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Africa faces significant challenges due to climate change, with rising temperatures, unpredictable rainfall patterns, and increased frequency of extreme weather events. Algeria, it’s one of the countries, is facing the pressing challenge of adapting its farming systems to the impacts of climate change. This paper provides an overview of the strategies and initiatives undertaken in Algeria to enhance agricultural resilience in the face of changing climatic conditions. The agriculture sector in Algeria is vital for food security and economic stability, yet it is highly vulnerable to the effects of climate change such as unpredictable rainfall patterns, increased temperatures, and extreme weather events. The Algerian government, in collaboration with various stakeholders, has implemented a range of adaptation measures. One key strategy has been the promotion of climate-smart agriculture practices, including the use of drought-resistant crop varieties, improved irrigation techniques, and conservation agriculture methods. Furthermore, investments in agricultural infrastructure, such as water storage facilities and efficient irrigation systems, have been crucial in mitigating the impacts of water scarcity and ensuring reliable access to water for farming activities. Power farmers with the knowledge and skills needed to adapt to changing conditions. These programs focus on climate information services, agro-ecological practices, and efficient use of inputs. The adaptation of farming systems to climate change in Algeria requires a multifaceted approach that integrates policy support, technological innovations, and community engagement. By building resilience at the farm level and enhancing adaptive capacity, Algeria aims to safeguard its agricultural sector and ensure food security for future generations

Our study was conducted at the faculty of Sciences of the nature and life from Mentouri Brothers University of Constantine, (36°21′54″ N: 6°36′52″ E), altitude above sea level by 574 m in March 2022. Cereals and pseudo-cereals, the world's most important crop, are an important source of sustenance for humans and animals. In addition, they are distinguished by their high tolerance to abiotic stressors. Hydrological deficit is a major factor limiting agricultural production; the impact varies according to the species, the stage of development of the plant and the severity of the stress. This research aims to evaluate the impact of water stress on H2O2 and Malondialdehyde MDA adaptation mechanisms, as well as the quantification of proteins, glycine betaine, phenols and flavonoids that can affect drought in three local species (Triticale, Barley and Maize) and one exotic plant (Quinoa). We also recorded an induced increase in triticale, barley, maize and quinoa stressed in Hydrogen Peroxide (H2O2), Malondialdehyde (MDA), proteins and glycine betaine with a concentration varied from 228.75 and 404.58 µmol.g-1 FM, 4.92 and 20.84 µmol.g-1 DM, 1.35 and 3.21 mg.g-1 FM, 0.34 and 0.54mg.g-1 DM, respectively. While the concentration of flavonoids and phenols total was recorded in maize by 20.14 mg QE g-1 DM and 375.47 mg GAE g-1 DM, respectively. Moreover, it reduced in triticale, barley and quinoa, with a value of 4.26-9.9 mg. EQ g-1 DM and 185.97-421.31 mg. EAGg-1 DM. The study demonstrated the species' resistance to and effectiveness in the face of water stress.

The quality of four samples of honey, from the eastern of Algeria, was evaluated by determining the physicho-chemical characteristics of honey. In this study, water content (%), Total sugar (%), Proline (mg/Kg) and hydroxymethylfurfural (HMF) (mg/Kg) were determined in different types of four flora honey. The main components of honey are sugar and water, the dominant types of carbohydrate are glucose and fructose which contains approximately 70–83 %, the results of analysis showed that the total sugar estimated by the refractometre ranged from 79 to 80.5%. The water content ranged from 16.5 to 18 % within the accepted range proposed by Codex Alimentarius of no more than 20 %. In addition, HMF values confined between 0.248 and 49.30 mg/Kg, the highest value registered in the imported honey indicate that this sample was stored for longer time at elevated temperatures. Proline content of honey constantly decreases during storage therefore the proline might be indicator of honey ripeness, the proline content in the four honey samples tested varied between 205 and 1161 mg/kg, within the accepted d range proposed by Codex Alimentarius of more than 180 mg/kg. Overall, the local different flora honeys revealed that eastern Algeria honey is fulfils national and International standards.

Purpose: to determine the most significant kinematic indicators in the sports selection of beginner shot putters. Material and Methods: This study was carried out on a sample of 9 students at the fourth stage of the competition in Division 1, which took place in the 2017/2018 academic year at the Faculty of Physical Education of Maysan University. The following kinematic (biomechanical) parameters were analyzed: the angle of release of the nucleus, the velocity of release, the height of the point of ejection of the nucleus and the speed of swing. The correlation coefficients were determined between the kinematic indicators and the result in the shot put, as well as the regression equation for the dependence of the result in the shot put on the knematic indicators. The data obtained in the study were presented in the form of the arithmetic mean, standard deviation, median, skewness coefficient, Pearson's correlation coefficient, analysis of variance and linear regression, which included the contribution coefficients of each analyzed indicator, standard error, reliability of the regression equation as a whole, and reliability of the coefficients contribution to the shot put result of each kinematic exponent. Results. It has been shown that the swing speed has the greatest influence on the result in the shot put among beginner athletes. The swing speed, shot angle, shot speed and shot height have significant relationships with the shot put result. The multiple regression equation for the dependence of the shot put result on the swing speed, shot angle, shot height and shot point turned out to be reliable in general. However, only the swing speed has a reliable coefficient of the regression equation. The shot angle tends to be the determining factor in the shot put result. The release rate and the height of the release point have significant correlations with the shot put result, although in the regression equation they have unreliable indicators of influence on the shot put result. Conclusions. When teaching beginner shot putters, the greatest attention should be paid to the pushing swing technique, namely the swing speed. The second most important indicator is the angle of the shot put, it is recommended to use the basic prediction equation, which determines the expected results in the selection of young athletes in shot put, with high reliability of the results obtained. These characteristics are recommended to be used for evaluating young athletes, as well as in the process of training and preparing athletes for competitions.

Aortic stenosis (AS) is the most common valvular heart disease in developed countries, and its prevalence is higher in older patients. Clinical studies have shown gender disparity in the pathogenesis and the progression of aortic stenosis. This disparity has led to several overwhelming questions regarding its impact on the clinical outcomes and treatment of the disease and the requirement of personalized sex-specific approaches for its management. Indeed, aortic stenosis differs in the pathophysiological response to pressure overload created by the stenosis in women compared to men, which would translate into differences in cardiac remodeling and clinical outcomes. Several studies have focused on understanding the differences regarding disease progression according to biological gender and have found that sex hormones play a crucial role. Sex hormones affect many metabolic processes, thus activating crucial cell signaling and energy metabolism through mitochondrial activity. Yet, there is still a significant gap in knowledge on how biological sex influences the pathophysiology of AS. In this review, we have discussed studies that point to the role of sex-related physiological differences in the molecular pathways and the clinical presentation of the disease and outcome in women and men. We used the format of narrative review to review and summarize the body of literature without being systematic but with taking great care of considering the most impactful data available to date on the topic, especially randomized trials, metanalyses, and prospective studies and registries when available, as well as experimental studies with rigorous methodological approaches regarding the basic mechanisms and pathophysiology of the disease in women compared to men. The opinion of the authors on a particular issue or finding was expressed when appropriate for clarification.

Fibromuscular dysplasia (FMD) is a poorly understood disease affecting 3-5% of adult females. The pathobiology of FMD involves arterial lesions of stenosis, dissection, tortuosity, dilation and aneurysm, which can lead to hypertension, stroke, myocardial infarction and even death. Currently, there are no animal models for FMD and few insights as to its pathobiology. In this study, by integrating DNA genotype and RNA sequence data from primary fibroblasts of 83 patients with FMD and 71 matched healthy controls, we inferred 18 gene regulatory co-expression networks, four of which were found to act together as an FMD-associated supernetwork in the arterial wall. After in vivo perturbation of this co-expression supernetwork by selective knockout of a top network key driver, mice developed arterial dilation, a hallmark of FMD. Molecular studies indicated that this supernetwork governs multiple aspects of vascular cell physiology and functionality, including collagen/matrix production. These studies illuminate the complex causal mechanisms of FMD and suggest a potential therapeutic avenue for this challenging disease., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Biohydrogen is considered an alternative energy reserve. Dark fermentation is one of the important green hydrogen production techniques that utilizes organic waste as raw material. It is a promising bioconversion, easy, not expensive, and cost-effective process. Milk processing wastewater (MPWW) is an organic effluent generated in large volumes on a daily basis and disposed directly into the environment. In this research, the study of biochemical hydrogen potential (BHP) test of MPWW was evaluated and used as substrate (S). A waste sludge was used as an inoculum (I) and source of bacteria. Both substrate and inoculum were analyzed and the study was based mainly on the ratio of volatile solids (VS) of inoculum and substrate subsequently, which was noted as I/S. Different substrate pretreatments were performed: ultrasonic, thermal, chemical, and enzymatic hydrolysis. The I/S ratio impact was investigated and evaluated the hydrogen production improvement. Modified Gompertz and modified Logistic kinetic models were employed for the kinetic modeling of cumulative hydrogen production values. Results show that I/S ratio of 1/4 gVS/gVS resulted from the best hydrogen production of 59.96 mL during 30 days of MPWW fermentation without pretreatment. It was also shown that all the adopted pretreatments enhanced hydrogen production, whereas ultrasonic pretreatment for 5 min increased the production by only 14.84%. Heat pretreatment was more efficient, where the hydrogen production increased from 60 to 162 mL (170% of improvement) using heat shock at 90 °C for 30 min. The impact of chemical pretreatment was different from a reagent to another. Pretreatment using calcium hydroxide resulted in the biggest hydrogen production of 165.3 mL (175.5%) compared to the other chemical pretreatments. However, the best hydrogen production was given by the biological pretreatment using enzymatic hydrolysis (Lactase) resulting in 254 mL of hydrogen production, which is equivalent to 323.62% of production improvement. Modified Gompertz and Logistic kinetic models fitted well with experimental data. Thus, the enzymatic hydrolysis of MPWW proved to be a promising technique for biohydrogen production enhancement., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Biological pretreatment and enzymatic hydrolysis have a potential role in the economic production of sugars and fuels from starch biomass. In this study, the Inoculum/Substrate (I/S) ratio effect and enzymatic pretreatments of potato peels for biohydrogen production in batch reactors were investigated. Two enzymes, α- Amylase and Cellulase , were tested separately and coexistent. Results showed that enzymatic hydrolysis using α- Amylase in mesophilic conditions enhanced carbohydrate concentration from 24.10 g/L to 53.47 g/L, whereas, the use of Cellulase and equi-volumetric mixture of both tested enzymes resulted in 47.16 and 48.16 g/L, respectively. The maximum biohydrogen cumulative production of 263 mL (equivalent to 430.37 mL H 2 /gVS added ) was obtained using the optimum I/S ratio of 1/6 gVS/gVS at pH 5.5 and incubation temperature of 55°C after 20 days of dark fermentation of potato waste without enzymatic treatment. Under the same operating conditions of the I/S ratio, pH, temperature and the best enzymatic treatment (3 h of substrate enzymatic hydrolysis by α- Amylase), the maximum yield of biohydrogen was 1088 mL (1780.39 mL H 2 /gVS added ). The enzymatic hydrolysis method adopted in this study can make overall biohydrogen production an effective process. The modified Gompertz model was found to be an adequate fit for biohydrogen production.

The aim of this research is to study the ability of Cactus leaves to act as a biocoagulants for the removal of lead in water. Different solvents, such as distilled water, NaCl, NaOH, and HCl, were used as chemical activators to extract the active components from the Cactus. The Cactus was utilized as an organic coagulant in five different forms: (i) Cactus juice (CJ); Cactus extract using (ii) distilled water (C-H 2 O); (iii) NaCl at 0.5 M concentration (C-NaCl); (iv) NaOH at 0.05 M concentration (C-NaOH); and (v) HCl at 0.05 M concentration (C-HCl). In order to establish the optimal conditions for the coagulation, this study employed the jar test as an experimental technique and the Box-Behnken design (BBD) as an experimental approach. According to BBD, there are three factors (k = 3), namely pH, biocoagulant dosage, and settling time. The R 2 and R 2 adjusted for all coagulants were close to 100%, confirming the validity of all the mathematical models. The results were significant; the highest lead removal efficiencies were 98.11%, 98.34%, 95.65, 96.19%, and 97.49%, utilizing CJ, C-H 2 O, C-NaCl, C-HCl, and C-NaOH as natural coagulants. The Cactus has been characterized using FTIR, XRD, and SEM to identify the active components that remove lead., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The lifetime risk of kidney disease in people with diabetes is 10-30%, implicating genetic predisposition in the cause of diabetic kidney disease (DKD). Here we identify an expression quantitative trait loci (QTLs) in the cis-acting regulatory region of the xanthine dehydrogenase, or xanthine oxidoreductase (Xor), a binding site for C/EBPβ, to be associated with diabetes-induced podocyte loss in DKD in male mice. We examine mouse inbred strains that are susceptible (DBA/2J) and resistant (C57BL/6J) to DKD, as well as a panel of recombinant inbred BXD mice, to map QTLs. We also uncover promoter XOR orthologue variants in humans associated with high risk of DKD. We introduced the risk variant into the 5'-regulatory region of XOR in DKD-resistant mice, which resulted in increased Xor activity associated with podocyte depletion, albuminuria, oxidative stress and damage restricted to the glomerular endothelium, which increase further with type 1 diabetes, high-fat diet and ageing. Therefore, differential regulation of Xor contributes to phenotypic consequences with diabetes and ageing., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Bioprosthetic valve fracture (BVF) can be used to improve transcatheter heart valve (THV) haemodynamics following a valve-in-valve (ViV) intervention. However, whether BVF should be performed before or after THV deployment and the implications on durability are unknown.  Aims: We sought to assess the impact of BVF timing on long-term THV durability., Methods: The impact of BVF timing was assessed using small ACURATE neo (ACn) or 23 mm SAPIEN 3 (S3) THV deployed in 21 mm Mitroflow valves compared to no-BVF controls. Valves underwent accelerated wear testing up to 200 million (M) cycles (equivalent to 5 years). At 200M cycles, THV were evaluated by hydrodynamic testing, second-harmonic generation (SHG) microscopy, scanning electron microscopy (SEM) and histology., Results: At 200M cycles, the regurgitant fraction (RF) and effective orifice area (EOA) for the ACn were 8.03±0.30%/1.74±0.01 cm 2 (no BVF), 12.48±0.70%/1.97±0.02 cm 2 (BVF before ViV) and 9.29±0.38%/2.21±0.0 cm 2 (BVF after ViV), respectively. For the S3 these values were 2.63±0.51%/1.26±0.01 cm 2 , 2.03±0.42%/1.65±0.01 cm 2 , and 1.62±0.38%/2.22±0.01 cm 2 , respectively. Further, SHG and SEM revealed a higher degree of superficial leaflet damage when BVF was performed after ViV for the ACn and S3. However, the histological analysis revealed significantly less damage, as determined by matrix density analysis, through the entire leaflet thickness when BVF was performed after ViV with the S3 and a similar but non-significant trend with the ACn.  Conclusions: BVF performed after ViV appears to offer superior long-term EOA without increased RF. Ultrastructure leaflet analysis reveals that the timing of BVF can differentially impact leaflets, with more superficial damage but greater preservation of overall leaflet structure when BVF is performed after ViV.

In this research, nanoparticles derived from water extract of Centaurea solstitialis leaves were used as green adsorbent in Fenton reaction for Reactive Red 180 (RR180) and Basic Red 18 (BR18) dyes removal. At optimum operating conditions, nanoparticles proved high performance in the tested dyes removal with more than 98% of removal elimination. The free-radical scavenging, DNA nuclease, biofilm inhibition capability, antimicrobial activity, microbial cell viability, and antimicrobial photodynamic therapy activities of the iron oxide nanoparticles (FeO-NPs) derived from water and methanol extract of plant were investigated. Each of the following analysis: SEM-EDX, XRD, and Zeta potential was implemented for the prepared NPs characterization and to describe their morphology, composition and its behavior in an aqueous solution, respectively. It was found that, the DPPH scavenging activities increased when the amount of nanoparticles increased. The highest radical scavenging activity achieved with FeO-NPs derived from water extract of plant as 97.41% at 200 mg/L. The new green synthesized FeO-NPs demonstrated good DNA cleavage activity. FeO-NPs showed good in vitro antimicrobial activities against human pathogens. The results showed that both synthesized FeO-NPs displayed 100% antimicrobial photodynamic therapy activity after LED irradiation. The water extract of FeO-NPs and methanol extract of FeO-NPs also showed a significant biofilm inhibition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fenton oxidation is an effective and valuable method for wastewater treatment. To inhibit environmental impacts and increase overall reaction efficiencies, it is important to develop advanced catalysts. This paper illustrates an experimental study on the elimination of RR180 dye from synthetic aqueous solutions with raw leonardite and different iron-loaded leonardite powders, Fe(0)-loaded leonardite, and Fe(II)-loaded leonardite. The effect of solution pH (2.0-6.0), catalyst amount (0.10-1.5 g/L), H 2 O 2 concentration (10-50 µL/L), and dye concentration (10-30 ppm) was tested to achieve maximum color removal efficiency using the three catalysts. At pH = 2, color removal efficiencies were higher and more suitable. Initial experiments showed the advantage of using Fe(II)-loaded leonardite on using Fe(0)-loaded leonardite. Fe(II)-loaded leonardite catalyst was the most efficient in RR180 color removal compared to the other tested reagents. Color removal in function of solution pH did not decrease much when Fe(II)-loaded leonardite was used (100 to 96%) when pH was increased from 2.0 to 6.0. In the other hand, dye removal has been significantly affected in the case of using raw leonardite, Fe(0)-loaded leonardite (93 to 0%), and (100 to 13%) in the same pH range, respectively. At optimum experimental conditions, catalyst amount: 0.75 g/L for Fe(II) and Fe(0)-loaded leonardite and 1.5 g/L for raw leonardite; dye concentration: 10 ppm; solution pH: 2.0; H 2 O 2 concentration: 50 µL/L; volume: 100 mL and reaction time: 60 min, RR180 dye removal efficiencies were 91%, 100%, and 100% by raw leonardite, Fe(0)-loaded leonardite and Fe(II)-loaded leonardite, respectively. The stability and reusability of the tested catalyst was investigated up to ten cycles. The experimental results revealed that both Fe(0)-loaded leonardite and Fe(II)-loaded leonardite can be used in Fenton reaction up to four cycles without decreasing their efficiency in RR180 color removal. The characterization of the catalysts was established using scanning electron microscope with energy dispersive X-ray spectroscopy (SEM-EDX). The synthesized catalyst can be used at large scale in any textile industry to effectively remove dyes resulting in high elimination rates at the optimal determined and studied conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Shahzad et al. examined the underlying mechanisms of sterile inflammation in diabetic kidney disease, specifically the role of NLRP3 inflammasome activation in podocytes. Using mouse models with gain-of-function and loss-of-function mutations in podocyte Nlrp3, or caspase-1 loss-of-function mutations in podocytes, they identified that Nlrp3 activation in these cells is central for development of diabetic kidney disease but not solely dependent on canonical mechanisms and caspase-1. These findings position podocyte-mediated immune cell-like functions as potential therapeutic targets for diabetic kidney disease., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

One of the most important problems affecting the environment today is the inability to adequately treat wastewater containing dyes. Among of the many treatment processes used in the treatment of dye-containing wastewater, photocatalytic based wastewater treatment processes attract the attention of scientists as a new, economically feasible, and promising approach which has been in practice for a few decades. However, in order to use these processes in wider areas, cheap and effective catalysts are still being developed today. In this study, the photocatalytic activity of eggshell-CaO produced from waste chicken eggshells was investigated for decolorization of Safranin (Basic Red 2) and Reactive Red 180 (RR180) dyes. First, sintering process was applied to the waste chicken eggshells at different temperatures (300, 600, 900 °C) in order to observe CaO formation from the eggshells. Second, the parameters such as photocatalyst amount, pH, concentration of dyes, and reaction time were optimized on dye removal efficiency in photocatalytic experiments. The optimum conditions were performed under visible light and found to be 1 g/L of catalyst amount (sintered at 900 °C), original solution pH (6.80 for Safranin and 6.60 for RR180), and 5 mg/L of dye concentration. The photocatalytic removal efficiencies of Safranin and RR180 dyes were 100% and 97.90%, respectively, under the determined optimum experimental conditions. The adsorption efficiency of the dyes that could be realized during the photocatalytic experiment was measured as 20.99% and 9.99% for Safranin and RR180 dyes, respectively., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Glomerular endothelial cell (GEC) dysfunction can initiate and contribute to glomerular filtration barrier breakdown. Increased mitochondrial oxidative stress has been suggested as a mechanism resulting in GEC dysfunction in the pathogenesis of some glomerular diseases. Historically the isolation of GECs from in vivo models has been notoriously challenging due to difficulties in isolating pure cultures from glomeruli. GECs have complex growth requirements in vitro and a very limited lifespan. Here, we describe the procedure for isolating and culturing conditionally immortalized GECs with fluorescent mitochondria, enabling the tracking of mitochondrial fission and fusion events. GECs were isolated from the kidneys of a double transgenic mouse expressing the thermolabile SV40 TAg (from the Immortomouse), conditionally promoting proliferation and suppressing cell differentiation, and a photo-convertible fluorescent protein (Dendra2) in all mitochondria (from the photo-activatable mitochondria [PhAM excised ] mouse). The stable cell line generated allows for cell differentiation after inactivation of the immortalizing SV40 TAg gene and photo-activation of a subset of mitochondria causing a switch in fluorescence from green to red. The use of mitoDendra2-GECs allows for live imaging of fluorescent mitochondria's distribution, fusion, and fission events without staining the cells.

Background: Patients with thoracic aortopathy are at increased risk of catastrophic aortic dissection, carrying with it substantial mortality and morbidity. Although granular medial calcinosis (medial microcalcification) has been associated with thoracic aortopathy, its relationship to disease severity has yet to be established., Methods: One hundred one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathologic scores, immunohistochemistry, and nanoindentation (tissue elastic modulus) were compared with the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography., Results: Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71-10.39]; P ≤0.00010) or moderate histopathologic degeneration (n=30; 3.74 [0.87-11.80]; P <0.042) compared with control samples (n=18; 0.79 [0.36-1.90]). Alkaline phosphatase (n=26; P =0.0019) and OPN (osteopontin; n=26; P =0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathologic degeneration was related to reduced microcalcification (n=82; Spearman ρ, -0.51; P <0.0001)-a process closely linked with elastin loss (n=82; Spearman ρ, -0.43; P <0.0001) and lower tissue elastic modulus (n=28; Spearman ρ, 0.43; P =0.026). 18 F-sodium fluoride autoradiography demonstrated good correlation with histologically quantified microcalcification (n=66; r=0.76; P <0.001) and identified areas of focal weakness in vivo., Conclusions: Medial microcalcification is a marker of aortopathy, although progression to severe aortopathy is associated with loss of both elastin fibers and microcalcification. 18 F-sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible noninvasive imaging modality for identifying aortic wall disruption with major translational promise.

Aims: Increased resistin (Retn) levels are associated with development of cardiovascular diseases. However, the role of Retn in heart failure (HF) is still unclear. Here we probed the functional and molecular mechanism underlying the beneficial effect of Retn deletion in HF., Methods and Results: Wild-type (WT) and adipose tissue-specific Retn-knockout (RKO) mice were subjected to transverse aortic constriction (TAC)-induced HF. Cardiac function and haemodynamic changes were measured by echocardiography and left ventricular catheterization. Adipose tissue Retn deletion attenuated while Retn cardiac-selective overexpression, via a recombinant adeno-associated virus-9 vector, exacerbated TAC-induced hypertrophy, cardiac dysfunction, and myocardial fibrosis in WT and RKO mice. Mechanistically, we showed that Gadd45α was significantly increased in RKO HF mice while cardiac overexpression of Retn led to its downregulation. miR148b-3p directly targets Gadd45α and inhibits its expression. Retn overexpression upregulated miR148b-3p expression and triggered DNA damage response (DDR) in RKO-HF mice. Inhibition of miR148b-3p in vivo normalized Gadd45α expression, decreased DDR, and reversed cardiac dysfunction and fibrosis. In vitro Retn overexpression in adult mouse cardiomyocytes activated miR148b-3p and reduced Gadd45α expression. Gadd45α overexpression in H9C2-cardiomyoblasts protected against hydrogen peroxide- and Retn-induced DDR., Conclusion: These findings reveal that diminution in circulating Retn reduced myocardial fibrosis and apoptosis, and improved heart function in a mouse model of HF, at least in part, through attenuation of miR148b-3p and DDR. The results of this study indicate that controlling Retn levels may provide a potential therapeutic approach for treating pressure overload-induced HF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Calcific Aortic Valve Disease (CAVD) is a fibrocalcific disease. Lipoproteins and oxidized phospholipids play a substantial role in CAVD; the level of Lp(a) has been shown to accelerate the progression of valve calcification. Indeed, oxidized phospholipids carried by Lp(a) into the aortic valve stimulate endothelial dysfunction and promote inflammation. Inflammation and growth factors actively promote the synthesis of the extracellular matrix (ECM) and trigger an osteogenic program. The accumulation of ECM proteins promotes lipid adhesion to valve tissue, which could initiate the osteogenic program in interstitial valve cells. Statin treatment has been shown to have the ability to diminish the death rate in subjects with atherosclerotic impediments by decreasing the serum LDL cholesterol levels. However, the use of HMG-CoA inhibitors (statins) as cholesterol-lowering therapy did not significantly reduce the progression or the severity of aortic valve calcification. However, new clinical trials targeting Lp(a) or PCSK9 are showing promising results in reducing the severity of aortic stenosis. In this review, we discuss the implication of lipids in aortic valve calcification and the current findings on the effect of lipid-lowering therapy in aortic stenosis.

In this study, a hybrid process for leachate wastewater treatment including evaporation and reverse osmosis (RO) membrane or biological treatment systems was suggested. Experiments were performed on a real landfill leachate wastewater. The leachate was subjected to evaporation; as a result, a distillate was obtained containing less organic matter and less substantial amounts of other pollutants, as ammonium salts and total phenols were removed. Tests were carried out at different evaporation temperatures and times. The initial leachate pH was adjusted and optimized. For optimum conditions, each of chemical oxygen demand (COD), total phenol, and ammonium salt concentrations were reduced to 99.99%, 95.00%, and 83.00%, respectively. The distillate of the first stage of the proposed process was then exposed to RO membrane system, as a first study, under different transmembrane pressure of 20, 30, and 40 bar and at different pH values of 7, 8, and 9. As a second suggested treatment system, the distillate was subjected to a biological treatment process for 30 days as a retention time, pH = 6, and room temperature 25°C ± 1°C. At the end of the research study, a comparison was conducted between results obtained with RO membrane separation and biological treatment system as two distinct treatment systems proposed for leachate landfill wastewater treatment. Although both systems were effective for landfill leachate wastewater treatment, however, with the RO membrane separation system, COD removal efficiency reached 99.99%. In the other hand, with biological treatment process, COD elimination was as much as 90.00%. Certainly, evaporation and RO are not novel ways of landfill leachate treatment; however, few studies have attempted to use similar combined system for landfill leachate wastewater treatment and attained effective results of treated water. PRACTITIONER POINTS: A hybrid process of evaporation and RO membrane or biological treatment systems was suggested for leachate wastewater treatment. For optimum conditions, COD, total phenols, and ammonium salt reductions were achieved to 99.99%, 95%, and 83%, respectively, after the first evaporation stage. The distillate of the first stage of the proposed process was then exposed to RO membrane system and biological treatment system. Different transmembrane pressure and different pH values were optimized for RO., (© 2022 Water Environment Federation.)

Calcific aortic valve disease (CAVD) is heritable, as revealed by recent GWAS. While polymorphisms linked to increased expression of CACNA1C - encoding the CaV1.2 L-type voltage-gated Ca2+ channel - and increased Ca2+ signaling are associated with CAVD, whether increased Ca2+ influx through the druggable CaV1.2 causes CAVD is unknown. We confirmed the association between increased CaV1.2 expression and CAVD in surgically removed aortic valves from patients. We extended our studies with a transgenic mouse model that mimics increased CaV1.2 expression within aortic valve interstitial cells (VICs). In young mice maintained on normal chow, we observed dystrophic valve lesions that mimic changes found in presymptomatic CAVD and showed activation of chondrogenic and osteogenic transcriptional regulators within these valve lesions. Chronic administration of verapamil, a CaV1.2 antagonist used clinically, slowed the progression of lesion development in vivo. Exploiting VIC cultures, we demonstrated that increased Ca2+ influx through CaV1.2 drives signaling programs that lead to myofibroblast activation of VICs and upregulation of genes associated with aortic valve calcification. Our data support a causal role for Ca2+ influx through CaV1.2 in CAVD and suggest that early treatment with Ca2+ channel blockers is an effective therapeutic strategy.

This study intended to evaluate and compare the efficiency of electrochemical oxidation (EO), nanofiltration (NF), and reverse osmosis (RO) membranes processes in the treatment of yarn fabric dyeing wastewater (YFDW) in terms of chemical oxygen demand (COD) removal, color removal, salinity reduction, and conductivity removal. EO tests of the textile effluent were conducted under various current densities and solution pH conditions employing a graphite electrode. Membrane filtration experiments were conducted using two different NF membranes: NP010 and NP030 and two distinct RO membranes: BW30 and SW30 flat-sheet membranes. The experimental results showed that NF membrane process is not suitable for yarn fabric wastewater treatment showing low removal efficiencies for COD, color, and conductivity. However, both EO and RO membranes could reduce COD and color to high removal performances. EO results showed more than 99% of color removal and 80% of COD elimination at pH = 6 and current density of 50 mA/cm 2 after 180 min of reaction. Using RO membrane for yarn fabric wastewater treatment demonstrated relatively complete removal of color concentration and 98% of COD elimination. However, EO process showed less performance in conductivity removal efficiency compared to the RO membranes. EO treatment of YFDW decreased conductivity by 31.2%, whereas RO membrane process reduced conductivity to a greater extent and recorded 97.1% of removal elimination percentage. Therefore, the treated water by RO membrane could be recycled back to the process such as washing and dyeing, in that way offering economic profits by decreasing water consumption and wastewater treatment cost. PRACTITIONER POINTS: Electrochemical oxidation and membrane filtration processes were combined for the treatment of yarn fabric dyeing wastewater (YFDW). A 100% color removal of color and 98.5% COD elimination efficiencies were obtained for the electrochemical oxidation (EO) + RO combined process. EO treatment of YFDW decreased conductivity by 32.7%, whereas the RO membrane process reduced conductivity to a greater extent and recorded 97.7% of removal elimination percentage., (© 2021 Water Environment Federation.)

Aortic stenosis (AS) is the most common heart valve disease requiring surgery in developed countries, with a rising global burden associated with aging populations. The predominant cause of AS is believed to be driven by calcific degeneration of the aortic valve and a growing body of evidence suggests that platelets play a major role in this disease pathophysiology. Furthermore, platelets are a player in bioprosthetic valve dysfunction caused by their role in leaflet thrombosis and thickening. This review presents the molecular function of platelets in the context of recent and rapidly evolving understanding the role of platelets in AS, both of the native aortic valve and bioprosthetic valves, where there remain concerns about the effects of subclinical leaflet thrombosis on long-term prosthesis durability. This review also presents the role of antiplatelet and anticoagulation therapies on modulating the impact of platelets on native and bioprosthetic aortic valves, highlighting the need for further studies to determine whether these therapies are protective and may increase the life span of surgical and transcatheter aortic valve implants. By linking molecular mechanisms through which platelets drive disease of native and bioprosthetic aortic valves with studies evaluating the clinical impact of antiplatelet and antithrombotic therapies, we aim to bridge the gaps between our basic science understanding of platelet biology and their role in patients with AS and ensuing preventive and therapeutic implications., Competing Interests: Dr Sellers has been supported by fellowships from the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research. Dr Pibarot has provided core lab services for Edwards Lifesciences and Medtronic, makers of bioprosthetic valves, for which he receives no direct compensation. Dr Leipsic has been supported by a Canadian Research Chair in Advanced Cardiopulmonary Imaging and has consulted for Edwards Lifesciences, Heartflow Inc, and Circle Cardiovascular Imaging and provides CT core lab services for Edwards Lifesciences, Medtronic, Neovasc, Boston Scientific, and Tendyne Holdings, for which no direct compensation is received. Dr Sathananthan has received speaker fees from Edwards Lifesciences; and has been a consultant for Edwards Lifesciences, Boston Scientific, and Medtronic. Dr Gulsin has been supported by a British Heart Foundation Travel Fellowship., (© 2021 The Authors.)

This study aims to investigate the treatability of the wastewater generated from the sesame seeds dehulling process by a combination of electrochemical techniques with a membrane filtration system. Chemical oxygen demand (COD) and phenol removal performances were studied for four different cathodes material (iron (Fe), aluminum (Al), platinum (Pt), and boron-doped diamond (BDD)) at different current densities in the electrochemical treatment stage. The maximum removal efficiency was obtained when the BDD electrodes were used. The optimum conditions were 100 A/m 2 of current density and 120 min of electrolysis period, where 40% and 85% of COD and phenol removals subsequently were achieved. The generated water from the first stage was passed through two different membrane systems. The membrane systems were microfiltration and ultrafiltration. The uptake performance for microfiltration was 22% and 17% for COD and phenol reduction subsequently. The ultrafiltration performed well and has given an additional removal of 27% and 20% of both COD and phenol reduction, respectively. The final results showed the importance of the studied combined systems and the additional value to the final obtained water quality.

An enhanced and different method for the active coagulant agent extraction from Moringa Oleifera seeds powder (MOSP) was established and compared to the conventional extraction method in distillate water. In the improved method, MOSP were extracted using sodium chloride as solvent at different concentrations to extract more coagulant agent from Moringa Oleifera and enhance coagulation activity. In this study, MOSP were initially processed and oil content was removed to minimize coagulant concentration usage (MOSP-EO). Moringa Oleifera seeds powder was characterized by both X-ray and FTIR analysis. Ultrasound treatment as well was considered as an additional treatment for MOSP-EO to investigate its effect on coagulant agent extraction process improvement. Coagulation/flocculation experiments were conducted to assess coagulant extraction performance realized through various conditions. The effect of coagulant dosage, solvent concentration and ultrasound exposition duration were investigated for a real effluent of municipal wastewater treatment. Among the three studied NaCl concentrations, 1.0 M was found to be the best solvent concentration for high turbidity removal of more than 97% using 140 mg/L of MOSP-EO compared to extraction in distillate water 88% using 170 mg/L of the same coagulant. NaCl 1.0 M demonstrated the best performance in biochemical oxygen demand (BOD 5 ) removal as well, where more than 98% of municipal wastewater initial BOD 5 was eliminated. Mixing MOSP-EO assisted with ultrasound waves at different treatment periods did decrease the active coagulant agent extraction and thus showed its inconvenient for Moringa Oleifera coagulation activity usage.

The calcification of aortic valve cells is the hallmark of aortic stenosis and is associated with valve cusp fibrosis. Valve interstitial cells (VICs) play an important role in the calcification process in aortic stenosis through the activation of their dedifferentiation program to osteoblast-like cells. Mouse VICs are a good in vitro tool for the elucidation of the signaling pathways driving the mineralization of the aortic valve cell. The method described herein, successfully used by these authors, explains how to obtain freshly isolated cells. A two-step collagenase procedure was performed with 1 mg/mL and 4.5 mg/mL. The first step is crucial to remove the endothelial cell layer and avoid any contamination. The second collagenase incubation is to facilitate the migration of VICs from the tissue to the plate. In addition, an immunofluorescence staining procedure for the phenotype characterization of the isolated mouse valve cells is discussed. Furthermore, the calcification assay was performed in vitro by using the calcium reagent measurement procedure and alizarin red staining. The use of mouse valve cell primary culture is essential for testing new pharmacological targets to inhibit cell mineralization in vitro.

Cardiac fibrosis is characterized by excessive deposition of extracellular matrix proteins and myofibroblast differentiation. Our previous findings have implicated resistin in cardiac fibrosis; however, the molecular mechanisms underlying this process are still unclear. Here we investigated the role of resistin in fibroblast-to-myofibroblast differentiation and elucidated the pathways involved in this process. Fibroblast-to-myofibroblast transdifferentiation was induced with resistin or TGFβ1 in NIH-3T3 and adult cardiac fibroblasts. mRNA and protein expression of fibrotic markers were analyzed by qPCR and immunoblotting. Resistin-knockout mice, challenged with a high-fat diet (HFD) for 20 weeks to stimulate cardiac impairment, were analyzed for cardiac function and fibrosis using histologic and molecular methods. Cardiac fibroblasts stimulated with resistin displayed increased fibroblast-to-myofibroblast conversion, with increased levels of αSma, col1a1, Fn, Ccn2 and Mmp9, with remarkable differences in the actin network appearance. Mechanistically, resistin promotes fibroblast-to-myofibroblast transdifferentiation and fibrogenesis via JAK2/STAT3 and JNK/c-Jun signaling pathways, independent of TGFβ1. Resistin-null mice challenged with HFD showed an improvement in cardiac function and a decrease in tissue fibrosis and reduced mRNA levels of fibrogenic markers. These findings are the first to delineate the role of resistin in the process of cardiac fibroblast-to-myofibroblast differentiation via JAK/STAT3 and JNK/c-Jun pathways, potentially leading to stimulation of cardiac fibrosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Recently, the utilization of wastes, recovery of high value-added products from waste, and their use as raw materials in other industries with the logic of industrial symbiosis has become an important issue. In this study, removal efficiency of Reactive Orange 16 (RO16) dye from aqueous solution was studied using TiO 2 catalyst recycled from an industrial waste effluent. The recycling of TiO 2 waste from a paints manufacturing industry was carried out by sintering the TiO 2 -containing waste. The catalyst usability of TiO 2 -containing powder was then investigated in the removal of RO16 dye by photocatalytic oxidation process. In photocatalytic oxidation studies, TiO 2 /UV and TiO 2 /UV/H 2 O 2 processes were investigated, where the effect of annealing temperature, the effect of H 2 O 2 concentration, and the adsorption and photocatalytic effects on RO16 dye removal were studied. The results showed that 100% RO16 removal was obtained for the 10 mg/L initial RO16 concentration using the TiO 2 (1 g/L)/UV process. At high initial RO16 concentration (50 mg/L), 100% RO16 removal was achieved by adding 10 mM H 2 O 2 .

This study analyzed the expression of extracellular matrix (ECM) proteins during aortic valve calcification with mass spectrometry, and further validated in an independent human cohort using RNAseq data. The study reveals that valve calcification is associated with significant disruption in ECM and metabolic pathways, and highlights a strong connection between metabolic markers and ECM remodeling. It also identifies FNDC1 and MXRA5 as novel ECM biomarkers in calcified valves, electing them as potential targets in the development and progression of aortic stenosis., Competing Interests: Dr. Bouchareb was supported in part by a National Institutes of Health (NIH) grant T32 HL7824-19; Dr. Lebeche was supported by National Institutes of Health grant R01HL137220. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Myocardial fibrosis is a major determinant of clinical outcomes in heart failure (HF) patients. It is characterized by the emergence of myofibroblasts and early activation of pro-fibrotic signaling pathways before adverse ventricular remodeling and progression of HF. Boron has been reported in recent years to augment the innate immune system and cell proliferation, which play an important role in the repair and regeneration of the injured tissue. Currently, the effect of boron on cardiac contractility and remodeling is unknown. In this study, we investigated, for the first time, the effect of boron supplementation on cardiac function, myocardial fibrosis, apoptosis and regeneration in a rat model myocardial infarction (MI)-induced HF. MI was induced in animals and borax, a sodium salt of boron, was administered for 7 days, p.o., 21 days post-injury at a dose level of 4 mg/kg body weight. Transthoracic echocardiographic analysis showed a significant improvement in systolic and diastolic functions with boron treatment compared to saline control. In addition, boron administration showed a marked reduction in myocardial fibrosis and apoptosis in the injured hearts, highlighting a protective effect of boron in the ischemic heart. Interestingly, we observed a tenfold increase of nuclei in thin myocardial sections stained positive for the cell cycle marker Ki67 in the MI boron-treated rats compared to saline, indicative of increased cardiomyocyte cell cycle activity in MI hearts, highlighting its potential role in regeneration post-injury. We similarly observed increased Ki67 and BrdU staining in cultured fresh neonatal rat ventricular cardiomyocytes. Collectively, the results show that boron positively impacted MI-induced HF and attenuated cardiac fibrosis and apoptosis, two prominent features of HF. Importantly, boron has the potential to induce cardiomyocyte cell cycle entry and potentially cardiac tissue regeneration after injury. Boron might be beneficial as a supplement in MI and may be a good candidate substance for anti-fibrosis approach.

Background and Aims: Poor dietary habits contribute to the obesity pandemic and related cardiovascular diseases but the respective impact of high saturated fat versus added sugar consumption remains debated. Herein, we aimed to disentangle the individual role of dietary fat versus sugar in cardiometabolic disease progression., Methods: We fed pro-atherogenic LDLr -/- ApoB 100/100 mice either a low-fat/high-sucrose (LFHS) or a high-fat/low-sucrose (HFLS) diet for 24 weeks. Weekly body weight gain was registered. 16S rRNA gene-based gut microbial analysis was performed to investigate gut microbial modulations. Intraperitoneal insulin (ipITT) and oral glucose tolerance test (oGTT) were conducted to assess glucose homeostasis and insulin sensitivity. Cytokines were assessed in fasted plasma, epididymal white adipose tissue and liver lysates. Heart function was evaluated by echocardiography. Aortic atheroma lesions were quantified according to the en face technique., Results: HFLS feeding increased obesity, insulin resistance and dyslipidemia compared to LFHS feeding. Conversely, high sucrose consumption decreased gut microbial diversity while augmenting inflammation and the adaptative immune defense against metabolic endotoxemia and reduced macrophage cholesterol efflux capacity. This led to more severe cardiovascular complications as revealed by remarkably high level of atherosclerotic lesions and the early development of cardiac dysfunction in LFHS vs HFLS fed mice., Conclusions: We uncoupled obesity-associated insulin resistance from cardiovascular diseases and provided novel evidence that dietary sucrose, not fat, is the main driver of metabolic inflammation accelerating severe atherosclerosis in hyperlipidemic mice., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Fibromuscular dysplasia (FMD) is a poorly understood disease that predominantly affects women during middle-life, with features that include stenosis, aneurysm, and dissection of medium-large arteries. Recently, plasma proteomics has emerged as an important means to understand cardiovascular diseases. Our objectives were: (i) to characterize plasma proteins and determine if any exhibit differential abundance in FMD subjects vs. matched healthy controls and (ii) to leverage these protein data to conduct systems analyses to provide biologic insights on FMD, and explore if this could be developed into a blood-based FMD test., Methods and Results: Females with 'multifocal' FMD and matched healthy controls underwent clinical phenotyping, dermal biopsy, and blood draw. Using dual-capture proximity extension assay and nuclear magnetic resonance-spectroscopy, we evaluated plasma levels of 981 proteins and 31 lipid sub-classes, respectively. In a discovery cohort (Ncases = 90, Ncontrols = 100), we identified 105 proteins and 16 lipid sub-classes (predominantly triglycerides and fatty acids) with differential plasma abundance in FMD cases vs. controls. In an independent cohort (Ncases = 23, Ncontrols = 28), we successfully validated 37 plasma proteins and 10 lipid sub-classes with differential abundance. Among these, 5/37 proteins exhibited genetic control and Bayesian analyses identified 3 of these as potential upstream drivers of FMD. In a 3rd cohort (Ncases = 506, Ncontrols = 876) the genetic locus of one of these upstream disease drivers, CD2-associated protein (CD2AP), was independently validated as being associated with risk of having FMD (odds ratios  = 1.36; P = 0.0003). Immune-fluorescence staining identified that CD2AP is expressed by the endothelium of medium-large arteries. Finally, machine learning trained on the discovery cohort was used to develop a test for FMD. When independently applied to the validation cohort, the test showed a c-statistic of 0.73 and sensitivity of 78.3%., Conclusion: FMD exhibits a plasma proteogenomic and lipid signature that includes potential causative disease drivers, and which holds promise for developing a blood-based test for this disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Calcific aortic valve stenosis (CAVS) is characterized by a fibrocalcific process. Studies have shown an association between CAVS and the activation of platelets. It is believed that shear stress associated with CAVS promotes the activation of platelets. However, whether platelets actively participate to the mineralization of the aortic valve (AV) and the progression of CAVS is presently unknown. To identify the role of platelets into the pathobiology of CAVS., Methods and Results: Explanted control non-mineralized and mineralized AVs were examined by scanning electron microscope (SEM) for the presence of activated platelets. In-depth functional assays were carried out with isolated human valve interstitial cells (VICs) and platelets as well as in LDLR-/- apoB100/100 IGFII (IGFII) mice. Scanning electron microscope and immunogold markings for glycoprotein IIb/IIIa (GPIIb/IIIa) revealed the presence of platelet aggregates with fibrin in endothelium-denuded areas of CAVS. In isolated VICs, collagen-activated platelets induced an osteogenic programme. Platelet-derived adenosine diphosphate induced the release of autotaxin (ATX) by VICs. The binding of ATX to GPIIb/IIIa of platelets generated lysophosphatidic acid (LysoPA) with pro-osteogenic properties. In IGFII mice with CAVS, platelet aggregates were found at the surface of AVs. Administration of activated platelets to IGFII mice accelerated the development of CAVS by 2.1-fold, whereas a treatment with Ki16425, an antagonist of LysoPA receptors, prevented platelet-induced mineralization of the AV and the progression of CAVS., Conclusions: These findings suggest a novel role for platelets in the progression of CAVS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Despite its functional importance in various fundamental bioprocesses, studies of N 6 -methyladenosine (m6A) in the heart are lacking. Here, we show that the FTO (fat mass and obesity-associated protein), an m6A demethylase, plays a critical role in cardiac contractile function during homeostasis, remodeling, and regeneration., Methods: We used clinical human samples, preclinical pig and mouse models, and primary cardiomyocyte cell cultures to study the functional role of m6A and FTO in the heart and in cardiomyocytes. We modulated expression of FTO by using adeno-associated virus serotype 9 (in vivo), adenovirus (both in vivo and in vitro), and small interfering RNAs (in vitro) to study its function in regulating cardiomyocyte m6A, calcium dynamics and contractility, and cardiac function postischemia. We performed methylated (m6A) RNA immunoprecipitation sequencing to map transcriptome-wide m6A, and methylated (m6A) RNA immunoprecipitation quantitative polymerase chain reaction assays to map and validate m6A in individual transcripts, in healthy and failing hearts, and in myocytes., Results: We discovered that FTO has decreased expression in failing mammalian hearts and hypoxic cardiomyocytes, thereby increasing m6A in RNA and decreasing cardiomyocyte contractile function. Improving expression of FTO in failing mouse hearts attenuated the ischemia-induced increase in m6A and decrease in cardiac contractile function. This is performed by the demethylation activity of FTO, which selectively demethylates cardiac contractile transcripts, thus preventing their degradation and improving their protein expression under ischemia. In addition, we demonstrate that FTO overexpression in mouse models of myocardial infarction decreased fibrosis and enhanced angiogenesis., Conclusions: Collectively, our study demonstrates the functional importance of the FTO-dependent cardiac m6A methylome in cardiac contraction during heart failure and provides a novel mechanistic insight into the therapeutic mechanisms of FTO.

Objectives: This study investigated processes causing leaflet thickening and structural valve degeneration (SVD)., Background: Although transcatheter aortic valve replacement (TAVR) has changed the treatment of aortic stenosis, concerns remain regarding SVD, potentially related to valve thrombosis and thickening, based on studies using computed tomography (CT). Detailed histological analyses are provided to help attain insights into these processes., Methods: Explanted transcatheter heart valves (THVs) were evaluated for thrombosis, fibrosis, and calcification for quantification of leaflet thickness. Immunohistochemical and microscopy approaches were used to investigate SVD-associated mechanisms., Results: THVs (n = 23) were obtained from 22 patients (median 81 years of age; 50% male) from 0 to 2,583 days post TAVR. Maximal leaflet thickness increased relative to implant duration (ρ = 0.427; p = 0.027). THVs explanted after >2 years were thicker than those explanted after <2 years (p = 0.007). All THVs had adherent thrombus on both aortic and ventricular sides, which beyond 60 days was seen in combination with fibrosis and beyond 4 years had calcification. Early thrombus formation (<60 days) occurred despite rapid endothelialization with an abnormal hyperplastic phenotype. Fibrosis was observed in 6 patients on both the aortic and the ventricular THV surfaces, remodeled over time, and was associated with matrix metalloproteinase-1 expression. Five THVs showed overt calcification associated with adherent thrombus and fibrosis., Conclusions: There is a time-dependent degeneration of THVs consisting of thrombus formation, endothelial hyperplasia, fibrosis, tissue remodeling, proteinase expression, and calcification. Future investigation is needed to further understand these mechanisms contributing to leaflet thickening and SVD., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)