Structures and bonding characteristics of KCl(H2O)n clusters with n = 1-10 based on density functional theory.

Aqueous inorganic salt solutions play a prominent role in both physiological and chemical experiments, and significant attention has been directed toward understanding the mechanisms underlying salt dissolution. In our effort to elucidate the hydration process of potassium chloride, we employed a comprehensive genetic algorithm to explore the structures of KCl(H2O)n (n = 1-10). A series of stable structures were identified by high-level ab initio optimization and single-point energy calculations with a zero-point energy correction. An analysis of the probability distribution of KCl(H2O)1-10 revealed that clusters with high probability at low temperatures exhibit reduced probabilities at higher temperatures, while others become more prevalent. When n = 1-9, the contact ion pair configurations or partially dissociated structures dominate in the system, and the probability distribution plot shows that the proportion of the solvent-separated ion pair (SSIP) structures of KCl(H2O)n is very small, while the SSIP configuration in KCl(H2O)10 becomes a stable structure with increasing temperature. The results from natural bond orbital analysis reveal a stronger interaction between chloride ions and water molecules. These findings provide valuable insights for a more comprehensive understanding of the intricacies of potassium chloride dissolution in water.

On the nature of Con±/0 clusters reacting with water and oxygen.

Bulk cobalt does not react with water at room temperature, but cobalt nanometals could yield corrosion at ambient conditions. Insights into the cobalt cluster reactions with water and oxygen enable us to better understand the interface reactivity of such nanometals. Here we report a comprehensive study on the gas-phase reactions of Con±/0 clusters with water and oxygen. All these Con±/0 clusters were found to react with oxygen, but only anionic cobalt clusters give rise to water dissociation whereas the cationic and neutral ones are limited to water adsorption. We elucidate the influences of charge states, bonding modes and dehydrogenation mechanism of water on typical cobalt clusters. It is unveiled that the additional electron of anionic Con- clusters is not beneficial to H2O adsorption, but allows for thermodynamics- and kinetics-favourable H atom transfer and dehydrogenation reactions. Apart from the charge effect, size effect and spin effect play a subtle role in the reaction process. The synergy of multiple metal sites in Con- clusters reduces the energy barrier of the rate-limiting step enabling hydrogen release. This finding of water dissociation on cobalt clusters put forward new connotations on the activity series of metals, providing new insights into the corrosion mechanism of cobalt nanometals.

Fluoride promotes the secretion of inflammatory factors in microglia through NLRP3/Caspase-1/GSDMD pathway.

It is widespread of endemic fluorosis in China, and the exposure of excessive fluoride will cause nervous system disease and activate microglia. However, the mechanism of the damage is not clear. It is well-known that NLRP3/Caspase-1/GSDMD pathway, a classic pyroptosis pathway, is widely involved in the occurrence and development of nervous system-related diseases, infectious diseases, and atherosclerotic diseases. This research aimed to explore the molecular mechanism of sodium fluoride on inflammation and pyroptosis in BV2 microglia based on the NLRP3/Caspase-1/GSDMD signaling pathway. BV2 microglia was treated with sodium fluoride at the dose of 0.25, 1, and 2 mmol/L for 24, 48, and 72 h, respectively. Cell viability, cell morphology, lactate dehydrogenase content, and related proteins and genes were examined to investigate if sodium fluoride caused damage to BV2 microglia through the pyroptosis pathway. Dithiolam (5 µmol/L), a pyroptosis inhibitor, was added for further verification. NaF could induced BV2 cells injury in a dose-dependent fashion through disrupting the integrity of cell membranes and increasing IL-1ß via upregulating NLRP3, Caspase-1, and its downstream protein GSDMD. Disulfiram could improve these changes caused by NaF. In conclusion, our results suggested that NLRP3/Caspase-1/GSDMD-mediated classical pyroptosis pathway was involved in fluoride-induced BV2 microglia damage.

Modulating the Oxygen Reduction Reaction Performance via Precisely Tuned Reactive Sites in Porphyrin-Based Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as promising electrocatalysts due to their controllable architectures, highly exposed molecular active sites, and ordered structures. In this study, a series of porphyrin-based COFs (TAPP-x-COF) with various transition metals (Co, Ni, Fe) were synthesized via a facile post-metallization strategy under solvothermal synthesis. The resulting porphyrin-based COFs showed oxygen reduction reaction (ORR) activity with a trend in Co > Fe > Ni. Among them, TAPP-Co-COF exhibited the best ORR activity (E1/2 = 0.66 V and jL = 4.82 mA cm-2) in alkaline media, which is comparable to those of Pt/C under the same conditions. Furthermore, TAPP-Co-COF was employed as a cathode in a Zn-air battery, demonstrating a high power density of 103.73 mW cm-2 and robust cycling stability. This work presents a simple method for using COFs as a smart platform to fabricate efficient electrocatalysts.

Structural and photoelectron spectroscopic study on the heterotrinuclear nickel-titanium dioxide carbonyl complexes Ni2TiO2(CO) n - (n = 2-4).

Herein, the configurations and intrinsic electronic properties of heteronuclear transition metal dioxide carbonyl anions Ni2TiO2(CO) n - (n = 2-4) in the gas phase were investigated using mass spectrometry coupled anionic photoelectron spectroscopy, ab initio calculations, and simulated density-of-state (DOS) spectra. The results clearly show that the binding of electrons is enhanced by the addition of CO. The ground state structures of Ni2TiO2(CO) n - (n = 2-4) are characterized to show that three transition metal atoms (one Ti atom and two Ni atoms) forming a quasi-line is favored. The interaction between Ni and C becomes weaker as the cluster size increases. The natural electron configuration shows that the extra electron is enriched on O atoms attached to Ti, and there is strong interaction between Ti and O atoms. This work gives significant insight into the configuration and electronic structures of nickel-titanium dioxide carbonyl anions, which has potential application in adsorption of carbon monoxide on the surfaces/interfaces of alloys.

Ground-State Structures of Hydrated Calcium Ion Clusters From Comprehensive Genetic Algorithm Search.

We searched the lowest-energy structures of hydrated calcium ion clusters Ca2+(H2O)n (n = 10-18) in the whole potential energy surface by the comprehensive genetic algorithm (CGA). The lowest-energy structures of Ca2+(H2O)10-12 clusters show that Ca2+ is always surrounded by six H2O molecules in the first shell. The number of first-shell water molecules changes from six to eight at n = 12. In the range of n = 12-18, the number of first-shell water molecules fluctuates between seven and eight, meaning that the cluster could pack the water molecules in the outer shell even though the inner shell is not full. Meanwhile, the number of water molecules in the second shell and the total hydrogen bonds increase with an increase in the cluster size. The distance between Ca2+ and the adjacent water molecules increases, while the average adjacent O-O distance decreases as the cluster size increases, indicating that the interaction between Ca2+ and the adjacent water molecules becomes weaker and the interaction between water molecules becomes stronger. The interaction energy and natural bond orbital results show that the interaction between Ca2+ and the water molecules is mainly derived from the interaction between Ca2+ and the adjacent water molecules. The charge transfer from the lone pair electron orbital of adjacent oxygen atoms to the empty orbital of Ca2+ plays a leading role in the interaction between Ca2+ and water molecules.

Inhibition of hypoxia inducible factor 1 by YC-1 attenuates tissue plasminogen activator induced hemorrhagic transformation by suppressing HMGB1/TLR4/NF-κB mediated neutrophil infiltration in thromboembolic stroke rats.

Hemorrhagic transformation (HT) is a frequent complication of ischemic stroke after thrombolytic therapy and seriously affects the prognosis of stroke. Due to the limited therapeutic window and hemorrhagic complications, tissue plasminogen activator (t-PA) is underutilized in acute ischemic stroke. Currently, there are no clinically effective drugs to decrease the incidence of t-PA-induced HT. Hypoxia-inducible factor 1 (HIF-1) is an important transcription factor that maintains oxygen homeostasis and mediates neuroinflammation under hypoxia. However, the effect of HIF-1 on t-PA-induced HT is not clear. The aim of this study was to investigate the role of HIF-1 in t-PA-induced HT by applying YC-1, an inhibitor of HIF-1. In the present study, we found that HIF-1 expression was significantly increased in ischemic brain tissue after delayed t-PA treatment and was mainly localized in neurons and endothelial cells. Inhibition of HIF-1 by YC-1 improved infarct volume and neurological deficits. YC-1 inhibited matrix metalloproteinase protein expression, increased tight junction protein expression, and ameliorated BBB disruption and the occurrence of HT. Furthermore, YC-1 suppressed the release of inflammatory factors, neutrophil infiltration and the activation of the HMGB1/TLR4/NF-κB signaling pathway. These results demonstrated that inhibition of HIF-1 could protect BBB integrity by suppressing HMGB1/TLR4/NF-κB-mediated neutrophil infiltration, thereby reducing the risk of t-PA-induced HT. Thus, HIF-1 may be a potential therapeutic target for t-PA-induced HT.

Spectroscopic Identification of Transition-Metal M[η2-(O,O)C] Species for Highly-Efficient CO2 Activation.

The CO2 activation by transition metals is important in CO2 utilization but has proven to be challenging for experimental targets. Here we report first synthesis and spectroscopic characterization of transition-metal M[η2-(O,O)C] species with bidentate double oxygen metal-CO2 coordination in the [ZrO(CO2)n≥4]+ complexes. The Zr[η2-(O,O)C] species yields a CO2- radical ligand, showing a high efficiency in CO2 activation. We find that two important prerequisites are demanded for certain metals to form this intriguing M[η2-(O,O)C] species. One is that the metal center has high reduction capability, and the other is that the oxidation state of the metal center is lower than its highest one by 1. This study highlights the pivotal roles played by the M[η2-(O,O)C] species in CO2 activation and also open new avenues toward the development of related single-atom catalysts with isolated transition-metal atoms dispersed on supports.

Stability and NMR Chemical Shift of Amorphous Precursors of Methane Hydrate: Insights from Dispersion-Corrected Density Functional Theory Calculations Combined with Machine Learning.

Clathrate hydrates of natural gases are important backup energy sources. It is thus of great significance to explore the nucleation process of hydrates. Hydrate clusters are building blocks of crystalline hydrates and represent the initial stage of hydrate nucleation. Using dispersion-corrected density functional theory (DFT-D) combined with machine learning, herein, we systematically investigate the evolution of stabilities and nuclear magnetic resonance (NMR) chemical shifts of amorphous precursors from monocage clusters CH4(H2O)n (n = 16-24) to decacage clusters (CH4)10(H2O)n (n = 121-125). Compared with planelike configurations, the close-packed structures formed by the water-cage clusters are energetically favorable. The 512 cages are dominant, and the emerging amorphous precursors may be part of sII hydrates at the initial stage of nucleation. Based on our data set, the possible initial fusion pathways for water-cage clusters are proposed. In addition, the 13C NMR chemical shifts for encapsulated methane molecules also showed regular changes during the fusion of water-cage clusters. Machine learning can reproduce the DFT-D results well, providing a structure-energy-property landscape that could be used to predict the energy and NMR chemical shifts of such multicages with more water molecules. These theoretical results present vital insights into the hydrate nucleation from a unique perspective.

[Advances in molecular mechanisms of meiotic arrest and luteinizing hormone-induced meiotic resumption in oocytes].

Mammalian oocytes within Graafian follicles are arrested at prophase I of meiosis. C-type natriuretic peptide (NPPC), secreted by mural granulosa cells (MGCs), maintains oocyte meiotic arrest via binding to its cognate receptor natriuretic peptide receptor 2 (NPR2) and producing cyclic guanosine monophosphate (cGMP). NPR2 is most concentrated in the cumulus cells. In addition, cAMP, gap junction, inosine monophosphate dehydrogenase (IMPDH) and other important regulatory factors are also involved in meiotic arrest. Luteinizing hormone (LH) then rapidly decreases cGMP and induces oocyte meiotic resumption. In this paper, advances in the molecular mechanisms of meiotic arrest and LH-induced meiotic resumption were reviewed. This paper may provide new ideas for the prevention, diagnosis and treatment of related reproductive diseases.

Polygalasaponin F inhibits neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation through the PI3K/Akt pathway.

Cerebral ischaemia is a common cerebrovascular disease and often induces neuronal apoptosis, leading to brain damage. Polygalasaponin F (PGSF) is one of the components in Polygala japonica Houtt, and it is a triterpenoid saponin monomer. This research focused on anti-apoptotic effect of PGSF during oxygen-glucose deprivation and reoxygenation (OGD/R) injury in rat adrenal pheochromocytoma cells (PC12) and primary rat cortical neurons. OGD/R treatment reduced viability of PC12 cells and primary neurons. This reduced viability was prevented by PGSF, as shown by MTT assay. OGD/R insult decreased expression of Bcl-2/Bax both in PC12 cells and primary neurons but elevated levels of caspase-3 in primary neurons. However, PGSF may up-regulate expression of Bcl-2/Bax and down-regulate caspase-3 in these particular cells. Furthermore, Bcl-2/Bax and the ratio between phosphorylated Akt and total Akt were decreased in PC12 cells treated with OGD/R, and both were increased by PGSF. Moreover, increase in the ratios of Bcl-2/Bax and phosphorylated Akt/total Akt in PC12 cells was suppressed by phosphatidylinositol 3-kinase (PI3K) inhibitor. Data suggest PGSF might prevent OGD/R-induced injury via activation of PI3K/Akt signalling. The ability of PGSF to block the effects of OGD/R appears to involve regulation of Bcl-2, Bax and caspase-3, which are related to apoptosis.

Distinguishing between halogenated alkanes containing the same halogen based on the reaction kinetic parameter using negative ion mobility spectrometry at atmospheric pressure.

Electron adsorption ionization ion mobility spectrometry can be used to detect halogen-containing volatile organic compounds with high sensitivity. However, this traditional electron attachment detection method cannot distinguish between volatile organic compounds containing the same halogen. For different organic compounds containing the same halogen, the product ions formed by the dissociation electron attachment process are the same. In this article, we propose a novel negative corona discharge ion mobility spectrometry method to distinguish between and detect halogenated alkanes containing the same halogen according to the different electron attachment rates and reaction kinetic parameters of the different halogenated alkanes. Although these halogenated alkanes, which contain the same halogen, produce the same type of ions through the electron attachment process, their electron attachment rates are different from each other. In this work, the kinetic information is used as the fingerprint information for the tested samples to distinguish different halogenated alkanes. Five halogenated alkanes were successfully detected using this method. The results show that the method based on the electron attachment rate constant is feasible for the determination of halogenated alkanes containing the same halogen.

Hydrated Sodium Ion Clusters [Na+(H2O)n (n = 1-6)]: An ab initio Study on Structures and Non-covalent Interaction.

Structural, thermodynamic, and vibrational characteristics of water clusters up to six water molecules incorporating a single sodium ion [Na+(H2O)n (n = 1-6)] are calculated using a comprehensive genetic algorithm combined with density functional theory on global search, followed by high-level ab initio calculation. For n ≥ 4, the coordinated water molecules number for the global minimum of clusters is 4 and the outer water molecules connecting with coordinated water molecules by hydrogen bonds. The charge analysis reveals the electron transfer between sodium ions and water molecules, providing an insight into the variations of properties of O-H bonds in clusters. Moreover, the simulated infrared (IR) spectra with anharmonic correction are in good agreement with the experimental results. The O-H stretching vibration frequencies show redshifts comparing with a free water molecule, which is attributed to the non-covalent interactions, including the ion-water interaction, and hydrogen bonds. Our results exhibit the comprehensive geometries, energies, charge, and anharmonic vibrational properties of Na+(H2O)n (n = 1-6), and reveal a deeper insight of non-covalent interactions.

5-Aza-2'-deoxycytidine increases hypoxia tolerance-dependent autophagy in mouse neuronal cells by initiating the TSC1/mTOR pathway.

BACKGROUND: Our previous study found that 5-Aza-2'-deoxycytidine (5-Aza-CdR) can repress the expression and activity of protein serine/threonine phosphatase-1γ (PP1γ) in mouse hippocampus. It is well known that PP1γ regulates cell metabolism, which is related to hypoxia/ischaemia tolerance. It has been reported that it can also induce autophagy in cancer cells. Autophagy is important for maintaining cellular homeostasis associated with metabolism. In this study, we examined whether 5-Aza-CdR increases hypoxia tolerance-dependent autophagy by initiating the TSC1/mTOR/autophagy signalling pathway in neuronal cells. METHODS: 5-Aza-CdR was either administered to mice via intracerebroventricular injection (i.c.v) or added to cultured hippocampal-derived neuronal cell line (HT22 cell) in the medium for cell culture. The hypoxia tolerance of mice was measured by hypoxia tolerance time and Perl's iron stain. The mRNA and protein expression levels of tuberous sclerosis complex 1 (TSC1), mammalian target of rapamycin (mTOR) and autophagy marker light chain 3 (LC3) were measured by real-time PCR and western blot. The p-mTOR and p-p70S6k proteins were used as markers for mTOR activity. In addition, the role of autophagy was determined by correlating its intensity with hypoxia tolerance in a time-dependent manner. At the same time, the involvement of the TSC1/mTOR pathway in autophagy was also examined through transfection with TSC1 (hamartin) plasmid. RESULTS: 5-Aza-CdR was revealed to increase hypoxia tolerance and induce autophagy, accompanied by an increase in mRNA and protein expression levels of TSC1, reduction in p-mTOR (Ser2448) and p-p70S6k (Thr389) protein levels, and an increase in the ratio of LC3-II/LC3-I in both mouse hippocampus and hippocampal-derived neuronal cell line (HT22). The fluorescence intensity of hamartin was enhanced in the hippocampus of mice exposed to 5-Aza-CdR. Moreover, HT22 cells that over-expressed TSC1 showed more autophagy. CONCLUSIONS: 5-Aza-CdR can increase hypoxia tolerance by inducing autophagy by initiating the TSC1/mTOR pathway.

Evolution of atomic structures of SnN, SnN -, and SnNCl- clusters (N = 4-20): Insight from ab initio calculations.

An unbiased global search was employed to explore the low-energy structures of SnN, SnN -, and SnNCl- clusters with N = 4-20 atoms based on the genetic algorithm combined with density functional theory calculations. Some unprecedented low-energy isomers are reported for SnN and SnNCl- clusters. The theoretical electronic properties such as binding energy per atom, ionization potential, adiabatic detachment energy, and vertical detachment energy compare well with the experimental data. Based on the equilibrium structures, the simulated photoelectron spectra are in good agreement with the experimental data in the range of N = 4-20. With addition of a Cl atom on the SnN - cluster, which causes almost no rearrangement on the structural framework, the first peaks in all original photoelectron spectra of SnN - clusters disappear and other peaks nearly retain the original feature at most sizes.

Cage fusion from bi-cages to tri-cages during nucleation of methane hydrate: a DFT-D simulation.

Water-cage clusters encapsulating guest molecules are the basic components of hydrate crystal structures. Herein, we investigated the fusion process from bi-cages to tri-cages to probe the nucleation mechanism at the initial stage of CH4 hydrate formation by employing dispersion-corrected density functional theory. We found that tri-cages possess high stability by sharing three, rather than two, polygonal faces. In addition, any mono-cage combined with a nonstandard 4151062 cage could achieve considerable stability regardless of which face is shared; this finding illustrates that 4151062 cages are more likely to appear at the early stages of CH4 hydrate nucleation than other nonstandard cages. We then simulated the Raman spectra of CH4 molecules in water-cage to characterize the spectral characteristics of the CH4 hydrate. The C-H symmetric stretching frequency of encapsulated CH4 molecules red-shifted with increasing mono-cage size, which follows the prediction of the "loose cage-tight cage" model. The symmetric stretching vibrational frequencies of trapped CH4 molecules in the tri-cage revealed a clear red-shift compared with those in the component mono- and bi-cages. The cage fusion process and spectroscopic properties described in this work are expected to provide new atomistic insights into CH4 hydrates at the initial nucleation stage.

Revisit the landscape of protonated water clusters H+(H2O)n with n = 10-17: An ab initio global search.

Using a genetic algorithm incorporated with density functional theory, we explore the ground state structures of protonated water clusters H+(H2O)n with n = 10-17. Then we re-optimize the isomers at B97-D/aug-cc-pVDZ level of theory. The extra proton connects with a H2O molecule to form a H3O+ ion in all H+(H2O)10-17 clusters. The lowest-energy structures adopt a monocage form at n = 10-16 and core-shell structure at n = 17 based on the MP2/aug-cc-pVTZ//B97-D/aug-cc-pVDZ+ZPE single-point-energy calculation. Using second-order vibrational perturbation theory, we further calculate the infrared spectra with anharmonic correction for the ground state structures of H+(H2O)10-17 clusters at the PBE0/aug-cc-pVDZ level. The anharmonic correction to the spectra is crucial since it reproduces the experimental results quite well. The extra proton weakens the O-H bond strength in the H3O+ ion since the Wiberg bond order of the O-H bond in the H3O+ ion is smaller than that in H2O molecules, which causes a red shift of the O-H stretching mode in the H3O+ ion.

Structures and Spectroscopic Properties of F-(H2O) n with n = 1-10 Clusters from a Global Search Based On Density Functional Theory.

Using a genetic algorithm incorporated in density functional theory, we explore the ground state structures of fluoride anion-water clusters F-(H2O) n with n = 1-10. The F-(H2O) n clusters prefer structures in which the F- anion remains at the surface of the structure and coordinates with four water molecules, as the F-(H2O) n clusters have strong F--H2O interactions as well as strong hydrogen bonds between H2O molecules. The strong interaction between the F- anion and adjacent H2O molecule leads to a longer O-H distance in the adjacent molecule than in an individual water molecule. The simulated infrared (IR) spectra of the F-(H2O)1-5 clusters obtained via second-order vibrational perturbation theory (VPT2) and including anharmonic effects reproduce the experimental results quite well. The strong interaction between the F- anion and water molecules results in a large redshift (600-2300 cm-1) of the adjacent O-H stretching mode. Natural bond orbital (NBO) analysis of the lowest-energy structures of the F-(H2O)1-10 clusters illustrates that charge transfer from the lone pair electron orbital of F- to the antibonding orbital of the adjacent O-H is mainly responsible for the strong interaction between the F- anion and water molecules, which leads to distinctly different geometric and vibrational properties compared with neutral water clusters.

Expression level of 12-amino acid triggering receptor on myeloid cells-like transcript 1 derived peptide alleviates lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) is a critical illness with a high morbidity and mortality rate due to severe inflammation in the lungs. The effects and underlying mechanism of the triggering receptor expressed on myeloid cells­1 (TREM­1)­like transcript­1­derived peptide (LR12) on ALI remain unclear. The aim of the present study was to determine whether LR12 attenuates lipopolysaccharide (LPS)­induced ALI and elucidate the mechanism underlying it. Male C57BL/6 mice were randomly assigned to three groups as follows: Sham group, LPS + scramble group and LPS + LR12 group. Normal saline (NS) or LPS was administrated by intratracheal instillation, and NS, LR12 or LR12 scramble was administered intraperitoneally 30 min later. The treatment was repeated every 3 h three times. Mice were sacrificed 24 h later. Pulmonary pathological changes, the lung wet/dry weight ratio, the macrophage and neutrophil counts in bronchoalveolar lavage fluid and myeloperoxidase (MPO) activity in the lung tissues were observed. The inflammatory cytokines were evaluated by enzyme­linked immunosorbent assay and lung neutrophil infiltration was detected by immunohistochemistry. Nuclear factor (NF)­κB p65 and TREM­1 were analyzed by western blotting, and the activation of NF­κB was detected by electrophoretic mobility shift assay. LPS­induced pathohistological injury, edema and neutrophil infiltration were significantly alleviated by TREM­1 inhibitor, LR12. The proinflammatory cytokines [interleukin (IL)­6, IL­1ß, tumor necrosis factor­α] and chemokines (keratinocyte chemokine and monocyte chemoattractant protein­1) were significantly reduced, whereas the anti­inflammatory cytokines, IL­10 were significantly increased by LR12. LR12 was identified to significantly decrease p65 expression levels in the nucleus and inhibit the activity of NF­κB. Furthermore, LR12 alleviated LPS­induced ALI by reducing the expression of TREM­1, increasing the release of soluble TREM­1 and inhibiting activation of the NF-κB signaling pathway.

Remote Limb Ischaemic Postconditioning Protects Against Myocardial Ischaemia/Reperfusion Injury in Mice: Activation of JAK/STAT3-Mediated Nrf2-Antioxidant Signalling.

BACKGROUND: This study aimed to evaluate the protective effect and mechanisms of remote limb ischaemic postconditioning (RIPostC) against myocardial ischaemia/reperfusion (IR) injury. METHODS: Male mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. RIPostC was achieved by three cycles of 5 min of ischaemia and 5 min of reperfusion in the left hind limb at the start of the reperfusion period. After 2 h of cardiac reperfusion, myocardial infarct size, cardiac enzyme release, apoptosis and oxidative stress were assessed. Protein expression and phosphorylation were measured by Western blotting. RESULTS: RIPostC significantly decreased cardiac IR injury, as reflected by reduced infarct size and cellular apoptosis (22.9 ± 3.3% vs 40.9 ± 6.2% and 13.4% ± 3.1% vs 26.2% ± 3.1%, respectively, both P < 0.01) as well as plasma creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release (21.97 ± 4.08 vs 35.86 ± 2.91 ng/ml and 6.17 ± 0.58 vs 8.37 ± 0.89 U/ml, respectively, both P < 0.01) compared with the IR group. RIPostC significantly increased the phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.01). In addition, RIPostC elevated the nuclear translocation of Nrf2 and the expression of HO-1 and reduced myocardial oxidative stress (P < 0.05). Interestingly, pretreatment with the JAK/STAT3 inhibitor AG490 blocked the cardioprotective effect of RIPostC accompanied by decreased phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.05), decreased nuclear translocation of Nrf2 and expression of HO-1, as well as increased oxidative stress (P < 0.05). CONCLUSION: RIPostC attenuates apoptosis and protects against myocardial IR injury, possibly through the activation of JAK/STAT3-mediated Nrf2-antioxidant signalling.