Quantitative Proteomics Explore the Potential Targets and Action Mechanisms of Hydroxychloroquine.

Hydroxychloroquine (HCQ) is an autophagy inhibitor that has been used for the treatment of many diseases, such as malaria, rheumatoid arthritis, systemic lupus erythematosus, and cancer. Despite the therapeutic advances in these diseases, the underlying mechanisms have not been well determined and hinder the rational use of this drug in the future. Here, we explored the possible mechanisms and identified the potential binding targets of HCQ by performing quantitative proteomics and thermal proteome profiling on MIA PaCa-2 cells. This study revealed that HCQ may exert its functions by targeting some autophagy-related proteins such as ribosyldihydronicotinamide dehydrogenase (NQO2) and transport protein Sec23A (SEC23A), or regulating the expression of galectin-8 (LGALS8), mitogen-activated protein kinase 8 (MAPK8), and so on. Furthermore, HCQ may prevent the progression of pancreatic cancer by regulating the expression of nesprin-2 (SYNE2), protein-S-isoprenylcysteine O-methyltransferase (ICMT), and cotranscriptional regulator FAM172A (FAM172A). Together, these findings not only identified potential binding targets for HCQ but also revealed the non-canonical mechanisms of HCQ that may contribute to pancreatic cancer treatment.

Controlled 2H/1T phase transition in MoS2 monolayers by a strong interface with M2C MXenes: a computational study.

Due to the high conductivity and abundant active sites, the metallic 1T phase of a two-dimensional molybdenum sulfide monolayer (1T-MoS2) has witnessed a broad range of potential applications in catalysis, and spintronic and phase-switching devices, which, however, are greatly hampered by its poor stability. Thus, the development of particular strategies to realize the phase transition from the stable 2H phase to the metastable 1T phase for MoS2 nanosheets is highly desirable. Herein, by means of density functional theory (DFT) computations, we systematically explored the potential of the interfacial interaction of 2H- and 1T-MoS2 monolayers with a series of M2C MXenes (M = Ti, V, Cr, Zr, Nb, Mo, Hf, Ta, and W) for achieving the 2H/1T phase transformation. Our results revealed that the 2H → 1T transition for MoS2 monolayers can occur thermodynamically by anchoring on Ti2C, Zr2C, or Hf2C substrates with the extremely strong metal-S interaction, which can be well rationalized by the analysis of the charge transfer, work function, and density of states. Specially, these obtained stable 1T-MoS2/M2C hybrid materials exhibit excellent metallic features, outstanding magnetism, and enhanced mechanical properties. Our findings provide a new avenue to tune the phase transformation for MoS2 monolayers by strong interfacial interactions, which helps to further widen the potential applications of MoS2 monolayers.

Rheological and microstructural characterization of wheat dough formulated with konjac glucomannan.

BACKGROUND: This work aimed to investigate the effects of different levels of konjac glucomannan (KGM) on the thermomechanical and pasting properties, water distribution, gelatinization, texture, and microstructural characteristics of wheat flour and dough. RESULTS: The thermomechanical properties assessed with a Mixolab showed that KGM could increase the water absorption and degree of softening and decrease the stability time of wheat dough. In addition, wheat flour starch with KGM underwent significant (P < 0.05) gelatinization changes according to the rapid viscosity analyzer and differential scanning calorimetry results. These results demonstrated that KGM enhanced the thermal stability and anti-aging capacity of wheat flour. All doughs with KGM exhibited viscoelastic behavior but lower hardness and gumminess. Low-field nuclear magnetic resonance showed that water, with a tight binding force, migrated to the weaker binding forces in the dough. A noticeable disruption of the gluten network was observed at the highest level of KGM. However, an intermediate level of KGM addition (10 or 15 g kg-1 flour) still rendered dough with satisfactory properties. CONCLUSION: A certain amount of KGM could enhance the thermal stability and anti-aging ability of wheat flour, improve the viscoelastic behavior, and decrease the hardness and gumminess of dough. In general, the mixing of flour and dough with KGM addition of 10 or 15 g kg-1 flour was of good quality. © 2021 Society of Chemical Industry.

Tuning the electronic structures of monolayer triphosphides MP3 (M = Sn and Ge) for CO2 electroreduction through interface engineering: a theoretical prediction.

Interface engineering by integrating various two-dimensional materials to form heterostructures can not only preserve the desired properties of individual components, but also induce new functions. Herein, by means of density functional theory (DFT) computations, we have investigated the effects of interface engineering of the graphene substrate on the electronic structures of monolayer triphosphides MP3 (M = Sn and Ge) and their catalytic performance for the electroreduction of carbon dioxide (CO2ER). Our results revealed that the MP3/graphene interfaces exhibit good structural stability, enhanced electrical conductivity, superior CO2ER performance, and obvious suppressing effects on hydrogen evolution due to the charge transfer at the interface. Thus, our results suggested that SnP3/graphene and GeP3/graphene heterostructures can be utilized as promising CO2ER catalysts with high-efficiency and high-selectivity, offering cost-effective opportunities to convert CO2 for renewable energy supply via interface engineering.

PtN3-Embedded graphene as an efficient catalyst for electrochemical reduction of nitrobenzene to aniline: a theoretical study.

The electrochemical reduction of nitrobenzene (NBER) holds great promise for not only removing toxic pollutants, but also producing valuable aniline, in which the development of catalysts with high-efficiency still remains a huge challenge. In this work, by means of density functional theory (DFT) computations, we proposed several single transition metal (TM) atoms embedded into the single vacancy of graphene with nitrogen-doping (TMN3/G, TM = Ni, Cu, Pd, and Pt) as the catalysts for NBER. Our results revealed that, among these candidates, PtN3/G is the most active catalyst for the NBER due to its smallest limiting potential (-0.21 V), in which the hydrogenation of Ph-NO2* to Ph-NOOH* is identified as the potential-determining step. Compared with other catalysts, the strongest binding strength of Ph-NOOH* with PtN3/G is responsible for its superior catalytic activity towards NBER, which can be deeply understood on the basis of the corresponding electronic structure analysis. Thus, PtN3/G is a quite promising single-atom-catalyst with high efficiency for nitrobenzene reduction, which provides a rational paradigm for converting harmful nitrobenzene to valuable aniline under ambient conditions.

Single transition metal atoms anchored on a C2N monolayer as efficient catalysts for hydrazine electrooxidation.

Searching for highly-efficient and low-cost electrocatalysts for the hydrazine oxidation reaction (HzOR) is a key issue in the development of direct hydrazine fuel cells for hydrogen production, which is a promising energy-efficient conversion technology to replace the sluggish oxygen evolution reaction in water splitting. Herein, the potential of a series of single transition metal atoms anchored on nitrogenated holey graphene (TM@C2N, TM = Ti, Mn, Fe, Co, Ni, Cu, Mo, Rh, Ru, Pd, Pt, Au, Ag, and W) as catalysts for the HzOR was systematically explored by means of comprehensive density functional theory (DFT) computations. Our results revealed that these TM atoms anchored on a C2N monolayer exhibit high stability due to their strong interactions with the N atoms on the C2N monolayer. Furthermore, on the basis of the computed free energy profiles, Ru@C2N, Mo@C2N, Ti@C2N, Co@C2N, and Fe@C2N were shown to display high HzOR catalytic activity due to their lower (or comparable) limiting potential compared to the well-established Fe-doped CoS2 nanosheet. In particular, Ru@C2N is identified as the best catalyst with the lowest limiting potential of -0.24 V due to its optimum difference between the adsorption strength of N2H3* and N2H2* species. More interestingly, we found that single Mo and Ti atoms also exhibit excellent catalytic performance for the hydrogen evolution reaction, suggesting their bifunctional activity towards hydrazine splitting for H2 production. Our findings provide a new avenue to develop an efficient single-atom electrocatalyst for experimental validation to convert hydrazine into hydrogen.

Optimal Configuration of N-Doped Carbon Defects in 2D Turbostratic Carbon Nanomesh for Advanced Oxygen Reduction Electrocatalysis.

The charge redistribution strategy driven by heteroatom doping or defect engineering has been developed as an efficient method to endow inert carbon with significant oxygen reduction reaction (ORR) activity. The synergetic effect between the two approaches is thus expected to be more effective for manipulating the charge distribution of carbon materials for exceptional ORR performance. Herein we report a novel molecular design strategy to achieve a 2D porous turbostratic carbon nanomesh with abundant N-doped carbon defects (NDC). The molecular level integration of aromatic rings as the carbon source and urea units as the N source and sacrificial template into the novel precursor of polyurea (PU) promises the formation of abundant carbon edge defects and N doping sites. A special active site-a carbon edge defect doped with a graphitic valley N atom-was revealed to be responsible for the exceptional ORR performance of NDC material.

Cryopreserved platelets augment the inflammatory response: role of phosphatidylserine- and P-selectin-mediated platelet phagocytosis in macrophages.

BACKGROUND: Cryopreservation in dimethyl sulfoxide and storage at -80 °C extends the shelf life of platelets to at least 2 years, allowing greater availability in rural and military areas. While cryopreserved platelets (CPPs) have been extensively characterized for coagulation and thrombin generation, reports on the mechanism of adverse reactions to CPPs transfusion are scarce. Here, we tested the hypothesis that CPPs facilitate phagocytosis by Kupffer cells and subsequently promote the inflammatory response in Kupffer cells. STUDY DESIGN AND METHODS: P-selectin expression, glycoprotein Ibα clustering and phosphatidylserine (PS) surface exposure on platelets stored at 22 °C, 4 °C and - 80 °C for 3 days were examined by flow cytometry. The phagocytosis of mepacrine-labeled platelets coincubated with THP-1 cells was examined by flow cytometry and confocal microscopy, and the release of cytokines from THP-1 cells was measured by enzyme-linked immunosorbent assay. RESULTS: CPPs showed a marked enhancement of exposed PS but dramatically reduced glycoprotein Ibα expression and clustering compared with platelets stored at 4 °C. Activation of THP-1 cells was stronger by CPPs than by platelets stored at 22 °C and 4 °C. CPP interference tests using annexin V and anti-P-selectin showed that CPPs induced increases in PS- and P-selectin-mediated phagocytosis, as well as secretion of the proinflammatory cytokine tumor necrosis factor-α, and interleukins IL-1ß and IL-6, but a decrease in transforming growth factor-ß production in THP-1 cells. Surface-exposed PS was more effective than P-selectin for the activation of THP-1 cells. CONCLUSION: CPPs triggered PS and P-selectin-mediated phagocytosis by macrophages and stimulated the inflammatory response of macrophages.

Acute high-altitude exposure shortens survival after uncontrolled hemorrhagic shock in rats.

BACKGROUND: Uncontrolled hemorrhage (UH) remains the most common cause of death on the battlefield. This study examined the pathophysiological characteristics of UH in rats acutely exposed to high altitude. MATERIAL AND METHODS: Rats raised at sea level were randomly divided into two groups. Rats in the high-altitude group were exposed to hypobaric hypoxia in a hypobaric chamber (simulating 4000 m above sea level) for 2 d and then were performed a hemorrhagic shock protocol in the hypobaric chamber. Rats that underwent the same hemorrhage procedure at sea level were used as control. Anesthetized rats were bled to maintain their mean arterial pressure at 45 mmHg for 1 h. The distal quarter of the tail was amputated to allow free blood loss. After 1 h, the tail cut was ligated to induce hemostasis. mean arterial pressure, acid-base balance, blood loss, and survival were recorded. Rats were killed, and tissues were obtained for histological analysis. RESULTS: Rats in the high-altitude group suffered less uncontrolled blood loss, more severe acidosis (lower pH and base excess), and inferior tissue oxygen supply (lower oxygen saturation and higher arterial lactate concentration) during the hemorrhage periods compared with the control group. Survival rates were significantly lower in the high-altitude group than those in the control group (P < 0.05), which was consistent with the results of pathological tissue injury. CONCLUSIONS: In this rat model of hemorrhagic shock, acute high-altitude exposure resulted in decreased UH but more serious hemorrhagic shock injuries than that at sea level.

Computational screening of a single transition metal atom supported on the C2N monolayer for electrochemical ammonia synthesis.

The nitrogen reduction reaction (NRR) under ambient conditions using renewable energy is a green and sustainable strategy for the synthesis of NH3, which is one of the most important chemicals and carbon-free carriers. Thus, the search for low-cost, highly efficient, and stable NRR electrocatalysts is critical to achieve this goal. Herein, using comprehensive density functional theory (DFT) computations, we design a new class of NRR electrocatalysts based on a single transition metal (TM) atom supported on the experimentally feasible two-dimensional C2N monolayer (TM@C2N). Based on the computed free energies of each elementary pathway, Mo@C2N is predicted to exhibit the best catalytic activity among the TM@C2N, in which the proton-coupled electron transfer of the NH2* species to NH3(g) is the potential-determining step. Especially, the computed onset potential of the NRR on Mo@C2N is -0.17 V, which is even lower than that for the well-established stepped Ru(0001) surface (-0.43 V). Furthermore, the NRR catalytic performance of these TM@C2N can be well explained by their adsorption strength with N2H* species. Our findings open a new avenue for optimizing the TM catalytic performance for the NRR with the lowest number of metal atoms on porous low-dimensional materials.

Single transition metal atom embedded into a MoS2 nanosheet as a promising catalyst for electrochemical ammonia synthesis.

The electrochemical reduction of N2 to NH3 (NRR) under ambient conditions is significant for sustainable agriculture. Here, by means of density functional theory (DFT) computations, the potential of a series of single transition metal (TM) atoms embedded into a MoS2 monolayer with an S-vacancy (TM/MoS2) as electrocatalysts for NRR was systematically investigated. Our DFT results revealed that among all these considered candidate catalysts, the single Mo atom embedded into the MoS2 nanosheet was found to be the most active catalyst for NRR with an onset potential of -0.53 V, in which the hydrogenation of the adsorbed N2* to N2H* is the potential-determining step. The high stabilization of the N2H* species is responsible for the superior performance of the embedded Mo atom for the NRR, which is well consistent with its d-band center. Our findings may facilitate the further design of single-atom electrocatalysts with high efficiency for NH3 synthesis at room temperature.

Single Mo Atom Supported on Defective Boron Nitride Monolayer as an Efficient Electrocatalyst for Nitrogen Fixation: A Computational Study.

The production of ammonia (NH3) from molecular dinitrogen (N2) under mild conditions is one of the most attractive and challenging processes in chemistry. Here by means of density functional theory (DFT) computations, we systematically investigated the potential of single transition metal atoms (Sc to Zn, Mo, Ru, Rh, Pd, and Ag) supported on the experimentally available defective boron nitride (TM-BN) monolayer with a boron monovacancy as a N2 fixation electrocatalyst. Our computations revealed that the single Mo atom supported by a defective BN nanosheet exhibits the highest catalytic activity for N2 fixation at room temperature through an enzymatic mechanism with a quite low overpotential of 0.19 V. The high spin-polarization, selective stabilization of N2H* species, or destabilizing NH2* species are responsible for the high activity of the Mo-embedded BN nanosheet for N2 fixation. This finding opens a new avenue of NH3 production by single-atom electrocatalysts under ambient conditions.

CO2 electroreduction performance of a single transition metal atom supported on porphyrin-like graphene: a computational study.

Searching for low-cost, efficient, and stable electrocatalysts for CO2 electroreduction (CO2ER) reactions is highly desirable for the reduction of CO2 emission and its conversion into useful products, but remains a great challenge. In this work, single transition metal atoms supported on porphyrin-like graphene catalysts, i.e., TMN4/graphene, acting as electrocatalysts for CO2 reduction were explored by means of comprehensive density functional theory (DFT) computations. Our results revealed that these anchored TM atoms possess high stability due to their strong hybridization with the unsaturated N atoms of the substrate and function as the active sites. On the basis of the calculated adsorption strength of CO2ER intermediates, we have identified that single Co, Rh, and Ir atoms exhibit superior catalytic activity towards CO2 reduction. In particular, CH3OH is the preferred product of CO2ER on the CoN4/graphene catalyst with an overpotential of 0.59 V, while the RhN4/graphene and IrN4/graphene catalysts prefer to reduce CO2 to CH2O with an overpotential of 0.35 and 0.29 V, respectively. Our work may open a new avenue for the development of catalytic materials with high efficiency for CO2 electroreduction.

How to make inert boron nitride nanosheets active for the immobilization of polysulfides for lithium-sulfur batteries: a computational study.

The search for effective anchoring nanomaterials for the immobilization of soluble lithium polysulfide (Li2Sn) species to suppress their shuttling effect has been a key scientific issue for the large-scale practical application of lithium-sulfur (Li-S) batteries. In this work, by means of comprehensive density functional theory (DFT) computations, we systematically investigated the potential of a series of doped and defective boron nitride (BN) nanosheets as chemical immobilizers for the soluble Li2Sn species. Our results revealed that the introduction of dopants and defects can enhance the binding strength of Li2Sn species with BN nanosheets due to the strong LiN or SB interaction. In particular, the doped BN nanosheets that can moderately interact with Li2Sn species are shown to exhibit outstanding anchoring effects for Li-S batteries because they can keep a balance between the binding strength and integrity of Li2Sn species. Therefore, by carefully controlling the type of dopants, the inert BN nanosheet can be converted to quite a promising electrode material with high efficiency for Li-S batteries.

Effects of Plasma-lyte A, lactated Ringer's, and normal saline on acid-base status and intestine injury in the initial treatment of hemorrhagic shock.

BACKGROUND: Several kinds of crystalloid solutions have been used in the treatment of hemorrhagic shock (HS). Clinicians are faced with how to select the resuscitation fluids. The aim of the present study is to compare the effects of 3 crystalloid solutions, such as normal saline (NS), lactated Ringer's (LR), and Plasma-lyte A (PA), on acid-base status and intestine injury in rats subjected to HS. METHODS: Thirty Wistar rats were divided into 4 groups. The sham group had no blood withdrawal. The other groups were subjected to severe HS and then injected with NS, LR, or PA. All treatments were followed with an infusion of red blood cell suspension. The mean arterial pressure was monitored throughout the experiment. The arterial blood gas, malonaldehyde, and myeloperoxidase levels in the small intestine were assayed 120 minutes after resuscitation. RESULTS: Plasma-lyte A treatment could restore the pH, base excess (BE), HCO3-, Pao2, and Paco2. Comparing with sham group, NS failed to correct the decreased pH, BE, and HCO3- (P < .05), whereas LR treatment showed the decreased BE and HCO3- (P < .05) and increased Pao2 (P < .05). There were no significant differences in malonaldehyde among the 4 groups (P > .05). Both PA and LR were more effective than NS in decreasing the myeloperoxidase level in the small intestine (P < .01). CONCLUSIONS: Although the 3 crystalloid solutions play different roles, PA is better at correcting the acid-base balance and improving intestine injury during HS than NS and LR.

Pyrrolic-nitrogen doped graphene: a metal-free electrocatalyst with high efficiency and selectivity for the reduction of carbon dioxide to formic acid: a computational study.

Searching for metal-free catalysts for the carbon dioxide reduction reaction (CO2RR) has been a key challenge in the electrosynthesis of fuels for CO2 utilization. In this work, we investigated the potential of N-doped graphene as the electrocatalyst of CO2RR by means of comprehensive density functional theory (DFT) computations. The computations revealed that N-doping can modify the electronic properties of graphene for enhancing the electrochemical reduction of CO2 into CO and HCOOH, resulting in a low free energy barrier for the potential-limiting step to form the key intermediate COOH as well as the strong adsorption energy of adsorbed COOH and the weak adsorption energy of CO or HCOOH. The highest catalytic activity toward CO2RR is shown by pyrrolic N-doped graphene due to its lowest overpotential of 0.24 V among all N-doped graphenes, and leads exclusively to HCOOH as the product. Therefore, our results demonstrated that N-doped graphene holds great promise as an electrocatalyst for the CO2RR with high efficiency and selectivity by suitably tuning its N species.

Pyridine derivative/graphene nanoribbon composites as molecularly tunable heterogeneous electrocatalysts for the oxygen reduction reaction.

In this study, a strategy to design a new class of metal-free electrocatalysts for the oxygen reduction reaction (ORR) was proposed by means of density functional theory (DFT) computations. The electrocatalysts consist of various pyridine derivatives that are anchored on the edge sites of armchair graphene nanoribbons (AGNRs). Our results revealed that these anchored pyridine derivatives have considerably high stability, and the C atoms around the "external" N-dopant possess the largest positive charge, thus facilitating the ORR though a more efficient 4e pathway, in which the first electron is transferred into O2 molecules over a long range in the outer Helmholtz plane (i.e., the ET-OHP mechanism). Among these designed catalysts, the pyrimidine/AGNR exhibits the highest catalytic activity, which can be comparable to that of Pt-based catalysts. Therefore, our computations suggested that the combination of pyridine derivatives with graphene nanoribbons can constitute a novel and well-defined heterogeneous electrocatalyst with good stability and tunable active sites for the ORR, which provides a useful guidance to develop the next-generation of low-cost and metal-free electrocatalysts with accurate N species and content for the ORR in fuel cells.

Addition of Sodium Pyruvate to Stored Red Blood Cells Attenuates Liver Injury in a Murine Transfusion Model.

RBCs undergo numerous changes during storage and stored RBCs may induce adverse effects, ultimately resulting in organ injury in transfusion recipients. We tested the hypothesis that the addition of SP to stored RBCs would improve the quality of the stored RBCs and mitigate liver injury after transfusion in a murine model. RBCs were harvested from C57BL/6J mice and stored for 14 days in CPDA-1 containing either a solution of SP in saline or saline alone. Haemolysis, the 24-hour posttransfusion recovery, the oxygen-carrying capacity, and the SOD activity of stored RBCs were evaluated. The plasma biochemistry, hepatic MDA level, MPO activity, IL-6, TNF-α concentrations, and histopathology were measured two hours after the transfusion of stored RBCs. Compared with RBCs stored in CPDA-1 and saline, the addition of SP to stored RBCs restored their oxygen-carrying capacity and SOD activity, reduced the AST activity, BUN concentrations, and LDH activity in the plasma, and decreased the MDA level, MPO activity, and concentrations of IL-6 and TNF-α in the liver. These data indicate that the addition of SP to RBCs during storage has a beneficial effect on storage lesions in vitro and subsequently alleviates liver injury after the transfusion of stored RBCs in vivo.

Impaired erythrocyte deformability in transgenic HO-1G143H mutant mice.

To investigate the potential effects of variation of HO-1 activity on hemorheology, this study compared the hemorheological properties between transgenic HO-1G143H mutant mice and wild-type (WT) control mice. Fresh blood samples were obtained from mice via the ocular venous sinus. The whole blood viscosity was measured using a cone-plate viscometer. Erythrocyte deformability and aggregation was measured using ektacytometry. The elongation index was significantly reduced in the HO-1G143H mutant mice compared to the WT mice at the shear rates of 600, 800, and 1,000 s(-1). The integrated elongation index was decreased in the HO-1G143H mutant mice compared to the WT mice. There was no statistically significant difference between the HO-1G143H mutant mice and the WT mice in terms of whole blood viscosity, aggregation index, amplitude of aggregation, and aggregation half time. The present study demonstrated that a reduction in HO-1 activity results in an impaired erythrocyte deformability. Although the mechanism underlying this effect remains unclear, our study brings to light the participation of HO-1 in the variations of hemorheology.

Gradually Increased Oxygen Administration Improved Oxygenation and Mitigated Oxidative Stress after Resuscitation from Severe Hemorrhagic Shock.

BACKGROUND: The optimal oxygen administration strategy during resuscitation from hemorrhagic shock (HS) is still controversial. Improving oxygenation and mitigating oxidative stress simultaneously seem to be contradictory goals. To maximize oxygen delivery while minimizing oxidative damage, the authors proposed the notion of gradually increased oxygen administration (GIOA), which entails making the arterial blood hypoxemic early in resuscitation and subsequently gradually increasing to hyperoxic, and compared its effects with normoxic resuscitation, hyperoxic resuscitation, and hypoxemic resuscitation in severe HS. METHODS: Rats were subjected to HS, and on resuscitation, the rats were randomly assigned to four groups (n = 8): the normoxic, the hyperoxic, the hypoxemic, and the GIOA groups. Rats were observed for an additional 1 h. Hemodynamics, acid-base status, oxygenation, and oxidative injury were observed and evaluated. RESULTS: Central venous oxygen saturation promptly recovered only in the hyperoxic and the GIOA groups, and the liver tissue partial pressure of oxygen was highest in the GIOA group after resuscitation. Oxidative stress in GIOA group was significantly reduced compared with the hyperoxic group as indicated by the reduced malondialdehyde content, increased catalase activity, and the lower histologic injury scores in the liver. In addition, the tumor necrosis factor-α and interleukin-6 expressions in the liver were markedly decreased in the GIOA group than in the hyperoxic and normoxic groups as shown by the immunohistochemical staining. CONCLUSIONS: GIOA improved systemic/tissue oxygenation and mitigated oxidative stress simultaneously after resuscitation from severe HS. GIOA may be a promising strategy to improve resuscitation from HS and deserves further investigation.