Search Medical Journals & Research Articles

MicroRNA‐Enriched Plant‐Derived Exosomes Alleviate Colitis by Modulating Systemic Immunity, Metabolic Homeostasis, and Gut Microbiota (Adv. Sci. 42/2025)

Plant‐Derived Exosomes Rooted in millennia‐old herbal wisdom, plant‐derived exosomes emerge as potent regulators of uncontrolled inflammatory cascades in colitis. Like turbulent crimson waters surging from the upstream Yarlung Tsangpo Dam, inflammation disrupts mucosal equilibrium. Yet, Nezha, depicted on lotus leaves, releases plant‐derived exosomes enriched with miRNAs through a metaphorical conduit. This natural cross‐kingdom dialogue transforms pathological chaos into physiological harmony, restoring immune balance, metabolic balance, and gut microbial symbiosis. More details can be found in the Research Article by Dong‐Hua Yang, Zhangfeng Zhong, and co‐workers (DOI: 10.1002/advs.202505921). Plant-Derived Exosomes Rooted in millennia-old herbal wisdom, plant-derived exosomes emerge as potent regulators of uncontrolled inflammatory cascades in colitis. Like turbulent crimson waters surging from the upstream Yarlung Tsangpo Dam, inflammation disrupts mucosal equilibrium. Yet, Nezha, depicted on lotus leaves, releases plant-derived exosomes enriched with miRNAs through a metaphorical conduit. This natural cross-kingdom dialogue transforms pathological chaos into physiological harmony, restoring immune balance, metabolic balance, and gut microbial symbiosis. More details can be found in the Research Article by Dong-Hua Yang, Zhangfeng Zhong, and co-workers (DOI: 10.1002/advs.202505921 ). Advanced Science, Volume 12, Issue 42, November 13, 2025.

Restoring NK Cell Cytotoxicity Post‐Cryopreservation via Synthetic Cells (Adv. Sci. 42/2025)

Boosting Cryopreserved Natural Killer Cytotoxicity In their Research Article (DOI: 10.1002/advs.202505731), Bin Qu and co‐workers present a strategy to enhance the cytotoxic activity of natural killer (NK) cells using IL‐2‐presenting synthetic cells. This approach significantly boosts the tumor‐killing function of both freshly isolated and cryopreserved NK cells‐including CAR‐engineered NK cells. Notably, synthetic cells displaying IL‐15 produce similar effects. This innovative platform provides a powerful and clinically relevant method to advance off‐the‐shelf NK cell‐based immunotherapies. Boosting Cryopreserved Natural Killer Cytotoxicity In their Research Article (DOI: 10.1002/advs.202505731 ), Bin Qu and co-workers present a strategy to enhance the cytotoxic activity of natural killer (NK) cells using IL-2-presenting synthetic cells. This approach significantly boosts the tumor-killing function of both freshly isolated and cryopreserved NK cells-including CAR-engineered NK cells. Notably, synthetic cells displaying IL-15 produce similar effects. This innovative platform provides a powerful and clinically relevant method to advance off-the-shelf NK cell-based immunotherapies. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Chemically‐Disordered Transparent Conductive Perovskites With High Crystalline Fidelity

Kinetically arrested, chemically disordered perovskite thin films exhibit exquisite crystalline fidelity, broad IR–UV transparency, and low resistivity, despite incorporating five mismatched 3d–5d cations, including Cr and W. This study unites electronic correlation, cation diversity, valence complexity, and disorder—enabling new transparent conductors and paving the way toward novel quantum and spintronic applications. Abstract This manuscript presents a working model linking chemical disorder and transport properties in correlated‐electron perovskites with high‐entropy formulations and a framework to actively design them. This work demonstrates this new learning in epitaxial Srx(Ti,Cr,Nb,Mo,W)O3 thin films that exhibit exceptional crystalline fidelity despite a diverse chemical formulation where most B‐site species are highly misfit with respect to valence and radius. X‐ray diffraction, X‐ray photoelectron spectroscopy, and transmission electron microscopy confirm a unique combination of chemical disorder and structural perfection in thin and thick epitaxial layers. This combination produces an optical transparency window that surpasses that of the constituent end‐members in the UV and IR, while maintaining relatively low electrical resistivity. This work addresses the computational challenges of modeling such systems and investigate short‐range ordering using cluster expansion. These results showcase that unusual d‐metal combinations access an expanded property design space that is predictable using end‐member characteristics and their interactions – though unavailable to them – thus offering performance advances in optical, high‐frequency, spintronic, and quantum devices. Kinetically arrested, chemically disordered perovskite thin films exhibit exquisite crystalline fidelity, broad IR–UV transparency, and low resistivity, despite incorporating five mismatched 3d–5d cations, including Cr and W. This study unites electronic correlation, cation diversity, valence complexity, and disorder—enabling new transparent conductors and paving the way toward novel quantum and spintronic applications. Abstract This manuscript presents a working model linking chemical disorder and transport properties in correlated-electron perovskites with high-entropy formulations and a framework to actively design them. This work demonstrates this new learning in epitaxial Sr x (Ti,Cr,Nb,Mo,W)O 3 thin films that exhibit exceptional crystalline fidelity despite a diverse chemical formulation where most B -site species are highly misfit with respect to valence and radius. X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy confirm a unique combination of chemical disorder and structural perfection in thin and thick epitaxial layers. This combination produces an optical transparency window that surpasses that of the constituent end-members in the UV and IR, while maintaining relatively low electrical resistivity. This work addresses the computational challenges of modeling such systems and investigate short-range ordering using cluster expansion. These results showcase that unusual d -metal combinations access an expanded property design space that is predictable using end-member characteristics and their interactions – though unavailable to them – thus offering performance advances in optical, high-frequency, spintronic, and quantum devices. Advanced Science, Volume 12, Issue 42, November 13, 2025.

PEDOT: PSS‐Enabled CNT and Bi0.5Sb1.5Te3 Interface Microengineering for Integrated Thermoelectric Energy Harvesting and Corrosion Protection in Cementitious Composite

In this study, PP and BST are used to synergistically enhance the dispersibility and thermoelectric performance of CNT cementitious materials. Further Author Manuscript research shows that the composite material maintains >80% compressive strength and chloride resistance performance at −20 or 70°C. A TEG assembled from 30 series‐connected specimens successfully powers a commercial LED and achieves a power supply for steel cathodic protection. Abstract Thermoelectric cement‐based composites integrate thermoelectric effects with structural capabilities, presenting an effective solution for harvesting environmental heat in self‐powered cathodic protection. While the prospects are promising, their performance has been constrained by the compatibility between functional fillers and cementitious materials. This study demonstrates that PEDOT: PSS(PP) significantly improves the dispersion of multi‐walled carbon nanotube (CNT) and Bi0.5Sb1.5Te3 (BST) in cementitious materials. The optimized composite(0.2 wt.% CNT, 1.0 vol% PP, and 1.0 wt.% BST) exhibits a 28.4% increase in conductivity and a 15.9% reduction in thermal conductivity compared to the control. Additionally, it achieves an impressive Seebeck coefficient of 450 µV K−1. Importantly, the composite maintains superior compressive strength (> 40 MPa) and chloride penetration resistance (< 7 × 10−12 m2 s−1), with over 80% property retention after 60 days under extreme temperatures of −20 or 70 °C. A thermoelectric generator (TEG) is assembled by connecting 30 specimens in series to form a 10 × 10 cm2 device. The TEG exhibits less than 8% voltage decay during 20 h of continuous operation and successfully powered an LED. The TEG also substantially mitigates steel corrosion in self‐powered cathodic protection, reducing corrosion current density and corrosion rate by more than 47%. In this study, PP and BST are used to synergistically enhance the dispersibility and thermoelectric performance of CNT cementitious materials. Further Author Manuscript research shows that the composite material maintains >80% compressive strength and chloride resistance performance at −20 or 70°C. A TEG assembled from 30 series-connected specimens successfully powers a commercial LED and achieves a power supply for steel cathodic protection. Abstract Thermoelectric cement-based composites integrate thermoelectric effects with structural capabilities, presenting an effective solution for harvesting environmental heat in self-powered cathodic protection. While the prospects are promising, their performance has been constrained by the compatibility between functional fillers and cementitious materials. This study demonstrates that PEDOT: PSS(PP) significantly improves the dispersion of multi-walled carbon nanotube (CNT) and Bi 0.5 Sb 1.5 Te 3 (BST) in cementitious materials. The optimized composite(0.2 wt.% CNT, 1.0 vol% PP, and 1.0 wt.% BST) exhibits a 28.4% increase in conductivity and a 15.9% reduction in thermal conductivity compared to the control. Additionally, it achieves an impressive Seebeck coefficient of 450 µV K −1. Importantly, the composite maintains superior compressive strength (> 40 MPa) and chloride penetration resistance (< 7 × 10 −12 m 2 s −1 ), with over 80% property retention after 60 days under extreme temperatures of −20 or 70 °C. A thermoelectric generator (TEG) is assembled by connecting 30 specimens in series to form a 10 × 10 cm 2 device. The TEG exhibits less than 8% voltage decay during 20 h of continuous operation and successfully powered an LED. The TEG also substantially mitigates steel corrosion in self-powered cathodic protection, reducing corrosion current density and corrosion rate by more than 47%. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Engineering Neutrophil Vesicles for Synergistic Protection against Ischemia/Reperfusion Injury after Lung Transplant

Engineered neutrophil‐derived vesicles (SOD2‐Fer‐1@CVs) co‐delivering antioxidant and ferroptosis‐inhibitory agents enable inflammation‐targeted, ROS‐responsive therapy for ischemia–reperfusion injury in lung transplantation. Synergizing with ex vivo lung perfusion, this strategy alleviates oxidative stress and inflammation, restores vascular integrity, and improves graft function, offering translational potential for enhancing lung transplant outcomes. Abstract Lung transplantation (LTx) is a life‐saving procedure for patients with end‐stage respiratory failure; however, primary graft dysfunction (PGD), primarily induced by ischemia/reperfusion injury (IRI), remains a major complication. Although ex vivo lung perfusion (EVLP) improves preservation, clinical translation remains challenging owing to IRI complexity. Here, a novel approach is presented to mitigate lung IRI by developing of neutrophil‐derived ROS‐responsive cellular vesicles (SOD2‐Fer‐1@CVs). This hybrid system integrates superoxide dismutase 2 (SOD2)‐overexpressing neutrophil nanovesicles with ROS‐responsive liposomes loaded with ferrostatin‐1 (Fer‐1), a potent ferroptosis inhibitor. SOD2‐Fer‐1@CVs enabled targeted delivery to inflamed tissues and high oxidative stress environments, enabling ROS‐triggered release of SOD2 and Fer‐1. The SOD2‐Fer‐1@CVs system mechanistically targeted the core pathological pathways of IRI, including oxidative stress alleviation, adsorption and neutralization of pro‐inflammatory cytokines, ferroptosis suppression, and restoration of endothelial barrier integrity, with concurrent promotion of macrophage M2 polarization. Using the proprietary small‐animal EVLP platform, the therapeutic administration of SOD2‐Fer‐1@CVs significantly mitigated of reperfusion‐related pathologies and improved graft performance, including enhanced oxygenation, reduced airway resistance, and restored lung compliance, attenuating lung injury after LTx. This study established a novel nanotherapeutic strategy that synergizes with EVLP to address multifactorial IRI, showing high translational potential for improving donor lung quality and LTx outcomes. Engineered neutrophil-derived vesicles (SOD2-Fer-1@CVs) co-delivering antioxidant and ferroptosis-inhibitory agents enable inflammation-targeted, ROS-responsive therapy for ischemia–reperfusion injury in lung transplantation. Synergizing with ex vivo lung perfusion, this strategy alleviates oxidative stress and inflammation, restores vascular integrity, and improves graft function, offering translational potential for enhancing lung transplant outcomes. Abstract Lung transplantation (LTx) is a life-saving procedure for patients with end-stage respiratory failure; however, primary graft dysfunction (PGD), primarily induced by ischemia/reperfusion injury (IRI), remains a major complication. Although ex vivo lung perfusion (EVLP) improves preservation, clinical translation remains challenging owing to IRI complexity. Here, a novel approach is presented to mitigate lung IRI by developing of neutrophil-derived ROS-responsive cellular vesicles (SOD2-Fer-1@CVs). This hybrid system integrates superoxide dismutase 2 (SOD2)-overexpressing neutrophil nanovesicles with ROS-responsive liposomes loaded with ferrostatin-1 (Fer-1), a potent ferroptosis inhibitor. SOD2-Fer-1@CVs enabled targeted delivery to inflamed tissues and high oxidative stress environments, enabling ROS-triggered release of SOD2 and Fer-1. The SOD2-Fer-1@CVs system mechanistically targeted the core pathological pathways of IRI, including oxidative stress alleviation, adsorption and neutralization of pro-inflammatory cytokines, ferroptosis suppression, and restoration of endothelial barrier integrity, with concurrent promotion of macrophage M2 polarization. Using the proprietary small-animal EVLP platform, the therapeutic administration of SOD2-Fer-1@CVs significantly mitigated of reperfusion-related pathologies and improved graft performance, including enhanced oxygenation, reduced airway resistance, and restored lung compliance, attenuating lung injury after LTx. This study established a novel nanotherapeutic strategy that synergizes with EVLP to address multifactorial IRI, showing high translational potential for improving donor lung quality and LTx outcomes. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Novel Role of Gut‐Derived Roseburia Intestinalis in Safeguarding Intestinal Barrier Integrity and Microenvironment Homeostasis During Arsenic Exposure

Arsenic exposure disrupts intestinal barriers and gut microenvironment. Fecal microbiota transplantation (FMT) alleviates arsenic‐induced damage, with gut‐derived Roseburia intestinalis (R.i) identified as a key protective strain. R.i administration counters arsenic toxicity through immunomodulatory pathways and metabolites. Supplementation with R.i presents a novel therapeutic strategy against arsenic‐related intestinal disorders. Abstract As a well‐known metalloid, arsenic usually causes human intestinal disorders via contaminated drinking water. However, the mechanisms underlying how arsenic induces intestinal injury remain unresolved, and the effective means of intervention are very limited. By establishing an acute arsenic exposure animal model, this work shows that arsenic disrupts the mechanical, chemical, immunological, and biological barriers of the intestine, and thereby changes the microenvironment in the gut. We further verify that the administration of fecal microbiota transplantation with a healthy gut microbiome alleviates the intestinal damage induced by arsenic. Intriguingly, by using 16S rRNA sequencing and anaerobic culture, we identify a novel role of gut‐derived strain, Roseburia intestinalis, which exhibits significant protection against arsenic‐induced intestinal toxicity in mice. By applying non‐targeted metabolomics after arsenic exposure, this work further establishes the beneficial effects and the potential metabolites associated with Roseburia intestinalis, including cacodylic acid, carindone, 3‐hydroxymelatonin and L‐galacto‐2‐heptulose, etc. Transcriptomic analysis reveals that the protective effects of Roseburia intestinalis against arsenic‐induced intestinal injury include mainly immune‐related pathways. Taken together, these findings highlight that supplementation with gut‐derived Roseburia intestinalis is an alternative strategy that could be used in the prevention and treatment of arsenic‐related intestinal disorders. Arsenic exposure disrupts intestinal barriers and gut microenvironment. Fecal microbiota transplantation (FMT) alleviates arsenic-induced damage, with gut-derived Roseburia intestinalis (R.i) identified as a key protective strain. R.i administration counters arsenic toxicity through immunomodulatory pathways and metabolites. Supplementation with R.i presents a novel therapeutic strategy against arsenic-related intestinal disorders. Abstract As a well-known metalloid, arsenic usually causes human intestinal disorders via contaminated drinking water. However, the mechanisms underlying how arsenic induces intestinal injury remain unresolved, and the effective means of intervention are very limited. By establishing an acute arsenic exposure animal model, this work shows that arsenic disrupts the mechanical, chemical, immunological, and biological barriers of the intestine, and thereby changes the microenvironment in the gut. We further verify that the administration of fecal microbiota transplantation with a healthy gut microbiome alleviates the intestinal damage induced by arsenic. Intriguingly, by using 16S rRNA sequencing and anaerobic culture, we identify a novel role of gut-derived strain, Roseburia intestinalis, which exhibits significant protection against arsenic-induced intestinal toxicity in mice. By applying non-targeted metabolomics after arsenic exposure, this work further establishes the beneficial effects and the potential metabolites associated with Roseburia intestinalis, including cacodylic acid, carindone, 3-hydroxymelatonin and L -galacto-2-heptulose, etc. Transcriptomic analysis reveals that the protective effects of Roseburia intestinalis against arsenic-induced intestinal injury include mainly immune-related pathways. Taken together, these findings highlight that supplementation with gut-derived Roseburia intestinalis is an alternative strategy that could be used in the prevention and treatment of arsenic-related intestinal disorders. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Green Synthesis and Flexibilization Engineering of (ECMP)2MnBr4 for Smart Textile‐Integrated Luminescence

Green‐synthesized (ECMP)2MnBr4 achieves near‐unity photoluminescence quantum yield (98.97%) and triple‐mode emission (photo/X‐ray/mechano), enabling wearable anti‐counterfeiting textiles, ultrasensitive X‐ray imaging (15.62 nGyair s−1), and demonstrating potential for optical stress sensing. Scalable wet‐spun fibers ensure mechanical robustness and ambient processability. Abstract 0D hybrid manganese halides represent an emerging class of luminescent materials, yet their practical application has been hindered by the intrinsic trade‐off between optical performance and mechanical flexibility. Here, a green synthesis of 0D (ECMP)2MnBr4 crystal is reported, exhibiting unprecedented triple‐mode emission (photoluminescence, X‐ray scintillation, and mechanoluminescence) through rationally designed highly symmetric [MnBr4]2− tetrahedra, achieving near‐unity photoluminescence quantum yield (98.97%), record‐low X‐ray detection limit (15.62 nGyair s−1) and multi‐stimuli responsiveness (rubbing, squeezing, stretching). The material's ultralow electron‐phonon coupling (S = 1.438) and defect‐suppressing π–π stacking enable exceptional environmental stability and closed‐loop recyclability via solvent‐mediated recrystallization. Innovatively, (ECMP)2MnBr4 is first integrated into thermoplastic polyurethane via wet‐spinning, simultaneously retaining single‐crystal emission intensity and achieving remarkable elasticity (>1000% strain) for deformation‐resistant wearable applications. This work establishes a new design paradigm for sustainable multifunctional optoelectronics, with immediate applications in wearable displays, high‐resolution X‐ray imaging, and self‐powered optical sensors. Green-synthesized (ECMP) 2 MnBr 4 achieves near-unity photoluminescence quantum yield (98.97%) and triple-mode emission (photo/X-ray/mechano), enabling wearable anti-counterfeiting textiles, ultrasensitive X-ray imaging (15.62 nGy air s −1 ), and demonstrating potential for optical stress sensing. Scalable wet-spun fibers ensure mechanical robustness and ambient processability. Abstract 0D hybrid manganese halides represent an emerging class of luminescent materials, yet their practical application has been hindered by the intrinsic trade-off between optical performance and mechanical flexibility. Here, a green synthesis of 0D (ECMP) 2 MnBr 4 crystal is reported, exhibiting unprecedented triple-mode emission (photoluminescence, X-ray scintillation, and mechanoluminescence) through rationally designed highly symmetric [MnBr 4 ] 2− tetrahedra, achieving near-unity photoluminescence quantum yield (98.97%), record-low X-ray detection limit (15.62 nGy air s −1 ) and multi-stimuli responsiveness (rubbing, squeezing, stretching). The material's ultralow electron-phonon coupling ( S = 1.438) and defect-suppressing π–π stacking enable exceptional environmental stability and closed-loop recyclability via solvent-mediated recrystallization. Innovatively, (ECMP) 2 MnBr 4 is first integrated into thermoplastic polyurethane via wet-spinning, simultaneously retaining single-crystal emission intensity and achieving remarkable elasticity (>1000% strain) for deformation-resistant wearable applications. This work establishes a new design paradigm for sustainable multifunctional optoelectronics, with immediate applications in wearable displays, high-resolution X-ray imaging, and self-powered optical sensors. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Hierarchically Porous Multiphase Si‐Based Ceramics with Synergistic Electromagnetic Wave Absorption Mechanisms

A novel multiphase Si‐based ceramic material with hierarchical porosity is devised via one‐step etching activation of carbon‐rich polycarbosilane ceramics. Integrating free carbon, SiC crystals, amorphous SiOC, and engineered porosity, the material surprisingly achieves exceptional electromagnetic absorption performance, offering new insights into the synergistic design of multiphase ceramics and porous architectures. Abstract The development of high‐performance electromagnetic wave absorbers is critical for mitigating electromagnetic pollution in modern electronic and communication systems. Here, a scalable strategy is developed to fabricate hierarchically porous, multiphase Si‐based ceramics (Six‐Oy‐Cz) via one‐step activation of carbon‐rich polycarbosilane precursors. The resulting material integrates β‐SiC crystals, amorphous SiOC, and conductive carbon within a tunable porous architecture. This combination creates abundant heterogeneous interfaces, defect structures, and enhanced impedance matching. The optimized sample achieves a minimum reflection loss of −70.44 dB at just 1.79 mm thickness and a broad 4.32 GHz bandwidth at a matching thickness of 1.86 mm. Structural, dielectric, and radar simulation analyses reveal that interfacial polarization, dipolar polarization, conduction loss, and pore‐induced scattering work synergistically to dissipate electromagnetic energy. This work offers a simple, cost‐effective approach to engineer next‐generation ceramic EMW absorbers. A novel multiphase Si-based ceramic material with hierarchical porosity is devised via one-step etching activation of carbon-rich polycarbosilane ceramics. Integrating free carbon, SiC crystals, amorphous SiOC, and engineered porosity, the material surprisingly achieves exceptional electromagnetic absorption performance, offering new insights into the synergistic design of multiphase ceramics and porous architectures. Abstract The development of high-performance electromagnetic wave absorbers is critical for mitigating electromagnetic pollution in modern electronic and communication systems. Here, a scalable strategy is developed to fabricate hierarchically porous, multiphase Si-based ceramics (Si x -O y -C z ) via one-step activation of carbon-rich polycarbosilane precursors. The resulting material integrates β-SiC crystals, amorphous SiOC, and conductive carbon within a tunable porous architecture. This combination creates abundant heterogeneous interfaces, defect structures, and enhanced impedance matching. The optimized sample achieves a minimum reflection loss of −70.44 dB at just 1.79 mm thickness and a broad 4.32 GHz bandwidth at a matching thickness of 1.86 mm. Structural, dielectric, and radar simulation analyses reveal that interfacial polarization, dipolar polarization, conduction loss, and pore-induced scattering work synergistically to dissipate electromagnetic energy. This work offers a simple, cost-effective approach to engineer next-generation ceramic EMW absorbers. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Inhaling Eugenol Inhibits NAFLD by Activating the Hepatic Ectopic Olfactory Receptor Olfr544 and Modulating the Gut Microbiota

A natural compound from the Chinese medicinal plant Syzygium aromaticum, eugenol, inhaling which can counteract NAFLD by activating the hepatic olfactory receptor olfr544 and enriching Lactobacillus sp. to promoting fat oxidation, catabolism and inhibit lipid synthesis, respectively. Abstract Non‐alcoholic fatty liver disease (NAFLD) is a major public health threat with currently limited therapeutic options. Inhalation therapy shows promise for treating metabolic disorders due to rapid absorption and high patient adherence, though relevant medications remain scarce. Eugenol (EUG), the primary component of Syzygium aromaticum volatile oil, emerges as a promising NAFLD inhibitor from lipid‐lowering aromatic Chinese medicine screening. EUG elicited significant anti‐steatotic effects in both cultured hepatocytes and comprehensive high‐fat diet‐induced NAFLD animal models. Mechanistically, EUG targeted the activation of the hepatic ectopic olfactory receptor Olfr544 and up‐regulated its downstream cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element binding protein signaling pathway, which further promoted fat lipolysis and oxidation. This effect is prevented by Olfr544 knockdown models both in vitro and in vivo, with supporting bioinformatics analysis. Moreover, EUG reversed gut microbiota dysbiosis and enriched two probiotic strains L. ruteri XR23 and L. johnsonii XR25, and oral gavage potently mitigated NAFLD in mice, with the key metabolites 3‐indolepropionic acid (IPA) and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) inhibiting lipid synthesis. Lower levels of 5‐HIAA and IPA are observed in patients with NAFLD. These results highlight the considerable potential of EUG as an agonist of Olfr544 for treating NAFLD by inhalation. A natural compound from the Chinese medicinal plant Syzygium aromaticum, eugenol, inhaling which can counteract NAFLD by activating the hepatic olfactory receptor olfr544 and enriching Lactobacillus sp. to promoting fat oxidation, catabolism and inhibit lipid synthesis, respectively. Abstract Non-alcoholic fatty liver disease (NAFLD) is a major public health threat with currently limited therapeutic options. Inhalation therapy shows promise for treating metabolic disorders due to rapid absorption and high patient adherence, though relevant medications remain scarce. Eugenol (EUG), the primary component of Syzygium aromaticum volatile oil, emerges as a promising NAFLD inhibitor from lipid-lowering aromatic Chinese medicine screening. EUG elicited significant anti-steatotic effects in both cultured hepatocytes and comprehensive high-fat diet-induced NAFLD animal models. Mechanistically, EUG targeted the activation of the hepatic ectopic olfactory receptor Olfr544 and up-regulated its downstream cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element binding protein signaling pathway, which further promoted fat lipolysis and oxidation. This effect is prevented by Olfr544 knockdown models both in vitro and in vivo, with supporting bioinformatics analysis. Moreover, EUG reversed gut microbiota dysbiosis and enriched two probiotic strains L. ruteri XR23 and L. johnsonii XR25, and oral gavage potently mitigated NAFLD in mice, with the key metabolites 3-indolepropionic acid (IPA) and 5-hydroxyindole-3-acetic acid (5-HIAA) inhibiting lipid synthesis. Lower levels of 5-HIAA and IPA are observed in patients with NAFLD. These results highlight the considerable potential of EUG as an agonist of Olfr544 for treating NAFLD by inhalation. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Chain Topology Engineering in Amphiphilic Block Copolymers: Crosslinking‐Induced Nanodomain Refinement for Ultrahigh Energy Density under Extreme Conditions

An amphiphilic block copolymer is constructed via self‐assembly‐induced nanoscale microphase separation. A crosslinker with dual electron‐withdrawing groups (─CF3/─O─) is introduced to refine the PEA phase domain. The crosslinking film achieves record‐high energy densities of 11.07 J cm−3 (150 °C/700 MV m−1) and 6.45 J cm−3 (200 °C/600 MV m−1) with an efficiency of >90%. Abstract The growing demand for high‐performance capacitors in extreme environments drives the development of polymer dielectrics with high energy capability and thermal stability. Here, an amphiphilic block copolymer constructed via self‐assembly‐induced nanoscale microphase separation is presented, in which fluorinated polyimide (FPI) and flexible polyetheramine (PEA) segments form thermally entropy‐driven domains. Density‐of‐state model reveals significant electronic heterogeneity of the resultant copolymer, in which FPI exhibits an energy gap of 3.49 eV while PEA demonstrates a wide gap of 7.31 eV, resulting in an interfacial offset of 5.28 eV that inherently restrains the migration of charge carriers. A trifunctional crosslinker with dual electron‐withdrawing groups (─CF3/─O─) is introduced to refine the PEA phase domain that decreases to 13.7 nm from an initial long period of 19.2 nm. The crosslinking system achieves record‐high energy densities of 11.07 J cm−3 (150 °C/700 MV m−1) and 6.45 J cm−3 (200 °C/600 MV m−1) with an efficiency of >90%, which is attributed to the diminished hopping distance of charge carriers under high‐temperature electric field. The received copolymer film retains 1.56 J cm−3 and an efficiency of 94% with fluctuation of <5% after 105 charge–discharge cycles at 200 °C and 300 MV m−1. By synergizing amphiphilic energy‐level engineering with entropy‐driven phase refinement, this strategy establishes a robust material platform for a high‐temperature capacitor, balancing ultrahigh energy storage and dielectric reliability. An amphiphilic block copolymer is constructed via self-assembly-induced nanoscale microphase separation. A crosslinker with dual electron-withdrawing groups (─CF 3 /─O─) is introduced to refine the PEA phase domain. The crosslinking film achieves record-high energy densities of 11.07 J cm −3 (150 °C/700 MV m −1 ) and 6.45 J cm −3 (200 °C/600 MV m −1 ) with an efficiency of >90%. Abstract The growing demand for high-performance capacitors in extreme environments drives the development of polymer dielectrics with high energy capability and thermal stability. Here, an amphiphilic block copolymer constructed via self-assembly-induced nanoscale microphase separation is presented, in which fluorinated polyimide (FPI) and flexible polyetheramine (PEA) segments form thermally entropy-driven domains. Density-of-state model reveals significant electronic heterogeneity of the resultant copolymer, in which FPI exhibits an energy gap of 3.49 eV while PEA demonstrates a wide gap of 7.31 eV, resulting in an interfacial offset of 5.28 eV that inherently restrains the migration of charge carriers. A trifunctional crosslinker with dual electron-withdrawing groups (─CF 3 /─O─) is introduced to refine the PEA phase domain that decreases to 13.7 nm from an initial long period of 19.2 nm. The crosslinking system achieves record-high energy densities of 11.07 J cm −3 (150 °C/700 MV m −1 ) and 6.45 J cm −3 (200 °C/600 MV m −1 ) with an efficiency of >90%, which is attributed to the diminished hopping distance of charge carriers under high-temperature electric field. The received copolymer film retains 1.56 J cm −3 and an efficiency of 94% with fluctuation of <5% after 10 5 charge–discharge cycles at 200 °C and 300 MV m −1. By synergizing amphiphilic energy-level engineering with entropy-driven phase refinement, this strategy establishes a robust material platform for a high-temperature capacitor, balancing ultrahigh energy storage and dielectric reliability. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Co‐Sensitized Solar Cell Achieves 13.7% Efficiency with Bis‐Hexylthiophene Dyes

The authors demonstrate that the longer excited state lifetime dye in combination with a copper electrolyte produces a high photovoltage of 1.22 V, owing to retarded interfacial charge recombination. The co‐sensitized solar cell achieves efficiencies of 13.7% under full sunlight and 29.7% under LED light. Abstract Efficient anti‐aggregation and superb light harvesting in the combination of large and narrow energy gap photosensitizers play a crucial role in suppressing interfacial charge recombination in dye‐sensitized solar cells (DSCs), enabling a high open‐circuit photovoltage (Voc). Here, two organic photosensitizers, H6 and H7, featuring the bulky donor N‐(2ʹ,4ʹ‐bis(hexyloxy)‐[1,1ʹ‐biphenyl]‐4‐yl)‐2ʹ,4ʹ‐bis(hexyloxy)‐N‐methyl‐[1,1ʹ‐biphenyl]‐4‐amine and N‐(2ʹ,4ʹ‐bis(dodecyloxy)‐[1,1ʹ‐biphenyl]‐4‐yl)‐2ʹ,4ʹ‐bis(dodecyloxy)‐N‐methyl‐[1,1ʹ‐biphenyl]‐4‐amine is reported, respectively, along with bis‐hexylthiophene as the π‐linker and the electron acceptor 4‐(benzo[c][1,2,5]thiadiazol‐4‐yl)benzoic acid. Although the significantly longer alkyl chains do not change the optical energy gap, for H7, it has been able to design molecular structures that exhibit longer excited‐state lifetimes in both dye‐grafted titania and alumina films compared to its H6 counterpart. The copper‐based DSC using the longer alkyl chain‐based photosensitizer H7 achieves a high Voc of 1.22 V, comparable to the recently explored hybrid methyl ammonium lead‐based perovskite semiconductors (PSK) in solar cells. The co‐sensitized device combined with XY1b results in an efficient DSC with an impressive fill factor of 82.1% and an excellent power conversion efficiency (PCE) of 13.7% under simulated AM1.5 G conditions at 100 mW cm−2. Furthermore, the best device achieves an outstanding efficiency of up to 29.7% under dim light overpassing compared to the PSK solar cells. The authors demonstrate that the longer excited state lifetime dye in combination with a copper electrolyte produces a high photovoltage of 1.22 V, owing to retarded interfacial charge recombination. The co-sensitized solar cell achieves efficiencies of 13.7% under full sunlight and 29.7% under LED light. Abstract Efficient anti-aggregation and superb light harvesting in the combination of large and narrow energy gap photosensitizers play a crucial role in suppressing interfacial charge recombination in dye-sensitized solar cells (DSCs), enabling a high open-circuit photovoltage ( V oc ). Here, two organic photosensitizers, H6 and H7, featuring the bulky donor N-(2ʹ,4ʹ-bis(hexyloxy)-[1,1ʹ-biphenyl]-4-yl)-2ʹ,4ʹ-bis(hexyloxy)-N-methyl-[1,1ʹ-biphenyl]-4-amine and N-(2ʹ,4ʹ-bis(dodecyloxy)-[1,1ʹ-biphenyl]-4-yl)-2ʹ,4ʹ-bis(dodecyloxy)-N-methyl-[1,1ʹ-biphenyl]-4-amine is reported, respectively, along with bis-hexylthiophene as the π-linker and the electron acceptor 4-(benzo[c][1,2,5]thiadiazol-4-yl)benzoic acid. Although the significantly longer alkyl chains do not change the optical energy gap, for H7, it has been able to design molecular structures that exhibit longer excited-state lifetimes in both dye-grafted titania and alumina films compared to its H6 counterpart. The copper-based DSC using the longer alkyl chain-based photosensitizer H7 achieves a high V oc of 1.22 V, comparable to the recently explored hybrid methyl ammonium lead-based perovskite semiconductors (PSK) in solar cells. The co-sensitized device combined with XY1b results in an efficient DSC with an impressive fill factor of 82.1% and an excellent power conversion efficiency (PCE) of 13.7% under simulated AM1.5 G conditions at 100 mW cm −2. Furthermore, the best device achieves an outstanding efficiency of up to 29.7% under dim light overpassing compared to the PSK solar cells. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Active Learning‐Assisted Exploration of [PO40Mo12]3− for Alzheimer's Therapy Insights

Bayesian Optimization coupled with active learning to uncover the interaction mechanism of [PO40Mo12]3− on amyloid‐β peptide. Abstract Alzheimer's disease (AD), involving amyloid‐β (Aβ) aggregation, has potential therapeutic modulators in polyoxometalates (POMs) like [PMo12O40]3−. To clarify their inhibitory mechanisms, a multiscale computational strategy integrating active‐learning Bayesian Optimization (BO) and density functional theory (DFT) is employed to explore low‐energy configurations of isolated amino acids, [PMo12O40]3−–amino acid complexes, and [PMo12O40]3−–peptide systems. Hydrogen bonding and Coulombic repulsion dominate adsorption stability. Crucially, oxygen atoms in the [PMo12O40]3− cluster form multiple weak interactions (e.g., van der Waals, hydrophobic) with alkyl side‐chain hydrogens in Aβ peptides. The synergistic effect of these weak interactions induces robust binding between the POM and peptide chains, stabilizing a tightly bound complex that sterically hinders Aβ self‐assembly. Notably, simulations predict that the cluster preferentially targets hydrophobic amino acids with alkyl chains (valine, lysine, leucine, isoleucine) located in Aβ regions critical for aggregation—specifically, namely Aβ12, Aβ16‐18, Aβ24, Aβ28, Aβ31‐32, Aβ34‐36, and Aβ39‐41. These insights highlight the role of multivalent weak interactions in POM‐mediated inhibition and identify key interfacial residues for therapeutic targeting. Bayesian Optimization coupled with active learning to uncover the interaction mechanism of [PO 40 Mo 12 ] 3− on amyloid-β peptide. Abstract Alzheimer's disease (AD), involving amyloid-β (Aβ) aggregation, has potential therapeutic modulators in polyoxometalates (POMs) like [PMo 12 O 40 ] 3−. To clarify their inhibitory mechanisms, a multiscale computational strategy integrating active-learning Bayesian Optimization (BO) and density functional theory (DFT) is employed to explore low-energy configurations of isolated amino acids, [PMo 12 O 40 ] 3 − –amino acid complexes, and [PMo 12 O 40 ] 3 − –peptide systems. Hydrogen bonding and Coulombic repulsion dominate adsorption stability. Crucially, oxygen atoms in the [PMo 12 O 40 ] 3 − cluster form multiple weak interactions (e.g., van der Waals, hydrophobic) with alkyl side-chain hydrogens in Aβ peptides. The synergistic effect of these weak interactions induces robust binding between the POM and peptide chains, stabilizing a tightly bound complex that sterically hinders Aβ self-assembly. Notably, simulations predict that the cluster preferentially targets hydrophobic amino acids with alkyl chains (valine, lysine, leucine, isoleucine) located in Aβ regions critical for aggregation—specifically, namely Aβ12, Aβ16-18, Aβ24, Aβ28, Aβ31-32, Aβ34-36, and Aβ39-41. These insights highlight the role of multivalent weak interactions in POM-mediated inhibition and identify key interfacial residues for therapeutic targeting. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Dnmt1 Alleviates S1PR1‐Mediated Pyroptosis after Spinal Cord Injury through Regulating Pon3 Expression

This study systematically explores the action mechanism of Pon3 and its regulatory targets in spinal cord injury (SCI). It demonstrates that Dnmt1 regulates Pon3 expression by modulating methylation levels, thereby inhibiting S1PR1‐mediated pyroptosis and improving SCI prognosis. Abstract Spinal cord injury (SCI), as a severe neurological disorder, remains a formidable challenge in clinical treatment. Pyroptosis‐triggered neuroinflammation exacerbates secondary damage, neuronal death, and impairs recovery after SCI, making it a critical pathological factor. However, the exact pathophysiological mechanisms are incompletely understood. In this study, bioinformatics tools are first employed to identify key targets associated with SCI. Subsequent western blot and immunofluorescence assays reveal a time‐dependent decrease in Pon3 expression, which is predominantly localized in neuronal cells. Conversely, Dnmt1 expression shows a progressive increase following SCI. By constructing a Pon3‐overexpressing virus, it is demonstrated that Pon3 overexpression mitigates pyroptosis in rat and PC12 cells. This process promotes autophagy, significantly improving the prognosis of SCI in rats. Moreover, it enhances the survival rate of PC12 cells. mRNA sequencing and follow‐up experiments revealed that Pon3 inhibits the downstream target S1PR1, promotes autophagy, and thereby suppresses pyroptosis. Additionally, through the use of a Dnmt1 inhibitor and the knockout of the Pon3 gene, it is shown that Dnmt1 alleviates SCI‐induced pyroptosis by modulating Pon3 expression. Collectively, this work reveals that Dnmt1 alleviates S1PR1‐mediated pyroptosis following SCI via regulating Pon3 expression. This study systematically explores the action mechanism of Pon3 and its regulatory targets in spinal cord injury (SCI). It demonstrates that Dnmt1 regulates Pon3 expression by modulating methylation levels, thereby inhibiting S1PR1-mediated pyroptosis and improving SCI prognosis. Abstract Spinal cord injury (SCI), as a severe neurological disorder, remains a formidable challenge in clinical treatment. Pyroptosis-triggered neuroinflammation exacerbates secondary damage, neuronal death, and impairs recovery after SCI, making it a critical pathological factor. However, the exact pathophysiological mechanisms are incompletely understood. In this study, bioinformatics tools are first employed to identify key targets associated with SCI. Subsequent western blot and immunofluorescence assays reveal a time-dependent decrease in Pon3 expression, which is predominantly localized in neuronal cells. Conversely, Dnmt1 expression shows a progressive increase following SCI. By constructing a Pon3-overexpressing virus, it is demonstrated that Pon3 overexpression mitigates pyroptosis in rat and PC12 cells. This process promotes autophagy, significantly improving the prognosis of SCI in rats. Moreover, it enhances the survival rate of PC12 cells. mRNA sequencing and follow-up experiments revealed that Pon3 inhibits the downstream target S1PR1, promotes autophagy, and thereby suppresses pyroptosis. Additionally, through the use of a Dnmt1 inhibitor and the knockout of the Pon3 gene, it is shown that Dnmt1 alleviates SCI-induced pyroptosis by modulating Pon3 expression. Collectively, this work reveals that Dnmt1 alleviates S1PR1-mediated pyroptosis following SCI via regulating Pon3 expression. Advanced Science, Volume 12, Issue 42, November 13, 2025.

Post‐Translational Modifications of TOE3 Regulate Antiviral Defense in Tobacco

CK2αL phosphorylates TOE3 and enhances its stability, while FBXL1 promotes the ubiquitination‐degradation of TOE3 via the 26S proteasome. Compared to CK2αL‐phosphorylated TOE3, nonphosphorylated TOE3 shows a much higher affinity for FBXL1 and is more susceptible to ubiquitination‐degradation, thus facilitating viral infection. The regulatory mechanisms provide insights into the roles of TOE3's PTMs in tobacco antiviral defense. Abstract Post‐translational modifications (PTMs) affect the function of transcription factors and regulate plant immune responses. APETALA2 (AP2) transcription factor TARGET OF EAT3 (TOE3) plays a pivotal role in plant antiviral immunity. However, little is known about the impact of PTMs on TOE3 function. Here, that casein kinase II α subunit‐like protein (CK2αL) is identified to interact with TOE3, phosphorylating it at serine 58 (S58) and threonine 128 (T128). Overexpression of CK2αL enhances the stability of TOE3 to upregulate the expression of defense‐related genes, thereby improving tobacco resistance to tobacco mosaic virus (TMV). Additionally, the F‐box protein FBXL1 interacts with TOE3 and promotes the ubiquitination‐degradation of TOE3 through the 26S proteasome, and overexpression of FBXL1 facilitates TMV infection in tobacco. Importantly, CK2αL‐phosphorylated TOE3 exhibits a lower binding affinity to FBXL1 compared to the nonphosphorylated TOE3, thereby protecting TOE3 from FBXL1‐mediated degradation by the 26S proteasome. The stable TOE3 activates the expression of defense‐related genes to enhance the resistance of plants to viral infection. Taken together, the findings demonstrate a mechanism by which phosphorylation and ubiquitination cooperatively regulate the stability of TOE3 to fine‐tune antiviral immunity in tobacco. CK2αL phosphorylates TOE3 and enhances its stability, while FBXL1 promotes the ubiquitination-degradation of TOE3 via the 26S proteasome. Compared to CK2αL-phosphorylated TOE3, nonphosphorylated TOE3 shows a much higher affinity for FBXL1 and is more susceptible to ubiquitination-degradation, thus facilitating viral infection. The regulatory mechanisms provide insights into the roles of TOE3's PTMs in tobacco antiviral defense. Abstract Post-translational modifications (PTMs) affect the function of transcription factors and regulate plant immune responses. APETALA2 (AP2) transcription factor TARGET OF EAT3 (TOE3) plays a pivotal role in plant antiviral immunity. However, little is known about the impact of PTMs on TOE3 function. Here, that casein kinase II α subunit-like protein (CK2αL) is identified to interact with TOE3, phosphorylating it at serine 58 (S58) and threonine 128 (T128). Overexpression of CK2αL enhances the stability of TOE3 to upregulate the expression of defense-related genes, thereby improving tobacco resistance to tobacco mosaic virus (TMV). Additionally, the F-box protein FBXL1 interacts with TOE3 and promotes the ubiquitination-degradation of TOE3 through the 26S proteasome, and overexpression of FBXL1 facilitates TMV infection in tobacco. Importantly, CK2αL-phosphorylated TOE3 exhibits a lower binding affinity to FBXL1 compared to the nonphosphorylated TOE3, thereby protecting TOE3 from FBXL1-mediated degradation by the 26S proteasome. The stable TOE3 activates the expression of defense-related genes to enhance the resistance of plants to viral infection. Taken together, the findings demonstrate a mechanism by which phosphorylation and ubiquitination cooperatively regulate the stability of TOE3 to fine-tune antiviral immunity in tobacco. Advanced Science, Volume 12, Issue 42, November 13, 2025.

A Natural Major Module Confers the Trade‐Off between Phenotypic Mean and Plasticity of Grain Chalkiness in Rice

This study reveals the genetic and molecular mechanisms controlling the general trade‐off between phenotypic mean and plasticity of grain chalkiness in rice and identifies two major external drivers (high temperature and wide grain) and a natural major module (GCP6‐MPC5) that control this trade‐off. This work holds significant implications for a proof‐of‐concept breeding strategy in integrating both phenotypic mean and plasticity. Abstract A critical challenge in crop breeding is the trade‐off between improving the mean of an important trait and maintaining its phenotypic plasticity. Grain chalkiness is a key cereal grain‐quality trait highly susceptible to environments. However, the genetic and molecular mechanisms controlling the trade‐off between phenotypic mean and plasticity of grain chalkiness remain unknown. Here, utilizing comprehensive genome‐wide association studies on ten grain chalkiness traits over five years in a mini‐core collection, substantial phenotypic plasticity of grain chanlkiness is found, which declines during modern breeding. A general trade‐off between phenotypic mean and plasticity of grain chalkiness is demonstrated, which are controlled by distinct genetic architectures revealed through a detailed QTL atlas. High temperature and wide grain significantly increase grain chalkiness mean but decrease its plasticity and genetic dissection, representing two major external drivers for the trade‐off. Two key quantitative trait genes MPC5 and GCP6 are identified to control this trade‐off. The transcription factor GCP6 biochemically and genetically inhibits MPC5 expression, forming a key module that confers the mean‐plasticity trade‐off of both grain chalkiness and width. Finally, minimal marker sets for molecular breeding accounted for two thirds of grain chalkiness variation. These findings elucidate the genetic architecture of the mean‐plasticity trade‐off in grain chalkiness and offer a proof‐of‐concept breeding strategy to simultaneously optimize both phenotypic mean and plasticity in crop improvement. This study reveals the genetic and molecular mechanisms controlling the general trade-off between phenotypic mean and plasticity of grain chalkiness in rice and identifies two major external drivers (high temperature and wide grain) and a natural major module (GCP6- MPC5 ) that control this trade-off. This work holds significant implications for a proof-of-concept breeding strategy in integrating both phenotypic mean and plasticity. Abstract A critical challenge in crop breeding is the trade-off between improving the mean of an important trait and maintaining its phenotypic plasticity. Grain chalkiness is a key cereal grain-quality trait highly susceptible to environments. However, the genetic and molecular mechanisms controlling the trade-off between phenotypic mean and plasticity of grain chalkiness remain unknown. Here, utilizing comprehensive genome-wide association studies on ten grain chalkiness traits over five years in a mini-core collection, substantial phenotypic plasticity of grain chanlkiness is found, which declines during modern breeding. A general trade-off between phenotypic mean and plasticity of grain chalkiness is demonstrated, which are controlled by distinct genetic architectures revealed through a detailed QTL atlas. High temperature and wide grain significantly increase grain chalkiness mean but decrease its plasticity and genetic dissection, representing two major external drivers for the trade-off. Two key quantitative trait genes MPC5 and GCP6 are identified to control this trade-off. The transcription factor GCP6 biochemically and genetically inhibits MPC5 expression, forming a key module that confers the mean-plasticity trade-off of both grain chalkiness and width. Finally, minimal marker sets for molecular breeding accounted for two thirds of grain chalkiness variation. These findings elucidate the genetic architecture of the mean-plasticity trade-off in grain chalkiness and offer a proof-of-concept breeding strategy to simultaneously optimize both phenotypic mean and plasticity in crop improvement. Advanced Science, Volume 12, Issue 42, November 13, 2025.