End-tidal carbon dioxide and arterial to end-tidal carbon dioxide gradient are associated with mortality in patients with neurological injuries.

Pre-hospital end-tidal carbon dioxide (EtCO2) monitoring and arterial to end-tidal carbon dioxide gradient (Pa-EtCO2) have been associated with mortality in patients with traumatic brain injury. Our study aimed to analyze the association between alveolar EtCO2 or Pa-EtCO2 and mortality in patients admitted in intensive care unit (ICU) with neurological injuries. In our retrospective analysis from using large de-identified ICU databases (MIMIC-III and -IV and eICU databases), we included 2872 ICU patients with neurological injuries, identified according to the International Classification of Diseases (ICD-9 and -10), who underwent EtCO2 monitoring. We performed logistic regression and extended Cox regression to assess the association between mortality and candidate covariates, including EtCO2 and Pa-EtCO2. In-hospital mortality was 26% (n = 747). In univariate analysis, both the Pa-EtCO2 gradient and EtCO2 levels during the first 24 h were significantly associated with mortality (for a 1 mmHg increase: OR = 1.03 [CI95 1.016-1.035] and OR = 0.94 [CI95 0.923-0.953]; p < 0.001). The association remained significant in multivariate analysis. The time-varying evolution of EtCO2 was independently associated with mortality (for a 1 mmHg increase: HR = 0.976 [CI95 0.966-0.985]; p < 0.001). The time-varying Pa-EtCO2 gradient was associated with mortality only in univariate analysis. In neurocritical patients, lower EtCO2 levels at admission and throughout the ICU stay were independently associated with mortality and should be avoided.

DEAD-box RNA helicase RH20 positively regulates RNAi-based antiviral immunity in plants by associating with SGS3/RDR6 bodies.

RNA silencing plays a crucial role in defending against viral infections in diverse eukaryotic hosts. Despite extensive studies on core components of the antiviral RNAi pathway such as DCLs, AGOs and RDRs proteins, host factors involved in antiviral RNAi remain incompletely understood. In this study, we employed the proximity labelling approach to identify the host factors required for antiviral RNAi in Nicotiana benthamiana. Using the barley stripe mosaic virus (BSMV)-encoded γb, a viral suppressor of RNA silencing (VSR), as the bait protein, we identified the DEAD-box RNA helicase RH20, a broadly conserved protein in plants and animals with a homologous human protein known as DDX5. We demonstrated the interaction between RH20 and BSMV γb. Knockdown or knockout of RH20 attenuates the accumulation of viral small interfering RNAs, leading to increased susceptibility to BSMV, while overexpression of RH20 enhances resistance to BSMV, a process requiring the cytoplasmic localization and RNA-binding activity of RH20. In addition to BSMV, RH20 also negatively regulates the infection of several other positive-sense RNA viruses, suggesting the broad-spectrum antiviral activity of RH20. Mechanistic analysis revealed the colocalization and interaction of RH20 with SGS3/RDR6, and disruption of either SGS3 or RDR6 undermines the antiviral function of RH20, suggesting RH20 as a new component of the SGS3/RDR6 bodies. As a counter-defence, BSMV γb VSR subverts the RH20-mediated antiviral defence by interfering with the RH20-SGS3 interaction. Our results uncover RH20 as a new positive regulator of antiviral RNAi and provide new potential targets for controlling plant viral diseases.

Effects of different VV ECMO blood flow rates on lung perfusion assessment by hypertonic saline bolus-based electrical impedance tomography.

OBJECTIVE: Our study aimed to investigate the effects of different extracorporeal membrane oxygenation (ECMO) blood flow rates on lung perfusion assessment using the saline bolus-based electrical impedance tomography (EIT) technique in patients on veno-venous (VV) ECMO. METHODS: In this single-centered prospective physiological study, patients on VV ECMO who met the ECMO weaning criteria were assessed for lung perfusion using saline bolus-based EIT at various ECMO blood flow rates (gradually decreased from 4.5 L/min to 3.5 L/min, 2.5 L/min, 1.5 L/min, and finally to 0 L/min). Lung perfusion distribution, dead space, shunt, ventilation/perfusion matching, and recirculation fraction at different flow rates were compared. RESULTS: Fifteen patients were included. As the ECMO blood flow rate decreased from 4.5 L/min to 0 L/min, the recirculation fraction decreased significantly. The main EIT-based findings were as follows. (1) Median lung perfusion significantly increased in region-of-interest (ROI) 2 and the ventral region [38.21 (34.93-42.16)% to 41.29 (35.32-43.75)%, p = 0.003, and 48.86 (45.53-58.96)% to 54.12 (45.07-61.16)%, p = 0.037, respectively], whereas it significantly decreased in ROI 4 and the dorsal region [7.87 (5.42-9.78)% to 6.08 (5.27-9.34)%, p = 0.049, and 51.14 (41.04-54.47)% to 45.88 (38.84-54.93)%, p = 0.037, respectively]. (2) Dead space significantly decreased, and ventilation/perfusion matching significantly increased in both the ventral and global regions. (3) No significant variations were observed in regional and global shunt. CONCLUSIONS: During VV ECMO, the ECMO blood flow rate, closely linked to recirculation fraction, could affect the accuracy of lung perfusion assessment using hypertonic saline bolus-based EIT.

Dead space volumes in cats and dogs with small body mass ventilated with a fixed tidal volume.

OBJECTIVE: To compare the portion of tidal volume (VT) ventilating dead space volumes in nonbrachycephalic cats and dogs with small body mass receiving volume-controlled ventilation (VCV) with a fixed VT. STUDY DESIGN: Prospective, experimental study. ANIMALS: A group of eight healthy adult cats and dogs [ideal body weight (IBW): 3.0 ± 0.5 and 3.8 ± 1.1 kg, respectively]. METHODS: Anesthetized cats and dogs received VCV with a 12 mL kg-1 VT (inspiratory pause ≥ 0.5 seconds). Respiratory rate (fR) was adjusted to maintain normocapnia. Airway dead space (VDaw) and alveolar tidal volume (VTalv) were measured by volumetric capnography. Physiological dead space (VDphys) and VDphys/VT ratio were calculated using the Bohr-Enghoff method. Data recorded before surgery were compared by an unpaired t-test or Mann-Whitney U test (p < 0.05 considered significant). RESULTS: The IBW (p = 0.07), PaCO2 (p = 0.40) and expired VT [VT(exp)] (p = 0.77) did not differ significantly between species. The VDaw (mL kg-1) was lower in cats (3.7 ± 0.4) than in dogs (7.7 ± 0.9) (p < 0.0001). The VTalv (mL kg-1) was larger in cats (8.3 ± 0.7) than in dogs (4.3 ± 0.7) (p < 0.0001). Cats presented a smaller VDphys/VT ratio (0.33 ± 0.03) and VDphys (4.0 ± 0.3 mL kg-1) than dogs (VDphys/VT: 0.60 ± 0.09; VDphys: 7.2 ± 1.4 mL kg-1) (p < 0.0001). The fR and minute ventilation (VT(exp) × fR) were lower in cats than in dogs (p = 0.048 and p = 0.038, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: A fixed VT results in more effective ventilation in cats than in dogs with small body mass because of species-specific differences in and VDaw and VDphys. Because of the smaller VDaw and VDphys in cats than in dogs, a lower fR is required to maintain normocapnia in cats.

Emergency nurses' experiences of caring for brought-in-dead persons and their relatives-a qualitative study.

AIM: To explore how emergency nurses experienced caring for brought-in-dead persons and their relatives, and what hindered or facilitated this care in an emergency setting. DESIGN: A qualitative study using Interpretive Description. METHODS: Data were collected as individual interviews with 13 nurses at seven Danish emergency departments from February to June 2023. FINDINGS: Our analysis revealed the overarching theme 'Navigating the complexities of providing holistic care in a constrained environment', covering five sub-themes: (1) An important yet not recognized nursing task; (2) Pending care needs of the living and the dead; (3) No physical or mental room for the brought-in-dead persons; (4) Utilizing personal experiences in the absence of formal education and training and (5) Navigating professionalism and empathy. CONCLUSION: Emergency departments posed unique challenges in providing care to brought-in-dead persons and their relatives. IMPLICATIONS FOR THE PROFESSION: The unrecognized nature of caring for brought-in-dead persons and their relatives suggests a universal undervaluation of this care in emergency departments. IMPACT: Care for brought-in-dead persons and their relatives is neither recognized nor evidence-based. This study initiates a discussion of the circumstances for delivering care for persons brought-in-dead and has an impact on nurses and nursing leaders employed in emergency departments. REPORTING METHOD: The Consolidated Criteria for Reporting Qualitative Research (COREQ). PATIENT OR PUBLIC CONTRIBUTION: None.

Step Length Estimation for Blind Walkers.

Wayfinding systems using inertial data recorded from a smartphone carried by the walker have great potential for increasing mobility independence of blind pedestrians. Pedestrian dead-reckoning (PDR) algorithms for localization require estimation of the step length of the walker. Prior work has shown that step length can be reliably predicted by processing the inertial data recorded by the smartphone with a simple machine learning algorithm. However, this prior work only considered sighted walkers, whose gait may be different from that of blind walkers using a long cane or a dog guide. In this work, we show that a step length estimation network trained on data from sighted walkers performs poorly when tested on blind walkers, and that retraining with data from blind walkers can dramatically increase the accuracy of step length prediction.

Completing the Circle: A History of Psychedelics and Harm Reduction.

Harm reduction officially entered the public health lexicon in the 1980s as a response to the HIV/AIDS crisis and its spread amongst intravenous drug users, but risk prevention has been an important part of psychedelic consumption in ways that predate this formal conceptualization.We look at psychedelic drug trials in the 1950s and 1960s to consider how people-first perspectives informed those early clinical studies, and how pioneering psychedelic researchers themselves approached risk management at a time that predates the formal recognition of harm reduction. Next, we follow psychedelic drugs out of the clinic and into music scenes and festivals that proliferated during the war on the drugs, where community-based organizations stepped up to support music fans who chose to combine psychoactive substances with dancing and drugs at all-day festivals. Finally, we reflect on the longer history and traditions of the Native American Church as one specific example of how Indigenous ceremonies involving psychedelic substances combined spirituality and healing in a community setting curated to promote wellness. Ultimately, we argue that psychedelic risk management has deep historical roots in psychedelic communities representing biomedical, cultural, and Indigenous perspectives - we might heed these historical lessons as we consider how to promote sustainable risk management strategies with psychedelics going forward.

SCI1, a flower regulator of cell proliferation, and its partners NtCDKG2 and NtRH35 interact with the splicing machinery.

Successful plant reproduction depends on the adequate development of flower organs controlled by cell proliferation and other processes. The SCI1 gene regulates cell proliferation and affects the final size of the female reproductive organ. To unravel the molecular mechanism exerted by SCI1 in cell proliferation control, we searched for its interaction partners through semi-in vivo pulldown experiments, uncovering a cyclin-dependent kinase, NtCDKG;2. Bimolecular fluorescence complementation (BiFC) and co-localization experiments showed that SCI1 interacts with NtCDKG;2 and its cognate NtCyclin L in nucleoli and splicing speckles. The screening of a yeast two-hybrid (Y2H) cDNA library using SCI1 as bait revealed a novel DEAD-box RNA helicase (NtRH35). The interaction between the NtCDKG;2-NtCyclin L complex, and NtRH35 was also shown. Subcellular localization experiments showed that SCI1, NtRH35, and the NtCDKG;2-NtCyclin L complex associate with each other within splicing speckles. The Y2H screening of NtCDKG;2 and NtRH35 identified the conserved spliceosome components U2a', NKAP, and CACTIN. This work presents SCI1 and its interactors NtCDKG;2-NtCyclin L complex, and NtRH35 as new spliceosome-associated proteins. Our findings reveal a network of interactions and suggest that SCI1 may regulate cell proliferation through the splicing process. This study provides new valuable insights into the intricate molecular pathways governing plant development.

Nonlinear adaptive robust control of tank bidirectional stabilizers with dead zone compensation based on extended state observer.

In this paper, the problem of highly performance motion control of tank bidirectional stabilizer with dead zone nonlinearity and uncertain nonlinearity is addressed. First, the electromechanical coupling dynamics model of bidirectional stabilizer is developed finely. Second, the dead zone nonlinearity in bidirectional stabilizer is characterized as the combination of an uncertain time-varying gain and a bounded disturbance term. Meanwhile, an adaptive robust controller with dead zone compensation is proposed by organically combining adaptive technique and extended state observer (ESO) through backstepping method. The adaptive technique is employed to reduce the impact of unknown system parameter and dead zone parameter. Furthermore, the ESO is constructed to compensate the lumped uncertainties including unmodeled dynamics and dead zone residual, and integrated together via a feedforward cancellation technique. Moreover, the adaptive robust control law is derived to ensure final global stability. In stability analysis, the asymptotic tracking performance of the proposed controller can be guaranteed as the uncertainty nonlinearities in tank bidirectional stabilizer are constant. It is also guaranteed to achieve bounded tracking performance when time-varying uncertainties exist. Extensive co-simulation and experimental results verify the superiority of the proposed strategy.

In Defense of Normothermic Regional Perfusion.

Normothermic regional perfusion (NRP) is a relatively new approach to procuring organs for transplantation. After circulatory death is declared, perfusion is restored to either the thoracoabdominal organs (in TA-NRP) or abdominal organs alone (in A-NRP) using extracorporeal membrane oxygenation. Simultaneously, surgeons clamp the cerebral arteries, causing a fatal brain injury. Critics claim that clamping the arteries is the proximate cause of death in violation of the dead donor rule and that the procedure is therefore unethical. We disagree. This account does not consider the myriad other factors that contribute to the death of the donor, including the presence of a fatal medical condition, the decision to withdraw life support, and the physician's actions in withdrawing life support and administering medication that may hasten death. Instead, we claim that physicians play a causative role in many of the events that lead to a patient's death and that these actions are often ethically and legally justified. We advance an "all things considered" view according to which TA-NRP may be considered ethically acceptable insofar as it avoids suffering and respects the wishes of the patient to improve the lives of others through organ donation. We conclude with a series of critical questions related to the practice of NRP and call for the development of national consensus on this issue in the United States.

Human RNA Polymerase II Segregates from Genes and Nascent RNA and Transcribes in the Presence of DNA-Bound dCas9.

RNA polymerase II (Pol II) dysfunction is frequently implied in human disease. Understanding its functional mechanism is essential for designing innovative therapeutic strategies. To visualize its supra-molecular interactions with genes and nascent RNA, we generated a human cell line carrying ~335 consecutive copies of a recombinant ß-globin gene. Confocal microscopy showed that Pol II was not homogeneously concentrated around these identical gene copies. Moreover, Pol II signals partially overlapped with the genes and their nascent RNA, revealing extensive compartmentalization. Using a cell line carrying a single copy of the ß-globin gene, we also tested if the binding of catalytically dead CRISPR-associated system 9 (dCas9) to different gene regions affected Pol II transcriptional activity. We assessed Pol II localization and nascent RNA levels using chromatin immunoprecipitation and droplet digital reverse transcription PCR, respectively. Some enrichment of transcriptionally paused Pol II accumulated in the promoter region was detected in a strand-specific way of gRNA binding, and there was no decrease in nascent RNA levels. Pol II preserved its transcriptional activity in the presence of DNA-bound dCas9. Our findings contribute further insight into the complex mechanism of mRNA transcription in human cells.

The Impact of Early Brain-Dead Donor Detection in the Emergency Department on the Organ Donation Process in Iran.

We aimed to assess the impact of hospital characteristics on the outcomes of detected possible brain-dead donors, in our organ procurement network in Iran. Data was collected through twice-daily calls with 57 hospitals' intensive care units and emergency departments over 1 year. The donation team got involved when there was suspicion of brain death before the hospital officially declared it. The data was categorized by hospital size, presence of neurosurgery/trauma departments, ownership, and referral site. Out of 813 possible donors, 315 were declared brain dead, and 203 were eligible for donation. After conducting family interviews (consent rate: 62.2%), 102 eligible donors became actual donors (conversion rate: 50.2%). While hospital ownership and the presence of trauma/neurosurgery care did not affect donation, early referral from the emergency department had a positive effect. Therefore, we strongly recommend prioritizing possible donor identification in emergency rooms and involving the organ donation team as early as possible. The use of twice-daily calls for donor identification likely contributed to the consistency in donation rates across hospitals, as this approach involves the donation team earlier and mitigates the impact of hospital characteristics. Early detection of possible donors from the emergency department is crucial in improving donation rates.

Essential functions of RNA helicase Vasa in maintaining germline stem cells and piRNA-guided Stellate silencing in Drosophila spermatogenesis.

DEAD-box RNA helicase Vasa is required for gonad development and fertility in multiple animals. Vasa is implicated in many crucial aspects of Drosophila oogenesis, including translation regulation, primordial germ cell specification, piRNA silencing of transposable elements, and maintenance of germline stem cells (GSCs). However, data about Vasa functions in Drosophila spermatogenesis remain controversial. Here we showed that loss-of-function vasa mutations led to failures of GSC maintenance in the testes, a severe loss of total germ cell content, and a cessation of male fertility over time. Defects in GSC maintenance in vasa mutant testes were not associated with an increasing frequency of programmed cell death, indicating that a premature loss of GSCs occurred via entering differentiation. We found that Vasa is implicated in the positive regulation of rhino expression both in the testes and ovaries. The introduction of a transgene copy of rhino, encoding a nuclear component of piRNA pathway machinery, in vasa mutant background allowed us to restore premeiotic stages of spermatogenesis, including the maintenance of GSCs and the development of spermatogonia and spermatocytes. However, piRNA-guided repression of Stellate genes in spermatocytes of vasa mutant testes with additional rhino copy was not restored, and male fertility was disrupted. Our study uncovered a novel mechanistic link involving Vasa and Rhino in a regulatory network that mediates GSC maintenance but is dispensable for the perfect biogenesis of Su(Ste) piRNAs in testes. Thus, we have shown that Vasa functions in spermatogenesis are essential at two distinct developmental stages: in GSCs for their maintenance and in spermatocytes for piRNA-mediated silencing of Stellate genes.

Multifunctional role of DEAD-box helicase 41 in innate immunity, hematopoiesis and disease.

DEAD-box helicases are multifunctional proteins participating in many aspects of cellular RNA metabolism. DEAD-box helicase 41 (DDX41) in particular has pivotal roles in innate immune sensing and hematopoietic homeostasis. DDX41 recognizes foreign or self-nucleic acids generated during microbial infection, thereby initiating anti-pathogen responses. DDX41 also binds to RNA (R)-loops, structures consisting of DNA/RNA hybrids and a displaced strand of DNA that occur during transcription, thereby maintaining genome stability by preventing their accumulation. DDX41 deficiency leads to increased R-loop levels, resulting in inflammatory responses that likely influence hematopoietic stem and progenitor cell production and development. Beyond nucleic acid binding, DDX41 associates with proteins involved in RNA splicing as well as cellular proteins involved in innate immunity. DDX41 is also a tumor suppressor in familial and sporadic myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML). In the present review, we summarize the functions of DDX helicases in critical biological processes, particularly focusing on DDX41's association with cellular molecules and the mechanisms underlying its roles in innate immunity, hematopoiesis and the development of myeloid malignancies.

Revitalizing Dead Zinc with Ferrocene/Ferrocenium Redox Chemistry for Deep-Cycle Zinc Metal Batteries.

Aqueous zinc (Zn) batteries are highly desirable for sustainable and large-scale electrochemical energy storage technologies. However, the ceaseless dendrite growth and the derived dead Zn are principally responsible for the capacity decay and insufficient lifespan. Here, we propose a dissolved oxygen-initiated revitalization strategy to reactivate dead Zn via ferrocene redox chemistry, which can be realized by incorporating a trace amount of poly(ethylene glycol) as a solubilizer to improve the solubility of water-insoluble ferrocene derivatives. Ferrocene scaffold can be spontaneously oxidized to ferricenium cations by dissolved oxygen, which eradicates the dissolved oxygen-involved Zn corrosion and insulating by-product generation. Subsequently, the generated ferricenium cations as the scavenger can rejuvenate electrically isolated dead Zn into electroactive Zn2+ ions to compensate the zinc loss. Through this design, the symmetric cell exhibited improved cycle life of 3700 h at 10 mA cm-2, and 220 h under a high depth of discharge of 80%. Importantly, the Zn||NaV3O8·1.5H2O full cells demonstrated the impressive cycling stability over 1000 cycles at a low N/P ratio of 3.0. This work presents an innovative solution for the revitalization of dead Zn to extend the lifespan of deep-cycling metal batteries.

Elucidating the Mechanism of Electro-Adsorption on Electrically Conductive Ultrafiltration Membranes via Modified Poisson-Boltzmann Equation.

Electrically conductive membranes (ECMs) were prepared by coating porous ethylenediamine-modified polyacrylonitrile (PAN-EDA) UF membranes with an ultrathin layer of platinum (Pt) nanoparticles through magnetron sputtering. These ECMs were used in electrofiltration to study the removal of brilliant blue dye from an aqueous solution under positive electrical potentials (0-2.5 V). Negative electrical potentials (-1.0--2.5 V) were also investigated to regenerate the membrane by desorbing the dye from the ECM surface. At +0 V, the EC PAN-EDA membrane adsorbed the dye due to its intrinsic positive charge. Application of -2.0 V resulted in a maximum of 39% desorption of the dye. A modified Poisson-Boltzmann (MPB) model showed that -2.0 V created a repulsive force within the first 24 nm of the membrane matrix, which had a minimal effect on dye ions adsorbed deeper within the membrane, thus limiting the electro-desorption efficiency to 39%. Moreover, increasing positive potentials from +0.5 V to +2.5 V led to increased dye electro-adsorption by 9.5 times, from 132 mg/m2 to 1112 mg/m2 at pH 8 (equivalent to the membrane's isoelectric point). The MBP simulations demonstrated that increasing electro-adsorption loadings are related to increasing attractive force, indicating electro-adsorption induced by attractive force is the dominant mechanism and the role of other mechanisms (e.g., electrochemical oxidation) is excluded. At pH 5, electro-adsorption further increased to 1390 mg/m2, likely due to the additional positive charge of the membrane (zeta potential = 9.2 mV) compared to pH 8. At pH 8, complete desorption of the dye from the ECM surface was achieved with a significant repulsive force at -2.0 V. However, as pH decreased from 8 to 5, the desorption efficiency decreased by 3.9% due to the membrane's positive charge. These findings help elucidate the mechanisms of electro-adsorption and desorption on ECMs using dye as a model for organic compounds like humic acids.

Preparation and characterization of structural and antifouling properties of chitosan/polyethylene oxide membranes.

It aims to prepare the chitosan (CS) and polyethylene oxide (PEO) hydrogel membranes with different CS/PEO blend ratios (100:0, 95:5, 90:10, 80:20 and 70:30) via solvent casting. The physicochemical properties of these membranes were investigated using various characterization techniques: Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive X-ray (EDX), contact angle, and tensile testing. The interaction of PEO and chitosan was investigated by DSC in terms of freezing bound, freezing free, and non-freezing PEO fraction. The cross-sectional surface morphology of membranes displayed a smoother surface with increasing PEO content up to 20 %, beyond which nonhomogeneity on the surface was visible. The antifouling behavior of membranes was investigated by bacterial adherence study, which showed an enhanced antifouling nature of membranes with the increase in the PEO content. The peeling strength of the membranes was measured using a 90° angle peeling test, and it was found that 20 % and more PEO content promotes easy removal from the gelatin slab. In addition to this, live/ dead assay of the CS was performed to visualize the presence of live and dead bacteria on the surface. The CS/PEO blend with 20 % PEO content has properties makes it suitable for use as a protective layer on wound dressings to prevent bacterial growth. It's use in wound dressings has the potential to reduce the pain during the time of dressing removal and improve patient outcomes. The present investigation leads to the development of a CS hydrogel matrix which exhibits very interesting interaction with the PEO moiety along with its innovative feature of antifouling and antimicrobial nature.

Rescue of dead MnO2 for stable electrolytic Zn-Mn redox-flow battery: a metric of mediated and catalytic kinetics.

The virtues of electrolytic MnO2 aqueous batteries are high theoretical energy density, affordability and safety. However, the continuous dead MnO2 and unstable Mn2+/MnO2 electrolysis pose challenges to the practical output energy and lifespan. Herein, we demonstrate bifunctional cationic redox mediation and catalysis kinetics metrics to rescue dead MnO2 and construct a stable and fast electrolytic Zn-Mn redox-flow battery (eZMRFB). Spectroscopic characterizations and electrochemical evaluation reveal the superior mediation kinetics of a cationic Fe2+ redox mediator compared with the anionic ones (e.g. I- and Br-), thus eliminating dead MnO2 effectively. With intensified oxygen vacancies, density functional theory simulations of the reaction pathways further verify the concomitant Fe-catalysed Mn2+/MnO2 electrolysis kinetics via charge delocalization and activated O 2p electron states, boosting its rate capability. As a result, the elaborated eZMRFB achieves a coulombic efficiency of nearly 100%, ultra-high areal capacity of 80 mAh cm-2, rate capability of 20 C and a long lifespan of 2500 cycles. This work may advance high-energy aqueous batteries to next-generation scalable energy storage.