Fractal analysis of left ventricular trabeculae in heart failure with preserved ejection fraction patients with multivessel coronary artery disease.

OBJECTIVES: Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD). METHODS: The retrospective study population consisted of 97 patients with multivessel CAD, 39 of them were diagnosed with HFpEF, while 46 healthy volunteers were recruited as controls. Fractal dimension (FD) was obtained through fractal analysis of endocardial trabeculae on LV short-axis cine images. Logistic regression analyses were used to confirm the predictors and compare different prediction models. RESULTS: Mean basal FD was significantly higher in patients with HFpEF than in patients without HFpEF or in the healthy group (median: 1.289; IQR: 0.078; p < 0.05). Mean basal FD was also a significant independent predictor in univariate and multivariate logistic regression (OR: 1.107 and 1.043, p < 0.05). Furthermore, adding FD to the prediction model improved the calibration and accuracy of the model (c-index: 0.806). CONCLUSION: The left ventricular FD obtained with fractal analysis can reflect the complexity of myocardial trabeculae and has an independent predictive value for the diagnosis of HFpEF in patients with multivessel CAD. Including FD into the diagnostic model can help improve the diagnosis. CRITICAL RELEVANCE STATEMENT: Differences show in the complexity of endocardial trabeculae in multivessel coronary artery disease patients, and obtaining fractal dimensions (FD) by fractal analysis can help identify heart failure with preserved ejection fraction (HFpEF) patients. KEY POINTS: The complexity of myocardial trabeculae differs among patients with multivessel coronary artery disease. Left ventricular fractal dimensions can reflect the complexity of the myocardial trabecular. Fractal dimensions have predictive value for the diagnosis of heart failure with preserved ejection fraction.

Peptide-Coated Bacteriorhodopsin-Based Photoelectric Biosensor for Detecting Rheumatoid Arthritis.

An effective early diagnosis is important for rheumatoid arthritis (RA) management. This study reveals a novel RA detection method using bacteriorhodopsin as a photoelectric transducer, a light-driven proton pump in purple membranes (PMs). It was devised by covalently conjugating a PM monolayer-coated electrode with a citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)542-556 peptide that recognizes the serum RA-associated autoantibodies. The direct serum coating decreased the photocurrents in the biosensor, with the reduction in the photocurrent caused by coating with an RA-patient serum that is significantly larger than that with a healthy-control serum (38.1% vs. 20.2%). The difference in the reduction in the photocurrent between those two serum groups widened after the serum-coated biosensor was further labeled with gold nanoparticle (AuNP)-conjugated anti-IgA (anti-IgA-AuNP) (53.6% vs. 30.6%). Both atomic force microscopic (AFM) and Raman analyses confirmed the sequential peptide, serum, and anti-IgA-AuNP coatings on the PM-coated substrates. The reductions in the photocurrent measured in both the serum and anti-IgA-AuNPs coating steps correlated well with the results using commercial enzyme-linked immunosorbent assay kits (Spearman rho = 0.805 and 0.787, respectively), with both a sensitivity and specificity close to 100% in both steps. It was shown that an RA diagnosis can be performed in either a single- or two-step mode using the developed biosensor.

Quantum Simulation of Topological Zero Modes on a 41-Qubit Superconducting Processor.

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

Late gadolinium enhancement entropy as a new measure of myocardial tissue heterogeneity for prediction of adverse cardiac events in patients with hypertrophic cardiomyopathy.

OBJECTIVES: Entropy is a new late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR)-derived parameter that is independent of signal intensity thresholds. Entropy can be used to measure myocardial tissue heterogeneity by comparing full pixel points of tissue images. This study investigated the incremental prognostic value of left ventricular (LV) entropy in patients with hypertrophic cardiomyopathy (HCM). METHODS: This study enrolled 337 participants with HCM who underwent 3.0-T CMR. The LV entropy was obtained by calculating the probability distribution of the LV myocardial pixel signal intensities of the LGE sequence. Patients who underwent CMR imaging were followed up for endpoints. The primary endpoint was defined as readmission to the hospital owing to heart failure. The secondary endpoint was the composite of the primary endpoint, sudden cardiac death and non-cardiovascular death. RESULTS: During the median follow-up of 24 months ± 13 (standard deviation), 43 patients who reached the primary and secondary endpoints had a higher entropy (6.20 ± 0.45, p < 0.001). The patients with increased entropy (≥ 5.587) had a higher risk of the primary and secondary endpoints, compared with HCM patients with low entropy (p < 0.001 for both). In addition, Cox analysis showed that LV entropy provided significant prognostic value for predicting both primary and secondary endpoints (HR: 1.291 and 1.273, all p < 0.001). Addition of LV entropy to the multivariable model improved model performance and risk reclassification (p < 0.05). CONCLUSION: LV entropy assessed by CMR was an independent predictor of primary and secondary endpoints. LV entropy assessment contributes to improved risk stratification in patients with HCM. CRITICAL RELEVANCE STATEMENT: Myocardial heterogeneity reflected by entropy the derived parameter of LGE has prognostic value for adverse events in HCM. The measurement of LV entropy helped to identify patients with HCM who were at risk for heart failure and sudden cardiac death. KEY POINTS: • Left ventricular entropy can reflect myocardial heterogeneity in HCM patients. • Left ventricular entropy was significantly higher in HCM patients who reached endpoint events. • Left ventricular entropy helps to predict the occurrence of heart failure and death in HCM patients.

Quantum simulation of Hawking radiation and curved spacetime with a superconducting on-chip black hole.

Hawking radiation is one of the quantum features of a black hole that can be understood as a quantum tunneling across the event horizon of the black hole, but it is quite difficult to directly observe the Hawking radiation of an astrophysical black hole. Here, we report a fermionic lattice-model-type realization of an analogue black hole by using a chain of 10 superconducting transmon qubits with interactions mediated by 9 transmon-type tunable couplers. The quantum walks of quasi-particle in the curved spacetime reflect the gravitational effect near the black hole, resulting in the behaviour of stimulated Hawking radiation, which is verified by the state tomography measurement of all 7 qubits outside the horizon. In addition, the dynamics of entanglement in the curved spacetime is directly measured. Our results would stimulate more interests to explore the related features of black holes using the programmable superconducting processor with tunable couplers.

KPC1 alleviates hypoxia/reoxygenation-induced apoptosis in rat cardiomyocyte cells though BAX degradation.

Bax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia-reperfusion (I/R)-induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R-myocardium in vivo and in hypoxia and reoxygenation (H/R)-induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short-hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress-induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R-induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1.

Versatile Protein-A Coated Photoelectric Immunosensors with a Purple-Membrane Monolayer Transducer Fabricated by Affinity-Immobilization on a Graphene-Oxide Complexed Linker and by Shear Flow.

Bacteriorhodopsin-embedded purple membranes (PM) have been demonstrated to be a sensitive photoelectric transducer for microbial detection. To efficiently prepare versatile BR-based immunosensors with protein A as antibody captures, a large, high-coverage, and uniformly oriented PM monolayer was fabricated on an electrode as an effective foundation for protein A conjugation through bis-NHS esters, by first affinity-coating biotinylated PM on an aminated surface using a complex of oxidized avidin and graphene oxide as the planar linker and then washing the coating with a shear flow. Three different polyclonal antibodies, each against Escherichia coli, Lactobacillus acidophilus, and Streptococcus mutans, respectively, were individually, effectively and readily adsorbed on the protein A coated electrodes, leading to selective and sensitive quantitative detection of their respective target cells in a single step without any labeling. A single-cell detection limit was achieved for the former two cells. AFM, photocurrent, and Raman analyses all displayed each fabricated layer as well as the captured bacteria, with AFM particularly revealing the formation of a massive continuous PM monolayer on aminated mica. The facile cell-membrane monolayer fabrication and membrane surface conjugation techniques disclosed in this study may be widely applied to the preparation of different biomembrane-based biosensors.

Three new norlignans from Glechoma longituba.

Three new norlignans, glechomols A-C (1-3, respectively), together with a known compound, 4-ethylcatechol (4), were isolated from the ethyl acetate extract of Glechoma longituba (NaKai) Kupr. Their structures were elucidated by the detailed analysis of 1D and 2D NMR and HR-MS data. Glechomols A-C were the first norlignans reported from genus Glechoma, and compound 4 was also isolated from genus Glechoma for the first time. Intracellular antioxidant assays showed that compounds 1-4 displayed significant protective effects on H2O2-induced cardiac cell injury.

Meta-analysis of clinical studies comparing coronary artery bypass grafting with percutaneous coronary intervention in patients with end-stage renal disease.

End-stage renal disease (ESRD) patients are at high risk for coronary artery disease (CAD). The optimal revascularization strategy remains unknown. We performed a meta-analysis of retrospective observational trials to compare coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for ESRD patients with CAD. A search of published reports was conducted to identify clinical studies comparing CABG with PCI in ESRD patients with CAD with a minimal follow-up of 12 months. Sixteen studies included 32 350 ESRD patients with revascularization. Compared with PCI, CABG was associated with a lower risk for late mortality [relative risk (RR) 0.90, 95% confidence interval (CI) 0.87-0.93], myocardial infarction event (RR 0.64, 95% CI: 0.61-0.68), repeat revascularization event (RR 0.22, 95% CI: 0.16-0.31) and cumulative events (RR 0.69, 95% CI: 0.65-0.73), despite having a higher risk for early mortality (RR 1.98, 95% CI: 1.51-2.60). In conclusion, the long-term results of PCI in ESRD patients are dismal, and CABG is significantly superior to PCI in this subset of patients.

1-(4-Chloro-2-fluoro-phen-yl)-4-difluoro-methyl-3-methyl-1H-1,2,4-triazol-5(4H)-one.

In the crystal structure of the title compound, C(10)H(7)ClF(3)N(3)O, pairs of mol-ecules are connected into dimers via pairs of C-H⋯O hydrogen bonds. The dihedral angle between the benzene ring and attached triazolone ring is 53.2 (1)°.

1-(3,3-Dichloro-all-yloxy)-2-nitro-benzene.

In the title compound, C(9)H(7)Cl(2)NO(3), the dihedral angle between the benzene ring and the plane of the nitro group is 50.2 (1)°, and that between the benzene ring and the best plane through the dichloro-allyl fragment is 40.1 (1)°.

[Effects on proliferation and apoptosis of serum-induced rabbit VSMCs by adenovirus-mediated transfer of the Gax gene].

AIM: To investigate the effect of a recombinant replication-incompetent Ad5-hGax vector on the proliferation and apoptosis of serum-induced rabbit vascular smooth muscle cells (VSMCs) in vitro, and to provide an important support that Gax would be an optimal gene for gene therapy in vein graft failure. METHODS: The Ad5-hGax vector was infected into rabbit VSMCs, then the protein level of rabbit VSMCs was detected at 1 d, 3 d, 5 d by Western blot, respectively. MTT was applied to observe the inhibitory effects of overexpressed hGax on serum-induced rabbit VSMCs. the apoptosis of serum-induced rabbit VSMCs was measured by using flow cytometry in 72 h after transfection. RESULTS: The protein expression of human Gax in the Ad5-hGax transfected cells on 1st day, 3rd day, 5th day was determined; MTT showed that the proliferation of serum-induced rabbit VSMCs was significantly inhibited in Ad5-hGax group at 48 h, 72 h and 96 h (P<0.05, respectively); After transfecting for 72 h, flow cytometry analysis showed that the number of the apoptosis cells was increased in serum-induced Rabbit VSMCs of Ad5-hGax group (P<0.05). CONCLUSION: Overexpressed hGax could inhibit the proliferation of serum-induced Rabbit VSMCs and induce their apoptosis. These findings carry significant implications for adenovirus vector-based Gax gene therapies for vein graft failure.

[Analysis on bone marrow feature of 56 clinic cases of benzene poisoning].

OBJECTIVE: To explore the bone marrow feature of hemopoietic system injured by benzene through analyzing 56 benzolism cases. METHODS: The 56 benzolism cases were divided into mild poisoning group, midrange poisoning group, aplastic anemia group, pancytopenia group and leukemia group. All cases progressed bone marrow aspiration and smear, and counted hundred karyocytes by Wright-Giemsa tinct bone marrow smear to classification and observe the cells' feature. RESULTS: The megakaryocytes and the extent of bone marrow hyperplasia were decreased by turns of mild poisoning group, midrange poisoning group and aplastic anemia group. The archaeocytes and juvenile cells proliferation in mild poisoning group and midrange poisoning group were inhibited and occurred cell paramorphia which related to intoxication. Comparing with the other groups and normal reference value, the pancytopenia group's percentage of bone marrow cells in karyocytes was significantly decreased (P < 0.01, P < 0.05) and the leukemia group's percentage of bone marrow cells in karyocytes was significantly increased (P < 0.01). The proportion of cell paramorphia and nucleus malformation of granulocytes and red blood cells in pancytopenia group and leukemia group were increased, especially in leukemia group. CONCLUSION: We saw the inhibition of archaeocytes and juvenile cells proliferation and some cell paramorphia appearances in mild poisoning and midrange poisoning cases of chronic benzolism. The abnormality changes which can be seen in bone marrow of severe benzolism cases were corresponding with the clinical classification.

A novel promising therapy for vein graft restenosis: overexpressed Nogo-B induces vascular smooth muscle cell apoptosis by activation of the JNK/p38 MAPK signaling pathway.

Coronary artery bypass grafting using autologous saphenous veins is a standard surgical therapy for coronary artery diseases. However, post-procedure vein graft restenosis impedes its effectiveness and often leads to a high morbidity and mortality, and a reduction in the quality of life. Neointimal hyperplasia is a major cause of vein graft occlusion, and is characterized by an imbalance between vascular smooth muscle cell (VSMC) proliferation and apoptosis. So far, there have been no optimally effective pharmacological or non-pharmacological interventions for the prevention and treatment of vein graft occlusion. Gene therapy has emerged as a potential therapeutic approach, as bypass grafts can be genetically modified ex vivo prior to grafting in the coronary vasculature. Nogo-B, recognized as a vascular protective factor, has been shown to reduce neointimal thickening in graft veins, but its specific mechanism is uncertain. Evidence from diverse sources has documented that overexpressed Nogo-B can induce apoptosis of variant cancer cell lines, suggesting that overexpressed Nogo-B may have a pro-apoptotic role in VSMC. Furthermore, we have found that Nogo-B is associated with the mitogen-activated protein kinase (MAPK) signaling pathway, which plays important roles in cell growth, differentiation, and apoptosis. Recent studies have shown that VSMC apoptosis can be induced by activation of the c-Jun-N-terminal kinase (JNK)/p38 MAPK pathway. Therefore, we propose that overproduction of Nogo-B in the graft vein could result in reduced neointimal hyperplasia, the mechanism of which involves increased VSMC apoptosis induced by activation of the JNK/p38 MAPK pathway. This study will provide a new clue for gene therapy in the treatment of vein graft failure.

Toll-like receptor 7/8 agonist resiquimod induces late preconditioning in neonatal cardiac myocytes.

AIM: To investigate whether R-848 (resiquimod, toll-like receptor 7/8 agonist) can induce late preconditioning in neonatal cardiac myocytes. METHODS: The protective effects of R-848 on neonatal myocytes against anoxia-reoxygenation-induced injury were tested, and intracellular reactive oxygen species (ROS) were determined. The protein synthesis inhibitor cyclohexamide (CH) and the ROS scavenger N-acetylcysteine (NAC) were used in this model to test if new protein synthesis and oxidative stress were necessary for their cardioprotective effects. The activation of nuclear factor kappa B (NFκB) and hypoxia inducible factor 1 (HIF1) was investigated by electrophoretic mobility shift assays (EMSA), and inducible nitric oxide synthase (iNOS) was assessed by immunoblotting. After iNOS was down-regulated by small interfering RNA (siRNA) transfection, the cardioprotective effect was reassessed. RESULTS: ROS were triggered soon after R-848 (0.01-1.0 µg/L) administration, however, the cardioprotective effect of which was induced 24 h later. This protection was abolished by CH or NAC pretreatment. NFκB and HIF1 activation and iNOS up-regulation were involved in this protective mechanism. The cardioprotective effect was also attenuated after iNOS was knocked down. CONCLUSION: R-848 provided a cardioprotective effect through a late preconditioning mechanism via a ROS/NFκB-HIF1/iNOS-dependent pathway.

[Construction of human Gax gene eukaryotic expression vector and its expression in vascular smooth muscle cells].

AIM: To construct human Gax eukaryotic expression vector of pEGFP-N1-Gax, and observe its expression in the rabbit vascular smooth muscle cells(VSMCs). METHODS: human Gax cDNA was obtained by polymerase chain reaction(PCR) from pCMV-SPORT6-Gax plasmid. After digested with Nhe I and Xho I, the PCR product was cloned into eukaryotic expression vector pEGFP-N1 of green fluorescent protein(GFP) reported gene encoding green fluorescence protein, and then the recombinant plasmid pEGFP-N1-Gax was transfected into rabbit VSMCs using Sofast after it was identified by restriction enzyme digestion analysis and gene sequencing. Human Gax expression in rabbit VSMCs was detected by examining GFP expression of transfected cells under fluorescence microscope and RT-PCR. RESULTS: Agarose gel electrophoresis detection showed that human Gax DNA segment was about 915 bp, which accorded with the expectation. The restriction enzyme digestion analysis and DNA sequencing assays of recombinant vector pEGFP-N1-Gax showed the correct orientation and sequence. The expression of GFP in rabbit VSMCs transfected with pEGFP-N1-Gax was observed by fluorescence microscopy, and the expression of human Gax mRNA was confirmed by RT-PCR. CONCLUSION: The recombinant plasmid pEGFP-N1-Gax is successfully constructed, and expressed positively in rabbit VSMCs, it provide experimental basis to study the effects of Gax gene on cardiovascular disease.

Pro-inflammatory cytokines may induce late preconditioning in unstable angina patients.

Late preconditioning can be induced by a wide variety of stimulus, including non-pharmacological and pharmacological. Thus, late preconditioning is a universal response of the heart to stress and it requires the simultaneous activation of multiple stress-responsive genes. Recently, compelling evidence has evolved that the up-regulation of pro-inflammatory cytokines plays an important role in induction of the late phase of ischemic preconditioning in rodent models. However, the role of cytokines in induction of late preconditioning in humans has not been explored. Patients with unstable coronary syndromes have a systemic inflammatory responses with increase of the pro-inflammatory cytokines, such as TNFalpha, IL-6. And some researchers find the patients undergoing CABG with unstable angina have a better cardioprotective effect caused by late preconditioning characterized by the activated NF-kappaB and synthesized effector proteins (HSP72 and eNOS). Therefore, we hypothesize that pro-inflammatory cytokines may induce late preconditioning in unstable angina patients directly or through remote preconditioning. It is difficult to test our hypotheses in vivo, but in vitro, human tissue culture with isolated atrial myocardium could be tested. If the hypotheses is true, the biological complication is immense. A new physiological function of pro-inflammatory cytokines is found, that is, inducing endogenous cytoprotection. From the clinical point of view, administering the appropriate pro-inflammatory cytokines will be beneficial to patients before cardiac surgery.

[Therapeutic effect of levamisole plus HBV vaccine and dipyridamole on patients chronically infected by HBV with precore mutation].

OBJECTIVE: To evaluate the incidence of precore mutation in HBeAg negative HBV infected patients and the therapeutic effect of the immune therapy (levamisole + HBV vaccine + dipyridamole) on patients chronically infected by HBV with precore mutation. METHODS: The precore region of HBV from the HBeAg (-) chronic hepatitis patients was sequenced and the patients suffered from HBV with precore mutation were treated with immune therapy. RESULTS: The precore mutation rate was 10/12. The therapeutic effect of the immune therapy on the precore mutation patients (5/7) was better than that on the HBsAg(+), HBeAg(+) patients (2/11), P less than 0.05. CONCLUSION: The precore mutation rate was quite high in the HBsAg(+), HBeAg(-) patients we studied. The immune-therapy has some therapeutic effects on the patients with precore mutation. But the number of cases was too small, further study is needed.