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Manipulating the Spin State of Perovskite Cs3Bi2Br9 by Co‐Doped for Efficient Photocatalytic CO2 Reduction

The photocatalytic conversion of CO2 into the renewable fuels is a promising strategy to address energy and environmental challenges. Here, we reported a spin‐polarization strategy using Co2+ doping in lead‐free perovskite Cs3Bi2Br9 synergized, to achieve highly efficient CO2 reduction. The optimized Co‐doped CBB exhibited a 2.6‐fold enhancement in CO production rate compared to the pristine CBB. Advanced characterizations and density functional theory calculations revealed that the Co doping introduces spin‐polarized electrons, suppresses charge recombination, and elongates the carrier lifetime, while the Co sites lower the energy barrier for *COOH intermediate formation. Abstract The photocatalytic conversion of CO2 into the renewable fuels is a promising strategy to address energy and environmental challenges, however, its limited application is mainly attributed to the inefficient charge separation and lack of active sites in conventional catalysts. Here, a spin‐polarization strategy using Co2⁺ doping in lead‐free perovskite Cs3Bi2Br9 (CBB) synergized with an external magnetic field (MF), is reported to achieve highly efficient CO2 reduction. The optimized Co‐doped CBB (0.2CBB) exhibited a 2.6‐fold enhancement in CO production rate (35.04 µmolg−1h−1) compared to the pristine CBB, with further improvement to 86.56 µmolg−1h−1 under 200 mT MF. Advanced characterizations together with the density functional theory calculations further revealed that the Co doping introduces spin‐polarized electrons, suppresses charge recombination, and elongates the carrier lifetime (6.68 ns vs 5.20 ns in CBB). The Zeeman effect under MF activates the additional spin‐polarized carriers, while the Co sites lower the energy barrier for *COOH intermediate formation (ΔG = −0.59 vs −0.38 eV in CBB), as confirmed by the in situ FT‐IR and Gibbs free energy analysis. This work pioneers the integration of spin manipulation and MF‐assisted catalysis in perovskites, offering a novel pathway for the design of high‐performance photocatalytic systems. The photocatalytic conversion of CO 2 into the renewable fuels is a promising strategy to address energy and environmental challenges. Here, we reported a spin-polarization strategy using Co 2+ doping in lead-free perovskite Cs 3 Bi 2 Br 9 synergized, to achieve highly efficient CO 2 reduction. The optimized Co-doped CBB exhibited a 2.6-fold enhancement in CO production rate compared to the pristine CBB. Advanced characterizations and density functional theory calculations revealed that the Co doping introduces spin-polarized electrons, suppresses charge recombination, and elongates the carrier lifetime, while the Co sites lower the energy barrier for *COOH intermediate formation. Abstract The photocatalytic conversion of CO 2 into the renewable fuels is a promising strategy to address energy and environmental challenges, however, its limited application is mainly attributed to the inefficient charge separation and lack of active sites in conventional catalysts. Here, a spin-polarization strategy using Co 2 ⁺ doping in lead-free perovskite Cs 3 Bi 2 Br 9 (CBB) synergized with an external magnetic field (MF), is reported to achieve highly efficient CO 2 reduction. The optimized Co-doped CBB (0.2CBB) exhibited a 2.6-fold enhancement in CO production rate (35.04 µmolg −1 h −1 ) compared to the pristine CBB, with further improvement to 86.56 µmolg −1 h −1 under 200 mT MF. Advanced characterizations together with the density functional theory calculations further revealed that the Co doping introduces spin-polarized electrons, suppresses charge recombination, and elongates the carrier lifetime (6.68 ns vs 5.20 ns in CBB). The Zeeman effect under MF activates the additional spin-polarized carriers, while the Co sites lower the energy barrier for * COOH intermediate formation (ΔG = −0.59 vs −0.38 eV in CBB), as confirmed by the in situ FT-IR and Gibbs free energy analysis. This work pioneers the integration of spin manipulation and MF-assisted catalysis in perovskites, offering a novel pathway for the design of high-performance photocatalytic systems. Advanced Science, EarlyView.

Dual‐Chamber One‐Step Molding Actuator with Straight‐Curved Crease Prismatic Design for Large‐Range Motions and Structural Stability

A dual‐chamber origami prismatic actuator is designed by integrating straight‐curved creases with folded partitions, enabling large‐range, multidirectional motions and enhanced structural stability. The actuator exhibits anisotropic stiffness and multiple actuation modes, and is fabricated via single‐material, one‐step molding. Its design supports diverse robotic applications, including assistive devices, a soft gripper, and a crawling robot. Abstract Soft actuators are gaining attention for their exceptional deformability and adaptability to meet the diverse demands of practical soft robotics applications. However, soft actuators with pneumatic actuation often struggle to simultaneously achieve large‐range motions and structural stability. Addressing this challenge, a dual‐chamber straight‐curved crease origami prismatic (SCOP) actuator is proposed that introduces anisotropic stiffness through origami‐inspired straight‐curved creases and a foldable partition, enabling multidimensional motions including elongation and contraction, with an axial displacement reaching 106.7% of the actuator's original length (elongation 51.1% and contraction 55.6%), over 160° bidirectional bending, and a 209% increase in structural stability compared to curve crease bellows. The actuator is fabricated through one‐step molding using a single material, and its principles, modeling, and design are systematically analyzed. The versatility and feasibility of the SCOP actuator are validated through its integrations into a wearable assistive device, a soft gripper, and a single‐actuator crawling robot, which leverage various combinations of the SCOP's actuation modes to meet diverse motion requirements. This design provides a high‐performance and practical solution for soft robotic systems requiring large‐range, multidirectional motions with enhanced strength and reliability. A dual-chamber origami prismatic actuator is designed by integrating straight-curved creases with folded partitions, enabling large-range, multidirectional motions and enhanced structural stability. The actuator exhibits anisotropic stiffness and multiple actuation modes, and is fabricated via single-material, one-step molding. Its design supports diverse robotic applications, including assistive devices, a soft gripper, and a crawling robot. Abstract Soft actuators are gaining attention for their exceptional deformability and adaptability to meet the diverse demands of practical soft robotics applications. However, soft actuators with pneumatic actuation often struggle to simultaneously achieve large-range motions and structural stability. Addressing this challenge, a dual-chamber straight-curved crease origami prismatic (SCOP) actuator is proposed that introduces anisotropic stiffness through origami-inspired straight-curved creases and a foldable partition, enabling multidimensional motions including elongation and contraction, with an axial displacement reaching 106.7% of the actuator's original length (elongation 51.1% and contraction 55.6%), over 160° bidirectional bending, and a 209% increase in structural stability compared to curve crease bellows. The actuator is fabricated through one-step molding using a single material, and its principles, modeling, and design are systematically analyzed. The versatility and feasibility of the SCOP actuator are validated through its integrations into a wearable assistive device, a soft gripper, and a single-actuator crawling robot, which leverage various combinations of the SCOP's actuation modes to meet diverse motion requirements. This design provides a high-performance and practical solution for soft robotic systems requiring large-range, multidirectional motions with enhanced strength and reliability. Advanced Science, Volume 13, Issue 2, 9 January 2026.

Cation Substitution in High‐Entropy Layered Double Hydroxide Driving D‐Band Center Tuning for Oxygen Evolution Reaction

The d‐band center position of layered double hydroxide is adjusted via multication insertion in the octahedral site. The optimal position of the d‐band, near the Fermi level, enhances OER performance through optimal OH− adsorption kinetics, resulting in a 55% reduction in overpotential compared to the native catalyst. Abstract The development of electrocatalysts with optimized intermediate adsorption and low energy barriers is crucial for the oxygen evolution reaction (OER). In this work, the d‐band center position of high‐entropy layered double hydroxides (HE‐LDHs) is modulated by substituting Mg2⁺ sites with Fe2+, Cu2+, Co2+, and Ni2+. It is demonstrated that the d‐band center position relative to the Fermi level is modified, reaching an optimal energy in (FeCuCoNi)6Al2‐LDH. The nature of the incorporated transition metals significantly influenced OH− adsorption kinetics and reduced the overpotential for OER by 55%, compared to native LDH. The stepwise substitution of Mg2⁺ by Fe2⁺ particularly induces charge carrier transfer, switching into Faradaic processes favorable to the enhancement of OER kinetics. This work provides an effective approach that allows decreasing the OER overpotential through adjusting the position of the d‐band center, and suggests that d‐band tuning via multication insertion can directly shift the material toward an optimal binding strength region, which underlies the observed performance. The d-band center position of layered double hydroxide is adjusted via multication insertion in the octahedral site. The optimal position of the d-band, near the Fermi level, enhances OER performance through optimal OH − adsorption kinetics, resulting in a 55% reduction in overpotential compared to the native catalyst. Abstract The development of electrocatalysts with optimized intermediate adsorption and low energy barriers is crucial for the oxygen evolution reaction (OER). In this work, the d-band center position of high-entropy layered double hydroxides (HE-LDHs) is modulated by substituting Mg 2 ⁺ sites with Fe 2+, Cu 2+, Co 2+, and Ni 2+. It is demonstrated that the d-band center position relative to the Fermi level is modified, reaching an optimal energy in (FeCuCoNi) 6 Al 2 -LDH. The nature of the incorporated transition metals significantly influenced OH − adsorption kinetics and reduced the overpotential for OER by 55%, compared to native LDH. The stepwise substitution of Mg 2 ⁺ by Fe 2 ⁺ particularly induces charge carrier transfer, switching into Faradaic processes favorable to the enhancement of OER kinetics. This work provides an effective approach that allows decreasing the OER overpotential through adjusting the position of the d-band center, and suggests that d-band tuning via multication insertion can directly shift the material toward an optimal binding strength region, which underlies the observed performance. Advanced Science, EarlyView.

A Virtual Clinical Trial of Psychedelics to Treat Patients With Disorders of Consciousness

Disorders of consciousness after severe brain injury are marked by reduced complexity of brain activity and limited treatment options. Using personalized whole‐brain models, this study shows that simulated lysergic acid diethylamide (LSD) and psilocybin shift patient brain dynamics closer to criticality. This proof‐of‐principle study investigates this novel therapeutic avenue and demonstrates the potential of virtual clinical trials in precision medicine. Abstract Disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have limited treatment options and are characterized by low complexity of brain activity. Recent research suggests that psychedelic drugs, which enhance the complexity of brain activity, could offer promising therapies. Here, individualized whole‐brain computational models are developed for patients with DoC, optimized with empirical functional magnetic resonance imaging data and diffusion‐weighted imaging data, upon which the administration of lysergic acid diethylamide (LSD) and psilocybin is simulated. An in silico perturbation protocol is applied to assess brain dynamics, first distinguishing between different states of consciousness, including DoC, anesthesia, and the psychedelic state. Then, brain dynamics are assessed before and after a simulation of psychedelic drugs on patients with DoC. Findings indicated that the simulation of LSD and psilocybin shifted the brain activity of patients with DoC closer to criticality (the point at a phase transition between order and chaos), with a greater effect in patients in the MCS. In patients with UWS, the treatment response correlated with structural connectivity, while in patients in the MCS, it aligned with baseline functional connectivity. These results offer a computational foundation for using psychedelics in DoC treatment and highlight the potential future role of computational modeling in drug discovery and personalized medicine. Disorders of consciousness after severe brain injury are marked by reduced complexity of brain activity and limited treatment options. Using personalized whole-brain models, this study shows that simulated lysergic acid diethylamide (LSD) and psilocybin shift patient brain dynamics closer to criticality. This proof-of-principle study investigates this novel therapeutic avenue and demonstrates the potential of virtual clinical trials in precision medicine. Abstract Disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have limited treatment options and are characterized by low complexity of brain activity. Recent research suggests that psychedelic drugs, which enhance the complexity of brain activity, could offer promising therapies. Here, individualized whole-brain computational models are developed for patients with DoC, optimized with empirical functional magnetic resonance imaging data and diffusion-weighted imaging data, upon which the administration of lysergic acid diethylamide (LSD) and psilocybin is simulated. An in silico perturbation protocol is applied to assess brain dynamics, first distinguishing between different states of consciousness, including DoC, anesthesia, and the psychedelic state. Then, brain dynamics are assessed before and after a simulation of psychedelic drugs on patients with DoC. Findings indicated that the simulation of LSD and psilocybin shifted the brain activity of patients with DoC closer to criticality (the point at a phase transition between order and chaos), with a greater effect in patients in the MCS. In patients with UWS, the treatment response correlated with structural connectivity, while in patients in the MCS, it aligned with baseline functional connectivity. These results offer a computational foundation for using psychedelics in DoC treatment and highlight the potential future role of computational modeling in drug discovery and personalized medicine. Advanced Science, EarlyView.

HUWE1 in Skeletal Muscle Prevents Muscle Fatigue via Maintaining Iron and Calcium Homeostasis

This study investigates the impact of iron homeostasis on exercise. Loss of the HECT domain‐containing ubiquitin ligase E3 (HUWE1) in skeletal muscle restrains the exercise performance in mice with downregulated ferroportin expression leading to iron overload, which is ameliorated by dietary iron restriction. Therefore, it unveils a key function for HUWE1 in skeletal muscle to coordinate iron homeostasis during exercise. Abstract Iron is critical to optimal athletic performance because of its role in energy metabolism, oxygen transport, and acid‐base balance. However, the precise mechanism how skeletal muscle maintains iron homeostasis during exercise remains enigmatic. Here, it is demonstrated that the HECT‐domain containing ubiquitin ligase E3 Huwe1 (also known as MULE or ARF‐BP1) in skeletal muscle is suppressed upon exhausted exercise. Loss of Huwe1 in skeletal muscle restrains the exercise performance of Huwe1 conditional knockout (cKO) mice, accompanied with pronounced oxidative stress. Mechanistically, Huwe1 depletion stabilizes c‐Myc protein, leading to upregulated sarcolipin (Sln) expression with inhibited SarcoEndoplasmic Reticulum Calcium ATPase (SERCA) activity, and downregulated ferroportin (Fpn, also known as Slc40a1) expression with iron overload. Silencing of c‐Myc restores SERCA activity and iron export. Consistently, SERCA activator CDN1163, Sln silencing, or dietary iron restriction ameliorates the exercise performance of Huwe1 cKO mice. Of note, improved exercise performance is accompanied with diminished oxidative stress in Huwe1 cKO mice upon iron restriction. Taken together, the results unveil a key function for HUWE1 in skeletal muscle as a fundamental coordinator of iron and calcium homeostasis by regulating SERCA activity and iron metabolism. These findings reveal a regulatory pathway on controlling iron/calcium homeostasis and exercise capacity. This study investigates the impact of iron homeostasis on exercise. Loss of the HECT domain-containing ubiquitin ligase E3 (HUWE1) in skeletal muscle restrains the exercise performance in mice with downregulated ferroportin expression leading to iron overload, which is ameliorated by dietary iron restriction. Therefore, it unveils a key function for HUWE1 in skeletal muscle to coordinate iron homeostasis during exercise. Abstract Iron is critical to optimal athletic performance because of its role in energy metabolism, oxygen transport, and acid-base balance. However, the precise mechanism how skeletal muscle maintains iron homeostasis during exercise remains enigmatic. Here, it is demonstrated that the HECT-domain containing ubiquitin ligase E3 Huwe1 (also known as MULE or ARF-BP1) in skeletal muscle is suppressed upon exhausted exercise. Loss of Huwe1 in skeletal muscle restrains the exercise performance of Huwe1 conditional knockout (cKO) mice, accompanied with pronounced oxidative stress. Mechanistically, Huwe1 depletion stabilizes c-Myc protein, leading to upregulated sarcolipin (Sln) expression with inhibited SarcoEndoplasmic Reticulum Calcium ATPase (SERCA) activity, and downregulated ferroportin (Fpn, also known as Slc40a1) expression with iron overload. Silencing of c-Myc restores SERCA activity and iron export. Consistently, SERCA activator CDN1163, Sln silencing, or dietary iron restriction ameliorates the exercise performance of Huwe1 cKO mice. Of note, improved exercise performance is accompanied with diminished oxidative stress in Huwe1 cKO mice upon iron restriction. Taken together, the results unveil a key function for HUWE1 in skeletal muscle as a fundamental coordinator of iron and calcium homeostasis by regulating SERCA activity and iron metabolism. These findings reveal a regulatory pathway on controlling iron/calcium homeostasis and exercise capacity. Advanced Science, EarlyView.

CD27 and ICOS as Targets of PD‐1/PD‐L1 Signaling to Regulate Resident Memory CD8+ T‐Cell‐Mediated Pulmonary Protection and Pathology

Here it is revealed that the costimulatory receptors CD27 and ICOS are essential for the long‐term maintenance of PD‐1high CD8+ TRM cells following influenza infection. PD‐L1 blockade enhances the proliferation and activation of these cells through Nur77 activation downstream of the CD27/ICOS signaling axis, thereby boosting host immunity against secondary viral challenges while concurrently exacerbating pulmonary fibrosis sequelae. Abstract Tissue‐resident memory CD8+ T cells (TRM cells) provide superior frontline defense against pathogens. While the role of costimulation in effector and memory CD8+ T‐cell development is well characterized, how costimulatory signaling governs CD8+ TRM cells homeostasis at the memory phase remains poorly defined. Here it is revealed that the costimulatory receptors CD27 and ICOS coordinately sustain PD‐1high CD8+ TRM cell populations following resolution of acute influenza infection. These costimulatory signals serve as critical targets for PD‐1/PD‐L1 blockade, thereby facilitating the rejuvenation of PD‐1high TRM cells and influencing the progression of fibrotic sequelae during the memory phase. Mechanistic dissection identifies the nuclear receptor Nur77 (NR4A1) as the convergent transcriptional hub downstream of CD27/ICOS, governing proliferative renewal and maintenance of PD‐1high TRM cells. Therapeutic administration of a CD27 agonist not only amplified this TRM cell subset in late‐stage memory but also conferred cross‐protective immunity against heterosubtypic viral challenges. Clinically, the expressions of CD27 and ICOS are enriched in CD8+ T cells within the lung tissues of patients with pulmonary fibrosis. Collectively, these findings establish the “CD27/ICOS‐NR4A1‐proliferation” axis as a linchpin of PD‐1/PD‐L1‐mediated TRM cell homeostasis, revealing druggable targets for intercepting infection‐associated fibrotic progression. Here it is revealed that the costimulatory receptors CD27 and ICOS are essential for the long-term maintenance of PD-1 high CD8 + T RM cells following influenza infection. PD-L1 blockade enhances the proliferation and activation of these cells through Nur77 activation downstream of the CD27/ICOS signaling axis, thereby boosting host immunity against secondary viral challenges while concurrently exacerbating pulmonary fibrosis sequelae. Abstract Tissue-resident memory CD8 + T cells (T RM cells) provide superior frontline defense against pathogens. While the role of costimulation in effector and memory CD8 + T-cell development is well characterized, how costimulatory signaling governs CD8 + T RM cells homeostasis at the memory phase remains poorly defined. Here it is revealed that the costimulatory receptors CD27 and ICOS coordinately sustain PD-1 high CD8 + T RM cell populations following resolution of acute influenza infection. These costimulatory signals serve as critical targets for PD-1/PD-L1 blockade, thereby facilitating the rejuvenation of PD-1 high T RM cells and influencing the progression of fibrotic sequelae during the memory phase. Mechanistic dissection identifies the nuclear receptor Nur77 (NR4A1) as the convergent transcriptional hub downstream of CD27/ICOS, governing proliferative renewal and maintenance of PD-1 high T RM cells. Therapeutic administration of a CD27 agonist not only amplified this T RM cell subset in late-stage memory but also conferred cross-protective immunity against heterosubtypic viral challenges. Clinically, the expressions of CD27 and ICOS are enriched in CD8 + T cells within the lung tissues of patients with pulmonary fibrosis. Collectively, these findings establish the “CD27/ICOS-NR4A1-proliferation” axis as a linchpin of PD-1/PD-L1-mediated T RM cell homeostasis, revealing druggable targets for intercepting infection-associated fibrotic progression. Advanced Science, EarlyView.

Subicular Astrocytes Govern Seizure‐Impaired Fear Memory

Astrocytes in dorsal subiculum act as a critical modulator of seizure‐associated cognitive dysfunction, operating through a Ca2+‐dependent adenosine‐linked astrocyte‐neuron signaling pathway that disrupts neuronal circuit homeostasis. This research highlights the potential of astrocyte‐targeted interventions as a therapeutic strategy, moving beyond the conventional neuron‐centric view for treating seizure‐related fear memory disorders. Abstract The mechanisms underlying seizure‐associated cognitive impairment remain incompletely characterized. Emerging evidence positions the subiculum, a hippocampal output hub critically involved in both epileptic seizure and cognitive performance, as a putative nexus for this comorbidity. Here, it is demonstrated that astrocytic activation in the subiculum mediates seizure‐induced fear memory deficits. Subicular astrocytes dynamically respond to conditioned fear memory learning, acting as a “scavenger” for the inhibition of context memory. Seizure activity hyperactivates these leaning‐associated astrocytes and amplifies their engagement during fear processing. Suppression of subicular astrocyte Ca2+ signaling fully rescues seizure‐induced fear memory deficits, while Gq pathway activation in the subicular astrocytes replicates cognitive impairment. Mechanistically, this seizure‐induced astrocyte dysregulation specifically involves Ca2+‐dependent gliotransmitter adenosine‐mediated inhibition through A1 receptors, reducing local neuronal excitability during fear processing. Collectively, these findings identify subicular astrocytes as critical modulators of seizure‐associated cognitive dysfunction, operating through a Ca2+‐dependent adenosine‐linked pathway that disrupts neural circuit homeostasis. This work highlights the potential for astrocyte‐targeted interventions as a therapeutic strategy for seizure‐related memory disorders. Astrocytes in dorsal subiculum act as a critical modulator of seizure-associated cognitive dysfunction, operating through a Ca 2+ -dependent adenosine-linked astrocyte-neuron signaling pathway that disrupts neuronal circuit homeostasis. This research highlights the potential of astrocyte-targeted interventions as a therapeutic strategy, moving beyond the conventional neuron-centric view for treating seizure-related fear memory disorders. Abstract The mechanisms underlying seizure-associated cognitive impairment remain incompletely characterized. Emerging evidence positions the subiculum, a hippocampal output hub critically involved in both epileptic seizure and cognitive performance, as a putative nexus for this comorbidity. Here, it is demonstrated that astrocytic activation in the subiculum mediates seizure-induced fear memory deficits. Subicular astrocytes dynamically respond to conditioned fear memory learning, acting as a “scavenger” for the inhibition of context memory. Seizure activity hyperactivates these leaning-associated astrocytes and amplifies their engagement during fear processing. Suppression of subicular astrocyte Ca 2+ signaling fully rescues seizure-induced fear memory deficits, while Gq pathway activation in the subicular astrocytes replicates cognitive impairment. Mechanistically, this seizure-induced astrocyte dysregulation specifically involves Ca 2+ -dependent gliotransmitter adenosine-mediated inhibition through A 1 receptors, reducing local neuronal excitability during fear processing. Collectively, these findings identify subicular astrocytes as critical modulators of seizure-associated cognitive dysfunction, operating through a Ca 2+ -dependent adenosine-linked pathway that disrupts neural circuit homeostasis. This work highlights the potential for astrocyte-targeted interventions as a therapeutic strategy for seizure-related memory disorders. Advanced Science, EarlyView.

Systematic Benchmarking of a Noise‐Tolerant Conductive Hydrogel Electrode for Epidermal Bioelectronics

General schematic of the approach. Abstract Conventional Silver/Silver Chloride (Ag/AgCl) electrodes remain the clinical standard for electrophysiological monitoring but are hindered by poor skin conformity, mechanical rigidity, and signal degradation, particularly under motion or sweat. Here, two hydrogel‐based alternatives are presented and benchmarked using a wireless commercial platform: a porous poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate scaffold infused with hydrogel (PPSCF), and an all‐hydrogel, crosslinker‐free electrode (PPHG) synthesizes via a scalable, one‐pot process. PPHG demonstrates intrinsic stretchability, self‐adhesion, and biocompatibility, forming stable, low‐impedance contacts with skin. Electrochemical measurements reveal that PPHG maintains a capacitive interface with reduced resistive losses, low loss tangent, high dielectric constant, and fast relaxation dynamics, features that enable intrinsic signal smoothing and noise suppression. In a cohort of 39 participants, PPHG electrodes outperform Ag/AgCl in electrocardiography (ECG), showing reduced motion artifacts, higher signal‐to‐noise ratios, and clear preservation of P‐, R‐, and T‐waves. Electroencephalography (EEG) recordings demonstrate enhanced alpha–delta separation, while electrooculography (EOG) and electromyography (EMG) signals exhibit greater amplitude and sharper features. Machine learning analysis of ECG signals reveals a 2.2‐fold improvement in inter‐lead classification accuracy. These findings position PPHG as a soft, adhesive, and sustainable alternative for high‐fidelity, multimodal bioelectronic interfaces, with strong potential for wearables and clinical monitoring systems. General schematic of the approach. Abstract Conventional Silver/Silver Chloride (Ag/AgCl) electrodes remain the clinical standard for electrophysiological monitoring but are hindered by poor skin conformity, mechanical rigidity, and signal degradation, particularly under motion or sweat. Here, two hydrogel-based alternatives are presented and benchmarked using a wireless commercial platform: a porous poly(3,4-ethylenedioxythiophene):polystyrene sulfonate scaffold infused with hydrogel (PPSCF), and an all-hydrogel, crosslinker-free electrode (PPHG) synthesizes via a scalable, one-pot process. PPHG demonstrates intrinsic stretchability, self-adhesion, and biocompatibility, forming stable, low-impedance contacts with skin. Electrochemical measurements reveal that PPHG maintains a capacitive interface with reduced resistive losses, low loss tangent, high dielectric constant, and fast relaxation dynamics, features that enable intrinsic signal smoothing and noise suppression. In a cohort of 39 participants, PPHG electrodes outperform Ag/AgCl in electrocardiography (ECG), showing reduced motion artifacts, higher signal-to-noise ratios, and clear preservation of P-, R-, and T-waves. Electroencephalography (EEG) recordings demonstrate enhanced alpha–delta separation, while electrooculography (EOG) and electromyography (EMG) signals exhibit greater amplitude and sharper features. Machine learning analysis of ECG signals reveals a 2.2-fold improvement in inter-lead classification accuracy. These findings position PPHG as a soft, adhesive, and sustainable alternative for high-fidelity, multimodal bioelectronic interfaces, with strong potential for wearables and clinical monitoring systems. Advanced Science, EarlyView.

Formation of Condition‐Dependent Alpha‐Synuclein Fibril Strain in Artificial Cerebrospinal Fluid

α‐synuclein aggregation in artificial cerebrospinal fluid (aCSF) leads to a distinct conformation with an electron density pocket motif found in aggregates from PD and MSA patients. Such fibrils has low stability outside the reaction conditions, hinting about the influence of cerebrospinal fluid components not only on the formation, but also on the stability of α‐synuclein aggregates. Abstract α‐Synuclein (aSyn) is an intrinsically disordered protein involved in neurotransmission and synaptic plasticity. The pathological aggregation of this protein is a hallmark of synucleinopathies such as Parkinson's disease (PD) or Multiple System Atrophy (MSA). Misfolded aSyn, which primarily originates in the cell cytosol, transmits between neurons, promoting a prion‐like propagation. However, extracellular environments such as interstitial and cerebrospinal fluids (ISF & CSF) play a major role in its clearance and pathological transformation. The molecular components of CSF, including proteins, glycosaminoglycans, and metal ions, may influence the aggregate morphology, structure, and cytotoxicity to cells. To better understand how extracellular composition affects aggregates and their formation, artificial cerebrospinal fluid (aCSF) is employed to mimic potential aggregation processes occurring in CSF. Distinct aSyn fibrils are observed that exhibited low stability outside aCSF, and the removal of key CSF components led to its structural alterations. Cryo‐electron microscopy revealed that these fibrils possess an electron density pocket coordinated with polar basic AAs (K43, K45, H50) that is also observed in aggregates obtained from PD and MSA patients. The findings illustrate the importance of physiologically relevant conditions in studying aSyn aggregation and may explain why disease‐related fibril structure replication in vitro has not yet been successful. α-synuclein aggregation in artificial cerebrospinal fluid (aCSF) leads to a distinct conformation with an electron density pocket motif found in aggregates from PD and MSA patients. Such fibrils has low stability outside the reaction conditions, hinting about the influence of cerebrospinal fluid components not only on the formation, but also on the stability of α-synuclein aggregates. Abstract α-Synuclein (aSyn) is an intrinsically disordered protein involved in neurotransmission and synaptic plasticity. The pathological aggregation of this protein is a hallmark of synucleinopathies such as Parkinson's disease (PD) or Multiple System Atrophy (MSA). Misfolded aSyn, which primarily originates in the cell cytosol, transmits between neurons, promoting a prion-like propagation. However, extracellular environments such as interstitial and cerebrospinal fluids (ISF & CSF) play a major role in its clearance and pathological transformation. The molecular components of CSF, including proteins, glycosaminoglycans, and metal ions, may influence the aggregate morphology, structure, and cytotoxicity to cells. To better understand how extracellular composition affects aggregates and their formation, artificial cerebrospinal fluid (aCSF) is employed to mimic potential aggregation processes occurring in CSF. Distinct aSyn fibrils are observed that exhibited low stability outside aCSF, and the removal of key CSF components led to its structural alterations. Cryo-electron microscopy revealed that these fibrils possess an electron density pocket coordinated with polar basic AAs (K43, K45, H50) that is also observed in aggregates obtained from PD and MSA patients. The findings illustrate the importance of physiologically relevant conditions in studying aSyn aggregation and may explain why disease-related fibril structure replication in vitro has not yet been successful. Advanced Science, EarlyView.

Alternative Pathway for Methyl Supply through the Coupling of SHMT1 and PEMT to Maintain Astrocytic Homeostasis in Parkinson's Disease

In Parkinson's disease, SHMT1 downregulation disrupts its interaction with PEMT in astrocytes, reducing SAM levels. This leads to H3K4me1 hypomethylation and decreased Slc1a2/Glul expression, ultimately exacerbating neuroexcitotoxicity and dopaminergic neuron loss. This study reveals a novel SHMT1‐PEMT link connecting one‐carbon and membrane phospholipid metabolism in PD pathogenesis. Abstract Serine Hydroxymethyltransferase 1 (SHMT1) plays a pivotal role in one‐carbon metabolism, facilitating the production of SAM. In this study, dysregulation of one‐carbon metabolism is reported in both Parkinson's disease (PD) patients and animal models, characterized by significantly downregulated expression of SHMT1. Astrocyte‐specific conditional knockout of Shmt1 decreased SAM level, exacerbated motor dysfunction, and dopaminergic neuronal loss in a PD mouse model. While SAM is conventionally generated through the one‐carbon cycle, the data indicate that, despite significant alterations in SHMT1, SAM remains unaffected while labeled 13C‐Serine. Intriguingly, isotopic labeling experiments revealed a significant association between SHMT1 and the production of PDME, an intermediate metabolite of the phosphatidylethanolamine methylation pathway. Consequently, PEMT is discovered as interacting with SHMT1. It is demonstrated that disruption of the interaction between SHMT1 and PEMT leads to SAM depletion, causing H3K4me1 hypomethylation, which in turn reduces the expression of Slc1a2 and Glul. As a result, decoupling of SHMT1 and PEMT in astrocytes ultimately exacerbates neuroexcitotoxicity and dopaminergic neuron loss in PD. Thus, the study elucidates the novel metabolic connection between SHMT1 and PEMT that links the astrocytic one‐carbon cycle and membrane phospholipid metabolism in PD. In Parkinson's disease, SHMT1 downregulation disrupts its interaction with PEMT in astrocytes, reducing SAM levels. This leads to H3K4me1 hypomethylation and decreased Slc1a2/Glul expression, ultimately exacerbating neuroexcitotoxicity and dopaminergic neuron loss. This study reveals a novel SHMT1-PEMT link connecting one-carbon and membrane phospholipid metabolism in PD pathogenesis. Abstract Serine Hydroxymethyltransferase 1 (SHMT1) plays a pivotal role in one-carbon metabolism, facilitating the production of SAM. In this study, dysregulation of one-carbon metabolism is reported in both Parkinson's disease (PD) patients and animal models, characterized by significantly downregulated expression of SHMT1. Astrocyte-specific conditional knockout of Shmt1 decreased SAM level, exacerbated motor dysfunction, and dopaminergic neuronal loss in a PD mouse model. While SAM is conventionally generated through the one-carbon cycle, the data indicate that, despite significant alterations in SHMT1, SAM remains unaffected while labeled 13 C-Serine. Intriguingly, isotopic labeling experiments revealed a significant association between SHMT1 and the production of PDME, an intermediate metabolite of the phosphatidylethanolamine methylation pathway. Consequently, PEMT is discovered as interacting with SHMT1. It is demonstrated that disruption of the interaction between SHMT1 and PEMT leads to SAM depletion, causing H3K4me1 hypomethylation, which in turn reduces the expression of Slc1a2 and Glul. As a result, decoupling of SHMT1 and PEMT in astrocytes ultimately exacerbates neuroexcitotoxicity and dopaminergic neuron loss in PD. Thus, the study elucidates the novel metabolic connection between SHMT1 and PEMT that links the astrocytic one-carbon cycle and membrane phospholipid metabolism in PD. Advanced Science, EarlyView.

Allelic Variation in Maize Malate Dehydrogenase 7 Shapes Promoter Methylation and Banded Leaf and Sheath Blight Resistance

In this study maize chloroplastic malate dehydrogenase7 (ZmMDH7), is identified as a Rhizoctonia solani resistance gene in maize. ZmMDH7 is regulated by transcription factor ZmWRKY44 via pathogens challenge to elevate mitochondrial ROS and SA signaling pathway. A transposable element insertion in promotor of ZmRRS1 dampens ZmWRKY44‐mediated expression of ZmMDH7, that suppress maize resistance to R. solani. Abstract Rhizoctonia solani, a globally distributed phytopathogen, causes banded leaf and sheath blight (BLSB) in maize and sheath blight in rice, severely threatening crop productivity. Here, this work identifies ZmRRS1 (Resistance to Rhizoctonia solani 1), which encodes maize malate dehydrogenase, as a key positive regulator of BLSB resistance in the field through a genome‐wide association study. ZmRRS1 knockout lines exhibit increased susceptibility to BLSB, whereas overexpression of ZmRRS1 and its homologs confer enhanced resistance to R. solani in both maize and rice. Using heterozygote inbred families (HIF), this work uncovers that the presence and absence of a 831‐bp transposable element (TE) element is the causal polymorphism that determines the differential expression pattern of the two ZmRRS1 alleles in response to R. solani. Furthermore, the absence of the TE increases the binding of the ZmWRKY44 transcription factor to the W‐box motif in the promoter of ZmRRS1, thereby enhancing BLSB resistance. Transcriptomic analysis reveals that ZmRRS1 potentiates reactive oxygen species (ROS)‐mediated immunity against BLSB. Notably, the overexpression of ZmRRS1 does not incur agronomic penalties under normal growth conditions. Collectively, this work identifies ZmRRS1 as a positive regulator of BLSB resistance, offering valuable genetic resources for breeding BLSB‐resistant maize and rice varieties. In this study maize chloroplastic malate dehydrogenase7 ( ZmMDH7 ), is identified as a Rhizoctonia solani resistance gene in maize. ZmMDH7 is regulated by transcription factor ZmWRKY44 via pathogens challenge to elevate mitochondrial ROS and SA signaling pathway. A transposable element insertion in promotor of ZmRRS1 dampens ZmWRKY44-mediated expression of ZmMDH7, that suppress maize resistance to R. solani. Abstract Rhizoctonia solani, a globally distributed phytopathogen, causes banded leaf and sheath blight (BLSB) in maize and sheath blight in rice, severely threatening crop productivity. Here, this work identifies ZmRRS1 (Resistance to Rhizoctonia solani 1), which encodes maize malate dehydrogenase, as a key positive regulator of BLSB resistance in the field through a genome-wide association study. ZmRRS1 knockout lines exhibit increased susceptibility to BLSB, whereas overexpression of ZmRRS1 and its homologs confer enhanced resistance to R. solani in both maize and rice. Using heterozygote inbred families (HIF), this work uncovers that the presence and absence of a 831-bp transposable element (TE) element is the causal polymorphism that determines the differential expression pattern of the two ZmRRS1 alleles in response to R. solani. Furthermore, the absence of the TE increases the binding of the ZmWRKY44 transcription factor to the W-box motif in the promoter of ZmRRS1, thereby enhancing BLSB resistance. Transcriptomic analysis reveals that ZmRRS1 potentiates reactive oxygen species (ROS)-mediated immunity against BLSB. Notably, the overexpression of ZmRRS1 does not incur agronomic penalties under normal growth conditions. Collectively, this work identifies ZmRRS1 as a positive regulator of BLSB resistance, offering valuable genetic resources for breeding BLSB-resistant maize and rice varieties. Advanced Science, EarlyView.

Cidea Targeting Protects Cochlear Hair Cells and Hearing Function From Drug‐ and Noise‐Induced Damage

Acquired sensorineural hearing loss is primarily caused by the damage or loss of cochlear hair cells, induced by factors such as noise exposure and ototoxic drugs. The deficiency of apoptosis‐inducing gene Cidea in Cidea KO mice or by delivering CRISPR/SlugCas9‐HF via AAV to edit Cidea effectively alleviated hair cell damage and hearing loss caused by neomycin treatment and noise exposure. Abstract Acquired sensorineural hearing loss (SNHL) is primarily caused by the damage or loss of hair cells (HCs), induced by factors such as noise exposure and ototoxic drugs. However, clinical treatments for SNHL remain limited. Here, the role of the apoptosis‐inducing gene Cidea in SNHL is investigated. It is initially observed that Cidea expression is specifically increased in neomycin‐damaged HCs at both the protein and mRNA levels. To further explore its role, Cidea knockout (Cidea‐/‐) mice are obtained, and it is found that the absence of Cidea effectively alleviates HC apoptosis caused by neomycin treatment and noise exposure in vivo. Moreover, a novel therapeutic strategy for SNHL has been developed by delivering CRISPR/SlugCas9‐HF via AAV to edit Cidea, and this approach significantly reduced HC loss induced by both neomycin and noise exposure. These findings suggest that Cidea may serve as a promising target for the prevention of neomycin‐ and noise‐induced SNHL in clinical settings. Acquired sensorineural hearing loss is primarily caused by the damage or loss of cochlear hair cells, induced by factors such as noise exposure and ototoxic drugs. The deficiency of apoptosis-inducing gene Cidea in Cidea KO mice or by delivering CRISPR/SlugCas9-HF via AAV to edit Cidea effectively alleviated hair cell damage and hearing loss caused by neomycin treatment and noise exposure. Abstract Acquired sensorineural hearing loss (SNHL) is primarily caused by the damage or loss of hair cells (HCs), induced by factors such as noise exposure and ototoxic drugs. However, clinical treatments for SNHL remain limited. Here, the role of the apoptosis-inducing gene Cidea in SNHL is investigated. It is initially observed that Cidea expression is specifically increased in neomycin-damaged HCs at both the protein and mRNA levels. To further explore its role, Cidea knockout (Cidea-/-) mice are obtained, and it is found that the absence of Cidea effectively alleviates HC apoptosis caused by neomycin treatment and noise exposure in vivo. Moreover, a novel therapeutic strategy for SNHL has been developed by delivering CRISPR/SlugCas9-HF via AAV to edit Cidea, and this approach significantly reduced HC loss induced by both neomycin and noise exposure. These findings suggest that Cidea may serve as a promising target for the prevention of neomycin- and noise-induced SNHL in clinical settings. Advanced Science, EarlyView.

A Tangentially Sensitive Tactile Sensor Reveals the Stick‐Slip Mechanism and Enhances Robotic Tactile Sensing

An ultralight, multilayer anisotropic tactile sensor—an artificial Pacinian corpuscle—exhibits ultrahigh tangential sensitivity (1022 kPa−1) and spatiotemporal sensing. It discriminates static, sliding, and rolling contacts, detects incipient stick–slip via high‑frequency signatures, and enhances robotic touch (100%/98.18% accuracy for active/passive interaction), offering insight into the tangential sensing mechanisms of Pacinian corpuscles. Abstract The mechanism of human tactile perception offers inspiration for developing a high‐performance artificial sensory system. Pacinian corpuscles (PCs) allowing high‐frequency tangential sensitivity that endows humans with the ability to perceive multidimensional tactile stimuli. However, replicating similar high‐frequency and tangential perception as that of PCs in artificial systems remains a significant challenge. Here, an artificial PC (APC) from ultralight aerogel with a multilayer‐stacked and anisotropic structure analogous to that of PC via a multi‐directional freeze‐drying method is reported. The APC sensor with radial‐axial anisotropy exhibits tangential sensitivity (1022 kPa−1), detects multidimensional tactile stimuli, and identifies stick‐slip states with high precision. By mimicking PC clusters, the APC sensor system achieves spatiotemporal sensing capabilities for discriminating frictional patterns (static, sliding, or rolling) and tracking slip. A robot equipped with the APC sensory system possesses enhanced tactile perception for diverse tactile events in active (100% accuracy) and passive (98.18% accuracy) interaction with humans. It is found that high‐frequency components are crucial for stick‐slip detection, providing insights into the underlying tangential tactile sensing mechanisms of PCs. The work exemplifies a bidirectional enhancement of understanding between technological innovation and biological mechanisms. An ultralight, multilayer anisotropic tactile sensor—an artificial Pacinian corpuscle—exhibits ultrahigh tangential sensitivity (1022 kPa −1 ) and spatiotemporal sensing. It discriminates static, sliding, and rolling contacts, detects incipient stick–slip via high‑frequency signatures, and enhances robotic touch (100%/98.18% accuracy for active/passive interaction), offering insight into the tangential sensing mechanisms of Pacinian corpuscles. Abstract The mechanism of human tactile perception offers inspiration for developing a high-performance artificial sensory system. Pacinian corpuscles (PCs) allowing high-frequency tangential sensitivity that endows humans with the ability to perceive multidimensional tactile stimuli. However, replicating similar high-frequency and tangential perception as that of PCs in artificial systems remains a significant challenge. Here, an artificial PC (APC) from ultralight aerogel with a multilayer-stacked and anisotropic structure analogous to that of PC via a multi-directional freeze-drying method is reported. The APC sensor with radial-axial anisotropy exhibits tangential sensitivity (1022 kPa −1 ), detects multidimensional tactile stimuli, and identifies stick-slip states with high precision. By mimicking PC clusters, the APC sensor system achieves spatiotemporal sensing capabilities for discriminating frictional patterns (static, sliding, or rolling) and tracking slip. A robot equipped with the APC sensory system possesses enhanced tactile perception for diverse tactile events in active (100% accuracy) and passive (98.18% accuracy) interaction with humans. It is found that high-frequency components are crucial for stick-slip detection, providing insights into the underlying tangential tactile sensing mechanisms of PCs. The work exemplifies a bidirectional enhancement of understanding between technological innovation and biological mechanisms. Advanced Science, EarlyView.

Rapid Arbitrary‐Shape Microscopy of Unsectioned Tissues for Precise Intraoperative Tumor Margin Assessment

This study presents a novel microscopic imaging system capable of rapid, section‐free scanning of irregular tissue surfaces, delivering high sensitivity for detecting cancer cell clusters during intraoperative tumor margin assessment. Abstract Rapid and accurate intraoperative examination of tumor margins is crucial for precise surgical treatment, yet current methods are limited by incomplete tissue sampling and time‐consuming sample sectioning. The Rapid Arbitrary‐Shape Microscope (RAM) is developed, a bedside imaging system that enables high‐speed, 3D microscopy of irregular tissue surfaces without sectioning, providing cellular‐resolution images within minutes while preserving tissue morphology post‐excision. RAM precisely integrates a 3D scanning module with a robotic platform, seamlessly combining morphological measurements with robotic‐driven pathological microscopy. In studies involving metastatic tumors in 39 mouse liver and spleen samples, RAM demonstrated high accuracy in detecting positive margins containing cancer cells, achieving a sensitivity of 99.1% and a specificity of 82.9%. The system's capability is further validated on 12 skin cancer samples from 10 human subjects using nondestructive imaging, highlighting its potential to reduce surgical time and minimize the risk of overlooking residual cancer at surgical margins during intraoperative evaluation. This study presents a novel microscopic imaging system capable of rapid, section-free scanning of irregular tissue surfaces, delivering high sensitivity for detecting cancer cell clusters during intraoperative tumor margin assessment. Abstract Rapid and accurate intraoperative examination of tumor margins is crucial for precise surgical treatment, yet current methods are limited by incomplete tissue sampling and time-consuming sample sectioning. The Rapid Arbitrary-Shape Microscope (RAM) is developed, a bedside imaging system that enables high-speed, 3D microscopy of irregular tissue surfaces without sectioning, providing cellular-resolution images within minutes while preserving tissue morphology post-excision. RAM precisely integrates a 3D scanning module with a robotic platform, seamlessly combining morphological measurements with robotic-driven pathological microscopy. In studies involving metastatic tumors in 39 mouse liver and spleen samples, RAM demonstrated high accuracy in detecting positive margins containing cancer cells, achieving a sensitivity of 99.1% and a specificity of 82.9%. The system's capability is further validated on 12 skin cancer samples from 10 human subjects using nondestructive imaging, highlighting its potential to reduce surgical time and minimize the risk of overlooking residual cancer at surgical margins during intraoperative evaluation. Advanced Science, EarlyView.

Targeting G3BP1 Condensate Topology Promotes Stress Granule Assembly via m6A‐IGF2BP1 for Ischemic Stroke Rescue

Our research reveals that small‐molecule icariin (ICA) directly binds Ras‐GTPase‐activating protein SH3 domain‐binding protein 1 (G3BP1), inducing conformational change and oligomerization. This interaction confers neuroprotection by recruiting insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) and modulating N6‐methyladenosine (m6A) modifications. Moreover, a distinct neuronal subset exhibits ICA sensitivity correlated with G3BP1 expression, suggesting therapeutic potential for stroke. Abstract Ras‐GTPase‐activating protein SH3 domain‐binding protein 1 (G3BP1) mediates stress granules (SGs) via phase separation. However, there is limited understanding of the allosteric mechanism and the identification of regulatory molecules. Here, we identify icariin (ICA), a small‐molecule inducer that promotes G3BP1‐driven biomolecular condensate formation, which effectively restructures SGs architecture. Moreover, we demonstrate that ICA interacts with the N‐terminal nuclear transport factor 2‐like (NTF2L) domain of G3BP1, inducing a conformational switch from “closed‐to‐open” that facilitates G3BP1 oligomerization and phase separation. Crucially, G3BP1 condensates recruit N6‐methyladenosine (m6A) reader insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) through topology‐selective scaffolding, establishing epitranscriptomic hubs that resolve proteotoxic stress via m6A‐dependent AMP‐activated protein kinase (AMPK)‐mitogen‐activated protein kinase (MAPK)‐glutathione peroxidase 4 (GPX4) signaling pathways. Strikingly, this chemical intervention shows translational potential, as ICA reduces cerebral infarct volume in ischemia models via G3BP1‐dependent SGs remodeling. Additionally, single‐nucleus transcriptomics identify Fezf2, Pou3f1, and Kcnn2 neuronal subpopulations as mechanistically aligned responders. Furthermore, ischemic stroke patients reveal G3BP1–IGF2BP1–m6A axis within peripheral blood mononuclear cells. Taken together, this study redefines SGs as dynamically druggable epitranscriptomic processors for precision neuroprotection. In particular, a framework for leveraging biomolecular condensate topology in the development of next‐generation neurological therapeutics is offered. Our research reveals that small-molecule icariin (ICA) directly binds Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1), inducing conformational change and oligomerization. This interaction confers neuroprotection by recruiting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and modulating N 6 -methyladenosine (m 6 A) modifications. Moreover, a distinct neuronal subset exhibits ICA sensitivity correlated with G3BP1 expression, suggesting therapeutic potential for stroke. Abstract Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) mediates stress granules (SGs) via phase separation. However, there is limited understanding of the allosteric mechanism and the identification of regulatory molecules. Here, we identify icariin (ICA), a small-molecule inducer that promotes G3BP1-driven biomolecular condensate formation, which effectively restructures SGs architecture. Moreover, we demonstrate that ICA interacts with the N-terminal nuclear transport factor 2-like (NTF2L) domain of G3BP1, inducing a conformational switch from “closed-to-open” that facilitates G3BP1 oligomerization and phase separation. Crucially, G3BP1 condensates recruit N 6 -methyladenosine (m 6 A) reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) through topology-selective scaffolding, establishing epitranscriptomic hubs that resolve proteotoxic stress via m 6 A-dependent AMP-activated protein kinase (AMPK)-mitogen-activated protein kinase (MAPK)-glutathione peroxidase 4 (GPX4) signaling pathways. Strikingly, this chemical intervention shows translational potential, as ICA reduces cerebral infarct volume in ischemia models via G3BP1-dependent SGs remodeling. Additionally, single-nucleus transcriptomics identify Fezf2, Pou3f1, and Kcnn2 neuronal subpopulations as mechanistically aligned responders. Furthermore, ischemic stroke patients reveal G3BP1–IGF2BP1–m 6 A axis within peripheral blood mononuclear cells. Taken together, this study redefines SGs as dynamically druggable epitranscriptomic processors for precision neuroprotection. In particular, a framework for leveraging biomolecular condensate topology in the development of next-generation neurological therapeutics is offered. Advanced Science, EarlyView.