Integrated CO2 capture and conversion (iCCC) technology is promising for carbon neutrality, but the high-temperature deactivation of dual-functional materials (DFMs) limits its practicality. Herein, we develop adaptive metallic nano-catalysts via in-situ exsolution-dissolution in perovskite-based DFMs, enabling self-adjustment during cyclic CO2/CH4 redox switching. Al-doping induces the Jahn-Teller distortion in LaNiO3 perovskite, making the lattice contracted to enrich Ni2+ and oxygen vacancies; thereby tailoring the smooth exsolution-dissolution of Ni nano-catalyst and creating fast O2- migration channels for facilitating CO2 adsorption. The optimized perovskite LaNi0.8Al0.2O3/CaO exhibits exceptional durability over 50 cycles, achieving a high CO2 capture capacity of 10.2 mmol gDFM-1 and both high conversions of 91.5% for CO2 and 93.5% for CH4. The mechanism study by the in-situ characterizations and surface energy calculations confirms that heteroatomic doping modulates the metal-support interactions, providing a solution for the long-sought deactivation problems of sintering and coking.
Conductive polymer hydrogels offer unique advantages for soft, stretchable biointerfaces by combining tissue-like mechanics with high ionic conductivity. However, their reliable integration with hydrophobic substrates and encapsulants essential for electrical insulation and chemical protection remains a major challenge due to poor wetting and interfacial delamination in aqueous environments. Here, we report a facile strategy for the in situ stabilization of conductive polymer hydrogels on hydrophobic substrates using a photoactivable surfactant (PAS). PAS reduces interfacial surface energy and, upon UV activation, forms covalent bonds with stretchable substrates, thereby yielding strong adhesion and long-term stability under wet conditions. This molecular design also enables photopatterning of hydrogels without compromising performance. Notably, PAS not only stabilizes and patterns conductive hydrogels in situ but also enhances their mechanical and electrical properties. PAS-integrated hydrogel biointerfaces exhibit robust operation in aqueous environments and demonstrate reliable in vivo electromyographic (EMG) signal recording, underscoring the potential of this approach for next-generation implantable and wearable bioelectronics.
Cervical cancer continues to pose a significant public health burden. In Germany, prevention relies heavily on regular screening and HPV vaccination. To analyze trends in cervical cancer incidence over a 50-year period in Saarland, Germany, with a focus on cohort effects and the impact of screening programs. Data from the Saarland Cancer Registry were evaluated for the period 1970-2023. Trends in cervical carcinoma (ICD-10: C53, ICD-9: 180) and carcinoma in situ (ICD-10: D06, ICD-9: 233.1) were analyzed, stratified by age and birth cohort. Additionally, model-based age-period-cohort analyses were derived. The D06/C53 ratio was calculated by age group and calendar period. Since the introduction of Pap smear screening in 1971, the age-standardized incidence of cervical cancer declined by 74%. Subsequently, sharp decreases were observed in women born in 1933 or earlier. Women who grew into screening never reached the high pre-screening rates. Concurrently, in situ carcinoma incidence rose more than tenfold, with detection concentrated in women aged 30-39, indicating a shift toward earlier detection. The D06/C53 ratio increased across all age groups, most strongly in women ≤ 39 years. Overall mortality fell by 71%, although no significant further decline was observed over the last two to three decades. This analysis underscores the substantial impact of cervical cancer screening in reducing both incidence and mortality, particularly among women of screening age. The increasing D06/C53 ratios point to a shift toward earlier detection and treatment of lesions, although cancer registry-based data cannot fully distinguish prevented progression from overdiagnosis. While the effects and benefits of screening are already well established, the first effects of HPV vaccination are only beginning to emerge. To build on these achievements, sustained efforts to enhance both screening uptake and HPV vaccine coverage are imperative.
Extracellular vesicles (EVs) secreted by glioblastoma (GBM) cells carry tumor-specific biomarkers such as microRNA-1246 (miR-1246), offering significant potential for noninvasive GBM detection. However, the efficient isolation of EVs from complex biofluids and ultrasensitive detection of their low-abundance miRNAs encapsulated in EVs remain formidable challenges. To address this, we designed a multifunctional nanoplatform of UiO-66-NH2@Au@MSDC (UAM), which integrates EV capture and in situ miRNA analysis. The initial construction of UiO-66-NH2@Au (UA) provided a high density of thiol-binding sites for the attachment of mercapto (SH)-spacer-DNA-cholesterol (MSDC) probes to form UiO-66-NH2@Au@MSDC (UAM). The abundant cholesterol motifs on these probes subsequently enabled highly efficient EV capture, achieving a recovery rate of 84.8 ± 2.4% under a low centrifugal force of 8000g while preserving EV structural integrity and bioactivity. For the downstream analysis of EVs, we developed an innovative EXPAR-based strategy, termed Y-EXPAR, to address the specificity challenge in detecting miR-1246. The entire detection system employs a temperature-synergistic strategy at 55 °C, which simultaneously triggers the membrane fusion of EVs with synthetic cationic liposomes (preloaded with Y-EXPAR reagents) and activates the Y-EXPAR. The resulting fusion creates confined nanoreactors that concentrate trace amounts of miR-1246, thereby enabling ultrasensitive detection with detection limits of 1.4 fM for miR-1246 and 22 particles/μL for EVs. This integrated platform overcomes key bottlenecks in EV-based liquid biopsy, providing a practical, low-equipment-demand approach for the early diagnosis of GBM and laying a foundation for advancing precision oncology diagnostics.
Insufficient carbon availability remains a critical limitation for efficient biological nutrient removal in wastewater treatment plants (WWTPs). Although sludge fermentation has been widely investigated as a sustainable approach for generating volatile fatty acids (VFAs), most existing strategies rely on separate fermentation units, limiting process integration and increasing operational complexity. In this study, a full-scale WWTP was retrofitted to enhance in-situ primary sludge fermentation through limited sludge recirculation and controlled solids withdrawal. By recirculating a fraction of secondary sludge and regulating the apparent solids retention time (SdRT) to 3-4 days, fermentation was promoted within the primary sedimentation tank. Long-term operation under varying seasonal conditions demonstrated a significant increase in effluent soluble chemical oxygen demand (SCOD) from 97.5 ± 13.3 to 151.1 ± 20.6 mg/L, corresponding to an improvement in the C/N ratio by 11.7 ± 6.3% (Effluent/Influent). Batch experiments further explored the influence of sludge concentration and stratification on fermentation performance. Microbial analysis further revealed introduction and retention of fermentative bacteria, particularly in the upper sludge layer, which exhibited more stable fermentation performance compared to the bottom sludge. This study provides a potentially practical and scalable strategy for enhancing carbon availability through front-end regulation, offering significant potential to improve downstream biological nutrient removal processes without additional infrastructure.
Understanding the fundamentals of water under nanoconfinement and finding a way to manipulate the properties of interfacial water are crucial to many processes and have attracted intense interest. Here, we demonstrate that the self-induced nanoconfinement arising during the final stage of evaporation of an aqueous droplet can be monitored in situ by using a millimeter-scale interdigitated array electrode sensor. Just before the complete evaporation, the confined water exhibits a conductivity enhancement of up to approximately an order of magnitude compared to bulk water. Moreover, this simple electrical readout provides a rapid and practical platform for screening aqueous electrolytes and colloids, enabling systematic investigation and manipulation of nanoconfinement-induced effects in water.
Superior vena cava (SVC) thrombosis after Glenn palliation constitutes acute cavopulmonary circuit failure. A 6-month-old boy with hypoplastic left heart syndrome developed SVC syndrome on postoperative day 13 after bidirectional Glenn, secondary to catheter-associated SVC-Glenn thrombosis with distal pulmonary embolisms. Alteplase infused in situ through the existing catheter (0.2 mg/kg/h, 72 hours) achieved complete recanalization without bleeding. Mediastinal hemorrhage and 4-day veno-arterial extracorporeal membrane oxygenation precluded thrombolysis and surgery, and mechanical disruption risked embolization into the compromised pulmonary bed. When an indwelling catheter traverses the thrombus, catheter-directed alteplase achieves complete recanalization, even after hemorrhage and extracorporeal support.
In situ simulation (ISS) has seen broad use in academic emergency medicine (EM). Studies with limited clinical data suggest a dual paradigm model to assess the efficacy of these educational activities based on their impact on both ongoing and future quality of care. We conducted a retrospective cohort study to assess the impact of government-mandated mass casualty incident (MCI) ISS drills on ongoing department operations and quality clinical care. We conducted a retrospective study of patients presenting to an adult tertiary academic emergency department during scheduled and unscheduled ISS MCI drills. We assessed the impact of ISS on operational and triage metrics by comparing scheduled and unscheduled drills. Being treated during an ongoing MCI ISS, in both the scheduled and unscheduled simulation formats, was associated with a higher average door to triage times (20.6 min in the MCI ISS cohort vs 15.8 min in the control cohort; p<0.005) and lower Canadian Triage and Acuity Scale (CTAS) scores (CTAS 1 and 2: 0.8% and 14.5% in the MCI ISS cohort vs 1.6% and 17.1% in the control cohort, p<0.025). Secondary analysis, evaluating differences between case and control cohorts in distinct scheduled and unscheduled ISS subgroups, showed that unscheduled but not scheduled ISS were associated with higher average door to triage times (29.0 min in the unscheduled MCI ISS case cohort vs 21.2 min in the unscheduled MCI ISS control cohort; p<0.001) and lower CTAS acuity scores (CTAS 1 and 2: 0.0% and 17.9% in the unscheduled MCI ISS cohort vs 2.8% and 27.9% in the unscheduled MCI ISS control cohort; p<0.001). In this study, there was a significant association between increased door to triage time and lower acuity triage score designation for patients treated during an ongoing MCI ISS education drill. Secondary analysis demonstrated that these findings were only observed during unscheduled simulations, suggesting that the effects may be modifiable.
Photothermal therapy has emerged as a minimally invasive cancer treatment strategy, yet poor nanoparticle (NP) stability, nonspecific accumulation, and inefficient laser delivery to deep tumor tissues markedly limit conventional approaches. Here, we report the rational design of intrinsically disordered polypeptides (IDPs) as next-generation stealth materials for photothermal cancer therapy applications using a novel contact-mode laser irradiation system. IDP1 was computationally designed as a hydrophilic IDP inspired by albumin's primary sequence. IDP1 exhibited an exceptional fourfold prolonged blood circulation half-life (t 1/2 = 150.5 min) relative to PEG (t 1/2 = 17.8 min). IDP1-conjugated lipid NPs encapsulating carbon nanohorns and indocyanine green (IDP1-CNH/ICG) demonstrated efficient tumor accumulation via the enhanced permeability and retention effects. We developed a graded-index plastic optical fiber endoscope system with integrated real-time fluorescence imaging capability, enabling image-guided contact-mode near-infrared laser irradiation and achieving superior photothermal conversion compared to conventional noncontact irradiation, representing 27% higher heating efficiency. In Colon26-bearing mice, complete tumor regression occurred within 14 days after single-dose IDP1-CNH/ICG administration combined with contact-mode laser irradiation, without recurrence or systemic toxicity. Overall, this study establishes IDP1 as versatile stealth biomaterials and demonstrates the synergistic potential of advanced NP design with innovative laser delivery systems for effective cancer therapy.
Alginate hydrogels are widely used as biocompatible carriers for controlled delivery, yet bulk triggering methods typically provide ensemble-averaged responses and limited control at the level of individual carriers. Redox-active cross-linking offers a route to electrochemical actuation because coordination strength and network rigidity can depend strongly on metal-ion oxidation state. In Fe-chelated alginate, Fe3+ forms rigid, cross-linked structures, whereas Fe2+ yields a viscous, liquid-like phase. These properties motivate electrochemical triggering strategies that convert Fe3+ to Fe2+ to modulate gel integrity and enable on-demand payload release. Herein, we demonstrate electrochemically controlled release of biomolecules (e.g., enzymes) from single microsized Fe-chelated alginate hydrogel particles upon collision with a biased indium tin oxide (ITO) electrode in aqueous solution. Guided by the Fe redox behavior in the slowly diffusing alginate matrix, microsized particles were employed to enable rapid, particle-scale conversion. Upon particle-electrode contact under cathodic bias, alginate-chelated Fe3+ within an individual particle is reduced to alginate-chelated Fe2+, leading to liquefaction of the hydrogel matrix and release of encapsulated biomolecules. A millimeter-scale ITO electrode served as the triggering electrode; its sub-nanoampere background current enabled clear resolution of discrete current spikes reporting rapid intra-particle electrolysis during collision events. Enzyme release was confirmed by an enzymatic reaction that generates a colorimetric precipitate in solution. This collision-triggered, electrochemical actuation scheme provides a reproducible platform for regulating biomolecule release from individual hydrogel carriers with electrical control. The low-background ITO configuration enables sensitive, real-time identification of single-particle triggering events and supports quantitative control by tuning the applied potential and actuation duration. This approach is promising for precision drug-delivery concepts and sensor-integrated release systems requiring controlled dosing and on-demand activation.
The development of highly selective coordination complexes requires a precise understanding of how electronic structure dictates ligand affinity. We employ density functional theory (DFT) and conceptual DFT (cDFT) to elucidate the structural and redox-driven mechanisms of diruthenium paddlewheel complexes. Our analysis reveals a critical electronic-structural switch: the cationic Ru(III)Ru(III) core is paradoxically the softest Lewis acid among all accessible redox states. This finding contravenes simple electrostatic predictions of the Hard and Soft Acids and Bases (HSAB) principle, demonstrating that the significant Ru-Ru bond contraction upon oxidation (from 2.24 Å to 2.19 Å) dominates the electronic structure, creating a highly polarizable Lewis acid center. This unique structural property dictates a pronounced thermodynamic affinity for soft nucleophiles like cysteine (Cys) and selenocysteine (Sec), yielding highly exergonic substitution energies of -33.3 and -26.6 kcal mol-1, respectively. We characterize this mechanism as a redox-gated thermodynamic trap, where the complex remains in a lower-affinity state until localized oxidation "switches on" the maximally potent Ru(III)Ru(III) form. Detailed frontier molecular orbital analysis confirms that the lowering of the dz2 orbital energy and the availability of empty dπ orbitals in the oxidized state enable superior σ-donation and π-acceptance. These results provide quantitative structural design principles, demonstrating that tuning the equatorial ligands to control oxidation potentials is key to ensuring site-specific activation and irreversible binding to soft biological targets.
Nanosecond electric pulses (NEP) are being explored as a novel bioelectric stimulus to modulate neurosecretion. Recently we reported that NEP trigger transient, voltage-gated Ca2+ channel-mediated Ca2+ influx in cultured murine adrenal chromaffin cells (ACC) expressing the genetically-encoded Ca2+ indicator GCaMP6f. The present study investigated ACC Ca2+ responses to NEP in acute adrenal slices from mice that expressed GCaMP6f in both ACC and satellite glial cells (SGC), as well as exclusively in SGC. Adrenal glands from male and female mice were sectioned into 100 μm slices that were placed in a chamber and perfused at a rate of 3-4 mL/min with a balanced salt solution maintained at 35°C. A custom-fabricated non-contact electrode delivered NEP ranging from 12 to 90 ns to a large area of the adrenal medulla. Our results show that a single 30 ns pulse elicited a rapid, transient rise in intracellular Ca2+ in ACC in situ. Like NEP-induced Ca2+ responses in cultured ACC, ACC Ca2+ responses in situ depended on extracellular Ca2+ and voltage-gated Ca2+ channel activation. The nicotinic receptor antagonist hexamethonium failed to inhibit these responses, indicating that NEP stimulation, in contrast to stimulation with conventional duration electrical pulses, activates ACC directly rather than indirectly through activation of splanchnic nerve terminals. Furthermore, NEP exposure of the adrenal medulla also resulted in Ca2+ increases in surrounding SGC that were slower in onset and longer in duration than those evoked by NEP in ACC. Finally, comparison of Ca2+ responses elicited by NEP trains in ACC in situ to those evoked by such trains in ACC in vitro revealed that the native tissue environment promotes more highly synchronized Ca2+ responses. Together, these results lay the foundation for future studies exploring the potential for NEP to modulate catecholamine release from ACC remotely and non-invasively in vivo.
Fluorogenic probes are highly useful tools for the detection of target molecules in chemical biology and (bio)material science, as they can often be applied in situ and do not depend on purification. Over the past years, a variety of alkyne-based fluorogenic probes have been proposed to detect azides, paving the way for live cell imaging and biomaterial analysis. Unfortunately, undesirable photophysical properties and poor solubility in aqueous solutions hamper the widespread use of these fluorogenic compounds. This work describes a water-soluble azide probe with high fluorescence enhancement (130-fold increase in intensity) upon reaction. We find accurate determination of azide densities on a polymer scaffold at low micromolar concentrations in PBS buffer. Additionally, by functionalizing the probe with biomolecules, we built a single-step (bio)molecule labeling and analysis vehicle. As proof of principle, a peptide was conjugated to polymer scaffolds and conversions could be accurately followed in situ. Altogether, our probe is a promising new chemical biology tool for analysis in physiological conditions.
Momentary feelings of safety carry significant implications for well-being in later life. Yet the role of social and built environments beyond residential neighborhoods remains underexplored. We investigated how dynamic social, physical features and spatial knowledge of activity spaces affect older adults' in situ feelings of safety. Using unique data from the Chicago Health and Activity in Real-Time (CHART) study, we analyzed 5,833 geolocated ecological momentary assessments (EMAs) from 93 older adults. We linked EMA locations to Google Street View Images to measure streetscape features and Advan mobility flows to capture spatial knowledge. We estimated race-stratified multilevel models with EMAs nested within respondents and used a within-between decomposition to distinguish momentary exposure from between-person differences in average exposure. Momentary safety varied substantially across contexts, with distinct racial patterns. Being outdoors reduced safety for both race groups. White respondents reported lower safety in areas predominantly Black and of low socioeconomic status (SES) but greater safety in racially mixed, higher-SES neighborhoods. In contrast, Black respondents felt less safe in racially mixed and affluent White neighborhoods, reflecting varied experiences of being socially out of place. Physical disorder and built-environment cues predicted safety only among Whites, indicating that the meaning of disorder is socially conditioned rather than universal. Across both groups, spatial knowledge consistently increased perceived safety. Findings underscore the situational and racialized nature of safety in later life. While White older adults' safety perceptions respond to visible streetscape cues, Black older adults' perceptions reflect broader structural and contextual neighborhood characteristics.
Methods for constructing polyubiquitin chains have greatly advanced our understanding of their structures, dynamics, and cellular functions. However, efficiently assembling multiple ubiquitin (Ub) units into well-defined chains with controlled lengths and distinct linkages under physiological conditions, while preserving the native three-dimensional structures of target proteins, remains a challenge. Addressing these issues would facilitate high-resolution characterization of dynamics and interactions of polyubiquitin chains involved in physiological processes using biophysical techniques. Herein, we report a versatile strategy for constructing multitype polyubiquitin chains via orthogonal ligation of expressed Ub units by combining 5-fluoro-4-(phenylsulfonyl)pyridine-2-carbonitrile (FPPN)-mediated consecutive protein-protein coupling with transulfurase-catalyzed protection and deprotection of the C-terminal cysteine. Both the thiol cross-ligation and the enzymatic protection-deprotection reactions rapidly proceed under physiological conditions with high conversion efficiency, enabling directional and controllable assembly of polyubiquitin chains. The approach allows the preparation of various homogeneous and mixed polyubiquitin chains with defined linkages and lengths, as well as branched polyubiquitin chains. Construction of polyubiquitin chains containing isotopically enriched Ub units and/or site-directed spin-labeled conjugates further demonstrates that this strategy permits high-resolution elucidation of polyubiquitin-chain conformations by NMR and EPR in solution and in situ, revealing that the conformational ensemble of K11/K48-branched Ub3 shifts toward a more compact state in the cellular environment. This work presents a robust and broadly applicable platform for constructing diverse ubiquitin chains and ubiquitinated proteins, facilitating in situ high-resolution characterization of polyubiquitin-associated structures, dynamics, and interactions.
The electrochemical conversion of CO2 into multi-carbon (C2+) products offers a promising route toward sustainable energy and carbon neutrality, but is hindered by inefficient C-C coupling, especially for C3 products. Here we show a Ni single atom/Cu single cluster catalyst (Ni SAC/Cu SCC) that achieves a total Faradaic efficiency (FE) of 84.1% for C2+ products (ethanol, ethylene glycol, and acetone) in a flow cell. The FE for acetone (a C3 product) reaches 48.8%. The high acetone selectivity on Ni SAC/Cu SCC is attributed to the synergistic interplay among in-tandem catalysis, the confinement effect, and in situ-formed Cu0/Cu+ sites. Mechanistically, CO spills over from Ni sites to adjacent Cu sites and is confined within the hierarchical pore structure of the reduced graphene oxide (rGO) support, resulting in high local CO coverage on Cu sites. Concurrently, the in situ-formed Cu0/Cu+ sites enhance adsorption of the key *CO intermediate. Together, this synergy lowers the energy barriers for C-C coupling. This work provides insights into the electrosynthesis of multi-carbon products.
The Na2S-MoO3-P2O5 glass is assessed as a positive electrode in a NaPF6-based electrolyte for sodium-ion batteries. Impedance and DC polarization measurements indicate mixed conduction with a Na+ transference number of 0.90 and a bulk conductivity of approximately 1.20 × 10-7 S m-1 at room temperature. In the Na half-cells, the electrode initially delivers more than 170 mAh g-1, followed by about 50% capacity decay after approximately 100 cycles. The remaining capacity is sustained for over 300 cycles. Ex situ SEM and EDS analyses highlight Na incorporation and partial extraction during cycling, with no evidence of microcrack formation. The Na/P atomic ratio increases upon discharge and partially returns to its initial value, consistent with the Na+ diffusion coefficient decreasing from 7.3 × 10-12 to 1.2 × 10-12 cm2 s-1 for the pristine sample and after the first cycle, respectively. This indicates the partial trapping of sodium ions within the disordered glass network structure, while ex situ XRD analysis reveals the formation of a stable crystalline sodium molybdate (Na2MoO4) phase on the cycled electrode surfaces. These findings suggest that the Na2S-MoO3-P2O5 glass is a cathode material with promising characteristics for the further development of sodium-ion batteries.
As a representative member of neonicotinoid insecticides, imidacloprid (IMI) has seen growing application in agricultural seed coating treatments, raising widespread concerns over its associated environmental accumulation and food chain contamination. Graphdiyne (GDY), an emerging star carbon nanomaterial following graphene, has demonstrated exceptional versatility in analytical sensing; however, its application for electrochemical detection of IMI remains unexplored. Herein, we reported the fabrication and systematic characterization of a novel electrochemical sensing platform based on graphdiyne-coated carbon nanotube (GDY/CNTs) nanohybrids, synthesized via a facile in-situ growth strategy, for sensitive IMI detection. Key operational parameters including PBS buffer pH and GDY/CNTs modification loading were systematically optimized to enhance sensing performance. Under optimal conditions, the GDY/CNTs sensor exhibited a wide linearity of 0.01-10 µM, with a low limit of detection of 3.2 nM and a high sensitivity of 1.4656 µA·µM-1. Importantly, the developed sensor achieved satisfactory recovery rates (≥ 95%) in real sample analysis, revealing its practical applicability. This work established a reliable GDY-based electrochemical approach for rapid, sensitive, and accurate IMI detection in complex matrices, expanding the analytical applications of GDY-based materials.
The rapid insurgence of antimicrobial resistance poses a critical threat to global health exacerbated by the dwindling supply of the effective arsenal of therapeutics. Nanomaterials provide alternative strategies by enabling novel antimicrobials that evade pathogens' intrinsic defense systems; yet their translation is constrained by complex synthesis, limited activity, and suboptimal invivo biocompatibility and efficacy. Silver-based systems rely on the release of Ag+ ions; however, achieving a controlled flux of Ag+ with therapeutic efficacy, stability, and biocompatibility remains a challenge. To circumvent this, we report a water-soluble polymeric biphasic Ag/AgCl nanocomposite (PBNP) synthesized via in situ nanoprecipitation and partial reduction by an inherently antibacterial quaternized thiolated chitosan polymer without using any external reducing agent. PBNP enables the controlled release of Ag+ ions over 10 days, demonstrating broad-spectrum antimicrobial activity, including the clearance of intracellular methicillin-resistant S. aureus (MRSA) infection, suppression of virulence factors and disruption of polymicrobial biofilm (MRSA and C. albicans), an outcome not achieved by conventional silver-based solutions. Additionally, PBNP reduced > 99.999% MRSA burden in murine skin infection without inducing dermal toxicity or genotoxicity when biocompatibility was assessed in zebrafish, emphasizing its potential as a therapeutic.
Aqueous zinc-ion batteries (AZIBs) possess distinct benefits in cost and safety, but bilateral interfacial failures on Zn anodes and MnO2 cathodes constrain their practical applications. Inspired by zymogen-to-enzyme activation, this work proposes a biomimetic, intelligent electrolyte additive strategy that enables on-demand protection on both electrodes. This strategy employs an inert additive, 1,4-butane sultone (BS), which preferentially adsorbs on the electrode surfaces. Upon water attack and localized pH increase, BS can be activated, generating open-ring derivatives (OBS) to facilitate the in situ construction of bilateral protective interphases with organic-inorganic composite components. Concurrently, it optimizes Zn2+ solvation structures to lower the desolvation energy barrier. Residual BS further traps SO4 2- and H2O and sustains the OBS formation for preventing interfacial alkalization. Consequently, the BS-modified Zn//Zn cell delivers a lifespan exceeding 4000 h, and the Zn//Cu cell attains an ultrahigh initial Coulombic efficiency of 97.62%. Zn//MnO2 full cells maintain capacity retention of 92.7% and 80.5% after 100 cycles at 0.2 A g-1 and 8000 cycles at 6 A g-1, respectively. Such a strategy not only delivers a high-performance electrolyte additive for AZIBs but also offers biomimetic inspiration for the development of electrolytes in other metal-based battery systems.