Reduction In Fraction Research Articles

Abstract Mo002: Pharmacological Inhibition of p38 MAPK Attenuates Doxorubicin-induced Cardiotoxicity, Senescence, and Inflammation in C57BL/6 mice

Introduction: Doxorubicin (DOX)-induced cardiotoxicity has been associated with induction of senescence, inflammation, and activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Losmapimod (LOSM), an orally active p38 MAPK inhibitor, is an anti-inflammatory agent with cardioprotective effects. Nevertheless, the effect of LOSM against DOX-induced cardiotoxicity has not been reported. The objective of the current work is to determine the effects of LOSM on DOX-induced chronic cardiotoxicity in C57BL/6 mice with particular focus on senescence and inflammatory pathways. Methods: Five-week-old C57BL/6 mice were fed diet containing LOSM (estimated daily intake 12 mg/kg/day) or a control diet for four days. Thereafter, mice were randomized to receive six weekly intraperitoneal injections of either DOX (4 mg/kg/week for 6 weeks) or saline. Three days after the last injection, cardiac function was assessed by trans-thoracic echocardiography. Gene expressions of senescence and inflammatory markers were quantified using real-time PCR and serum inflammatory markers were assessed by Luminex. Results: LOSM ameliorated DOX-induced cardiac dysfunction as evidenced by mitigated DOX-induced reduction in left ventricular fraction and fractional shortening. Notably, LOSM attenuating DOX-induced upregulation of p21 Cip1 , a marker of senescence, in the heart and the liver. Additionally, LOSM demonstrated anti-inflammatory effects, with reduced cardiac interleukin-1α and interleuken-6 gene expression in DOX-treated mice suggesting a senomorphic effect of LOSM. Systemic inflammation, assessed by serum cytokine levels, showed decreased interleukin-6 concentration in both DOX-treated mice and LOSM-treated mice. Conclusion: This is the first study to determine the effect of pharmacological inhibition of p38 MAPK against DOX-induced cardiotoxicity in vivo. Our study underscores the potential therapeutic efficacy of p38 MAPK inhibition in ameliorating DOX-induced cardiotoxicity, offering insights into novel strategies for mitigating chemotherapy-related cardiac complications, and suggesting a possible senomorphic effects of losmapimod.

Abstract We064: Investigating the Cardioprotective Role of Neutrophil-Specific STING in Myocardial Ischemia/Reperfusion Injury

Introduction: Inflammation following myocardial ischemia/reperfusion injury (MI/R) plays a significant role in damaging cardiomyocytes and influencing infarct size, with neutrophils being the most rapid and numerous cells recruited to the myocardium post reperfusion. Single-cell RNA sequencing data identified neutrophils with upregulated type I interferon (IFN) signaling in the hearts of mice 24 hours post-MI/R. Aim: This study aims to address how the type I IFN neutrophil phenotype identified affects inflammation in MI/R. We hypothesize that neutrophils with upregulated type I IFN signaling are cardioprotective in MI/R. Methods: Male neutrophil-specific STING knockout (KO) mice underwent 60 minutes of ischemia followed by reperfusion for 24 hours. Immune cells were isolated from the left ventricle for flow cytometry. Subsequently, mice underwent 60 minutes of ischemia followed by reperfusion, and cardiac function was assessed two weeks-post reperfusion. Results: Flow cytometry revealed a significant decrease in the number of neutrophils in the myocardium of neutrophil-specific STING KO mice compared to wildtype mice after 24 hours of reperfusion (5.7x10 4 ± 1.0x10 4 ; 8.7x10 4 ± 1.9x10 4 , Two-way ANOVA, N=5-6, p=0.0006). Neutrophil-specific STING KO mice showed significant reduction in ejection fraction (29.2% ± 6.4) compared to wildtype mice (38.3% ± 6.7; Two-way ANOVA, N=4-5, p=0.036), and significantly increased left ventricular end systolic volume (4.39mm ± 0.48) compared to wildtype mice (3.59 ± 0.62; Two-way ANOVA, N=4-5, p=0.017), indicating impaired cardiac function in knockout mice. Conclusion: These data suggest that neutrophil STING plays a cardioprotective role in MI/R. These studies provide the foundation to further investigate the cardioprotective mechanisms behind neutrophil-specific STING. Identifying a novel cardioprotective mechanism could be a clinically feasible point of intervention to improve recovery after MI/R.

Abstract We144: Fto Deficiency Causes Cardiac Dysfunction by Altering Expression of Serca2a mRNA

Introduction and Research Question: The impact of post-transcriptional regulation of gene expression, including N6-methyladenosine (m6A) messenger RNA methylation, on cardiac function has not yet been fully understood. Our study found that the absence of the m6A eraser, Fat mass and obesity-associated protein (Fto), in cardiomyocytes of adult mice led to cardiac dysfunction and cardiac hypertrophy. Methods and Results: To evaluate Fto physiological functions, we generated a tamoxifen-inducible cardiac-specific Fto knockout mouse model (Fto cKO). This resulted in a substantial reduction of Fto at both mRNA and protein levels in the whole heart, leading to an almost complete absence of Fto within cardiomyocytes. Echocardiography analyses showed that Fto cKO mice exhibit impaired cardiac functions, indicated by a 30% reduction in ejection fraction and 40% decrease in fractional shortening after one month of deletion of cardiac Fto ( p<0.01 ). We found a significant increase in heart weight to body weight ratios in Fto cKO animals ( p<0.05 ). This result corresponded with an increased expression of hypertrophic markers including Nppb and Myh7 mRNA in the absence of Fto ( p<0.01 ). We noted an increase in the length of Fto cKO cardiomyocytes ( p<0.05 ) in isolated cardiomyocytes, a characteristic feature of eccentric pathologic hypertrophy. Electron microscopy analysis of intact hearts showed ultrastructure abnormalities in cardiomyocytes from Fto cKO mice including Z-line density loss and disarray in cristae alignment of mitochondria. Moreover, cardiomyocytes from Fto cKO mice demonstrated defects in sarcomeric shortening including a prolongation of time to 90% peak, time to 90% rest, and decay time constant of relaxation for sarcomere shortening ( p<0.001 ), compared to control mice. Mechanistically, we found down-regulation of Serca2a and Ryr2 mRNA in cardiomyocytes lacking Fto. We further demonstrated that Fto binds Serca2a mRNA and controls its cytoplasmic-nuclear shuttling. Fto deficiency led to accumulation of Serca2a mRNA in the nucleus. Conclusion: These findings suggest that Fto plays a pivotal role as a crucial regulator for cardiac function. Consequently, our results unveil a significant and novel mechanism through which Fto-dependent regulation contributes to the preservation of cardiac homeostasis.

High-sensitivity cardiac troponin I-guided combination angiotensin receptor blockade and beta blocker therapy to prevent anthracycline cardiotoxicity: the Cardiac CARE RCT

Background Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by rises in plasma cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy. Methods In a multicentre prospective randomised open-label blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent plasma high-sensitivity cardiac troponin concentration monitoring and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Randomised controlled trial – patients at high risk of cardiotoxicity (plasma cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomised to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary end point was 6-month change in left ventricular ejection fraction. Prognostic cohort study – in low-risk non-randomised patients with plasma cardiac troponin I concentrations in the lower two tertiles, we hypothesised the absence of a 6-month change in left ventricular ejection fraction (± 2%). Results Between October 2017 and June 2021, 175 patients (mean age 53 years; 87% female; 71% breast cancer) were recruited. Patients randomised to cardioprotection (n = 29) or standard care (n = 28) had mean left ventricular ejection fractions of 65.7 ± 6.6% and 64.9 ± 5.9%, respectively, at 6 months. Twenty patients (68.9%) were adherent to cardioprotection therapy at 6 months. Adverse events were more commonly reported in the cardioprotection group, with 71.4% of patients having at least one adverse event compared with 12.7% non-randomised and 10.3% standard care patients. After adjusting for age, pre-treatment left ventricular ejection fraction and planned anthracycline dose, the estimated mean percentage-point difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was –0.4% (95% confidence interval –3.59 to 2.85%; p = 0.82). In low-risk non-randomised patients, baseline and 6-month left ventricular ejection fractions were 69.3 ± 5.7% and 66.4 ± 6.3%, respectively (estimated mean difference 2.9%, 95% confidence interval 1.45 to 4.28%; p = 0.92, not equivalent). The main secondary objective of demonstrating zero percentage-point change with equivalence of ± 2% was not met. Conclusions Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment plasma cardiac troponin I concentrations. Low-risk non-randomised patients had similar modest declines in left ventricular ejection fraction, suggesting that the clinical utility of routine cardiac troponin monitoring remains undefined. The modest short-term declines in left ventricular ejection fraction suggest that early cardioprotection therapy has a limited role in patients receiving anthracycline-based chemotherapy. Limitations Treatment effect might have been influenced by several patients stopping cardioprotection treatment within 2 months of randomisation. Across all groups, reduction in left ventricular ejection fraction was lower than expected and patients with high-risk cardiac troponin I concentrations did not exhibit a greater fall in left ventricular ejection fraction than low-risk patients. These factors, together with the trial being powered to detect a 5-percentage-point change in left ventricular ejection fraction, mean that a small treatment effect was not excluded. Future work Future work should aim to understand the transition from small changes in cardiac function, 6 months after completion of anthracycline chemotherapy, to the late development of heart failure in this population. Trial registration This trial is registered as ISRCTN24439460 and EudraCT 2017-000896-99. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 15/48/20) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 12. See the NIHR Funding and Awards website for further award information.

Predicting factors for omitting beta-blockers in patients with tachycardia-induced cardiomyopathy after successful catheter ablation for atrial fibrillation.

Tachycardia induces a reduction in the left ventricular ejection fraction (LVEF), which is defined as tachycardia-induced cardiomyopathy (TIC). Conversion to and maintenance of sinus rhythm by catheter ablation can improve LVEF in patients with TIC due to atrial fibrillation (AF). Beta-blockers are mandatory for the treatment of heart failure with reduced LVEF(HFrEF), but the necessity of beta-blockers in TIC patients even after catheter ablation remains unclear. We examined the effect of beta-blockers on cardiac function in TIC patients after catheter ablation. We retrospectively analyzed 124 patients with a history of heart failure and an LVEF of ≤ 50% who underwent catheter ablation for AF. TIC was defined as a ≥ 10% improvement in the baseline LVEF and an improvement to an LVEF of ≥ 50% at 6months after ablation. Patients with other cardiomyopathy diagnosed before the ablation were excluded. LVEF was significantly increased with the reductions of the left ventricular and left atrial volumes at the 6-month follow-up in all 80 patients with TIC. No beta-blockers were prescribed during the post-ablation follow-up in 21 patients with TIC. The absolute values of and changes in the echocardiographic parameters between before and after ablation were not significantly different between patients with and without beta-blockers after the ablation. A simple score using the history of hospitalization for heart failure and use of beta-blockers or diuretics prior to ablation was useful in identifying TIC patients who did not need prescription of beta-blockers after catheter ablation. LVEF similarly improved in both patients with and without prescription of beta-blockers after the ablation. Beta-blockers may not need to be prescribed after successful catheter ablation for AF in LVEF of ≤ 50% patients without other cause of cardiomyopathy diagnosed before the ablation, a history of hospitalization for heart failure and prescription of beta-blockers and diuretics before the ablation.

Chemical fractionation of heavy metals and zinc isotope source identification in sediments of the Huangpu River, Shanghai, China

BackgroundThe Huangpu River serves as a vital water source for around 24 million individuals residing in the metropolitan area of Shanghai. Despite this, elevated levels of heavy metals persist in the sediments of the river, with their chemical fractionation and sources remaining inadequately understood.ResultsTo improve the management of heavy metal contamination, sequential extractions and zinc (Zn) isotopic compositions were utilized to evaluate pollution levels in the Huangpu River. The findings reveal that the majority of heavy metals in the river sediments are present in residual fractions, constituting an average of 67.5% for Cd, 57.6% for Cu, 60.6% for Ni, 56.2% for Pb, and 74.4% for Cr, with the exception of Zn (33.8%). Furthermore, a substantial portion of Zn, exceeding 66%, was found in acid-exchangeable, reducible, and oxidizable fractions, indicating a high potential for Zn release into aquatic ecosystems.ConclusionFurther analysis of Zn isotopes pinpointed traffic emissions, including exhaust fumes and tire wear particles (account for ~ 34.0%), along with anthropogenic emissions and fertilizer (~ 31.7%), as the major culprits behind this contamination. These findings highlight the critical need for stricter regulations to control heavy metal contamination from traffic and domestic sources within the Huangpu River basin.

Extremal functions for twisted sharp Sobolev inequalities with lower order remainder terms. The high-dimensional case

Abstract We prove existence of extremal functions and compactness of the set of extremal functions for twisted sharp 𝑛-dimensional Sobolev inequalities with lower order remainder terms when n ≥ 5 n\geq 5 .

Precipitate Dissolution and Grain Growth during Solution Treatment of Ce‐Containing 15Cr–22Ni–1Nb Austenitic Heat‐Resistant Steel

The precipitate dissolution and grain growth during the solution treatment of a newly developed Ce‐containing 15Cr–22Ni–1Nb steel are investigated. The dissolution of eutectic NbC is the result of the elements diffusion along the concentration gradients, and honeycomb (Fe,Cr,Ni,Si)2(Nb,Mo) Laves phase transforms into a more stable Mo2C‐type M2C carbide. As the cerium content is increased from 0 to 0.0630 mass%, the area fraction of eutectic precipitates in forged and solution‐treated 15Cr–22Ni steel is decreased first and then increased. For the steel with 0.0055 mass% cerium content, the substantial reduction in the area fraction of precipitates during hot forging and solution treatment is ascribed to the severe abnormal grain growth. In the case of 15Cr–22Ni steel with 0.0019 and 0.0630 mass% cerium content, the average size of austenite grains after solution treatment is reduced, the multipeak development of grain size distribution is restrained, the range of grain size distribution is narrowed, and the variation coefficient of grain growth, the critical size of abnormally grown grain, and the proportion of abnormally grown grain are all decreased. The variation coefficient of grain growth and the critical size of abnormally grown grain in the steel are increased as the solution time is extended, whereas the proportion of abnormally grown grain presents a general trend of reduction. The established mathematical model of grain growth in the paper can be well applied to predict and control the average size of austenite grains in 15Cr–22Ni steel after solution treatment.

Neoadjuvant inetetamab and pertuzumab with taxanes and carboplatin (TCbIP) In locally advanced HER2-positive breast cancer: a prospective cohort study with propensity-matched analysis

BackgroundInetetamab is the first domestically developed innovative anti-HER2 monoclonal antibody in China, proven effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remain to be validated.MethodsThis prospective cohort study aimed to evaluate the efficacy and safety of inetetamab combined with pertuzumab, taxanes, and carboplatin (TCbIP) in neoadjuvant therapy for HER2-positive LABC, comparing it to data from patients treated with the TCbHP regimen (trastuzumab combined with pertuzumab, taxanes, and carboplatin) using propensity score matching (PSM). The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints.ResultsForty-four patients with clinical stage IIA-IIIC HER2-positive LABC were prospectively enrolled and treated with the TCbIP regimen. The tpCR rate among 28 patients who completed surgery was 60.7%, comparable to and slightly higher than the TCbHP group in PSM (60.7% vs. 53.6%, P = 0.510). The ORR was 96.4%, and the DCR reached 100.0%. The most common ≥ grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs.ConclusionNeoadjuvant therapy with TCbIP showed good efficacy and safety in patients with HER2-positive LABC and might be another promising option for neoadjuvant treatment.Trial registrationNCT05749016 (registration date: Nov 01, 2021).

Effects of Wind Speed on Size-Dependent Morphology and Composition of Sea Spray Aerosols.

Variable wind speeds over the ocean can have a significant impact on the formation mechanism and physical-chemical properties of sea spray aerosols (SSA), which in turn influence their climate-relevant impacts. Herein, for the first time, we investigate the effects of wind speed on size-dependent morphology and composition of individual nascent SSA generated from wind-wave interactions of natural seawater within a wind-wave channel as a function of size and their particle-to-particle variability. Filter-based thermal optical analysis, atomic force microscopy (AFM), AFM infrared spectroscopy (AFM-IR), and scanning electron microscopy (SEM) were employed in this regard. This study focuses on SSA with sizes within 0.04-1.8 μm generated at two wind speeds: 10 m/s, representing a wind lull scenario over the ocean, and 19 m/s, indicative of the wind speeds encountered in stormy conditions. Filter-based measurements revealed a reduction of the organic mass fraction as the wind speed increases. AFM imaging at 20% relative humidity of individual SSA identified six main morphologies: prism-like, rounded, core-shell, rod, rod inclusion core-shell, and aggregates. At 10 m/s, most SSA were rounded, while at 19 m/s, core-shells became predominant. Based on AFM-IR, rounded SSA at both wind speeds had similar composition, mainly composed of aliphatic and oxygenated species, whereas the shells of core-shells displayed more oxygenated organics at 19 m/s and more aliphatic organics at 10 m/s. Collectively, our observations can be attributed to the disruption of the sea surface microlayer film structure at higher wind speeds. The findings reveal a significant impact of wind speed on morphology and composition of SSA, which should be accounted for accurate assessment of their climate effects.

Effect of Ti3SiC2 concentration on corrosion resistance and ICR in bipolar plates composite ceramic coatings

Ti3SiC2, a MAX-phase ceramic, amalgamates metallic and ceramic traits, delivering exceptional electrical conductivity and corrosion resistance. In this research, Ti3SiC2 composite coatings were applied to 316 L stainless steel via low-power atmospheric plasma spraying (APS), aiming to bolster the electrical and corrosion resistance attributes of bipolar plates (BPPs). A power input of 15 kW notably enhanced coating density, yielding a Ti3SiC2 concentration of 19.2 wt% in the coating. Extremes in the spraying power led to either diminished deposition efficiency or a reduction of Ti3SiC2 mass fraction below 5 wt%. Tafel curves demonstrated that specimens with elevated Ti3SiC2 mass fractions exhibited robust corrosion resistance, characterized by a self-corrosion potential of −162.5 mV and a self-corrosion current density of 1.7217 × 10−6 A·cm−2. Moreover, the interfacial contact resistance (ICR) between the coating and the gas diffusion layer was remarkably low (down to 5.49 mΩ·cm−2), indicating enhanced surface electron transfer with increasing Ti3SiC2 mass fractions.

Distribution and transformation of potentially toxic elements in cracks under coal mining disturbance in farmland.

The ground cracks resulting from coal mining activities induce alterations in the physical and chemical characteristics of soil. However, limited knowledge exists regarding the impact of subsidence caused by coal mining on the distribution of potentially toxic elements (PTEs) fractions in farmland soil. In this study, we collected 19 soil profiles at varying depths from the soil surface and at horizontal distances of 0, 1, 2, and 5m from the vertical crack. Using BCR extraction fractionation, we determined the geochemical fractions and total concentrations of Chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd) and lead (Pb) to investigate their ecological risk, spatial fraction distribution, and main influencing factors. Results showed that the values of Cd appearing in 68.7% of the samples were higher than 40 and less than 80, presented a moderate ecological risk. Chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) were mainly bound to residual fractions (> 60%) with lower mobility and Cd was dominated by F1 (acid-soluble fractions, 50%) and F2 (reducible fractions, 29%) in surface soil (0-20cm). The geochemical fractionation revealed that the mobile fractions (F1-acid-soluble and F2-reducible) of PTEs were primarily located near the crack, influenced by available potassium. In contrast, the less mobile fractions (F3-oxidizable and F4-residual) exhibited higher concentrations at distances of 2 and 5m from the crack, except for arsenic, influenced by the presence of clay particles and available phosphorus.

Anticancer drugs and cardiotoxicity: the role of cardiomyocyte and non-cardiomyocyte cells.

Cardiotoxicity can be defined as "chemically induced heart disease", which can occur with many different drug classes treating a range of diseases. It is the primary cause of drug attrition during pre-clinical development and withdrawal from the market. Drug induced cardiovascular toxicity can result from both functional effects with alteration of the contractile and electrical regulation in the heart and structural changes with morphological changes to cardiomyocytes and other cardiac cells. These adverse effects result in conditions such as arrhythmia or a more serious reduction in left ventricular ejection fraction (LVEF), which can lead to heart failure and death. Anticancer drugs can adversely affect cardiomyocyte function as well as cardiac fibroblasts and cardiac endothelial cells, interfering in autocrine and paracrine signalling between these cell types and ultimately altering cardiac cellular homeostasis. This review aims to highlight potential toxicity mechanisms involving cardiomyocytes and non-cardiomyocyte cells by first introducing the physiological roles of these cells within the myocardium and secondly, identifying the physiological pathways perturbed by anticancer drugs in these cells.

Evaluation of low-temperature oxidation analysis and the development effect of high-pressure air injection in low-permeability reservoirs

In order to solve the problems of conventional water injection development difficulties and low recovery factor in low-permeability reservoirs, the method of high-pressure air drive is adopted to achieve the purpose of reservoir energy enhancement and efficiency improvement. This paper conducted an experimental study on the mechanism of low-temperature oxidation (LTO) for crude oil in the process of high-pressure air flooding, elaborated the relationship between the LTO properties of crude oil and the temperature, pressure, and water saturation of the reservoir, and analyzed the differences in LTO oxygen consumption and oil components under different reaction conditions. In addition, combined with the air flooding physical simulation experiment, the dynamic evolution law of recovery rate in the air flooding process was revealed. Findings from this inquiry indicate that an escalation in the oxidation temperature significantly amplifies the oxygen incorporation reaction within the crude oil matrix. This augmentation in oxidative conditions leads to an uptick in oxygen consumption, which subsequently precipitates a reduction in the lighter fractions of the oxidized oil while enriching its heavier components. Elevated pressures were found to enhance the propensity for the amalgamation of unstable hydrocarbons with oxygen, fostering comprehensive and heterogeneous oxidation reactions. Notably, an excessive presence of water was observed to detrimentally affect the thermal efficacy of crude oil oxidation processes. In the context of low-permeability reservoirs, air injection techniques have emerged as superior in effectuating oil displacement, although an increase in injection pressures has been associated with the phenomenon of gas channeling. Interestingly, adopting a sequential strategy of initiating water flooding before air flooding facilitated the conveyance of high-pressure air via established flushing channels, although it appeared to attenuate the intensity of crude oil oxidation, culminating in an oil recovery efficiency peaking at 51%.

Competition between Cubic and Tetragonal Phase Induced Unusual Vertical Magnetization Shift and Exchange Bias in CoxMn3−xO4 (1 ≤ x ≤ 2) Spinel Nanoparticles

CoxMn3−xO4 (1 ≤ x ≤ 2) spinel nanoparticles synthesized through conventional coprecipitation technique exhibit the coexistence of tetragonal and cubic phases in the range of 1 ≤ x ≤ 1.5, while a pure cubic phase is observed for 1.75 ≤ x ≤ 2 at room temperature. Reduction in tetragonal phase fraction from 92 % for x = 1 to 47% for x = 1.5 is attributed to diminution of Jahn–Teller (J–T) active Mn3+ ions occupying the octahedral site of spinel lattice. X‐ray photoelectron spectroscopy confirms both +2 and +3 oxidation states for Co and Mn. Surprisingly, cubic and tetragonal phases exhibit magnetic transition, Tc1 and Tc2, corresponding to a paramagnetic to a high and low temperature ferrimagnetic state, respectively. Tetragonal phase induces high spontaneous (HSEB) and conventional (HCEB) exchange bias with unusually high vertical magnetization shift (VMS) than that of the pure cubic phase, shows maximum HCEB of 4.062 kOe for x = 1.5 and a VMS of 2.5 emu g−1 for x = 1. Such dependence of VMS and exchange bias on tetragonal to cubic phase ratio in CoxMn3−xO4 is demonstrated for the first time and interpreted based on the interaction between different arrangement of spins in tetrahedral and octahedral sublattice.

Empagliflozin rescues pro-arrhythmic and Ca2+ homeostatic effects of transverse aortic constriction in intact murine hearts

We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2–6 weeks) challenge resulted in reduced late Na+ currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na+/Ca2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30–90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Isoproterenol shortened APD80 in sham-operated and TAC-only hearts, shortening CaTD80 and Decay30–90 but sparing TTP100 and Ca2+ transient alternans in all groups. All groups showed similar APD80, and TAC-only hearts showed greater CaTD80, heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts.

Environmental remediation potential of a pioneer plant (Miscanthus sp.) from abandoned mine into biochar: Heavy metal stabilization and environmental application

Pyrolysis stands out as an effective method for the disposal of phytoremediation residues in abandoned mines, yielding a valuable by-product, biochar. However, the environmental application of biochar derived from such residues is limited by the potential environmental risks of heavy metals. Herein, Miscanthus sp. residues from abandoned mines were pyrolyzed into biochars at varied pyrolysis temperatures (300–700 °C) to facilitate the safe reuse of phytoremediation residues. The results showed that pyrolysis significantly stabilizes heavy metals in biomass, with Cd exhibiting the most notable stabilization effect. Acid-soluble/exchangeable and reducible fractions of Cd decreased significantly from 69.91 % to 2.52 %, and oxidizable and residue fractions increased approximately 3.24 times at 700 °C. The environmental risk assessment indicated that biochar pyrolyzed over 500 °C pose lower environmental risk (RI < 30), making them optimal for the safe utilization of phytoremediation residues. Additionally, adsorption experiments suggested that biochars prepared at higher temperature (500–700 °C) exhibit superior adsorption capacity, attributed to alkalinity and precipitation effect. This study highlights that biochars produced by pyrolyzing Miscanthus sp. from abandoned mines above 500 °C hold promise for environmental remediation, offering novel insight into the reutilization of metal-rich biomass.

Patterns of Left Ventricular Remodelling in Children and Young Patients with Hypertrophic Cardiomyopathy.

Introduction: The aim of this study was to evaluate the age at onset, clinical course, and patterns of left ventricular (LV) remodelling during follow-up in children and young patients with hypertrophic cardiomyopathy (HCM). Methods: We included consecutive patients with sarcomeric or non-syndromic HCM below 18 years old. Three pre-specified patterns of LV remodelling were assessed: maximal LV wall thickness (MLVWT) thickening; MLVWT thinning with preserved LV ejection fraction; and MLVWT thinning with progressive reduction in LV ejection fraction (hypokinetic end-stage evolution). Results: Fifty-three patients with sarcomeric/non-syndromic HCM (mean age 9.4 ± 5.5 years, 68% male) fulfilled the inclusion criteria. In total, 32 patients (60%) showed LV remodelling: 3 patients (6%) exhibited MLVWT thinning; 16 patients (30%) showed MLVWT thickening; and 13 patients (24%) progressed to hypokinetic end-stage HCM. Twenty-one patients (40%) had no LV remodelling during follow-up. In multivariate analysis, MLVWT was a predictor of the hypokinetic end-stage remodelling pattern during follow-up (OR 1.17 [95%CI 1.01-1.36] per 1 mm increase, p-value 0.043), regardless of sarcomeric variants and New York Heart Association class. Two patients with sarcomeric HCM, showing a pattern of MLVWT regression during childhood, experienced progression during adolescence. Conclusions: Different patterns of LV remodelling were observed in a cohort of children with sarcomeric/non-syndromic HCM. Interestingly, a pattern of progressive MLVWT thinning during childhood, with new progression of MLVWT during adolescence, was noted. A better understanding of the remodelling mechanisms in children with sarcomeric HCM may be relevant to defining the timing and possible efficacy of new targeted therapies in the preclinical stage of the disease.

Preparation of porous lead zirconate titanate piezoelectric ceramics via vat photopolymerization combined with burnt polymer spheres technique

Porosity plays an important factor on the electric properties of piezoelectric ceramics. Here, we propose a promising method for the fabrication of Lead zirconate titanate (PZT) piezoelectric ceramics using vat photopolymerization, and effectively modulate porosity of printed PZT piezoceramics through adjusting the polystyrene (PS) content. After a post-process, the PZT piezoelectric ceramics showed single perovskite structure and porous microstructures formed by PS, with porosity ranging from 8.57 % to 27.02 %. With the increase of porosity, the piezoelectric strain constant (d33) and dielectric permittivity (ɛr) decreased gradually due to the reduction in the volume fraction of PZT phase per unit volume. When the PS content was 20 vol%, d33 and ɛr reached the maximum values. The sintered PZT piezoelectric ceramics exhibited excellent electrical properties (ɛr=2364, d33=399 pC/N, g33=1.91×10−2 Vm/N, d33g33=7.62×10−12 m2/N and Kt=43.94 %). This work not only provides technical support for manufacturing advanced ceramics with tunable porosity through the use of PS powders, but also lays the foundation for preparing functional ceramics with complicated designed structures through vat photopolymerization technology.

Fast shot speed induced microstructure and mechanical property evolution of high pressure die casting Mg-Al-Zn-RE alloys

In this study, the effects of fast shot speeds during high pressure die casting on the microstructure and mechanical properties of Mg-Al-Zn-RE (RE: rare earth) alloys were systematically investigated. The optimum mechanical performance was achieved at a fast shot speed of 6 m/s, and the ultimate tensile strength, yield strength, and elongation of the castings reached 290 MPa, 190 MPa, and 10.5 %, respectively. With an increase in fast shot speed, the yield strength, ultimate tensile strength, and elongation of the Mg-Al-Zn-RE alloy increased by 17 MPa, 82 MPa, and 8.2 %, respectively. These improvements are primarily attributed to the decreased area fraction of externally solidified crystals (ESCs) and the reduced volume fraction of pores. Furthermore, the enhancement in yield strength is due to grain boundary strengthening, solid-solution strengthening, and second-phase strengthening. The reduction in the area fraction of ESCs and porosity are the main contributors to the improvement in plasticity. The findings of this study provide valuable guidance for the intelligent design of novel high pressure die casting Mg alloys.