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This paper studies the distributed bipartite output formation control problem of heterogeneous discrete-time linear multi-agent systems (MASs) via cooperative output regulation theory. To construct the bipartite formation, under the structurally-balanced augmented directed signed graph, the followers of two antagonistic subgroups are supposed to respectively keep the desired relative positions with the leader, also called as the exosystem, in the same magnitude but the opposite sign. Since the information of exosystem can not be directly obtained by all followers, the distributed exosystem observer based on the discrete-time algebraic Riccati equality (ARE) is presented and the distributed state feedback controller is further designed. Moreover, in the case where the states of followers are not available, the distributed output feedback controller is proposed by introducing the state estimator. Finally, two numerical examples are given to demonstrate the effectiveness of analytic results.

This paper addresses the distributed secure consensus problem for linear multi-agent systems (MAS) with unmeasurable states and Denial-of-Service (DoS) attacks. The observer is designed to be used in estimating unmeasurable states of agents. Then, an observer-based distributed event-triggered control protocol is proposed to save network resources. By using the piecewise Lyapunov function approach, several sufficient conditions for ensuring secure consensus are obtained. Further, a rigorous theoretical analysis shows that the given event-triggering scheme exhibits no Zeno behavior. Finally, the effectiveness of the proposed method is verified by numerical simulation.

Abstract Background Unlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR). Methods A total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1–4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis. Results A total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05–1.12, P

Microcystis aeruginosa, as a typical alga, produces microcystin with strong liver toxicity, seriously endangering the liver health of human and animals. Inhibiting the bloom of the Microcystis aeruginosa in lakes becomes a significant and meaningful work. Ultrasonic cavitation is currently considered to be the most environmentally friendly and effective method for the removal of Microcystis aeruginosa. However, the commercialized ultrasonic algae removal systems require multi-Langevin transducers to achieve omnidirectional ultrasonic irradiation due to the single irradiation direction of the Langevin transducer, resulting in the complex design and high energy consumption. To achieve a low-cost, simple structure, and high-efficiency algae removal system, a novel omnidirectional ultrasonic cavitation removal system for Microcystis aeruginosa is proposed. The proposed system is major composed of a novel omnidirectional ultrasonic transducer, which generates the omnidirectional ultrasonic irradiation by its shaking-head motion coupled by two orthogonal bending vibration modes. Modal simulation, sound field simulation, and cavitation bubble radius simulation are first carried out to optimize the geometric sizes of the proposed transducer and verify the correctness of the omnidirectional ultrasonic irradiation principle. Then the vibration characteristics of the transducer prototype are measured by vibration tests and impedance tests. Finally, the feasibility and effectiveness of the proposed omnidirectional ultrasonic removal system for Microcystis aeruginosa are evaluated through the algae removal experiments. The experimental results exhibit that the algal cells damaged by ultrasonic irradiation from the proposed system do not have the ability to self-repair. In addition, the algal removal rates reached 55.41% and 72.97% after 30 min of ultrasonic treatment when the corresponding ultrasonic densities are 0.014 W/mL and 0.021 W/mL, respectively. The proposed omnidirectional ultrasonic algae removal system significantly simplifies the configuration and reduces energy consumption, presenting the potential promise of algae removal and environmental protection.

A 68-year-old man presented with chest distress recurring for the past 10 years. An echocardiogram demonstrated bicuspid aortic valve malformation with severe aortic stenosis and ventricular septal thickness of 22 mm. The patient underwent successful transcatheter aortic valve replacement (TAVR). Six months later, he complained of worsening dyspnea and chest distress (New York Heart Association Class III) on exertion. Besides a functional normal AV prosthesis, the echocardiography indicated the left ventricular outflow tract obstruction peak gradient of 122 mmHg at rest. Alcohol septal ablation was performed as the patient was unable to tolerate morrow procedure. His symptoms were relieved immediately after ablation, and no major cardiovascular events were observed during the 20-month follow-up. In conclusion, among patients with concomitant hypertrophic obstructive cardiomyopathy and severe aortic valvular stenosis, consideration for TAVR and alcohol septal ablation should only be made for patients who are at high surgical risk or cannot tolerate thoracotomy.

Nonalcoholic fatty liver disease (NAFLD) is considered as a liver manifestation of metabolic disorders. Previous studies indicate that the renin-angiotensin system (RAS) plays a complex role in NAFLD. As the only precursor of the RAS, decreased angiotensinogen (AGT) profoundly impacts RAS bioactivity. Here, we investigated the role of hepatocyte-derived AGT in liver steatosis. AGT floxed mice (hepAGT+/+) and hepatocyte-specific AGT-deficient mice (hepAGT−/−) were fed a Western diet and a normal laboratory diet for 12 weeks, respectively. Compared with hepAGT+/+ mice, Western diet-fed hepAGT−/− mice gained less body weight with improved insulin sensitivity. The attenuated severity of liver steatosis in hepAGT−/− mice was evidenced by histologic changes and reduced intrahepatic triglycerides. The abundance of SREBP1 and its downstream molecules, acetyl-CoA carboxylase and FASN, was suppressed in hepAGT−/− mice. Furthermore, serum derived from hepAGT+/+ mice stimulated hepatocyte SREBP1 expression, which could be diminished by protein kinase B (Akt)/mammalian target of rapamycin (mTOR) inhibition in vitro. Administration of losartan did not affect diet-induced body weight gain, liver steatosis severity, and hepatic p-Akt, p-mTOR, and SREBP1 protein abundance in hepAGT+/+ mice. These data suggest that attenuation of Western diet-induced liver steatosis in hepAGT−/− mice is associated with the alternation of the Akt/mTOR/SREBP-1c pathway.

Introduction It is the common clinical practice to prescribe indefinite aspirin for patients with non-valvular atrial fibrillation (NVAF) post left atrial appendage occlusion (LAAO). However, aspirin as a primary prevention strategy for cardiovascular diseases has recently been challenged due to increased risk of bleeding. Therefore, aspirin discontinuation after LAAO in atrial fibrillation (ASPIRIN LAAO) trial is designed to assess the uncertainty about the risks and benefits of discontinuing aspirin therapy at 6 months postimplantation with a Watchman LAAO device in NVAF patients.Methods and analysis The ASPIRIN LAAO study is a prospective, multicentre, randomised, double-blinded, placebo-controlled non-inferiority trial. Patients implanted with a Watchman device within 6 months prior to enrollment and without pre-existing conditions requiring long-term aspirin therapy according to current guidelines are eligible for participating the trial. Subjects will be randomised in a 1:1 allocation ratio to either the Aspirin group (aspirin 100 mg/day) or the control group (placebo) at 6 months postimplantation. A total of 1120 subjects will be enrolled from 12 investigational sites in China. The primary composite endpoint is stroke, systemic embolism, cardiovascular/unexplained death, major bleeding, acute coronary syndrome and coronary or periphery artery disease requiring revascularisation at 24 months. Follow-up visits are scheduled at 6 and 12 months and then every 12 months until 24 months after the last patient recruitment.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Xinhua Hospital, Shanghai, China (reference number XHEC-C-2018-065-5). The protocol is also submitted and approved by the institutional Ethics Committee at each participating centre. Results are expected in 2024 and will be disseminated through peer-reviewed journals and presentations at national and international conferences.Trial registration number NCT03821883.

Background Anticoagulants induce atherosclerosis regression in animal models but exploiting this clinically is limited by bleeding events. Here we test a novel thrombin inhibitor, PTL060, comprising hirulog covalently linked to a synthetic myristoyl electrostatic switch to tether to cell membranes. Methods and Results ApoE−/− mice were fed chow or high‐fat diets, before transplantation of congenic aortic segments or injection of PTL060, parental hirulog, control saline, or labeled CD11b positive cells. Aortic transplants from transgenic mice expressing anticoagulants on endothelium did not develop atherosclerosis. A single intravenous injection of PTL060, but not hirulog inhibited atheroma development by >50% compared with controls when assessed 4 weeks later. Mice had prolonged bleeding times for only one seventh of the time that PTL060 was biologically active. Repeated weekly injections of PTL060 but not hirulog caused regression of atheroma. We dissected 2 contributory mechanisms. First, the majority of CCR2+ (C‐C chemokine receptor type 2+) monocytes recruited into plaques expressed CCR7 (C‐C chemokine receptor type 7), ABCA1 (ATP‐binding cassette transporter – 1), and interleukin‐10 in PTL060 mice, a phenotype seen in

Tartary buckwheat has become popular healthful food due to its antidiabetic and antioxidant activities. In the current study, the in-vitro α-glucosidase inhibitory and antioxidative activities of different parts of Tartary buckwheat were evaluated throughout the growth stages. In addition, the phytochemical profiles and quantitative analysis were further achieved by HPLC-DAD. Tartary buckwheat root extracts at a concentration of 0.5 mg/mL showed significant inhibition more than 80% in the flowering and yield stage, while acarbose was 87.4% inhibition at 5 mg/mL. It also showed good antioxidant capacity using 2,2-diphenyl-1-picryl-hydrazyl, 2, 2ʹ-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, and ferric reducing antioxidant power determination. The antioxidant capacities of roots ranged from 128 to 158 μM VC, from 226 to 409 μM VC, and from 77 to 205 μM butylated hydroxytoluene (BHT) (equaling VC or BHT per 1 g of dry weight), respectively. Chemical composition analysis showed that the leaf contained more rutin and the root more phenylpropanoid. The results may provide a better understanding of the variation of Tartary buckwheat as a functional food for preventing diabetes and antioxidant.

Background: The primary cause of ischemic heart failure (HF) is myocardial infarction (MI) resulting in left ventricle (LV) wall motion abnormality secondary to ventricular remodeling. A prospective, nonrandomized study conducted in China was designed to assess safety and efficacy of the percutaneous ventricular restoration therapy using Parachute device (CardioKinetix, Inc., CA, USA) in ischemic HF patients as a result of LV remodeling after anterior wall MI. Methods: Thirty-one patients with New York Heart Association (NYHA) Class II, III ischemic HF, ejection fraction between 15% and 40%, and dilated akinetic or dyskinetic anterior-apical wall without the need to be revascularized were enrolled from seven sites in China from October to December 2014. The Parachute device was implanted through femoral artery. All patients received low-dose aspirin and anticoagulation with warfarin for at least 12 months postdevice implantation. The primary end-point was the assessment of efficacy as measured by the reduction in LV end-systolic volume index (LVESVI) against baseline LVESVI at 3 months postdevice implantation, determined by the echocardiography and measured by echocardiography core laboratory. Quality of life was assessed using EQ-5D and visual analog scale (VAS). For quantitative data comparison, paired t-test (normality data) and signed-rank test (abnormality data) were used; application of signed-rank test was for the ranked data comparison. Results: A change in LVESVI as measured by echocardiography from the preimplant baseline to 3-month postdevice implantation revealed a statistically significant reduction from 77.5 ± 20.0 ml/m2 to 53.1 ± 17.0 ml/m2 (P < 0.0001). The trial met its primary end-point. Of the 31 patients, the procedural success was 96.8%. Overall, NYHA HF class assessment results showed an improvement of more than half a class at 3 months (P < 0.001). Quality of life assessed by the VAS value increased 11.5 points (P < 0.01), demonstrating improvement at 3 months. Conclusion: The favorable outcomes observed in the high-risk patients provide reassuring safety and efficacy data to support adoption of this technology as a therapeutic option for ischemic HF patients. Trial Registration: ClinicalTrials.gov, NCT02240940; https://clinicaltrials.gov/ct2/show/NCT02240940.

Background: High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia, and a domestically developed pacemaker will help lower the burden. This study aimed to evaluate the safety and efficacy of Qinming8631 DR (Qinming Medical, Baoji, China), the first domestically developed dual-chamber pacemaker of China, compared with a commercially available pacemaker Talos DR (Biotronik, Berlin, Germany) in Chinese patients. Methods: A prospective randomized trial was conducted at 14 centers in China. Participants were randomized into trial (Qinming8631 DR) and control (Talos DR) groups. Parameters of the pacing systems were collected immediately after device implantation and during follow-ups. The effective pacing rate at 6-month follow-up was recorded as the primary end point. Electrical properties, magnet response, single- and double-pole polarity conversion, rate response function, and adverse events of the pacing system were analyzed. The Cochran-Mantel-Haenszel Chi-square test, paired t-test, and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data. Results: A total of 225 patients with a diagnosis of bradyarrhythmia and eligible for this study were randomly enrolled into the trial (n = 113) and control (n = 112) groups. They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity. Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set (81.4% vs. 79.5%, P = 0.712 and 95.4% vs. 89.5%, P = 0.143, respectively). In both data sets, noninferiority of the trial group was above the predefined noninferiority limit(−9.5%). Conclusions: This study established the noninferiority of Qinming8631 DR to Talos DR. The safety and efficacy of Qinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.

Cathepsin B (CatB) is a cysteine proteolytic enzyme widely expressed in various cells and mainly located in the lysosomes. It contributes to the pathogenesis and development of many diseases. However, the role of CatB in viral myocarditis (VMC) has never been elucidated. Here we generated the VMC model by intraperitoneal injection of coxsackievirus B3 (CVB3) into mice. At day 7 and day 28, we found CatB was significantly activated in hearts from VMC mice. Compared with the wild-type mice receiving equal amount of CVB3, genetic ablation of CatB (Ctsb-/-) significantly improved survival, reduced inflammatory cell infiltration, decreased serum level of cardiac troponin I, and ameliorated cardiac dysfunction, without altering virus titers in hearts. Conversely, genetic deletion of cystatin C (Cstc-/-), which markedly enhanced CatB levels in hearts, distinctly increased the severity of VMC. Furthermore, compared with the control, we found the inflammasome was activated in the hearts of wild-type mice with VMC, which was attenuated in the hearts of Ctsb-/- mice but was further enhanced in Cstc-/- mice. Consistently, the inflammasome-initiated pyroptosis was reduced in Ctsb-/- mice hearts and further increased in Cstc-/- mice. These results suggest that CatB aggravates CVB3-induced VMC probably through activating the inflammasome and promoting pyroptosis. This finding might provide a novel strategy for VMC treatment.

Background: Fractional flow reserve (FFR) is currently considered as the gold standard for evaluating the functional significance of coronary stenosis. However, its potential benefits in real-world practice remain unknown in China. This study aimed to test the hypothesis that the use of FFR is associated with improved outcome and reduced cost in Chinese real-world clinical practice. Methods: A retrospective cohort study was carried out using the database of Second Affiliated Hospital of Zhejiang University, a tertiary and high-volume center in China. Clinical events were compared using the Cox proportional hazards model during a median follow-up of 13 months. Results: The study cohort consisted of 366 consecutive patients referred for coronary revascularization with adjunct FFR and 366 matched controls, from 2010 to 2014. Major adverse cardiac events (MACEs) (death, myocardial infarction, repeated revascularization, or hospitalization for angina) at 4 years were found in 12.0% of angiography-guided patients and 4.9% in the FFR-guided group (P < 0.001). The mean number of implanted stents was significantly lower in FFR treated subjects (0.52 ± 0.82 stents) compared with the angiography-guided group (0.93 ± 0.96 stents) (P < 0.001). No difference in overall costs at initial hospitalization was observed between angiography-guided percutaneous coronary intervention (PCI) compared with FFR-guided PCI (RMB 33,000 Yuan, range: RMB 7393-44,700 Yuan) versus RMB 21,200 Yuan (RMB 19,100-47,100 Yuan) (P = 0.54). However, costs for MACEs during follow-up were significantly reduced in the FFR-guided arm (P < 0.001). Conclusions: In the contemporary clinical practice, FFR-guided PCI is associated with decreased use of stents, improved clinical outcome, and reduced costs, compared with angiography-guided PCI.

Objectives. The present study aimed to explore the major factors that account for the beneficial effects of mesenchymal stem cells (MSCs). Methods. Using isobaric tags for relative and absolute quantitation method, hepatoma-derived growth factor (HDGF) was identified as an important factor secreted by MSCs, but not by cardiac fibroblasts (CFs). The protective effects of conditioned medium (CdM) from MSCs or CFs were tested by using either H9C2 cells that were exposed by hypoxia-reoxygenation (H/R) insult or an in vivo mouse model of myocardial ischemia-reperfusion. Results. Compared to CF-CdM, MSC-CdM conferred protection against reperfusion injury. CdM obtained from MSCs that were treated with HDGF-targeted shRNA failed to offer any protection in vitro. In addition, administration of recombinant HDGF alone recapitulated the beneficial effects of MSC-CdM, which was associated with increased protein kinase C epsilon (PKCε) phosphorylation, enhanced mitochondria aldehyde dehydrogenase family 2 activity, and decreased 4-hydroxy-2-nonenal accumulation. A significant decrease in infarct size and ameliorated cardiac dysfunction was achieved by administration of HDGF in wild-type mice, which was absent in PKCε dominant negative mice, indicating the essential roles of PKCε in HDGF-mediated protection. Conclusions. HDGF secreted from MSCs plays a key role in the protection against reperfusion injury through PKCε activation.

Abstract Immunoglobulin E (IgE) activates mast cells (MCs). It remains unknown whether IgE also activates other inflammatory cells, and contributes to the pathogenesis of abdominal aortic aneurysms (AAAs). This study demonstrates that CD4+ T cells express IgE receptor FcεR1, at much higher levels than do CD8+ T cells. IgE induces CD4+ T‐cell production of IL6 and IFN‐γ, but reduces their production of IL10. FcεR1 deficiency (Fcer1a−/−) protects apolipoprotein E‐deficient (Apoe−/−) mice from angiotensin‐II infusion‐induced AAAs and reduces plasma IL6 levels. Adoptive transfer of CD4+ T cells (but not CD8+ T cells), MCs, and macrophages from Apoe−/− mice, but not those from Apoe−/−Fcer1a−/− mice, increases AAA size and plasma IL6 in Apoe−/−Fcer1a−/− recipient mice. Biweekly intravenous administration of an anti‐IgE monoclonal antibody ablated plasma IgE and reduced AAAs in Apoe−/− mice. Patients with AAAs had significantly higher plasma IgE levels than those without AAAs. This study establishes an important role of IgE in AAA pathogenesis by activating CD4+ T cells, MCs, and macrophages and supports consideration of neutralizing plasma IgE in the therapeutics of human AAAs.

Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acids to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on the cardiovascular system. However, whether increasing EETs production by CYP2J2 overexpression in vivo could prevent abdominal aortic aneurysm (AAA) remains unknown. Here we investigated the effects of recombinant adeno-associated virus (rAAV)-mediated CYP2J2 overexpression on angiotensin (Ang) II-induced AAA in apoE-deficient mice. rAAV-CYP2J2 delivery led to an abundant aortic CYP2J2 expression and increased EETs generation. It was shown that CYP2J2 overexpression attenuated matrix metalloproteinase expression and activity, elastin degradation, and AAA formation, which was associated with reduced aortic inflammation and macrophage infiltration. In cultured vascular smooth muscle cells (VSMCs), rAAV-mediated CYP2J2 overexpression and EETs markedly suppressed Ang II-induced inflammatory cytokine expression. Moreover, overexpressed CYP2J2 and EETs inhibited Ang II-induced macrophage migration in a VSMC-macrophage coculture system. We further indicated that these protective effects were mediated by peroxisome proliferator-activated receptor (PPAR)γ activation. Taken together, these results provide evidence that rAAV-mediated CYP2J2 overexpression prevents AAA development which is likely via PPARγ activation and anti-inflammatory action, suggesting that increasing EETs levels could be considered as a potential strategy to prevent and treat AAA.

The role of mitochondrial apoptotic pathway in cardiomyocytes subjected to hypoxia/reoxygenation(H/R) was studied. Cultured cardiomyocytes from neonatal Sprague-Dawley rats were exposed to hyoxia/reoxygenation, the apoptotic cardiomyocytes were stained with Annexin-V-FITC, Hoechst 33342 and TUNEL assay. Mitochondrial transmembrane potential of cardiomyocytes was assessed by JC-1 under fluorescence microscope, the expressions of bcl-2, bax, cytochrome c, apoptosis-induced factor (AIF), and caspase-3 were tested by western-blot. Our data showed apoptosis of cardiomyocytes was significantly increased during H/R, accompanied by translocation of bax to mitochondria, release of cytochrome c and AIF to cytosol. The results indicate that the mitochondrial-mediated apoptotic pathway is initiated as a result of H/R.

Ezetimibe, as a cholesterol absorption inhibitor, has been shown protecting against atherosclerosis when combined with statin. However, side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin. Herein, the study aimed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size.ApoE-/- male mice that were fed a saturated-fat supplemented diet were randomly assigned to different therapeutic regimens: vehicle, ezetimibe alone (10 mg/kg/day), atorvastatin (20 mg/kg/day) or combination of ezetimibe and atorvastatin through the drinking water. On 28 days, mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels. As a result, ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin, which was mediated by lowering serum cholesterol concentrations, inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines, such as monocyte chemoattractant protein (MCP-1) and tumor necrosis factor (TNF-α). In contrast to ezetimibe administration, atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects. There were no significance differences in lesion areas and serum concentrations of cholesterol, oxidized LDL and inflammatory cytokines between combination therapy and monotherapy (either ezetimibe or atorvastatin). There were significant correlations between the lesion areas and serum concentrations of cholesterol, MCP-1 and TNF-α, respectively. However, there were no significant correlations between the lesion areas and serum concentrations of TGF-β1 and oxLDL.Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin, which was associated with lowering serum cholesterol, decreasing circulating inflammatory cytokines, and inhibiting macrophage accumulation in the lesions.

The sampled-data synchronization problem for complex networks with random coupling strengths, probabilistic time-varying coupling delay, and distributed delay (mixed delays) is investigated. The sampling period is assumed to be time varying and bounded. By using the properties of random variables and input delay approach, new synchronization error dynamics are constructed. Based on the delay decomposition method and reciprocally convex approach, a delay-dependent mean square synchronization condition is established in terms of linear matrix inequalities (LMIs). According to the proposed condition, an explicit expression for a set of desired sampled-data controllers can be achieved by solving LMIs. Numerical examples are given to demonstrate the effectiveness of the theoretical results.

The problem of synchronization for a class of complex networks with probabilistic time-varying coupling delay and distributed time-varying coupling delay (mixed probabilistic time-varying coupling delays) using pinning control is investigated in this paper. The coupling configuration matrices are not assumed to be symmetric or irreducible. By adding adaptive feedback controllers to a small fraction of network nodes, a low-dimensional pinning sufficient condition is obtained, which can guarantee that the network asymptotically synchronizes to a homogenous trajectory in mean square sense. Simultaneously, two simple pinning synchronization criteria are derived from the proposed condition. Numerical simulation is provided to verify the effectiveness of the theoretical results.

Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion (IR) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired in hypercholesterolemia. Therefore, we investigate whether anesthetic-induced cardiac protection was maintained in hypercholesterolemic rats. In the present study, normocholesteolemic or hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals received 2.4% sevoflurane for 5 min or 3 cycles of 10-s ischemia/10-s reperfusion. The hemodynamic parameters, including left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate, were continuously monitored. The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3β were determined. We found that both sevoflurane and ischemic postconditioning significantly improved heart pump function, reduced infarct size and increased the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3β in the healthy rats. In the hypercholesterolemic rats, neither sevoflurane nor ischemic postconditioning improved left ventricular hemodynamics, reduced infarct size and increased the phosphorylated Akt, ERK1/2 and GSK3β. In contrast, GSK inhibitor SB216763 conferred cardioprotection against IR injury in healthy and hypercholesterolemic hearts. In conclusions, hyperchoesterolemia abrogated sevoflurane-induced cardioprotection against IR injury by alteration of upstream signaling of GSK3β and acute GSK inhibition may provide a novel therapeutic strategy to protect hypercholesterolemic hearts against IR injury.