Sex differences in cardiac structure and function following acute myocardial infarction: Insights from the PARADISE-MI echocardiographic substudy.

AIMS: The incidence of heart failure hospitalization is higher in women than in men after myocardial infarction (MI). Sex-related differences in left ventricular (LV) remodelling may contribute to the differences in post-MI outcomes. The aim of this study was to assess sex differences in echocardiographic parameters post-MI, and whether the relationship between echocardiographic parameters and clinical outcomes differs by sex. METHODS AND RESULTS: In the PARADISE-MI trial, patients were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of high-risk MI. In the pre-specified echocardiographic substudy, 544 patients underwent echocardiography at the time of randomization and after 8 months. We compared key echocardiographic parameters in men and women and their association with primary composite outcome (cardiovascular death or incident heart failure). At baseline, women had higher LV ejection fraction (LVEF), lower LV end-diastolic volume (LVEDV) index, LV end-systolic volume (LVESV) index, and LV mass index. After adjusting for baseline clinical differences, changes in these echocardiographic parameters from baseline to 8 months were not significantly different in women versus men. Lower LVEF, higher LVEDV, LVESV, left atrial volume index, and average E/e' were associated with a higher risk of the primary composite outcome. Sex did not modify the relationship between echocardiographic parameters and clinical outcome. CONCLUSIONS: Despite baseline differences in measures of cardiac function between men and women following acute high-risk MI, there were no significant sex-related changes in chamber size or LV function. Sex did not modify the association between echocardiographic parameters and clinical outcome.

Association between Higher Expression of Vav1 in Hepatocellular Carcinoma and Unfavourable Clinicopathological Features and Prognosis.

OBJECTIVE: The aim was to investigate the potential relationship between Vav1 protein and prognosis in patients with hepatocellular carcinoma (HCC). METHODS: Samples were collected from 96 patients with HCC. For each patient, cancerous tissue and adjacent non-cancerous tissue were obtained. The Vav1 expression levels in these tissues were determined using immunohistochemistry. Chi-square and Fisher's exact tests were used to analyse the associations between Vav1 expression and clinicopathological characteristics. Kaplan- Meier analysis was used to assess the relationship between Vav1 expression and 5-year overall survival (OS). RESULTS: The expression level of Vav1 protein in primary tumour samples (64.46%; 59/96) was higher (33.33%; 32/96; P<0.001). Moreover, the high expression rate of Vav1 was correlated with tumour differentiation, TNM stage, and tumour recurrence (P<0.05). Univariate and multivariate Cox analysis further demonstrated that tumour differentiation, TNM stage, vascular invasion, tumour recurrence and Vav1 expression were independent prognostic factors for 5-year OS. Notably, follow-up analysis determined that patients with HCC with higher Vav1 expression levels have lower survival rates (P<0.05). CONCLUSION: Vav1 may serve as a promising molecular prognostic biomarker for patients diagnosed with HCC.

Bonding-Directed Crystallization of Ultra-Long One-Dimensional NbS3 van der Waals Nanowires.

The rediscovery of one-dimensional (1D) and quasi-1D (q-1D) van der Waals (vdW) crystals ushered the realization of nascent physical properties in 1D that are suitable for applications in photonics, electronics, and sensing. However, despite renewed interest in the creation and understanding of the physical properties of 1D and q-1D vdW crystals, the lack of accessible synthetic pathways for growing well-defined nanostructures that extend across several length scales remains. Using the highly anisotropic 1D vdW NbS3-I crystal as a model phase, we present a catalyst-free and bottom-up synthetic approach to access ultralong nanowires, with lengths reaching up to 7.9 mm and with uniform thicknesses ranging from 13 to 160 nm between individual nanowires. Control over the synthetic parameters enabled the modulation of intra- and interchain growth modalities to selectively yield only 1D nanowires or quasi-2D nanoribbons. Comparative synthetic and density functional theory (DFT) studies with a closely related nondimerized phase, ZrS3, show that the unusual preferential growth along 1D can be correlated to the strongly anisotropic bonding and dimeric nature of NbS3-I.

Acute changes in kidney function and outcomes following an acute myocardial infarction: Insights from PARADISE-MI.

AIMS: Pharmacologic blockade of neurohormonal pathways in patients with acute myocardial infarction (MI) can result in acute changes in biomarkers of kidney function. We evaluated the effect of sacubitril/valsartan versus ramipril on initial changes in serum creatinine and the association of these changes with longer-term outcomes among participants in PARADISE-MI. METHODS AND RESULTS: In this randomized, double-blind, active-controlled, event-driven trial, 5661 patients with an acute MI were assigned to receive sacubitril/valsartan or ramipril, with no run-in. The frequency of an initial pre-specified increase in serum creatinine (≥26.5 or ≥44 µmol/L) from baseline to week 1 was compared between arms. Multivariable Cox regression models were fit to examine the association of acute changes in serum creatinine with the primary cardiovascular composite outcome (cardiovascular death, first heart failure hospitalization, or outpatient heart failure), all-cause mortality, and longer-term changes in estimated glomerular filtration rate (eGFR). An initial increase in serum creatinine ≥26.5 µmol/L occurred in 155 of 2604 (6.0%) patients assigned to sacubitril/valsartan and 120 of 2603 (4.6%) patients assigned to ramipril (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.03-1.68). The corresponding numbers for an increase ≥44 µmol/L were 57 (2.2%) and 42 (1.6%), respectively (OR 1.37; 95% CI 0.92-2.05). A higher odds of increased serum creatinine ≥26.5 and ≥44 µmol/L for sacubitril/valsartan versus ramipril appeared to be restricted to patients who had a greater decline in systolic blood pressure over the same period (p-interaction = 0.05 and 0.001, respectively). In multivariable analyses, neither an acute increase in serum creatinine ≥26.5 or ≥44 µmol/L was associated with a higher risk of cardiovascular outcomes, all-cause mortality, or differences in longer-term eGFR slope. Findings were similar across the randomized treatment arms (p-interaction >0.6 for all). CONCLUSIONS: Following acute MI, patients assigned to sacubitril/valsartan had a higher frequency of initial increases in serum creatinine at 1 week, compared with ramipril. In adjusted models, initial increases in serum creatinine with either treatment were not associated with adverse cardiovascular outcomes or changes in longer-term kidney function.

Exceptional electronic transport and quantum oscillations in thin bismuth crystals grown inside van der Waals materials.

Confining materials to two-dimensional forms changes the behaviour of the electrons and enables the creation of new devices. However, most materials are challenging to produce as uniform, thin crystals. Here we present a synthesis approach where thin crystals are grown in a nanoscale mould defined by atomically flat van der Waals (vdW) materials. By heating and compressing bismuth in a vdW mould made of hexagonal boron nitride, we grow ultraflat bismuth crystals less than 10 nm thick. Due to quantum confinement, the bismuth bulk states are gapped, isolating intrinsic Rashba surface states for transport studies. The vdW-moulded bismuth shows exceptional electronic transport, enabling the observation of Shubnikov-de Haas quantum oscillations originating from the (111) surface state Landau levels. By measuring the gate-dependent magnetoresistance, we observe multi-carrier quantum oscillations and Landau level splitting, with features originating from both the top and bottom surfaces. Our vdW mould growth technique establishes a platform for electronic studies and control of bismuth's Rashba surface states and topological boundary modes1-3. Beyond bismuth, the vdW-moulding approach provides a low-cost way to synthesize ultrathin crystals and directly integrate them into a vdW heterostructure.

Therapeutic potential of exosome derived from hepatocyte growth factor-overexpressing adipose mesenchymal stem cells in TGFß1-stimulated hepatic stellate cells.

Cirrhosis is a familiar end-stage of multiple chronic liver diseases. The gene-modified mesenchymal stem cells (MSCs) have become one of the most promising schemes for the treatment of cirrhosis. MSCs exhibit their therapeutic role mainly by secreting hepatocyte growth factor (HGF). The aim of this research was to probe the anti-fibrosis role of exosomes secreted by HGF modified-mouse adipose MSCs (ADMSCs) on activated hepatic stellate cells (HSCs) and to preliminarily explore the possible mechanism. Firstly, mouse ADMSCs were isolated and identified. Quantitative real-time polymerase chain reaction verified the transfection efficiency of ADMSC transfected with HGF lentivirus. Exosomes derived from ADMSC transfecting negative control/HGF (ADMSCNC-Exo/ADMSCHGF-Exo) were extracted by density gradient centrifugation. HSCs were allocated to the control, TGF-ß, TGF-ß + ADMSC-Exo, TGF-ß + ADMSCNC-Exo, and TGF-ß + ADMSCHGF-Exo groups. Moreover, all mice were distributed to the control, CCl4 (40% CCl4 in olive oil), CCl4+ADMSC-Exo, CCl4+ADMSCNC-Exo, and CCl4+ADMSCHGF-Exo groups. Exosomes derived from ADMSCs with or without HGF transfection suppressed HSC activation, as evidenced by attenuating cell viability and cell cycle arrest at S phase but inducing apoptosis. Moreover, ADMSC-Exo, ADMSCNC-Exo, and ADMSCHGF-Exo effectively repressed the gene and protein levels of α-SMA, Col-I, Rho A, Cdc42, and Rac1 in TGF-ß-treated HSCs, and ADMSCHGF-Exo had the best effect. ADMSCHGF-Exo had a stronger regulatory effect on serum liver index than ADMSCNC-Exo in CCl4-induced mice. In conclusion, ADMSCHGF-Exo alleviated liver fibrosis by weakening the Rho pathway, thus reducing collagen production.

Sensitive Thermochromic Behavior of InSeI, a Highly Anisotropic and Tubular 1D van der Waals Crystal.

Thermochromism, the change in color of a material with temperature, is the fundamental basis of optical thermometry. A longstanding challenge in realizing sensitive optical thermometers for widespread use is identifying materials with pronounced thermometric optical performance in the visible range. Herein, it is demonstrated that single crystals of indium selenium iodide (InSeI), a 1D van der Waals (vdW) solid consisting of weakly bound helical chains, exhibit considerable visible range thermochromism. A strong temperature-dependent optical band edge absorption shift ranging from 450 to 530 nm (2.8 to 2.3 eV) over a 380 K temperature range with an experimental (dEg/dT)max value extracted to be 1.26 × 10-3 eV K-1 is shown. This value lies appreciably above most dense conventional semiconductors in the visible range and is comparable to soft lattice solids. The authors further seek to understand the origin of this unusually sensitive thermochromic behavior and find that it arises from strong electron-phonon interactions and anharmonic phonons that significantly broaden band edges and lower the Eg with increasing temperature. The identification of structural signatures resulting in sensitive thermochromism in 1D vdW crystals opens avenues in discovering low-dimensional solids with strong temperature-dependent optical responses across broad spectral windows, dimensionalities, and size regimes.

Controllable strain-driven topological phase transition and dominant surface-state transport in HfTe5.

The fine-tuning of topologically protected states in quantum materials holds great promise for novel electronic devices. However, there are limited methods that allow for the controlled and efficient modulation of the crystal lattice while simultaneously monitoring the changes in the electronic structure within a single sample. Here, we apply significant and controllable strain to high-quality HfTe5 samples and perform electrical transport measurements to reveal the topological phase transition from a weak topological insulator phase to a strong topological insulator phase. After applying high strain to HfTe5 and converting it into a strong topological insulator, we found that the resistivity of the sample increased by 190,500% and that the electronic transport was dominated by the topological surface states at cryogenic temperatures. Our results demonstrate the suitability of HfTe5 as a material for engineering topological properties, with the potential to generalize this approach to study topological phase transitions in van der Waals materials and heterostructures.

Sacubitril/valsartan compared to ramipril in high-risk post-myocardial infarction patients stratified according to use of mineralocorticoid receptor antagonists: Insight from the PARADISE MI trial.

AIM: It is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor [ARNI]) are affected by mineralocorticoid receptor antagonists (MRA) in high-risk myocardial infarction (MI) patients. The aim of this study was to examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion. METHODS AND RESULTS: Patients (n = 5661) included in the PARADISE MI trial (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) were stratified according to MRA. Primary outcomes in this substudy were worsening heart failure or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalaemia >5.5 mmol/L, or permanent drug discontinuation. A total of 2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by ± MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalaemia or permanent drug discontinuation was not significantly altered by ARNI (p > 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA (hazard ratio [HR]MRA 0.96, 95% confidence interval [CI] 0.77-1.19 and HRMRA- 0.87, 95% CI 0.71-1.05, for the primary endpoint; p = 0.51 for interaction [Clinical Endpoint Committee adjudicated]); similar findings were observed if investigator-reported endpoints were evaluated (p = 0.61 for interaction). CONCLUSIONS: Use of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post-MI setting in patients with LVSD and/or congestion.

Geographic differences in patients with acute myocardial infarction in the PARADISE-MI trial.

AIM: The globalization of clinical trials has highlighted geographic differences in patient characteristics, treatments, and outcomes. We examined these differences in PARADISE-MI. METHODS AND RESULTS: Overall, 23.0% were randomized in Eastern Europe/Russia, 17.5% in Western Europe, 12.2% in Southern Europe, 10.1% in Northern Europe, 12.0% in Latin America (LA), 9.3% in North America (NA), 10.0% in East/South-East Asia and 5.8% in South Asia (SA). Those from Asia, particularly SA, were different from patients enrolled in the other regions, being younger and thinner. They also differed in terms of comorbidities (high prevalence of diabetes and low prevalence of atrial fibrillation), type of myocardial infarction (more often ST-elevation myocardial infarction), and treatment (low rate of primary percutaneous coronary intervention). By contrast, patients from LA did not differ meaningfully from those randomized in Europe or NA. Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (34.8%) and beta-blockers (65.5%) was low in SA, whereas mineralocorticoid receptor antagonist use was lowest in NA (22%) and highest in Eastern Europe/Russia (53%). Rates of the primary composite outcome of cardiovascular death or incident heart failure varied two-fold among regions, with the lowest rate in SA (4.6/100 person-years) and the highest in LA (9.2/100 person-years). Rates of incident heart failure varied almost six-fold among regions, with the lowest rate in SA (1.0/100 person-years) and the highest in Northern Europe (5.9/100 person-years). The effect of sacubitril/valsartan was not modified by region. CONCLUSION: In PARADISE-MI, there were substantial regional differences in patient characteristics, treatments and outcomes. Although the generalizability of these findings to a 'real-world' unselected population may be limited, these findings underscore the importance of considering both regional and within-region differences when designing global clinical trials.

Growth of Mesoscale Ordered Two-Dimensional Hydrogen-Bond Organic Framework with the Observation of Flat Band.

Flat bands (FBs), presenting a strongly interacting quantum system, have drawn increasing interest recently. However, experimental growth and synthesis of FB materials have been challenging and have remained elusive for the ideal form of monolayer materials where the FB arises from destructive quantum interference as predicted in 2D lattice models. Here, we report surface growth of a self-assembled monolayer of 2D hydrogen-bond (H-bond) organic frameworks (HOFs) of 1,3,5-tris(4-hydroxyphenyl)benzene (THPB) on Au(111) substrate and the observation of FB. High-resolution scanning tunneling microscopy or spectroscopy shows mesoscale, highly ordered, and uniform THPB HOF domains, while angle-resolved photoemission spectroscopy highlights a FB over the whole Brillouin zone. Density-functional-theory calculations and analyses reveal that the observed topological FB arises from a hidden electronic breathing-kagome lattice without atomically breathing bonds. Our findings demonstrate that self-assembly of HOFs provides a viable approach for synthesis of 2D organic topological materials, paving the way to explore many-body quantum states of topological FBs.

Electrical Manipulation of Topological Phases in a Quantum Anomalous Hall Insulator.

Quantum anomalous Hall phases arising from the inverted band topology in magnetically doped topological insulators have emerged as an important subject of research for quantization at zero magnetic fields. Though necessary for practical implementation, sophisticated electrical control of molecular beam epitaxy (MBE)-grown quantum anomalous Hall matter have been stymied by growth and fabrication challenges. Here, a novel procedure is demonstrated, employing a combination of thin-film deposition and 2D material stacking techniques, to create dual-gated devices of the MBE-grown quantum anomalous Hall insulator, Cr-doped (Bi,Sb)2 Te3 . In these devices, orthogonal control over the field-induced charge density and the electric displacement field is demonstrated. A thorough examination of material responses to tuning along each control axis is presented, realizing magnetic property control along the former and a novel capability to manipulate the surface exchange gap along the latter. Through electrically addressing the exchange gap, the capabilities to either strengthen the quantum anomalous Hall state or suppress it entirely and drive a topological phase transition to a trivial state are demonstrated. The experimental result is explained using first principle theoretical calculations, and establishes a practical route for in situ control of quantum anomalous Hall states and topology.

The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction: Insights From the PARADISE-MI Trial.

BACKGROUND: In patients who survive an acute myocardial infarction (AMI), angiotensin-converting enzyme inhibitors decrease the risk of subsequent major cardiovascular events. Whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan reduce major coronary events more effectively than angiotensin-converting enzyme inhibitors in high-risk patients with recent AMI remains unknown. We aimed to compare the effects of sacubitril/valsartan on coronary outcomes in patients with AMI. METHODS: We conducted a prespecified analysis of the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitors Trial to Determine Superiority in Reducing Heart Failure Events After MI), which compared sacubitril/valsartan (97/103 mg twice daily) with ramipril (5 mg twice daily) for reducing heart failure events after myocardial infarction in 5661 patients with AMI complicated by left ventricular systolic dysfunction, pulmonary congestion, or both. In the present analysis, the prespecified composite coronary outcome was the first occurrence of death from coronary heart disease, nonfatal myocardial infarction, hospitalization for angina, or postrandomization coronary revascularization. RESULTS: Patients were randomly assigned at a median of 4.4 [3.0-5.8] days after index AMI (ST-segment-elevation myocardial infarction 76%, non-ST-segment-elevation myocardial infarction 24%), by which time 89% of patients had undergone coronary reperfusion. Compared with ramipril, sacubitril/valsartan decreased the risk of coronary outcomes (hazard ratio, 0.86 [95% CI, 0.74-0.99], P=0.04) over a median follow-up of 22 months. Rates of the components of the composite outcomes were lower in patients on sacubitril/valsartan but were not individually significantly different. CONCLUSIONS: In survivors of an AMI with left ventricular systolic dysfunction and pulmonary congestion, sacubitril/valsartan-compared with ramipril-reduced the risk of a prespecified major coronary composite outcome. Dedicated studies are necessary to confirm this finding and elucidate its mechanism. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924727.

Sacubitril/valsartan versus ramipril for patients with acute myocardial infarction: win-ratio analysis of the PARADISE-MI trial.

AIM: The win ratio can incorporate different types of outcomes and enhance statistical power, making it a useful method for analysing composite outcomes in cardiovascular trials. The application of this approach to the PARADISE-MI trial provides an additional perspective into understanding the effects of sacubitril/valsartan in patients with acute myocardial infarction. METHODS AND RESULTS: We conducted a post-hoc analysis of the PARADISE-MI trial, which randomly assigned patients with acute myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril/valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to guideline-recommended therapy. The principal composite outcome was analysed in the hierarchical order of death due to cardiovascular causes, first hospitalization for heart failure, and first outpatient episode of symptomatic heart failure. We included events confirmed by the clinical events classification (CEC) committee as well as events identified by investigators that did not meet study definitions. Results were analysed by the unmatched win-ratio method. A win ratio that exceeds 1.00 reflects a better outcome. A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril/valsartan and 2831 to receive ramipril. The hierarchical analysis of the principal composite outcome demonstrated a larger number of wins (1 265 767 [15.7%]) than losses (1 079 502 [13.4%]) in the sacubitril/valsartan group (win ratio of 1.17, 95% confidence interval [CI] 1.03-1.33; p = 0.015). Sensitivity analyses using alternative definitions of the composite outcome showed results similar to those of the principal analysis, except for analysis restricted to events that met CEC definitions (win ratio of 1.11, 95% CI 0.96-1.30; p = 0.16). CONCLUSION: In this post-hoc analysis of the PARADISE-MI trial using the win ratio and including investigator-identified events not having CEC confirmation, sacubitril/valsartan was superior to ramipril among high-risk survivors of acute myocardial infarction.

Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy.

BACKGROUND: Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI. METHODS: In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes. RESULTS: Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF (P=0.79) or LAV (P =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume (P=0.025) and greater decline in LV mass index (P=0.037), increase in tissue Doppler e'lat (P=0.005), decrease in E/e'lat (P=0.045), and decrease in tricuspid regurgitation peak velocity (P=0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure. CONCLUSIONS: Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924727.

Excited quantum anomalous and spin Hall effect: dissociation of flat-bands-enabled excitonic insulator state.

Quantum anomalous Hall effect (QAHE) and quantum spin Hall effect (QSHE) are two interesting physical manifestations of 2D materials that have an intrinsic nontrivial band topology. In principle, they are ground-state equilibrium properties characterized by Fermi level lying in a topological gap, below which all the occupied bands are summed to a non-zero topological invariant. Here, we propose theoretical concepts and models of 'excited' QAHE (EQAHE) and EQSHE generated by dissociation of an excitonic insulator (EI) state with complete population inversion (CPI), a uniquemany-bodyground state enabled by two yin-yang flat bands (FBs) of opposite chirality hosted in a diatomic Kagome lattice. The two FBs have a trivial gap in between, i.e. the system is a trivial insulator in thesingle-particleground-state, but nontrivial gaps above and below, so that upon photoexcitation the quasi-Fermi levels of both electrons and holes will lie in a nontrivial gap achieved by the CPI-EI state, as demonstrated by exact diagonalization calculations. Then dissociation of singlet and triplet EI state will lead to EQAHE and EQSHE, respectively. Realizations of yin-yang FBs in real materials are also discussed.

Effect of electrolyte composition on electrochemical oxidation: Active sulfate formation, benzotriazole degradation, and chlorinated by-products distribution.

Electrochemical oxidation is an effective technique for treating persistent organic pollutants, which are hardly removed in conventional wastewater treatment plants. Sulfate and chloride salts commonly used and present in natural wastewater influence the electrochemical degradation process. In this study, the effect of electrolyte composition on the active sulfate species (SO4●⁻ and S2O82⁻) formation, benzotriazole degradation-a model organic compound, and chlorinated by-products distribution have been investigated while using a boron-doped diamond (BDD) anode. Different Na2SO4:NaNO3 and Na2SO4:NaCl ratios with constant conductivity of 10 mS/cm were used in the experiments and applied anode potential was kept constant at 4.3 V vs. Ag/AgCl. The electrogenerated SO4●⁻ and S2O82⁻ formation were faster in 10:1 and 2:1 Na2SO4:NaNO3 ratios than in the 1:0 ratio. The ●OH-mediated SO4●⁻ production has prevailed in 10:1 and 2:1 ratios. However, ●OH-mediated SO4●⁻ production has hindered the 1:0 ratio due to excess chemisorption of SO42⁻ on the BDD anode. Similarly, the faster benzotriazole degradation, mineralization, and lowest energy consumption were achieved in the 10:1 Na2SO4:NaNO3 and Na2SO4:NaCl ratio. Besides, chlorinated organic by-product concentration (AOX) was lower in the 10:1 Na2SO4:NaCl ratio but increased with the increasing chloride ratio in the electrolyte. LC-MS analysis shows that several chlorinated organic transformation products were produced in 0:1 to 2:1 ratio, which was not found in the 10:1 Na2SO4:NaCl ratio. A comparatively higher amount of ClO4⁻ was formed in the 10:1 ratio than in 2:1 to 0:1 ratio. This ClO4⁻ formation train evidence the effective ●OH generation in a sulfate-enriched condition because the ClO4⁻ formation is positively correlated to ●OH concentration. Overall results show that sulfate-enriched electrolyte compositions are beneficial for electrochemical oxidation of biorecalcitrant organic pollutants.

Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).