Efficacy of Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction by enhancing autophagy in rat.

OBJECTIVE: To elucidate the protective effects of Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction (MI) through regulating myocardial autophagy. METHODS: Thirty-one male Sprague-Dawley rats were randomized into five groups (n = 6 or 7 for each). After treatment for 3 weeks, electrocardiogram ( ECG ) and cardiac function were recorded. Hematoxylin and eosin (HE) staining was used to detect pathological changes in the heart. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum B-type brain natriuretic peptide (BNP), cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α), and serum inflammatory cytokines. Metabolomic analysis was used to identify differential biomarkers of MI in rats. Immunohistochemistry and western blotting were used to detect BNP, cTnT, TNF-α, LC3B, Beclin-1, p62, and adenosine monophosphate activated protein kinase (AMPK) expression in cardiac tissue. RESULTS: Fuzi (Radix Aconiti Lateralis Preparata) alone or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) markedly ameliorated cardiac dysfunction and abnormal ECGs, demonstrated by decreases in the heart weight/body weight ratio, BNP, and cTnT. Pro-inflammation cytokine interleukin (IL)-1α significantly decreased and anti-inflammatory cytokine IL-10 significantly increased in Renshen (Radix Ginseng) single or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) groups compared with the control group. HE results suggested that co-treatment produced a greater reduction in cardiomyocyte cross-sectional area than Renshen (Radix Ginseng) or Fuzi (Radix Aconiti Lateralis Preparata) alone. Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) reversed these changes to different degrees in MI rats. Furthermore, Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) down-regulated LC3B, Beclin-1, and AMPK expression in cardiac tissue and upregulated p62 expression. CONCLUSIONS: Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) may have a greater effect on heart injury induced by MI in rats than Fuzi (Radix Aconiti Lateralis Preparata) treatment alone, and the underlying mechanism may be associated with the regulation of myocardial autophagy and anti-inflammation effects. These results provide fresh insight into the mechanism of co-treatment with Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) for MI.

A highly tunable quadruple quantum dot in a narrow bandgap semiconductor InAs nanowire.

Quantum dots (QDs) made from semiconductors are among the most promising platforms for the development of quantum computing and simulation chips, and they have the advantages of high density integration and compatibility with the standard semiconductor chip fabrication technology compared to other platforms. However, the development of a highly tunable semiconductor multiple QD system still remains a major challenge. Here, we demonstrate the realization of a highly tunable linear quadruple QD (QQD) in a narrow bandgap semiconductor InAs nanowire via a fine finger gate technique. The QQD is studied by electron transport measurements in the linear response regime. Characteristic two-dimensional charge stability diagrams containing four groups of resonant current lines of different slopes are obtained for the QQD. It is shown that these current lines arise from and can be individually assigned to resonant electron transport through the energy levels of different QDs. Benefitting from the excellent gate tunability, we also demonstrate the tuning of the QQD to regimes where the energy levels of two QDs, three QDs and all four QDs are energetically in resonance, respectively, with the Fermi level of the source and drain contacts. A capacitance network model is developed for the linear QQD and the simulated charge stability diagrams based on this model show good agreement with the experiments. Our work provides solid experimental evidence that narrow bandgap semiconductor nanowire multiple QDs could be used as a versatile platform to achieve integrated qubits for quantum computing and to perform quantum simulations of complex many-body systems.

Measurements of anisotropic g-factors for electrons in InSb nanowire quantum dots.

We have measured the Zeeman splitting of quantum levels in few-electron quantum dots (QDs) formed in narrow bandgap InSb nanowires via the Schottky barriers at the contacts under application of different spatially orientated magnetic fields. The effective g-factor tensor extracted from the measurements is strongly anisotropic and level-dependent, which can be attributed to the presence of strong spin-orbit interaction (SOI) and asymmetric quantum confinement potentials in the QDs. We have demonstrated a successful determination of the principal values and the principal axis orientations of the g-factor tensors in an InSb nanowire QD by the measurements under rotations of a magnetic field in the three orthogonal planes. We also examine the magnetic field evolution of the excitation spectra in an InSb nanowire QD and extract a SOI strength of [Formula: see text] ∼ 180 µeV from an avoided level crossing between a ground state and its neighboring first excited state in the QD.

Pseudo-Yang-Lee Edge Singularity Critical Behavior in a Non-Hermitian Ising Model.

The quantum phase transition of a one-dimensional transverse field Ising model in an imaginary longitudinal field is studied. A new order parameter M is introduced to describe the critical behaviors in the Yang-Lee edge singularity (YLES). The M does not diverge at the YLES point, a behavior different from other usual parameters. We term this unusual critical behavior around YLES as the pseudo-YLES. To investigate the static and driven dynamics of M, the (1+1) dimensional ferromagnetic-paramagnetic phase transition ((1+1) D FPPT) critical region, (0+1) D YLES critical region and the (1+1) D YLES critical region of the model are selected. Our numerical study shows that the (1+1) D FPPT scaling theory, the (0+1) D YLES scaling theory and (1+1) D YLES scaling theory are applicable to describe the critical behaviors of M, demonstrating that M could be a good indicator to detect the phase transition around YLES. Since M has finite value around YLES, it is expected that M could be quantitatively measured in experiments.

Xin-Ji-Er-Kang Alleviates Myocardial Infarction-Induced Cardiovascular Remodeling in Rats by Inhibiting Endothelial Dysfunction.

The present study was designed to elucidate the beneficial effects of XJEK on myocardial infarction (MI) in rats, especially through the amelioration of endothelial dysfunction (ED). 136 Sprague-Dawley rats were randomized into 13 groups: control group for 0wk (n = 8); sham groups for 2, 4, and 6 weeks (wk); MI groups for 2, 4, and 6 wk; MI+XJEK groups for 2, 4, and 6w k; MI+Fosinopril groups for 2, 4, and 6 wk (n = 8~10). In addition, 8 rats were treated for Evans blue staining and Tetrazolium chloride (TTC) staining to determine the infarct size. Cardiac function, ECG, and cardiac morphological changes were examined. Colorimetric analysis was employed to detect nitric oxide (NO), and enzyme-linked immunosorbent assay (ELISA) was applied to determine N-terminal probrain natriuretic peptide (NT-ProBNP), endothelin-1 (ET-1), angiotensin II (Ang II), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH4), and endothelial NO synthase (eNOS) content. The total eNOS and eNOS dimer/(dimer+monomer) ratios in cardiac tissues were detected by Western blot. We found that administration of XJEK markedly ameliorated cardiovascular remodeling (CR), which was manifested by decreased HW/BW ratio, CSA, and less collagen deposition after MI. XJEK administration also improved cardiac function by significant inhibition of the increased hemodynamic parameters in the early stage and by suppression of the decreased hemodynamic parameters later on. XJEK also continuously suppressed the increased NT-ProBNP content in the serum of MI rats. XJEK improved ED with stimulated eNOS activities, as well as upregulated NO levels, BH4 content, and eNOS dimer/(dimer+monomer) ratio in the cardiac tissues. XJEK downregulated ET-1, Ang II, and ADMA content obviously compared to sham group. In conclusion, XJEK may exert the protective effects on MI rats and could continuously ameliorate ED and reverse CR with the progression of MI over time.

The protective effects of polysaccharide extract from Xin-Ji-Er-Kang formula on Ang II-induced HUVECs injury, L-NAME-induced hypertension and cardiovascular remodeling in mice.

BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis. METHODS: Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues. RESULTS: The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling. CONCLUSION: Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.

Protective effect of Xin-Ji-Er-Kang on cardiovascular remodeling in high-salt induced hypertensive mice: Role ofoxidative stress and endothelial dysfunction.

BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula that has beenreported to exert effective protection against cardiovascular diseases, such as hypertension and myocarditis. OBJECTIVE: The aim of the present study was to investigate the effect of XJEK on high-salt-induced hypertensive mice and its possible mechanism. METHODS: The model of hypertension was established through a high-salt diet. Sixty male Kunming mice were randomized into six groups, namely the Control, Model, Low-dose XJEK, Middle-dose XJEK, High-dose XJEK and Fosinopril groups (n=10 per group). Different steady interventions were given to each group: 0.9% Sodium chloride was added to the diet of the Control group and 8% sodium chloride to the diet of the other five groups from the very beginning. An additional 4, 8 and 12 g/kg/day XJEK were intragastrically administered to the Low-dose, Middle-dose and High-dose XJEK groups, respectively, and 2 mg/kg/day fosinopril to the fosinopril group, from the start of week 5. Systolic blood pressure (SBP) was measured weekly from weeks 1 to 8 using the tail-cuff method. At the end of week 8, left ventricular (LV) systolic pressure, LV end-diastolic pressure and rate of rise of LV pressure were examined using a TransonicScisense catheter (Transonic Systems Inc,Ithaca, NY,USA). Endothelium-dependent relaxations induced by acetylcholine were observed in an isolated thoracic aorta ring. Serum and heartsweresampled for the measurement of the following indexes:Serum nitric oxide (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content (determined by colorimetricanalysis); serum angiotensin II(Ang II), endothelin-1, endothelial NO synthase (eNOS), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH4) concentration and l-arginine (determined by enzyme-linked immunosorbent assay); heart to body weight (HW/BW) ratio; myocardial morphological change (determined by HE and VG staining); myocardial eNOS expression (determined by immunofluorescence), and myocardial endothelin receptor A (ETA) expression (determined by western blotting). RESULTS: Statistical data showed that the HW/BW ratio was significantly decreased in the drug treatment group. XJEK treatment could improve the heart systolic and diastolic function and ameliorate hemodynamic parameters and vascular remodeling indexes. Colorimetric results showed that, compared with the model group, XJEK increased serum SOD, NOlevels, and decreased those of serum MDA and Ang II. XJEK reverted changes in cardiac pathology, decreased the myocardial cross-sectional area, collagen volume fraction and perivascular collagen area and improved endothelial dysfunction (ED) by promoting eNOS activity, enhancing NO bioavailability, increasing the expression of BH4 and decreasing ETA content. In addition, treatment with XJEK decreased ADMA content in the myocardium. CONCLUSION: In conclusion, XJEK mitigates cardiac remodeling in high-salt-induced hypertensive mice. The potential mechanism involves improved oxidative stress and endothelial dysfunction, independently of ameliorating BP.

Anisotropic Pauli Spin-Blockade Effect and Spin-Orbit Interaction Field in an InAs Nanowire Double Quantum Dot.

We report on experimental detection of the spin-orbit interaction field in an InAs nanowire double quantum dot device. In the spin blockade regime, leakage current through the double quantum dot is measured and is used to extract the effects of spin-orbit interaction and hyperfine interaction on spin state mixing. At finite magnetic fields, the leakage current arising from the hyperfine interaction can be suppressed, and the spin-orbit interaction dominates spin state mixing. We observe dependence of the leakage current on the applied magnetic field direction and determine the direction of the spin-orbit interaction field. We show that the spin-orbit field lies in a direction perpendicular to the nanowire axis but with a pronounced off-substrate-plane angle. The results are expected to have an important implication in employing InAs nanowires to construct spin-orbit qubits and topological quantum devices.

Effects of Xin-Ji-Er-Kang on Anticardiovascular Remodeling in L-NAME Induced Hypertensive Mice and Its Potential Mechanisms.

BACKGROUND: Xin-Ji-Er-Kang (XJEK) shows protective effects on the myocardial ischemic diseases in our previous reports. We hypothesized that XJEK may exert preventing effects on L-NAME induced hypertensive mice by ameliorating oxidative stress (OS) and endothelial dysfunction (ED). METHODS: After treatment with XJEK for four weeks, cardiac function and cardiovascular pathology changes were evaluated. Then, endothelial-dependent vascular relaxation and serum NO, eNOS, AMDA, SOD, MDA content, and cardiac tissue eNOS expression were detected. RESULTS: The hypertensive mice displayed distinct cardiovascular remodeling including increased HW/BW index (4.7 ± 0.33 versus 5.2 ± 0.34), cross-section area, and collagen deposition. In addition, ED was found manifested by decreased serum NO (20.54 ± 8.05 versus 6.29 ± 2.33), eNOS (28.34 ± 2.36 versus 20.37 ± 2.30), content, and decreased eNOS expression in cardiac tissue and damaged endothelium-dependent diastolic function. Moreover, OS was detected confirmed by decreased SOD activity and increased MDA content in serum. However, treatment with XJEK for 4 wk could reverse cardiovascular remodeling (HW/BW index normalized from 5.2 ± 0.34 to 4.59 ± 0.25), ameliorate and preserve endothelial function (NO: 16.67 ± 7.24 versus 6.29 ± 2.33; eNOS: 16.67 ± 7.24 versus 6.29 ± 2.33), and suppress OS. CONCLUSION: XJEK has protective effects against cardiovascular remodeling in L-NAME induced hypertensive mice.

Effects of Xin-Ji-Er-Kang on heart failure induced by myocardial infarction: Role of inflammation, oxidative stress and endothelial dysfunction.

BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection on cardiovascular diseases like hypertension and myocarditis. PURPOSE: To elucidate the protective effects of XJEK on heart failure (HF) induced by myocardial infarction (MI) through the amelioration of inflammation, oxidative stress (OS) and endothelial dysfunction(ED). MATERIALS AND METHODS: Fifty-seven male KM mice were randomized into the following six groups (n = 9-10 for each): control group, model group, MI+XJEK low dose group(XJEKL) group, MI+XJEK middle dose group(XJEKM), MI+XJEK high dose group(XJEKH), and MI+fosinopril group (positive control group). After treatment for four weeks, electrocardiography (ECG) and haemodynamics were recorded. Serum and tissues were collected for further analysis. Endothelium-dependent relaxation induced by acetylcholine was assessed in isolated thoracic aorta ring experiment. Hematoxylin and eosin (HE) and Van Gieson (VG) staining were used to detect the pathological changes of heart and thoracic aorta. Colorimetric analysis was employed to determine serum nitric oxide level (NO), malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity. ELISA was used to detect serum B-type natriuretic peptide (BNP) and serum inflammatory cytokines, as well as endothelial NO synthetase (eNOS), angiotensinII (Ang II) and endothelin-1(ET-1) concentration in both serum and cardiac tissues. Immunohistochemistry and Western blotting (WB) were employed to detect eNOS and inflammatory cytokine expressions in cardiac tissues. RESULTS: XJEK administration markedly ameliorated cardiac dysfunction and abnormal ECG manifested by decreased weight/body weight (HW/BW) ratio, BNP and remedied hypertrophy of cardiomyocytes and deposition of collagen, which might be in part attributed to the increased SOD and decreased MDA in serum. Furthermore, XJEK administration improved ED with boosted eNOS activities in serum and cardiac tissues, as well as up-regulated NO levels in serum, down-regulated Ang II and ET-1 content in serum and cardiac tissues. Lastly, protein expression of pro-inflammation cytokines significantly decreased, and anti-inflammatory cytokine was significantly enhanced in serum and cardiac tissues compared to model group. CONCLUSION: XJEK may exert beneficial effects on HF induced by MI in mice, and the underlying mechanism may be attributable to the amelioration of ED, anti-OS and anti-inflammation effects.

Coherent Transport in a Linear Triple Quantum Dot Made from a Pure-Phase InAs Nanowire.

A highly tunable linear triple quantum dot (TQD) device is realized in a single-crystalline pure-phase InAs nanowire using a local finger gate technique. The electrical measurements show that the charge stability diagram of the TQD can be represented by three kinds of current lines of different slopes and a simulation performed based on a capacitance matrix model confirms the experiment. We show that each current line observable in the charge stability diagram is associated with a case where a QD is on resonance with the Fermi level of the source and drain reservoirs. At a triple point where two current lines of different slopes move together but show anticrossing, two QDs are on resonance with the Fermi level of the reservoirs. We demonstrate that an energetically degenerated quadruple point at which all three QDs are on resonance with the Fermi level of the reservoirs can be built by moving two separated triple points together via sophistically tuning of energy levels in the three QDs. We also demonstrate the achievement of direct coherent electron transfer between the two remote QDs in the TQD, realizing a long-distance coherent quantum bus operation. Such a long-distance coherent coupling could be used to investigate coherent spin teleportation and superexchange effects and to construct a spin qubit with an improved long coherent time and with spin state detection solely by sensing the charge states.

Protective effects of Xinji'erkang on myocardial infarction induced cardiac injury in mice.

BACKGROUND: Myocardial infarction (MI) is a major risk factor responsible for morbidity and mortality. Xinji'erkang (XJEK) has been clinically used as an effective medication in the treatment of coronary heart disease and myocarditis. The purpose of this study was to investigate the cardioprotective effect of Xinji'erkang on MI mice. METHODS: Forty male mice were randomly assigned into four groups as follows (n = 10): sham, model, MI with administration of XJEK and fosinopril for four weeks. At the end of studies, hemodynamic parameters and electrocardiography (ECG) were recorded. Heart and body mass were measured and heart weight/body weight (HW/BW) ratio was calculated as index of hypertrophy. The hypertrophy of heart and aorta was examined using the hematoxylin and eosin (HE) staining, and the collagen deposition was evaluated using Van Gieson (VG) staining. Serum nitric oxide level (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration were assayed by colorimetric analysis. The expressions of endothelial NO synthetase (eNOS) expression in serum and cardiac tissues were determined using ELISA assay and immunohistochemistry. Angiotensin II (Ang II) in serum and cardiac tissues was measured using ELISA assay. Besides, tumor necrosis factor-α (TNF-α), interleukin1ß (IL-1ß) and interleukin10 (IL-10) were observed in cardiac tissues with ELISA assay as well. RESULTS: The administration of XJEK significantly improved cardiac dysfunction and abnormal ECG with reduced HW/BW ratio and ameliorated cardiomyocyte hypertrophy and collagen deposition compared to MI, which was partly due to the decreased SOD and increased MDA in serum. Moreover, XJEK treatment also improved endothelial dysfunction (ED) with not only enhanced eNOS activities in serum and cardiac tissues and elevated NO levels in serum, but also decreased Ang II content in serum and cardiac tissues. Finally, protein expressions of pro-inflammation cytokines, TNF-α and IL-1ß in the cardiac tissues with XJEK treatment were significantly decreased compared to model. On the contrary, IL-10, an anti-inflammatory cytokine concentrated in cardiac tissues was significantly enhanced compared to model. CONCLUSION: Xinji'erkang exerts cardioprotective effect on myocardial infarction in mice, which may be due to the improvement of endothelial dysfunction and the reduction of oxidative stress and inflammation response.

Kibble-Zurek Scaling in the Yang-Lee Edge Singularity.

We study the driven dynamics across the critical points of the Yang-Lee edge singularities (YLESs) in a finite-size quantum Ising chain with an imaginary symmetry-breaking field. In contrast to the conventional classical or quantum phase transitions, these phase transitions are induced by tuning the strength of the dissipation in a non-Hermitian system and can occur even at finite size. For conventional phase transitions, universal behaviors in driven dynamics across critical points are usually described by the Kibble-Zurek mechanism, which states that the scaling in dynamics is dictated by the critical exponents associated with one critical point and topological defects will emerge after the quench. While the mechanism leading to topological defects breaks down in the YLES, we find that for small lattice size, the driven dynamics can still be described by the Kibble-Zurek scaling with the exponents determined by the (0+1)-dimensional YLES. For medium finite size, however, the driven dynamics can be described by the Kibble-Zurek scaling with two sets of critical exponents determined by both the (0+1)-dimensional and the (1+1)-dimensional YLESs.

Band-inverted gaps in InAs/GaSb and GaSb/InAs core-shell nanowires.

The [111]-oriented InAs/GaSb and GaSb/InAs core-shell nanowires have been studied by the 8 × 8 Luttinger-Kohn Hamiltonian to search for non-vanishing fundamental gaps between inverted electron and hole bands. We focus on the variations of the band-inverted fundamental gap, the hybridization gap, and the effective gap with the core radius and shell thickness of the nanowires. The evolutions of all the energy gaps with the structural parameters are shown to be dominantly governed by the effect of quantum confinement. With a fixed core radius, a band-inverted fundamental gap exists only at intermediate shell thicknesses. The maximum band-inverted gap found is ~4.4 meV for GaSb/InAs and ~3.5 meV for InAs/GaSb core-shell nanowires, and for the GaSb/InAs core-shell nanowires the gap persists over a wider range of geometrical parameters. The intrinsic reason for these differences between the two types of nanowires is that in the shell the electron-like states of InAs is more delocalized than the hole-like state of GaSb, while in the core the hole-like state of GaSb is more delocalized than the electron-like state of InAs, and both favor a stronger electron-hole hybridization.