Androgenetic alopecia (AGA) is the most common cause of hair loss, and current pharmacotherapies have limitations. Autologous platelet-derived therapies, including PRP, its standardized derivative PRGF, and other growth factor concentrates (GFC), have emerged as regenerative options, but differences in preparation and mixed clinical evidence remain. Following PRISMA guidelines, seven databases were searched for randomized and non-randomized studies on intralesional growth factor injections for AGA. Outcomes included hair density, thickness, satisfaction, and adverse events, with quality assessed using RoB2, MINORS, and MMS tools. Twelve studies (745 patients) were included. GFC showed progressive hair density gains from 19.6 hairs/cm2 at 1 month to 57.1 at 12 months, while PRP increased density by 34.4 at 6 months and 42.0 at 12 months. GFC also improved thickness (5.19-22.03 µm) with 94.3% patient satisfaction. Adverse events were mild, but RCTs had a high risk of bias, and non-randomized studies showed serious to critical bias. Autologous growth factor injections appear safe and improve hair density, thickness, and patient satisfaction over 12 months, especially with newer concentrates. However, high risk of bias, substantial heterogeneity (I2 > 90%), and non-standardized protocols limit the evidence, making findings hypothesis-generating until larger, standardized, double-blind trials with long-term follow-up are conducted. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .
Fenugreek's nutritional potential remains underexplored in processed foods, particularly regarding its integration, bioactive stability, and amino acid content post-baking. To address this gap, wheat bread was prepared with fenugreek seed powder (FSP) at 0% (control), 5% (sample A), 7.5% (sample B), and 10% (sample C) and assessed for nutritional, bioactive, amino acid, and sensory properties. The results showed that the protein and fiber contents increased progressively from control (15.14 ± 0.09%) to sample C (16.30 ± 0.06%), while carbohydrate levels declined with higher FSP inclusion. Bioactive compounds (total phenolics, flavonoids, and antioxidant capacity) increased with progressive inclusion of FSP, reaching the highest values in sample C (TPC 273.89 ± 0.10 mg GAE/100 g; TFC 61.34 ± 0.05 mg QE/100 g; antioxidant capacity 3.21 ± 0.01%), followed by sample B, sample A, and the control. Additionally, essential amino acids, notably arginine and lysine in sample C, increased with rising fenugreek levels, while nonessential amino acids decreased. However, sensory evaluation showed breads fortified up to 7.5% with FSP (sample B) achieved the highest acceptance, whereas higher inclusion of fenugreek reduced scores. These findings indicate that moderate fenugreek fortification enhances the nutritional and functional profile of bread while maintaining consumer acceptability. Such products could serve as affordable, functional alternatives to conventional breads, supporting dietary diversification and improved community nutrition.
Abdominoplasty has evolved from a purely aesthetic operation into a refined reconstructive procedure integrating both functional and contouring principles. Despite significant technical progress and standardized safety protocols, postoperative complications remain relatively common. Identifying independent predictors of these events is essential to improve outcomes and reduce morbidity. A retrospective analysis was conducted on 150 consecutive abdominoplasties performed between 2015 and 2023 by a single surgical team. Demographic data, comorbidities, and operative variables were recorded, including procedure type, Scarpa's fascia management, drain use, and operative time. Complications were categorized as major or minor. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of postoperative complications. The overall complication rate was 27.3%, including both minor and major events. The most frequent complications were seroma (14.6%), wound dehiscence (6.6%), and partial skin necrosis (4.6%). The reoperation rate was 6%. Multivariate analysis identified high body mass index (BMI ≥30 kg/m2) and active smoking as independent predictors of complications (p < 0.05). Preservation of Scarpa's fascia was independently associated with a significantly lower risk of seroma and wound morbidity (p < 0.05). High BMI and active smoking are the dominant independent predictors of postoperative complications following abdominoplasty, whereas preservation of Scarpa's fascia confers a protective effect by maintaining lymphatic continuity and reducing dead space. These findings emphasize the importance of careful patient selection, smoking cessation, and adherence to fascial preservation techniques to optimize safety and outcomes. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Ordered double transition-metal (DTM) MXenes are a subfamily of two-dimensional (2D) carbides, nitrides, and carbonitrides, predicted to outperform single-metal MXenes in hydrogen evolution reaction (HER) catalysis due to the synergistic effect of two metals and their nonmetal (X) sublattice tailoring (X = C, N), resulting in tunable electronic structures. However, all synthesized DTM MXenes to date contain only carbon in the X sublattice. Here, we report the synthesis of a series of out-of-plane ordered DTM carbonitride MXenes (o-MXenes), Mo2Ti(CN)2Tx and Mo2Ti2(CN)3Tx, to systematically investigate the role of carbon to nitrogen ratio. To determine the optimal nitrogen content, we first evaluated the HER activity of the Mo2TiC2-yNyTx MXenes with density functional theory calculations and identified that 0.3 to 0.6 mol of nitrogen give enhanced performance compared to the carbide. We next synthesized and characterized 11 carbonitride MXenes with varying their C:N ratios and found nitrogen incorporation enhances HER activity compared to their carbide counterparts. Among them, Mo2TiC2-yNyTx MXene with 0.6 mol of nitrogen (y = 0.6) achieved the best performance, with an overpotential of ∼155 mV at 10 mA/cm2 under acidic conditions, compared with ∼236 mV for Mo2TiC2Tx. Our experimental and computational findings indicate that carbonitrides with ∼25-30 atom % nitrogen outperform all other o-MXene counterparts, with the improved performance arising from nitrogen-induced modulation of the electronic structure. This study identifies nonmetal sublattice control as a critical frontier in optimizing MXenes for sustainable energy applications.
The optimal dosing strategy for valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) infection in pediatric patients after kidney transplantation (KT) remains uncertain because of the narrow therapeutic window between antiviral efficacy and safety. This study included pediatric patients who received VGCV prophylaxis after KT at a single center between December 2023 and December 2024. VGCV was administered once daily for 200 days using a reduced-dose regimen. Approximately 50% of the U.S. Food and Drug Administration-recommended dose was used for high-risk patients defined as donor-positive and recipient-negative, and 33% for intermediate-risk patients defined as recipient-positive. The incidence of CMV infection within 200 days after KT and VGCV-related adverse events (AEs) were evaluated. Nine patients with a median age of 8 years were included, with a median observational period of 431 days after KT. CMV infection within 200 days occurred in four patients, all of whom were high-risk patients. No CMV disease occurred during the observational period. Neutropenia occurred in six patients, including five high-risk patients and one intermediate-risk patient. Three high-risk patients developed febrile neutropenia. VGCV dose reduction and/or discontinuation due to hematologic AEs was required in four patients. The reduced-dose VGCV prophylaxis regimen was associated with a high incidence of CMV infection and AEs in high-risk patients, indicating a suboptimal balance between efficacy and safety. In intermediate-risk patients, the regimen appeared effective and tolerable. Further optimization of prophylactic strategies is required, particularly for high-risk pediatric recipients.
Adequate blood supply remains a challenge in sub-Saharan Africa (SSA). Malawi has a 13% shortfall in required blood supplies. Innovative recruitment and retention strategies are crucial to ensuring a sufficient number of donors and blood supply. We explored alternative approaches to enhance blood donation in Malawi to bridge the gap. A qualitative exploratory design was utilised with a sample of 135 participants purposively selected in eight districts, in the Northern, Central, Southern and Eastern regions of Malawi. Data were collected using in-depth interviews with 20 participants (first-time and repeat donors, lapsed and non-donors), 20 key informant interviews with community, policy-level stakeholders, Malawi Blood Transfusion Service (MBTS) staff and 16 focus group discussions (involving 95 participants). Thematic content analysis was used to categorise the strategies, and a qualitative software data package (NVivo version 12) was used to organise the qualitative data. Donor education emerged as a key strategy for donor recruitment and retention. Other strategies included the formation of blood donor clubs in secondary schools and for post-secondary students, accountability mechanisms related to blood: its collection and management of blood and blood products, the provision of incentives and youth-friendly motivation strategies, including school competitions (quizzes and sports) and entertainment. The study emphasised the significance of blood donor education in encouraging blood donation. Participants' views suggest that developing innovative approaches for education to increase awareness and understanding of blood-donation processes may help motivate more individuals to donate. In addition, participants suggested other youth-friendly approaches to support blood donor recruitment, including providing incentives preferred by young people, introducing intra-school competitions and incorporating entertainment activities. These insights point to the potential value of developing innovative strategies to support blood donor recruitment efforts.
This paper presents a lightweight balloon-dynamics method, built on the Position-Based Dynamics (PBD) framework, that reproduces real-time inflation-deflation-rotation as air is injected and released. Unlike volume/CFD approaches that require expensive fluid-structure coupling, our method avoids explicit fluid simulation by combining Bernoulli-derived reaction forces with PBD distance and volume constraints. Rotation is modeled as a global rigid-body motion (single rotation/quaternion update about the center of mass), while local shape changes are handled through constraint-based position correction-eschewing cluster-level or per-vertex local twisting. Geodesic-distance weighting of reaction forces and the separate treatment of translational and rotational components improve physical plausibility; minimal iterations and rigid-body rotation approximation preserve computational efficiency. Experiments on meshes with diverse geometries and mass distributions show consistent real-time performance on high-resolution models while capturing the characteristic balloon behaviors. The approach is well-suited for interactive applications such as games, VR/AR, and real-time physics-based content.
Drosophila melanogaster is a genetically tractable model organism with a compact yet functionally rich nervous system, making it ideal for investigating neural mechanisms and modeling neurological diseases. However, its small brain size poses challenges for real-time measurement of neurotransmitter dynamics. Recent advances in electrochemical methodologies, particularly fast-scan cyclic voltammetry (FSCV) and amperometry with carbon fiber microelectrodes, enable high spatiotemporal resolution measurements in vivo. The integration of electrochemistry with optogenetic tools further enhances experimental precision, allowing causal interrogation of neurotransmission. This review summarizes recent advances in electrochemical methodologies for monitoring neurotransmitter dynamics in Drosophila. FSCV has facilitated real-time, chemically selective quantitative analysis of dopamine and serotonin in defined brain regions, providing new insights into their roles in behavior and neurodegeneration, as well as their modulation by antidepressants and ketamine. Amperometry provides complementary capabilities, allowing detection of exocytic release events and quantification of vesicular neurotransmitter content. Amperometric studies have shown that octopamine primarily undergoes partial release at the neuromuscular junction, whereas serotonin in the ventral nerve cord exhibits both partial release and, notably, full vesicular release events. Looking forward, convergence with advanced imaging technologies promises multidimensional views of neurotransmitter signaling and may uncover novel therapeutic targets for neurological diseases. This review highlights key methodological innovations and their applications in Drosophila, underscoring its unique value in bridging molecular neuroscience, behavior, and translational research.
The rapid advancement of generative artificial intelligence technologies has introduced new security challenges, raising significant concerns. As deepfake technology becomes more sophisticated, it might be exploited by malicious actors to generate highly realistic fake images, thereby compromising the authenticity and reliability of the original content. Driven by this concern, this article introduces a universal deepfake detection model, multiscale spatial frequency-aware transformer and saturation analysis (MSFTSA), based on a multiscale, spatial-frequency-aware Transformer and saturation analysis. Unlike existing methods, MSFTSA reexamines fundamental differences between real and fake images across the frequency, spatial, and saturation domains. For this purpose, an efficient multiscale frequency-domain decoupling module has been designed to capture image features from different frequency bands, assisting in identifying inherent fake characteristics across multiple frequency scales. In addition, a spatial scattering module (SSM) is introduced to model global relationships between multiscale frequency features, achieving full-frequency interactive learning in the spatial domain. Furthermore, image saturation is used as a critical indicator to distinguish between real and fake images. Extensive experiments across multiple deepfake image datasets generated by generative adversarial networks (GANs) and diffusion models (DMs) demonstrate MSFTSA's performance, significantly outperforming existing state-of-the-art methods and showcasing exceptional generalization capability and robustness.
A novel bacterial strain, designated MF1-13ᵀ, was isolated from tidal-flat sediment collected in Gochang, Republic of Korea. Cells of strain MF1-13ᵀ are Gram-stain-negative, facultatively anaerobic, motile, and short rod-shaped to ovoid, forming pale yellow colonies on marine agar. The strain produces catalase and oxidase. It grows at 25-30 °C (optimum, 30 °C), at pH 6-8.0 (optimum, pH 7.0), and in the presence of 0-5% (w/v) NaCl, with optimal growth at 2% (w/v). Phylogenetic analysis based on 16 S rRNA and genome sequences placed strain MF1-13ᵀ within the family Roseobacteraceae (class Alphaproteobacteria), showing highest sequence similarity to Pseudooceanicola nitratireducens JLT1210ᵀ (97.2%), Pseudooceanicola onchidii XY-99ᵀ (96.8%) and Pseudooceanicola flagellatus DY470ᵀ (97.2%). The major polar lipids are phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine. The genome of strain MF1-13ᵀ is 4.24 Mbp in size, with a G + C content of 61.2%. The strain hydrolyzes starch, gelatin, and Tween 20, 40, and 80, but do not hydrolyze casein or DNase. The predominant cellular fatty acids are C16:0, C18:1 ω7c 11-methyl, and Summed Feature 8 (C18:1 ω7c/C18:1 ω6c). Genomic comparisons (ANI, AAI, and dDDH) between strain MF1-13ᵀ and related taxa were well below species delineation thresholds, supporting its classification as a novel species. Based on polyphasic taxonomic analysis, strain MF1-13ᴛ represents a novel species of the genus Pseudooceanicola, for which the name Pseudooceanicola aestuariicola sp. nov. is proposed. The type strain is MF1-13ᵀ (= KEMB 21563ᵀ = KCTC 8775ᵀ = JCM 37675ᵀ).
Insects have emerged as a promising sustainable feed alternative for ruminants, offering high nutrient density and potential environmental benefits in the context of growing pressures on conventional protein sources. This systematic review critically evaluates the state-of-the-art literature written in English and published in peer-reviewed journals from 2015 to 2025 on the use of insect-based feeds in ruminant nutrition, synthesising evidence from in vitro and in vivo studies, discussing their outcomes and elucidating underlying mechanisms to guide future research. Most insect species studied include black soldier fly (Hermetia illucens) larvae, housefly (Musca domestica) larvae, adult crickets (Gryllus bimaculatus), silkworm (Bombyx mori) pupae, and mealworm (Tenebrio molitor) larvae, with studies highlighting their favourable chemical composition, particularly high protein content and rich fatty acid profiles. In vitro and in vivo research, though occasionally inconsistent, shows promising effects on rumen fermentation, methane production, growth performance, product quality, and animal health. Nevertheless, inconsistent results, driven by variations in insect species, processing methods, and inclusion levels, highlight significant knowledge gaps. Challenges include non-standardised nutrient profiling, limited long-term health and performance studies, regulatory disparities, high production costs, scalability constraints, and underexplored consumer acceptance of sensory and market aspects. While insects offer opportunities for waste bioconversion and reduced ecological footprints, their integration requires targeted research into optimised feed formulations, longitudinal health studies, and robust regulatory frameworks. This review emphasises the necessity of multidisciplinary research to clarify the nutritional, environmental, and economic viability of insect-based feeds, paving the way for sustainable ruminant production systems.
Redo transcatheter aortic valve replacement (TAVR; TAV-in-TAV procedure) is technically challenging. We report a case of TAV-in-TAV requiring right coronary artery (RCA) protection. An 81-year-old man underwent TAVR with a self-expanding valve in 2021 and presented in 2025 with heart failure symptoms. Multimodality imaging demonstrated severe aortic regurgitation from premature structural valve degeneration. A short-in-tall TAV-in-TAV strategy was planned. Bulky leaflet calcification near the RCA ostium prompted coronary protection. After difficult RCA engagement requiring multiple access changes, the valve was deployed using the engaged guiding catheter as a fluoroscopic landmark. Coronary flow was preserved without bailout stenting. No residual regurgitation was observed on postprocedural imaging. We highlight the importance of preprocedural planning in redo TAVR and illustrate real-world challenges in coronary access despite meticulous planning. Preprocedural planning and access flexibility are essential in redo TAVR. Lifetime coronary access should be considered during index valve selection.
Arbuscular mycorrhizal (AM) fungi change phosphorus (P) uptake and plant growth. The degree of change is defined as mycorrhizal dependency. Mycorrhizal dependency differs among cultivars and among different levels of soil P availability. The purpose of this study was to study the effect of AM fungus colonization on Allium fistulosum (A. fistulosum) with different mycorrhizal dependency grown at different levels of soil P availability. Twenty cultivars of A. fistulosum were grown with or without (control) AM fungus Rhizophagus spp. strain R-10 for 82 days. Three cultivars of A. fistulosum with different mycorrhizal dependency were inoculated and grown in soils fertilized at the rate of 0.43, 0.87, 2.18, and 4.36 g P kg-1 soil (P1, P2, P3, and P4, respectively) with or without (control) the AM fungus for 82 days. AM colonization, root length, shoot dry weight, and P concentration were determined. AM colonization increased shoot P content and shoot dry weight. Mycorrhizal dependencies were different among 20 cultivars and Mogamigawa, Shonan, and Kannonhosonegi were used as high, middle and low mycorrhizal dependency cultivars, respectively. Shoot P content of Mogamigawa and Shonan cultivars was higher in the inoculated plants than that in the uninoculated plants at P1, P2 and P3 soil fertilization rates. Shoot P content of the Kannonhoso was higher in the inoculated plants than that in the uninoculated plants at P1. Shoot dry weight of the Mogamigawa and Shonan was higher in the inoculated plant than that in the uninoculated plant at P1. These results suggest that selection of an appropriate cultivar and soil P availability are important factors in determining possible mutualistic, commensalistic, and parasitic relationships between the AM fungus and the host plant.
Most patient-reported outcome measures for narcolepsy focus on excessive daytime sleepiness or do not focus on specific disease impacts (eg, cataplexy, cognitive difficulties, fatigue, daily function). The Functional Impacts of Narcolepsy Instrument (FINI) was developed to measure key functional impacts in people with narcolepsy type 1 and 2 (NT1/NT2). The instrument was developed separately in NT1/NT2 populations with input from patients, clinical experts experienced in narcolepsy management, and clinical outcome scientists. Development included: patient experience interview studies informing item development; item development including de novo items, and modified/original items from the Patient-Reported Outcomes Measurement Information System (PROMIS) library; two waves of patient-debriefing interviews testing initial/modified item drafts; determination of factor structure using exploratory factor and Rasch analyses, and confirmatory factor analyses for NT2; consensus meetings between clinical sleep experts/clinical outcome experts to finalize the FINI draft items and structure with a 7-day recall period. The final FINI for NT1 had 28 items within 6 independent domains: Tiredness, Cognitive Functioning, Cataplexy, Social Activities, Everyday Activities, and Everyday Responsibilities. The final NT2 version (FINI-NT2) included the same items excluding the Cataplexy domain (23 items). Final FINI and FINI-NT2 items demonstrated good content validity and covered the main impacts of NT1 and NT2, respectively, as confirmed by patient interviews, exploratory/confirmatory factor analyses, and Rasch analysis. The novel FINI assesses key functional impacts of narcolepsy in people with NT1/NT2 for use across clinical settings, and adds to the number of existing clinical outcome assessments for central disorders of hypersomnolence.
Exposure to environmental stressors such as hypoxia or heat has emerged as an effective strategy to stimulate physiological adaptations, enhance sport/physical performance and promote health. Both environmental stressors activate shared molecular pathways, notably through the stabilisation of hypoxia-inducible factor-1 alpha and the induction of heat shock proteins, which mediate cellular protection and systemic molecular adaptation. However, hypoxia and heat differ in several aspects, including induction modalities, monitoring methods, metrics used to assess physiological strain and substantial intra- and inter-individual variability. Together, these differences challenge direct comparison and/or combination. Therefore, this current opinion highlights research gaps by critically presenting the common and distinct physiological responses and adaptations to hypoxia and heat exposure. It also emphasises the importance of monitoring internal physiological strain rather than external environmental stress to better account for individual variability. Finally, we propose future research perspectives to address current methodological challenges.
Iron overload cardiomyopathy (IOC) is a rare cause of heart failure classically associated with hereditary or transfusion-related hemochromatosis. Although iron accumulation occurs in cirrhosis, the development and clinical course of IOC in this population remain poorly described. We report 2 patients with cirrhosis who developed IOC without hereditary hemochromatosis or transfusion-dependent anemia. Patient #1 was a 54-year-old man with alcohol-associated cirrhosis who developed severe cardiomyopathy (left ventricular ejection fraction 23%, 55% 1 year earlier). Patient #2 was a 56-year-old man with cryptogenic cirrhosis who presented with new cardiomyopathy (left ventricular ejection fraction 38%, 71% 9 months earlier). Both patients had elevated ferritin and transferrin saturation, along with reduced myocardial T2∗ relaxation time on cardiac magnetic resonance imaging, consistent with IOC. Both received iron chelation therapy; one patient died, and the other is awaiting combined heart-liver transplantation. These cases highlight IOC as an important consideration in patients with cirrhosis presenting with new cardiomyopathy.
Pulmonary valve endocarditis is rare, and large vegetations usually require surgery; however, operative risk may be prohibitive in frail patients. A 77-year-old man with chronic obstructive pulmonary disease and diabetes presented with persistent fever and Streptococcus gallolyticus bacteremia. Echocardiography demonstrated a >30-mm mobile pulmonary valve vegetation. Surgery was declined because of high operative risk. Under transesophageal echocardiographic guidance, percutaneous mechanical aspiration using the Inari FlowTriever system was performed. The Inari Triever20 Curve catheter enabled directional engagement and near-complete en bloc removal with immediate echocardiographic clearance. The postprocedural course was complicated by transient systemic inflammatory response syndrome requiring short-term vasopressor support, with full recovery on continued antibiotic therapy. Follow-up confirmed sustained infection clearance without recurrence. This case demonstrates the feasibility of adapting mechanical thrombectomy systems for percutaneous debulking of pulmonary valve endocarditis when surgery is not an option. Percutaneous aspiration of valvular vegetations using the FlowTriever system may represent a lifesaving alternative for selected inoperable patients.
The photothermal properties of MXenes originate from the localized surface plasmon resonance, which is attributed to their high free electron concentration. However, their intrinsic electron concentration is limited by suboptimal d-orbital occupancy and the electron-withdrawing effect from electronegative terminations. Herein, we report a sodium-mediated surface reduction strategy in molten salts, which optimizes the surface coordination environment via electronic modulation to mitigate the electron-withdrawing and electron-scattering effects, while simultaneously injecting electrons into the Ti-3d states for controlled state filling. This dual modulation enables the free electron concentration, carrier mobility, and electrical conductivity to reach 4.92, 2.63, and 12.96 times that of the pristine MXene, respectively. The optimized reduced Ti3C2 achieves a high photothermal conversion efficiency of 91.66% under 808-nanometer laser irradiation. A photothermal antibacterial woundplast with ultralow MXene content demonstrates a high bacterial kill rate. This work not only shows an effective method for tuning the photothermal properties of MXenes but also inspires applications that require tailored surface chemistry and high electron concentration.
Alzheimer's disease (AD) is a chronic neurological disorder manifested by cognitive decline, amyloid-β (Aβ) fibrillation, synaptic dysfunction, and neuronal loss. Furthermore, metal ion dysregulation is implicated in Aβ aggregation, oxidative stress, and neuronal toxicity, thereby exacerbating neurodegeneration. Thus, highly versatile chemical entities with a synergistic effect targeting Aβ aggregation, disintegrate Aβ fibrils, and impede Aβ-Cu2+ interactions hold considerable therapeutic potential against AD. With this aim, a novel tetrapeptide CarFL (β-Ala-His-Phe-Leu) was rationally designed in this work by conjugating a natural dietary endogenous metal chelator, Car, with an Aβ fibrillation inhibitor (FL). Remarkably, CarFL prevented Aβ42 aggregation and disaggregated the preformed Aβ42 fibrils by 75.7 ± 3.8%. Notably, CarFL displayed significant inhibitory activity against Cu2+-induced Aβ42 aggregation (83.6 ± 0.8%) and disaggregated preformed Aβ42/Cu2+ fibrils by 85.6 ± 0.7%. CarFL binds with Cu2+ ions in 1:1 stoichiometry and sequesters Cu2+ from the Aβ42/Cu2+ complex with a binding constant (Ka) of 2.9 × 106 M-1, which, in turn, blocked the Cu2+-catalyzed reactive oxygen species (ROS) production. Importantly, CarFL protected the PC12 cells from Aβ42-mediated toxicity and has a sufficient safety profile as determined by cell viability assay. Furthermore, molecular dynamics (MD) simulations highlighted high-affinity binding (ΔGfit = -11.94 ± 0.42 kcal/mol) of CarFL to the aggregation-prone regions [central hydrophobic core (CHC) and C-terminal] of Aβ42 monomer (Aβ42M) (PDB: 1IYT) with a noteworthy contribution of van der Waals interactions. Importantly, MD simulations depicted that CarFL blocked the conformational transitions in Aβ42M to the aggregation-competent β-sheet structures, consistent with various biophysical studies depicting CarFL-mediated inhibition of Aβ42 fibrillation and disaggregation of preformed fibrillar species. Interestingly, CarFL-mediated noteworthy rise in the helical content from 37.0 ± 1.8 to 54.5 ± 0.6% in Aβ42M-Cu2+ depicts the prevention of Cu2+-induced Aβ42 misfolding. To our knowledge, the present study for the first time depicts the synergistic potential of carnosine conjugated to FL as an inhibitor of multifaceted Aβ-induced cytotoxicity in AD.
In utero stenting of the atrial septum has been introduced for fetuses with hypoplastic left heart syndrome (HLHS) and intact atrial septum (IAS) to prevent secondary pulmonary vascular damage caused by left atrial hypertension. Previous reports revealed a high risk of significant or complete in-stent obstruction after successful intervention due to endothelial proliferation. We report a fetus with HLHS and IAS complicated by nutmeg lung who underwent successful fetal atrial septal stenting using an everolimus-eluting stent (Xience Sierra; Abbott). The procedure resulted in immediate left atrial decompression and maintained an unrestrictive interatrial communication until delivery. The use of a drug-eluting stent resulted in sustained stent patency without evidence of endothelial overgrowth and without detectable systemic adverse effects in the fetus. In utero use of an everolimus-eluting stent appears safe and may reduce the risk of in-stent obstruction in fetuses with HLHS and IAS.