristem (RM), disrupting cell integrity and inhibiting cell division, which impairs root development. Plants employ two key defense strategies to counteract this toxicity: i) upregulating genes associated with RM maintenance and ii) accumulating auxin in the roots by inhibiting the auxin efflux transporter PIN2‐dependent efflux of auxin, thereby reducing upward transport. However, this defensive response comes at a cost, as it also impairs root gravitropism, a critical process for plant adaptation to environmental changes. These findings provide valuable insights into the mechanisms of nanoplastic‐induced phytotoxicity and plant defense, establishing a foundation for the development of biosafe plastic products and strategies to genetically enhance plant resistance to tiny nanoparticle exposure by optimization of intrinsic detoxification pathways. Small nanoplastics can disrupt cell integrity and inhibit cell division in meristem zone of plant root. The plants can counteract the cell damage by upregulating genes associated with root meristem maintenance and increasing auxin accumulation by PIN2 transport inhibition. The defense strategies enhance stress tolerance but impair the gravitropic growth of plants. Abstract The pervasive prevalence of nanoplastics in environment poses a challenge that threatens ecosystem and agricultural production. Despite their ubiquity, the determinants of nanoplastics phytotoxicity and the mechanisms through which plants defend against this phytotoxicity remain poorly understand. In this study, it is demonstrated that the phytotoxicity of nanoplastics is inversely correlated with particle size. Specifically, polystyrene-nanoplastics sized at 20 nm dramatically inhibit root growth in Arabidopsis, while larger particles (100 to 1000 nm) have minimal effects. Mechanistically, these small nanoplastics primarily target the root meristem (RM), disrupting cell integrity and inhibiting cell division, which impairs root development. Plants employ two key defense strategies to counteract this toxicity: i) upregulating genes associated with RM maintenance and ii) accumulating auxin in the roots by inhibiting the auxin efflux transporter PIN2-dependent efflux of auxin, thereby reducing upward transport. However, this defensive response comes at a cost, as it also impairs root gravitropism, a critical process for plant adaptation to environmental changes. These findings provide valuable insights into the mechanisms of nanoplastic-induced phytotoxicity and plant defense, establishing a foundation for the development of biosafe plastic products and strategies to genetically enhance plant resistance to tiny nanoparticle exposure by optimization of intrinsic detoxification pathways. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Electro‐Thermally Controlled Active Mechanical Metamaterials with Programmable Stiffness and Nonreciprocity

Actively programmable mechanical metamaterial, featuring smart conductive polymers, designed instabilities, and compliant mechanisms. Capable of stiffness switching, local surface pressure modulation, and nonreciprocal shear relationships that allow local shielding from surface traction. Potential applications in soft robotic grippers and smart medical devices. Abstract Active mechanical metamaterials have the potential to revolutionize material capabilities, by switching between different properties. The active mechanical metamaterial presented here can be remotely programmed to switch between compressive and shear deformation modes that cause stark changes in stiffness. The considered metamaterial uses controlled instabilities to change the buckling mode of electro‐thermally activated beams. The beams form electrical circuits. When selectively charged, they heat (and soften). The effects of manufacturing imperfections are overcome by connecting the beams to a compliant mechanism, allowing reliable control over the compressive buckling modes that cause the stiffness changes. Connection points in the metamaterial resemble a fish‐bone structure, known to exhibit static nonreciprocity, which is actively controllable within the considered metamaterial. As such, it is shown (computationally) that this metamaterial is capable of modulating traction and pressure across a surface. Pressure can be doubled between adjacent unit‐cells while traction can be shielded (i.e., zero) in selected regions. This concept has potential applications in robotic gripper interfaces, and medical devices. Actively programmable mechanical metamaterial, featuring smart conductive polymers, designed instabilities, and compliant mechanisms. Capable of stiffness switching, local surface pressure modulation, and nonreciprocal shear relationships that allow local shielding from surface traction. Potential applications in soft robotic grippers and smart medical devices. Abstract Active mechanical metamaterials have the potential to revolutionize material capabilities, by switching between different properties. The active mechanical metamaterial presented here can be remotely programmed to switch between compressive and shear deformation modes that cause stark changes in stiffness. The considered metamaterial uses controlled instabilities to change the buckling mode of electro-thermally activated beams. The beams form electrical circuits. When selectively charged, they heat (and soften). The effects of manufacturing imperfections are overcome by connecting the beams to a compliant mechanism, allowing reliable control over the compressive buckling modes that cause the stiffness changes. Connection points in the metamaterial resemble a fish-bone structure, known to exhibit static nonreciprocity, which is actively controllable within the considered metamaterial. As such, it is shown (computationally) that this metamaterial is capable of modulating traction and pressure across a surface. Pressure can be doubled between adjacent unit-cells while traction can be shielded (i.e., zero) in selected regions. This concept has potential applications in robotic gripper interfaces, and medical devices. Advanced Science, Volume 12, Issue 43, November 20, 2025.

A Single‐Molecule Pleuripotent Scaffold for Combinational Therapy of Alzheimer's Disease via Intranasal Administration

Herein, guanidinium‐modified calix[5]arene (GC5AY) is developed featuring small size, positive charge, and desirable amphiphilicity, that can efficiently traverse the nasal mucosal barrier for brain drug delivery. Additionally, possessing inherent therapeutic functions, GC5AY can thus serve as a single‐molecule pleuripotent scaffold for multi‐target combinational therapy of Alzheimer's disease via intranasal administration. Abstract The intricate pathological mechanisms of Alzheimer's disease (AD), along with the restrictive nature of the blood‐brain barrier (BBB) that further impedes the drug brain entry, underscore the pressing need for innovative combinational therapy to achieve effective treatment outcomes. Intranasal administration, capable of bypassing BBB by direct transport through olfactory and trigeminal nerves, provides a promising approach for treating neurological disorders. Herein, the guanidinium‐modified calix[5]arene (GC5AY) is developed as a single‐molecule pleuripotent scaffold, demonstrating small size, positive charge and desirable amphiphilicity, which facilitate its efficient traverse of nasal mucosal barrier. The multifunctionality of GC5AY, including inhibiting amyloid fibrosis, scavenging reactive oxygen species and drug delivery, enables it to serve as a sophisticated platform for constructing multi‐target AD therapeutic agents. In light of this, by loading neuroprotective agent Trilobatin (TLB) into the cavity of GC5AY, intranasal administration of the TLB@GC5AY formulation is verified to effectively attenuate the cognitive impairment of AD mice, demonstrating multifaceted pathological improvements, while also possessing good biocompatibility. In response to the growing appeal for combinational therapy of AD, the approach proposed in this study has provided a readily generalizable strategy to fulfill this pursuit. Herein, guanidinium-modified calix[5]arene (GC5AY) is developed featuring small size, positive charge, and desirable amphiphilicity, that can efficiently traverse the nasal mucosal barrier for brain drug delivery. Additionally, possessing inherent therapeutic functions, GC5AY can thus serve as a single-molecule pleuripotent scaffold for multi-target combinational therapy of Alzheimer's disease via intranasal administration. Abstract The intricate pathological mechanisms of Alzheimer's disease (AD), along with the restrictive nature of the blood-brain barrier (BBB) that further impedes the drug brain entry, underscore the pressing need for innovative combinational therapy to achieve effective treatment outcomes. Intranasal administration, capable of bypassing BBB by direct transport through olfactory and trigeminal nerves, provides a promising approach for treating neurological disorders. Herein, the guanidinium-modified calix[5]arene (GC5AY) is developed as a single-molecule pleuripotent scaffold, demonstrating small size, positive charge and desirable amphiphilicity, which facilitate its efficient traverse of nasal mucosal barrier. The multifunctionality of GC5AY, including inhibiting amyloid fibrosis, scavenging reactive oxygen species and drug delivery, enables it to serve as a sophisticated platform for constructing multi-target AD therapeutic agents. In light of this, by loading neuroprotective agent Trilobatin (TLB) into the cavity of GC5AY, intranasal administration of the TLB@GC5AY formulation is verified to effectively attenuate the cognitive impairment of AD mice, demonstrating multifaceted pathological improvements, while also possessing good biocompatibility. In response to the growing appeal for combinational therapy of AD, the approach proposed in this study has provided a readily generalizable strategy to fulfill this pursuit. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Innovative Photon‐Engineered Fluorescent Tri‐Layer Polymeric Coatings for Sub‐Ambient Colored Radiative Cooling

This work provides a photoluminescence‐enhanced coating material solution for enhancing solar reflectance and coloration, systematically investigating the fluorescence’s role on the optical performance. All colored coatings exhibit excellent sub‐ambient cooling capacity (historically high solar reflectance and over 0.96 infrared emittance), while preserving vivid color and self‐cleaning performance for aesthetic and real‐world application requirements. Abstract Colored radiative cooling (CRC) materials provide a sustainable solution to thermal management, mitigating global warming while maintaining aesthetic appeal. Nevertheless, conventional CRC materials exhibit reduced cooling efficiency due to their significant sunlight absorption and degraded optical performance in dusty outdoor environments. Developing self‐cleaning CRC materials with high cooling performance and vibrant color remains challenging. Here, photon‐engineered fluorescent tri‐layer polymeric coatings (PFTPCs) is presented, which have an effective reflectance >100% at fluorescent emission wavelengths, yielding a historically high colored cooling capacity. By leveraging Purcell‐enhanced fluorescent emission along with optimized photonic structures, the PFTPCs exhibit an effective solar reflectance of 94%, 96.3%, and 96.1% for red, yellow, and green colors, respectively. These coatings also demonstrate long‐wave infrared emissivity surpassing 96%. Consequently, the PFTPCs achieve daytime sub‐ambient cooling of 5.4–7.2 °C, outperforming commercial colored counterparts by 3.7–5.1 °C. Simulations indicate that when applied as roof and wall coatings, PFTPCs can significantly contribute to building energy savings across diverse climate zones. PFTPCs also exhibit excellent superhydrophobic properties, anti‐fouling capability, and durability, providing strong resistance to ultraviolet irradiation, mechanical abrasion, rain, and soiling. This research paves the way for the rational design of high‐performance fluorescence‐assisted colored radiative cooling materials, promoting energy conservation and sustainability. This work provides a photoluminescence-enhanced coating material solution for enhancing solar reflectance and coloration, systematically investigating the fluorescence’s role on the optical performance. All colored coatings exhibit excellent sub-ambient cooling capacity (historically high solar reflectance and over 0.96 infrared emittance), while preserving vivid color and self-cleaning performance for aesthetic and real-world application requirements. Abstract Colored radiative cooling (CRC) materials provide a sustainable solution to thermal management, mitigating global warming while maintaining aesthetic appeal. Nevertheless, conventional CRC materials exhibit reduced cooling efficiency due to their significant sunlight absorption and degraded optical performance in dusty outdoor environments. Developing self-cleaning CRC materials with high cooling performance and vibrant color remains challenging. Here, photon-engineered fluorescent tri-layer polymeric coatings (PFTPCs) is presented, which have an effective reflectance >100% at fluorescent emission wavelengths, yielding a historically high colored cooling capacity. By leveraging Purcell-enhanced fluorescent emission along with optimized photonic structures, the PFTPCs exhibit an effective solar reflectance of 94%, 96.3%, and 96.1% for red, yellow, and green colors, respectively. These coatings also demonstrate long-wave infrared emissivity surpassing 96%. Consequently, the PFTPCs achieve daytime sub-ambient cooling of 5.4–7.2 °C, outperforming commercial colored counterparts by 3.7–5.1 °C. Simulations indicate that when applied as roof and wall coatings, PFTPCs can significantly contribute to building energy savings across diverse climate zones. PFTPCs also exhibit excellent superhydrophobic properties, anti-fouling capability, and durability, providing strong resistance to ultraviolet irradiation, mechanical abrasion, rain, and soiling. This research paves the way for the rational design of high-performance fluorescence-assisted colored radiative cooling materials, promoting energy conservation and sustainability. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Direct Carboboration of Aryl Alkenes with Stable Organoborons Through Ziegler‐Type Addition

The direct carboboration of vinyl arenes with benzylic boronates has been achieved using KOtBu as the catalyst. Vinylcyclopropanes and vinylcyclobutane also participate in this reaction, yielding the corresponding 1,5‐ and 1,6‐carboboration products. Both experimental and computational studies support a carbanion‐related mechanism for this transformation. Abstract Carbometallation reaction represents a classic strategy for the bifunctionalization of unsaturated hydrocarbons, yet conventional implementations predominantly rely on either highly reactive organometallic reagents or transition metal catalysts. Notably, the direct employment of metalloid organoboron reagents for such addition processes remains elusive except when specific substrate combinations are employed. Herein, a base‐catalyzed carboboration reaction of aryl alkenes with bench‐stable benzylic boronates is reported. This anionic‐based strategy is not only applicable to the carboboration of substituted styrenes but also to vinyl cyclopropanes and vinyl cyclobutane, affording the corresponding 1,5‐ and 1,6‐carboboration‐related products. Combined experimental and computational investigations reveal a mechanism that involves the Ziegler‐type carbometallation process. The synthetic utility is further highlighted by the facile one‐pot derivatization of the resulting benzylic boronates. Furthermore, a modified catalytic system offers an alternative to the anionic polymerization of styrene. The direct carboboration of vinyl arenes with benzylic boronates has been achieved using KO t Bu as the catalyst. Vinylcyclopropanes and vinylcyclobutane also participate in this reaction, yielding the corresponding 1,5- and 1,6-carboboration products. Both experimental and computational studies support a carbanion-related mechanism for this transformation. Abstract Carbometallation reaction represents a classic strategy for the bifunctionalization of unsaturated hydrocarbons, yet conventional implementations predominantly rely on either highly reactive organometallic reagents or transition metal catalysts. Notably, the direct employment of metalloid organoboron reagents for such addition processes remains elusive except when specific substrate combinations are employed. Herein, a base-catalyzed carboboration reaction of aryl alkenes with bench-stable benzylic boronates is reported. This anionic-based strategy is not only applicable to the carboboration of substituted styrenes but also to vinyl cyclopropanes and vinyl cyclobutane, affording the corresponding 1,5- and 1,6-carboboration-related products. Combined experimental and computational investigations reveal a mechanism that involves the Ziegler-type carbometallation process. The synthetic utility is further highlighted by the facile one-pot derivatization of the resulting benzylic boronates. Furthermore, a modified catalytic system offers an alternative to the anionic polymerization of styrene. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Decoupling Electron and Proton Transfer in Noncontact Catalytic Hydrogenation of Nitroaromatics

A noncontact catalytic system is constructed by modifying metal nanoparticles supported on conductive carbon with (hypo)phosphorous acid. This design effectively prevents the adsorption of unsaturated substrates while permitting H2 activation to generate electrons and protons. The hydrogenation is governed by electron transfer processes, which occur at carbon support surfaces and ligand/support‐metal interfaces, with protons transferred via protic solvents. Abstract Understanding the elementary reactions of active hydrogen species and electron transfer mechanisms during catalytic hydrogenation remains a fundamental challenge. This work elucidates electron and proton transfer pathways in nitroaromatics hydrogenation using a noncontact catalytic system. Strong coordination of (hypo)phosphorous acid on Pt/Pd surfaces prevents substrate adsorption while permitting H2 activation, generating electrons retained on the catalyst and protons solvated in protic solvents. Hydrogenation proceeds via sequential reduction (nitro to nitroso and then to hydroxylamine), governed primarily by electron transfer through conductive carbon supports and secondarily via catalyst interfaces, while proton transfer occurs through protic solvents. Disproportionation dominates hydroxylamine conversion due to its kinetic superiority over direct hydrogenation. By applying these mechanistic insights, the system is expanded to diverse catalysts, demonstrating that hypophosphorous acid‐modified commercial Pt/C catalyst achieves efficient nitroaromatics hydrogenation. Remarkably, this approach functionally mimics enzymatic catalysis, enabling selective hydrogenation of coenzyme Q10 and its analogues. This study advances fundamental understanding of hydrogenation mechanisms of nitroaromatics, carbon‐supported catalyst design, and enzyme‐mimetic catalysis development. A noncontact catalytic system is constructed by modifying metal nanoparticles supported on conductive carbon with (hypo)phosphorous acid. This design effectively prevents the adsorption of unsaturated substrates while permitting H 2 activation to generate electrons and protons. The hydrogenation is governed by electron transfer processes, which occur at carbon support surfaces and ligand/support-metal interfaces, with protons transferred via protic solvents. Abstract Understanding the elementary reactions of active hydrogen species and electron transfer mechanisms during catalytic hydrogenation remains a fundamental challenge. This work elucidates electron and proton transfer pathways in nitroaromatics hydrogenation using a noncontact catalytic system. Strong coordination of (hypo)phosphorous acid on Pt/Pd surfaces prevents substrate adsorption while permitting H 2 activation, generating electrons retained on the catalyst and protons solvated in protic solvents. Hydrogenation proceeds via sequential reduction (nitro to nitroso and then to hydroxylamine), governed primarily by electron transfer through conductive carbon supports and secondarily via catalyst interfaces, while proton transfer occurs through protic solvents. Disproportionation dominates hydroxylamine conversion due to its kinetic superiority over direct hydrogenation. By applying these mechanistic insights, the system is expanded to diverse catalysts, demonstrating that hypophosphorous acid-modified commercial Pt/C catalyst achieves efficient nitroaromatics hydrogenation. Remarkably, this approach functionally mimics enzymatic catalysis, enabling selective hydrogenation of coenzyme Q10 and its analogues. This study advances fundamental understanding of hydrogenation mechanisms of nitroaromatics, carbon-supported catalyst design, and enzyme-mimetic catalysis development. Advanced Science, Volume 12, Issue 43, November 20, 2025.