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Aims: The aim of this study was to evaluate whether biomarkers reflecting pathophysiological pathways are different between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) and whether the prognostic value of biomarkers is different in HFpEF vs. HFrEF.Methods and Results: A total of 458 HFrEF (LVEF ≤40%) and 112 HFpEF (LVEF ≥50%) patients aged ≥60 years with NYHA class ≥II from TIME-CHF were included. Endpoints are 18-month overall and HF hospitalization-free survival. After correction for baseline characteristics that differed between the HF types, i.e. age, gender, body mass index, systolic blood pressure, cause of HF, and AF, HFpEF patients exhibited higher soluble interleukin 1 receptor-like 1 [ST2; 37.6 (28.5-54.7) vs. 35.7 (25.6-52.2), P = 0.02], high sensitivity C-reactive protein (hsCRP; 8.54 (3.39-25.86) vs. 6.66 (2.42-15.39), P = 0.01), and cystatin-C [1.94 (1.57-2.37) vs. 1.75 (1.39-2.12), P = 0.01]. In contrast, HFrEF patients exhibited higher NT-proBNP [2142 (1473-4294) vs. 4202 (2239-7411), P < 0.001], high sensitivity troponin T [hsTnT; 27.7 (16.8-48.0) vs. 32.4 (19.2-59.0), P = 0.03], and haemoglobin [124 (110-135) vs. 134 (122-145), P < 0.001]. In addition to these clinical characteristics, NT-proBNP, haemoglobin, cystatin-C, hsTnT, and ST2 improved the area under the curve from 0.86 (0.82-0.89) to 0.91 (0.87-0.94; P < 0.001) for discriminating HFpEF from HFrEF. There were no significant interactions between HFpEF and HFrEF when considering the prognostic value of the investigated biomarkers (P > 0.10 for both endpoints), except for cystatin-C which had less prognostic impact in HFpEF (P < 0.01).Conclusion: Biomarker levels suggest a different amount of activation of several pathophysiological pathways between HFpEF and HFrEF. No important differences in the prognostic value of biomarkers in HFpEF vs. HFrEF were found except for cystatin-C, and for NT-proBNP in the NT-proBNP-guided study arm only, both of which had less prognostic value in HFpEF.Trial Registration: ISRCTN43596477. [ABSTRACT FROM AUTHOR]

Amyloid β aggregation is an important factor in Alzheimer's disease. Since calcium homeostasis plays an important role in amyloid β aggregation, it is crucial to study the interaction between calcium ions and amyloid β directly at the surface of the lipid membrane. With supercritical angle techniques, the signal of interest at the surface is easily separated from the bulk solution, making them a powerful tool for aggregation study. In this work, the influence of calcium ions on amyloid β aggregation over different aggregation time periods is investigated with supercritical angle Raman and fluorescence spectroscopy and microscopy. Note that calcium ions have a larger influence on amyloid β1–42 than on the 40 amino acid variant. We found that a small layer of calcium ions significantly protects the lipid membrane against the protein insertion process. [ABSTRACT FROM AUTHOR]

Novel biomaterials are becoming more crucial in treating human diseases. However, many materials require complex artificial modifications and synthesis, leading to potential difficulties in preparation, side effects, and clinical translation. Recently, significant progress has been achieved in terms of direct self‐assembly of natural products from herbal medicine (NPHM), an important source for novel medications, resulting in a wide range of bioactive supramolecular materials including gels, and nanoparticles. The NPHM‐based supramolecular bioactive materials are produced from renewable resources, are simple to prepare, and have demonstrated multi‐functionality including slow‐release, smart‐responsive release, and especially possess powerful biological effects to treat various diseases. In this review, NPHM‐based supramolecular bioactive materials have been revealed as an emerging, revolutionary, and promising strategy. The development, advantages, and limitations of NPHM, as well as the advantageous position of NPHM‐based materials, are first reviewed. Subsequently, a systematic and comprehensive analysis of the self‐assembly strategies specific to seven major classes of NPHM is highlighted. Insights into the influence of NPHM structural features on the formation of supramolecular materials are also provided. Finally, the drivers and preparations are summarized, emphasizing the biomedical applications, future scientific challenges, and opportunities, with the hope of igniting inspiration for future research and applications. [ABSTRACT FROM AUTHOR]

Introduction: Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. Methods: In this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. Results: The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E', or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = − 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = − 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = − 0.28; p < 0.001), peak VO2 (rho = − 0.26; p < 0.001), and ratio of minute ventilation/carbon dioxide production (rho = 0.12; p = 0.002). After adjustment for known confounders, the correlation with Physical Activity Scale in the Elderly and overall Kansas City Cardiomyopathy Questionnaire score was no longer significant. Conclusion: Among patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals. Trial registration: ARISE-HF, NCT 04083339 Date Registered August 23, 2019. Abnormal ECHO defined as Myocardial Global Longitudinal Strain < − 16 or left ventricular mass index > 95 for females or > 115 for males or E/e' >13 or left atrial volume index > 34. †Normal ECHO is defined as the absence of these abnormalities. Low NT-proBNP is defined as < 71 ng/L while high NT-proBNP is defined as ≥ 71 ng/L. [ABSTRACT FROM AUTHOR]

(1) Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity and mortality both in the general population and heart failure patients. Inflammation may promote the initiation, maintenance and perpetuation of AF, but the impact of inflammatory molecular signaling on the association between AF and heart failure remains elusive. (2) Materials and Methods: In 111 patients with chronic stable heart failure, baseline values of conventional (IL-6 and hsCRP) and selected novel inflammatory biomarkers (IL-10, IL-6/IL-10 ratio, orosomucoid and endocan) were determined. Inflammatory biomarkers were compared with respect to the presenting cardiac rhythm. (3) Results: Patients aged below 75 years with AF had significantly higher values of IL-6 and IL-6/IL-10 ratio; IL-6 levels were a significant predictor of AF in both univariate (OR 1.175; 95%CI 1.013–1.363; p = 0.034) and multivariate logistic regression analysis when accounting for other inflammatory biomarkers (OR 1.327; 95% CI 1.068–1.650; p = 0.011). Conversely, there was no association between other novel inflammatory biomarkers and AF. (4) Conclusions: IL-6 levels and the IL-6/IL-10 ratio are associated with AF in patients with chronic stable heart failure under the age of 75 years, suggesting that inflammatory molecular signaling may play a role in the development of AF in the heart failure population. [ABSTRACT FROM AUTHOR]

The area of drug delivery systems has witnessed significant advancements in recent years, with a particular focus on improving efficacy, stability, and patient compliance. Transdermal drug delivery offers numerous benefits compared to conventional methods of drug administration through the skin. It helps in avoiding gastric irritation, hepatic first-pass metabolism, and gastric degradation of the drug. It bypasses the gastrointestinal tract, eliminating the risk of first-pass metabolism and allowing drugs to be administered without being affected by pH, enzymes, or intestinal bacteria. Additionally, it allows for sustained release of the drug, is noninvasive, and enhances patient adherence to the treatment regimen. The transdermal drug delivery system (TDDS) can serve as an alternative route for drug administration in individuals who cannot tolerate oral medications, experience nausea, or are unconscious. When compared to intravenous, hypodermic, and other parenteral routes, TDDS stands out due to its ability to eliminate pain, reduce the risk of infection, and prevent disease transmission associated with needle reuse. Consequently, the overall patient compliance is significantly improved with the utilization of TDDS. Among the noteworthy developments are cubosomes and ethosomes, two distinct yet promising carriers that have garnered attention for their unique properties. In conclusion, this review synthesizes the current knowledge on cubosomes and ethosomes, shedding light on their individual strengths and potential synergies. The exploration of their application in various therapeutic areas underscores their versatility and establishes them as key players in the evolving landscape of drug delivery systems. [ABSTRACT FROM AUTHOR]

Heart failure (HF) caused by structural or functional cardiac abnormalities is a significant cause of morbidity and mortality worldwide. While HF with reduced ejection fraction (HErEF) is well understood, more than half of patients have HF with preserved ejection fraction (HFpEF). Currently, the treatment for HFpEF primarily focuses on symptom alleviation, lacking specific drugs. The stressed heart undergoes metabolic switches in substrate preference, which is a compensatory process involved in cardiac pathological remodeling. Although metabolic reprogramming in HF has gained attention in recent years, its role in HFpEF still requires further elucidation. In this review, we present a summary of cardiac mitochondrial dysfunction and cardiac metabolic reprogramming in HFpEF. Additionally, we emphasize potential therapeutic approaches that target metabolic reprogramming for the treatment of HFpEF. [ABSTRACT FROM AUTHOR]

Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration results in the accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility, eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long COVID), as well as treatment options, are discussed. [ABSTRACT FROM AUTHOR]

Background: Diabetic cardiomyopathy (DCM) is one of the serious microvascular complications of diabetes mellitus. It is often associated with clinical manifestations such as arrhythmias and heart failure, and significantly reduces the quality of life and years of survival of patients. Endoplasmic reticulum stress (ERS) is the removal of unfolded and misfolded proteins and is an important mechanism for the maintenance of cellular homeostasis. ERS plays an important role in the pathogenesis of DCM by causing cardiomyocyte apoptosis, insulin resistance, calcium imbalance, myocardial hypertrophy and fibrosis. Targeting ERS is a new direction in the treatment of DCM. A large number of studies have shown that Chinese herbal medicine and active ingredients can significantly improve the clinical outcome of DCM patients through intervention in ERS and effects on myocardial structure and function, which has become one of the hot research directions. Purpose: The aim of this review is to elucidate and summarize the roles and mechanisms of Chinese herbal medicine and active ingredients that have the potential to modulate endoplasmic reticulum stress, thereby contributing to better management of DCM. Methods: Databases such as PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data Knowledge Service Platform were used to search, analyze, and collect literature, in order to review the mechanisms by which phytochemicals inhibit the progression of DCM by targeting the ERS and its key signaling pathways. Keywords used included "diabetic cardiomyopathy" and "endoplasmic reticulum stress". Results: This review found that Chinese herbs and their active ingredients can regulate ERS through IRE1, ATF6, and PERK pathways to reduce cardiomyocyte apoptosis, ameliorate myocardial fibrosis, and attenuate myocardial hypertrophy for the treatment of DCM. Conclusion: A comprehensive source of information on potential ERS inhibitors is provided in this review. The analysis of the literature suggests that Chinese herbal medicine and its active ingredients can be used as potential drug candidates for the treatment of DCM. In short, we cannot ignore the role of traditional Chinese medicine in regulating ERS and treating DCM, and look forward to more research and new drugs to come. [ABSTRACT FROM AUTHOR]

An association between high Galectin-4 (Gal-4) and prevalence of diabetes in subjects with heart failure (HF) has previously been reported. The purpose of this study was to confirm these findings, as well as to further investigate this association, in a Swedish HF population. In addition, a second aim was to explore Gal-4's association with obesity and biomarkers of metabolism and heart failure. Gal-4 was measured using a proximity extension array technique in 324 hospitalized HF patients within the Swedish HeArt and bRain failure investigation trial cohort. Obesity was defined as BMI ≥ 30. Multivariable logistic regression models were used to explore associations between Gal-4 and diabetes/obesity, and linear regression models were used to explore the associations between Gal-4 and biomarkers. A total of 309 participants (29.1% female; mean age 74.8 years) provided complete data for the analysis of associations between Gal-4 and diabetes. Additionally, for the analysis of heart failure phenotype, complete data was available for 230 subjects. Gal-4 was positively associated with prevalent diabetes (OR 2.60; CI 95% 1.56–4.32). In multivariable models, Gal-4 levels were significantly associated with obesity, but only for subjects with diabetes (OR 2.48; 1.09–5.62). Additionally, Gal-4 demonstrated a significant association with the incretin Glucose-dependent insulinotropic polypeptide (GIP), as well as with biomarkers of HF. In the stratified analyses, the association between Gal-4 and diabetes was prominent in patients with reduced ejection fraction (n = 160, OR 3.26; 95%CI 1.88–5.66), while it was not observed in those without (n = 70, 1.96 (0.75–5.10)). In this cross-sectional, observational study, higher Gal-4 levels in HF patients were associated with higher GIP levels. Further, increased levels of Gal-4 were associated with increased likelihood of diabetes, and obesity. This association was particularly pronounced in individuals with HF characterized by reduced ejection fraction. Additionally, Gal-4 levels were significantly elevated in heart failure patients with diabetes and obesity. [ABSTRACT FROM AUTHOR]

Small‐Angle Scattering (SAS) techniques are essential tools for the characterization of catalysts before, during and after catalytic reactions. Either based on X‐Rays (SAXS) or neutrons (SANS), they provide unique structural information that helps to understand catalytic processes at the nanoscale level, allowing a rational improvement of the catalysts design. In this review, we present the key aspects involved in the use of these techniques in the catalysis field. Firstly, we introduce some of the fundamentals of the techniques and describe their main features and their impact in the catalyst design. Then, we analyze key examples of the use of SAS to study catalysts' structure through ex situ analysis, focusing on examples involving different porous materials and metallic nanoparticles. Afterwards, we discuss in situ and operando approaches for studying catalytical processes monitored using SAS. Finally, we present perspectives and challenges for the future use of SAS in the catalysis field. [ABSTRACT FROM AUTHOR]

Solar fuel production by photosynthetic systems strongly relies on developing efficient and stable oxygen-evolution catalysts (OECs). Cerium(IV) ammonium nitrate (CAN) has been the most commonly used sacrificial oxidant to investigate OECs. Although many metal oxides have been extensively investigated as OECs in the presence of CAN, mechanistic studies were rarely reported. Herein, first, Fe(III) (hydr)oxide (FeOxHy) was prepared by the reaction of Fe(ClO4)3 and KOH solution and characterized by some methods. Then, changes in Fe oxide in the presence of CAN during the OER were tracked using in situ Raman spectroscopy, in situ X-ray absorption spectroscopy, in situ visible spectroscopy, and in situ electron paramagnetic resonance spectroscopy. FeOxHy in the presence of CAN and during the OER converted to γ-Fe2O3 and [Fe(H2O)6]3+, and a small amount of oxygen was formed. A maximum turnover frequency and turnover number of 10−6 s−1 and 1.3 × 10−3 mol(O2)/mol(Fe) (for half an hour) in the presence of CAN (0.20 M) and FeOxHy were observed. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) now accounts for the majority of new heart failure diagnoses and continues to increase in prevalence in the United States. Importantly, HFpEF is a highly morbid, heterogeneous syndrome lacking effective therapies. Inflammation has emerged as a potential contributor to the pathogenesis of HFpEF. Many of the risk factors for HFpEF are also associated with chronic inflammation, such as obesity, hypertension, aging, and renal dysfunction. A large amount of preclinical evidence suggests that immune cells and their associated cytokines play important roles in mediating fibrosis, oxidative stress, metabolic derangements, and endothelial dysfunction, all potentially important processes in HFpEF. How inflammation contributes to HFpEF pathogenesis, however, remains poorly understood. Recently, a variety of preclinical models have emerged which may yield much needed insights into the causal relationships between risk factors and the development of HFpEF, including the role of specific immune cell subsets or inflammatory pathways. Here, we review evidence in animal models and humans implicating inflammation as a mediator of HFpEF and identify gaps in knowledge requiring further study. As the understanding between inflammation and HFpEF evolves, it is hoped that a better understanding of the mechanisms underlying immune cell activation in HFpEF can open up new therapeutic avenues. [ABSTRACT FROM AUTHOR]

Background: In a large randomized controlled trial (PARADIGM-HF), ARNI has been shown to significantly reduce cardiovascular mortality and hospitalization for patients with reduced ejection fraction in heart failure. This study analyzed the efficacy and safety of ARNI on the basis of various types of heart failure patients in southwestern Sichuan Province. Methods: This study included patients with heart failure who were treated at the Affiliated Hospital of North Sichuan Medical College from July 2017 to June 2021. This study analyzed the efficacy and safety of ARNI in the treatment of heart failure, and analyzed the risk factors for readmission after ARNI treatment. Results: After propensity score matching, a total of 778 patients were included in the study. The readmission rate for heart failure in patients treated with ARNI (8.7%) was significantly lower than that in the standard treatment group (14.5%) (P = 0.023). Both the proportion of patients with increased LVEF and with decreased LVEF were higher in the ARNI treatment group than in the conventional therapy group. Compared with receiving standard medical treatment, combined ARNI treatment resulted in a greater reduction in SBP (-10.00, 95%CI: -24.00-1.50 vs. -7.00, 95%CI: -20.00-4.14; P = 0.016) in HF patients. Combination ARNI therapy did not increase the risk of adverse events. The study found that age (> 65 vs. ≤65 years) (OR = 4.038, 95%CI: 1.360-13.641, P = 0.013) and HFrEF (OR = 3.162, 95%CI: 1.028–9.724, P = 0.045) were independent predictors of readmission in HF patients treated with ARNI. Conclusion: Patients with heart failure treated with ARNI can improve clinical symptoms and reduce the risk of readmitted hospital admission. Age > ~ 65 years and HFrEF were independent predictors of readmission in HF patients treated in ARNI group. [ABSTRACT FROM AUTHOR]

We report for the very first time the controlled structural changes in the self‐assemblies of N‐(9‐fluorenylmethoxycarbonyl)‐O‐tert‐butyl‐l‐threonine (Fmoc‐Thr(tBu)‐OH) (FTU) to well defined unique morphologies. The self‐assembling properties of FTU were very interesting and intriguing as it resulted in the formation of unusual structures which resembles fibrous dumbbells and double‐sided broomstick‐like morphologies along with conventional spheres and rods under controlled conditions of concentration and temperature. The self‐assembly of other derivatives of threonine as well as another hydroxyl containing amino acid with same modification that is, ((N‐(9H‐fluoren‐9‐yl)methoxy)carbonyl)‐O‐(tert‐butyl)‐l‐serine (Fmoc‐Ser(tBu)‐OH) (FSU) was also studied to understand the crucial role of –Fmoc, ‐tBu and an additional –CH3 group present in the structure of FTU in the process of self‐assembly. Solvent dependent morphological studies of FTU and FSU suggest important role of solubility parameters and crystallization in formation of these unusual structures. The control experiments of co‐incubation with tannic acid and urea and solution state 1H‐NMR studies elucidate π–π stacking interactions as the key driving force for the structure formation. Further, the interactions which can occur between pairs of FTU and FSU which cause initial self‐assembly was studied theoretically via computational modeling. These studies suggest pair of FTU can either interact via head‐to‐head (HH) or head‐to‐tail (HT) configurations and the most favorable probabilities of either of these interactions lead to morphological transitions in FTU self‐assembly under varying conditions. The studies reported herein hence demonstrate that bioorganic molecules like protected single amino acids can be efficiently used as scaffold for self‐assembly and provide a very simple and facile bottom‐up‐approach for the design of uncommon novel micro/nanoarchitects for multifarious applications. [ABSTRACT FROM AUTHOR]

The accumulation of the amyloid‐β peptides (Aβ) is central to the development of Alzheimer's disease. The mechanism by which Aβ triggers a cascade of events that leads to dementia is a topic of intense investigation. Aβ self‐associates into a series of complex assemblies with different structural and biophysical properties. It is the interaction of these oligomeric, protofibril and fibrillar assemblies with lipid membranes, or with membrane receptors, that results in membrane permeability and loss of cellular homeostasis, a key event in Alzheimer's disease pathology. Aβ can have an array of impacts on lipid membranes, reports have included: a carpeting effect; a detergent effect; and Aβ ion‐channel pore formation. Recent advances imaging these interactions are providing a clearer picture of Aβ induced membrane disruption. Understanding the relationship between different Aβ structures and membrane permeability will inform therapeutics targeting Aβ cytotoxicity. [ABSTRACT FROM AUTHOR]

In heart failure with reduced ejection fraction, edema and congestion are related to reduced cardiac function. Edema and congestion are further aggravated by chronic kidney failure and pulmonary abnormalities. Furthermore, together with edema/congestion, sodium/water retention is an important sign of the progression of heart failure. Edema/congestion often anticipates clinical symptoms, such as dyspnea and hospitalization; it is associated with a reduced quality of life and a major risk of mortality. It is very important for clinicians to predict the signs of congestion with biomarkers and, mainly, to understand the pathophysiological findings that underlie edema. Not all congestions are secondary to heart failure, as in nephrotic syndrome. This review summarizes the principal evidence on the possible roles of the old and new congestion biomarkers in HFrEF patients (diagnostic, prognostic, and therapeutic roles). Furthermore, we provide a description of conditions other than congestion with increased congestion biomarkers, in order to aid in reaching a differential diagnosis. To conclude, the review focuses on how congestion biomarkers may be affected by new HF drugs (gliflozins, vericiguat, etc.) approved for HFrEF. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are fascinating and complex structures with the multilayered chiral organization. Using the multimodal methodology, including VCD, ECD, cryo‐EM, and TEM, we characterized in detail different levels of organization (secondary structure/protofilament/mesoscopic structure) of amyloid fibrils prepared from proteins highly homologous in the structure (hen egg white and human lysozymes). Our results demonstrate that small changes in the native protein structure or preparation conditions translate into significant differences in the handedness and architecture of the formed fibrils at various levels of their complexity. In particular, fibrils of hen egg white and human lysozymes obtained in vitro at the same preparation conditions, possess different secondary structure, protofilament twist and ultrastructure. Yet, formed fibrils adopted a relatively similar mesoscopic structure, as observed in high‐resolution 3D cryo‐EM, scarcely used up to now for fibrils obtained in vitro in denaturing condition. Our results add to other puzzling experiments implicating the indeterministic nature of fibril formation. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) is a serious complication of type 1 and type 2 diabetes, which leads to the aggravation of myocardial fibrosis, disorders involving systolic and diastolic functions, and increased mortality of patients with diabetes through mechanisms such as glycolipid toxicity, inflammatory response, and oxidative stress. Ferroptosis is a form of iron-dependent regulatory cell death that is attributed to the accumulation of lipid peroxides and an imbalance in redox regulation. Increased production of lipid reactive oxygen species (ROS) during ferroptosis promotes oxidative stress and damages myocardial cells, leading to myocardial systolic and diastolic dysfunction. Overproduction of ROS is an important bridge between ferroptosis and DCM, and ferroptosis inhibitors may provide new targets for the treatment of patients with DCM. [ABSTRACT FROM AUTHOR]

Helix structures, which are frequently observed in nature, act as versatile structural templates for complex functionalities with asymmetry and anisotropy. However, atomically thin 2D materials, including graphene, transition metal dichalcogenides (TMDs), and MXenes, do not have inherent chirality in their planar geometry and cannot easily form such a structure. This study presents the macroscopic self‐assembly of 2D materials for helical screws with an Archimedean spiral arrangement. The naturally triggered spontaneous rotation upon the 1D fiber assembly of 2D materials forms helical screws consisting of multiple helices and perversions. For a clear understanding of the morphological evolution of helical screws, variations in the helical pitch and angle are systematically analyzed considering thermodynamic and kinetic conditions. Subsequently, the influence of spontaneous helix formation on the properties of the 2D assembled fibers is investigated in terms of the solvent‐driven actuator performance and electrical and electrothermal properties. The suggested approach provides a new perspective on the directed self‐assembly of inherently achiral 2D materials toward chiral helix formation. [ABSTRACT FROM AUTHOR]

Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden's angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF. [ABSTRACT FROM AUTHOR]

Sustained hypertension causes structural, functional, and neurohumoral abnormalities in the heart, a disease commonly termed hypertensive heart disease (HHD). Modern concepts of HHD, including processes of remodeling leading to the development of various LVH patterns, HF patterns accompanied by micro- and macrovasculopathies, and heart rhythm and conduction disturbances, are missing in the available definitions, despite copious studies being devoted to the roles of myocardial and vascular fibrosis, and neurohumoral and sympathetic regulation, in HHD development and progression. No comprehensive and generally accepted universal definition and classification of HHD is available to date, implementing diagnostic criteria that incorporate all the possible changes and adaptions to the heart. The aim of this review series is to summarize the relevant literature and data, leading to a proposal of a definition and classification of HHD. This first article reviews the processes of initial myocardial remodeling, and myocardial and vascular fibrosis, occurring in HHD. We discuss important pathophysiological and microstructural changes, the different patterns of fibrosis, and the biomarkers and imaging used to detect fibrosis in HHD. Furthermore, we review the possible methods of targeting myocardial fibrosis in HHD, and highlight areas for further research. [ABSTRACT FROM AUTHOR]

Aims: There is an increasing proportion of hospitalized heart failure (HF) patients classified as HF with preserved ejection fraction (HFpEF) around the world. Growth differentiation factor 15 (GDF‐15) is a promising biomarker in HFpEF prognostication; however, the majority of the existing data has been derived from the research on undifferentiated HF, whereas the studies focusing on HFpEF are still limited. This study aimed to determine the prognostic power of GDF‐15 in the hospitalized patients with HFpEF in a Chinese cohort. Methods and results: We analysed the levels of serum GDF‐15 in 380 patients hospitalized for acute onset of HFpEF measured by heart ultrasound at admission in a prospective cohort. The associations of GDF‐15 with 1 year risk of all‐cause death and 1 year HF readmission were assessed by the Cox proportional hazards model. Area under the receiver operating characteristic curves was used to compare predictive accuracy. GDF‐15 was strongly correlated with 1 year HF readmission and 1 year all‐cause death, with event rates of 24.8%, 40.0%, and 50.0% for 1 year HF readmission (P < 0.001), respectively, and with 11.2%, 13.6%, and 24.6% for 1 year all‐cause death (P = 0.004) in the corresponding tertile, respectively. In the multivariate linear regression model, GDF‐15 had a significantly negative correlation with haemoglobin (P = 0.01) and a positive correlation with creatinine (P = 0.01), alanine transaminase (P = 0.001), and therapy of aldosterone antagonist (P = 0.018). The univariate Cox regression model of GDF‐15 showed that c‐statistic was 0.632 for 1 year HF readmission and 0.644 for 1 year all‐cause death, which were superior to the N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) model with c‐statistics of 0.595 and 0.610, respectively. In the multivariable Cox regression model, GDF‐15 tertiles independently predicted 1 year HF readmission (hazard ratio 2.25, 95% confidence interval: 1.43–3.54, P < 0.001) after adjusting for baseline Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND‐HF) risk score, history of HF, NT‐proBNP, and high‐sensitivity cardiac troponin T. Compared with the model including all the adjusted variables, the model with the addition of GDF‐15 improved predictive power, with c‐statistic increasing from 0.643 to 0.657 for 1 year HF readmission and from 0.638 to 0.660 for 1 year all‐cause death. Conclusions: In hospitalized patients with HFpEF, GDF‐15 measured within 48 h of admission is a strong independent biomarker for 1 year HF readmission and even better than NT‐proBNP. GDF‐15 combined with the traditional indicators provided incremental prognostic value in this population. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy is characterized by abnormal myocardial structure or performance in the absence of coronary artery disease or significant valvular heart disease in patients with diabetes mellitus. The spectrum of diabetic cardiomyopathy ranges from subtle myocardial changes to myocardial fibrosis and diastolic function and finally to symptomatic heart failure. Except for sodium–glucose transport protein 2 inhibitors and possibly bariatric and metabolic surgery, there is currently no specific treatment for this distinct disease entity in patients with diabetes. The molecular mechanism of diabetic cardiomyopathy includes impaired nutrient-sensing signaling, dysregulated autophagy, impaired mitochondrial energetics, altered fuel utilization, oxidative stress and lipid peroxidation, advanced glycation end-products, inflammation, impaired calcium homeostasis, abnormal endothelial function and nitric oxide production, aberrant epidermal growth factor receptor signaling, the activation of the renin–angiotensin–aldosterone system and sympathetic hyperactivity, and extracellular matrix accumulation and fibrosis. Here, we summarize several important emerging treatments for diabetic cardiomyopathy targeting specific molecular mechanisms, with evidence from preclinical studies and clinical trials. [ABSTRACT FROM AUTHOR]

As high-order harmonic emitters, quantum dots are produced through laser-induced plasmas. Subsequently, we generate high-order harmonics with 800-nm and 30-fs pulses from laser-produced plasmas containing quantum dots of different metal sulfides (Ag2S, CdS, and Cd0.5Zn0.5S). The high-order harmonic generation is analyzed using different approaches, including two-color (800 nm + 400 nm) pump, application of alloyed quantum dots, and quasiphase matching of interacting waves. We discuss the self-phase modulation induced splitting of harmonics, the difference in the application of thick and thin crystals for second harmonic (400 nm) emission during two-color pumping of the quantum dot plasma, the spatial modulation of the quantum dot plasma for quasiphase matching, and the comparison of harmonic yields from monomer and quantum dot plasmas. This study allows us to determine the mechanisms of coherent extreme ultraviolet radiation generation using a few nanometer-sized emitters as well as optimal methods for further enhancing the high-order harmonic generation efficiency. [ABSTRACT FROM AUTHOR]

Biodegradable polymers obtained from renewable resources are urgently needed to help mitigating the environmental burden of plastic pollution. Herein, a green process is developed to obtain protein‐based bioplastics through valorization of rapeseed cake. First, the effects of different protein extraction protocols are investigated, including water extraction at pH values from 1 to 12 and salt extraction with isoelectric point precipitation (IP), on proteins profile and sample composition. It is demonstrated that alkaline extraction at pH 12 results in the highest extraction yields of proteins (≈70%) and total solutes (≈50%). The IP results in lower yields but in highest protein purity of ≈80%. Alkaline extraction at pH 10.5 results in the extraction of 36% total solutes and ≈50% of proteins, with a protein profile similar to that obtained by IP, rich in α and β polypeptides chains of cruciferin. AFM analysis shows that samples containing cruciferin allow self‐assembly into mature amyloid fibrils upon incubation. Rapeseed amyloids are blended with polyvinyl alcohol and glycerol to develop bioplastics films that are characterized by decreased water absorption, higher water contact angle, and elongation at break >600%, more than double compared to films obtained from native monomers. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) accounts for almost half of all heart failure (HF) cases worldwide. Unfortunately, its incidence is expected to continue to rise, and effective therapy to improve clinical outcomes is lacking. Numerous efforts currently directed towards the pathophysiology of human HFpEF are uncovering signal transduction pathways and novel therapeutic targets. The nitric oxide-cyclic guanosine phosphate-protein kinase G (NO-cGMP-PKG) axis has been described as an important regulator of cardiac function. Suppression of the NO-cGMP-PKG signalling pathway is involved in the progression of HFpEF. Therefore, the NO-cGMP-PKG signalling pathway is a potential therapeutic target for HFpEF. In this review, we aim to explore the mechanism of NO-cGMP-PKG in the progression of HFpEF and to summarize potential therapeutic drugs that target this signalling pathway. [ABSTRACT FROM AUTHOR]

Aims Heart failure (HF) in young adults is uncommon, and changes in its incidence and prognosis in recent years are poorly described. Methods and results The incidence and prognosis of HF in young adults (1850 years) were characterized using nationwide medico-administrative data from the French National Hospitalization Database (period 20132018). A total of 1,486 877 patients hospitalized for incident HF were identified, including 70 075 (4.7) patients aged 1850 years (estimated incidence of 0.44 for this age group). During the study period, the overall incidence of HF tended to decrease in the overall population but significantly increased by 0.041 in young adults (P 0.001). This increase was notably observed among young men (from 0.51 to 0.59, P 0.001), particularly those aged 3650 years. In these young men, ischaemic heart disease (IHD) was the most frequently reported cause of HF, whereas non-ischaemic HF was mainly observed in patients 35 years old. In contrast to non-ischaemic HF, the incidence of IHD increased over the study period, which suggests that IHD-related HF is progressively affecting younger patients. Concordantly, young HF patients presented with high rates of traditional IHD risk factors, including obesity, smoking, hypertension, dyslipidaemia, or diabetes. Lastly, the rates of re-hospitalization (for HF or for any cause) within two years after the first HF event and in-hospital mortality were high in all groups, indicating a poor-prognosis population. Conclusion Strategies for the prevention of HF risk factors should be strongly considered for patients under 50 years old. [ABSTRACT FROM AUTHOR]

Many patients with symptoms and signs of heart failure have a left ventricular ejection fraction ≥50%, termed heart failure with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous syndrome mainly affecting older people who have many other cardiac and non-cardiac conditions that often cast doubt on the origin of symptoms, such as breathlessness, or signs, such as peripheral oedema, rendering them neither sensitive nor specific to the diagnosis of HFpEF. Currently, management of HFpEF is mainly directed at controlling symptoms and treating comorbid conditions such as hypertension, atrial fibrillation, anaemia, and coronary artery disease. HFpEF is also characterized by a persistent increase in inflammatory biomarkers. Inflammation may be a key driver of the development and progression of HFpEF and many of its associated comorbidities. Detailed characterization of specific inflammatory pathways may provide insights into the pathophysiology of HFpEF and guide its future management. There is growing interest in novel therapies specifically designed to target deregulated inflammation in many therapeutic areas, including cardiovascular disease. However, large-scale clinical trials investigating the effectiveness of anti-inflammatory treatments in HFpEF are still lacking. In this manuscript, we review the role of inflammation in HFpEF and the possible implications for future trials. [ABSTRACT FROM AUTHOR]

The incidence of heart failure with preserved ejection fraction is increasing in patients with obesity, diabetes, hypertension, and in the aging population. However, there is a lack of adequate clinical treatment. Patients with obesity-related heart failure with preserved ejection fraction display unique pathophysiological and phenotypic characteristics, suggesting that obesity could be one of its specific phenotypes. There has been an increasing recognition that overnutrition in obesity causes adipose tissue expansion and local and systemic inflammation, which consequently exacerbates cardiac remodeling and leads to the development of obese heart failure with preserved ejection fraction. Furthermore, overnutrition leads to cellular metabolic reprogramming and activates inflammatory signaling cascades in various cardiac cells, thereby promoting maladaptive cardiac remodeling. Growing evidence indicates that the innate immune response pathway from the NLRP3 inflammasome, to interleukin-1 to interleukin-6, is involved in the generation of obesity-related systemic inflammation and heart failure with preserved ejection fraction. This review established the existence of obese heart failure with preserved ejection fraction based on structural and functional changes, elaborated the inflammation mechanisms of obese heart failure with preserved ejection fraction, proposed that NLRP3 inflammasome activation may play an important role in adiposity-induced inflammation, and summarized the potential therapeutic approaches. [ABSTRACT FROM AUTHOR]

Despite the number of available methods to predict prognosis in patients with heart failure, prognosis remains poor, likely because of marked patient heterogeneity and varied heart failure etiologies. Thus, identification of novel prognostic indicators to stratify risk in patients with heart failure is of paramount importance. The spleen is emerging as a potential novel prognostic indicator for heart failure. In this article, we provide an overview of the current prognostic tools used for heart failure. We then introduce the spleen as a potential novel prognostic indicator, before outlining the structure and function of the spleen and introducing the concept of the cardiosplenic axis. This is followed by a focused discussion on the function of the spleen in the immune response and in hemodynamics, as well as a review of what is known about the usefulness of the spleen as an indicator of heart failure. Expert insight into the most effective spleen-related measurement indices for the prognostication of patients with heart failure is provided, and suggestions on how these could be measured in clinical practice are considered. In future, studies in humans will be required to draw definitive links between specific splenic measurements and different heart failure manifestations, as well as to determine whether splenic prognostic measurements differ between heart failure classes and etiologies. These contributions will provide a step forward in our understanding of the usefulness of the spleen as a prognostic predictor in heart failure. [ABSTRACT FROM AUTHOR]

Background: Diabetic cardiomyopathy (DCM) results from pathological changes in cardiac structure and function caused by diabetes. Excessive oxidative stress is an important feature of DCM pathogenesis. MicroRNAs (miRNAs) are key regulators of oxidative stress in the cardiovascular system. In the present study, we screened for the expression of oxidative stress-responsive miRNAs in the development of DCM. Furthermore, we aimed to explore the mechanism and therapeutic potential of miR-92a-2-5p in preventing diabetes-induced myocardial damage. Methods: An experimental type 2 diabetic (T2DM) rat model was induced using a high-fat diet and low-dose streptozotocin (30 mg/kg). Oxidative stress injury in cardiomyocytes was induced by high glucose (33 mmol/L). Oxidative stress-responsive miRNAs were screened by quantitative real-time PCR. Intervention with miR-92a-2-5p was accomplished by tail vein injection of agomiR in vivo or adenovirus transfection in vitro. Results: The expression of miR-92a-2-5p in the heart tissues was significantly decreased in the T2DM group. Decreased miR-92a-2-5p expression was also detected in high glucose-stimulated cardiomyocytes. Overexpression of miR-92a-2-5p attenuated cardiomyocyte oxidative stress injury, as demonstrated by increased glutathione level, and reduced reactive oxygen species accumulation, malondialdehyde and apoptosis levels. MAPK interacting serine/threonine kinase 2 (MKNK2) was verified as a novel target of miR-92a-2-5p. Overexpression of miR-92a-2-5p in cardiomyocytes significantly inhibited MKNK2 expression, leading to decreased phosphorylation of p38-MAPK signaling, which, in turn, ameliorated cardiomyocyte oxidative stress injury. Additionally, diabetes-induced myocardial damage was significantly alleviated by the injection of miR-92a-2-5p agomiR, which manifested as a significant improvement in myocardial remodeling and function. Conclusions: miR-92a-2-5p plays an important role in cardiac oxidative stress, and may serve as a therapeutic target in DCM. [ABSTRACT FROM AUTHOR]

Shape‐memory elastomer composite (SMEC) sheets, made of a honeycomb structured electrospun poly(ε‐caprolactone) (PCL) fiber mat embedded in a silicone (PDMS) elastomer, fold on themselves upon uniaxial traction. The self‐folding of the composite sheet originates from a bi‐layered structure obtained by a simple one‐step impregnation process. Indeed, the impregnation of a structured PCL fiber mat by oily PDMS in a flat Teflon mold leads, after curing, to an asymmetric composite sheet made of one PDMS flat thin layer on the mold side and one rough PDMS/PCL composite layer on the other side due to specific affinities between the three polymers involved. The self‐folded shape of such structured single sheet obtained upon uniaxial stretching and stress release is controlled by the honeycomb pattern orientation versus stretching direction, by the pattern size and by the applied uniaxial stretching stress. High shape recovery and robust shape memory cycling are also demonstrated by dynamic mechanical analysis. This innovative process based on the mat structuration allows a straightforward one‐step fabrication of shape memory sheets, with a wide scope of tunable self‐folded curvatures exhibiting efficient temperature shape recovery. [ABSTRACT FROM AUTHOR]

Aims: Clinical data on the prognostic determinants over varying periods within the same cohort of heart failure with mid‐range or mildly reduced ejection fraction (HFmrEF) remain scarce. This study aimed to identify the short‐term, intermediate‐term, and long‐term risk factors of adverse cardiovascular (CV) outcomes in patients hospitalized for HFmrEF. Methods and results: This retrospective study included 1691 consecutive HFmrEF patients admitted to our hospital between January 2015 and August 2020. Baseline data including clinical characteristics, laboratory and cardiac imaging examinations were obtained. Patients completed at least 1 year clinical follow‐up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was defined as a composite of CV death or rehospitalization for heart failure (CV events) at 3, 12, and 33 months after the diagnosis of HFmrEF. Mean age of the whole cohort was 69 (61–77) years and 64.8% were male. The median clinical follow‐up was 33 (20–50) months. CV events were 17.5%, 28.2%, and 57.8% at 3, 12, and 33 months after discharge, respectively. Independent risk factors for CV events were uric acid >382 μmol/L, creatinine >100 μmol/L, N‐terminal pro‐B type natriuretic peptide (NT‐proBNP) > 3368 pg/mL and haemoglobin <120 g/L for men and <110 g/L for women at 3 and 12 months. Pulmonary artery systolic pressure >35 mmHg and the ratio of early transmitral flow velocity to early mitral annular velocity >18 served as independent risk factors for CV events at 12 months. At 33 months, uric acid > 382 μmol/L, NT‐proBNP >3368 pg/mL, and pulmonary artery systolic pressure >35 mmHg were the independent risk factors of CV events. Conclusions: Higher uric acid, creatinine, NT‐proBNP, and lower haemoglobin levels at baseline are valuable serum biomarkers for risk stratification of short‐term and long‐term CV outcomes of HFmrEF patients. Future studies are needed to verify if intensive heart failure therapy for identified high‐risk HFmrEF patients based on these four serum biomarkers could improve their short‐term and long‐term CV outcomes or not. [ABSTRACT FROM AUTHOR]

Aims: To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic trials in acute heart failure (AHF).Methods and Results: ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. >40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT-proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol-5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT-proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT-proBNP levels, reflecting the real-world clinical situation.Conclusion: ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real-world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF. [ABSTRACT FROM AUTHOR]

Aims: To define plasma concentrations, determinants, and optimal prognostic cut‐offs of soluble suppression of tumorigenesis‐2 (sST2), high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in women and men with chronic heart failure (HF). Methods and results: Individual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs‐cTnT, and NT‐proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all‐cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs‐cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT‐proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut‐off was lower in women for sST2 (28 vs. 31 ng/mL) and hs‐cTnT (22 vs. 25 ng/L), while NT‐proBNP cut‐off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex‐specific cut‐offs improved risk prediction compared with the use of previously standardized prognostic cut‐offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs‐cTnT than sST2 or NT‐proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex‐specific cut‐off of hs‐cTnT for the endpoint of 5 year cardiovascular death. Conclusions: In patients with chronic HF, concentrations of sST2 and hs‐cTnT, but not of NT‐proBNP, are lower in women. Lower sST2 and hs‐cTnT and higher NT‐proBNP cut‐offs for risk stratification could be used in women. [ABSTRACT FROM AUTHOR]