Advance Technologies in Biodegradable Flexible Solid-State Supercapacitors: A Mini Review on Clean and Sustainable Energy.

In the recent times research towards solid state supercapacitors (SSS) have increased drastically due to the promising performance in futuristic technologies particularly in portable and flexible electronics like smart watches, smart fabrics, foldable smartphones and tablets. Also, when compared to supercapacitors using liquid electrolyte, solid electrolyte has several advantages like high energy density, safety, high cycle life, flexible form factor, and less environmental impact. The crucial factor determining the sustainability of a technology is the eco-friendliness since the natural resources are being exploited in a wide scale. Numerous studies have focused on biodegradable materials for supercapacitor electrodes, electrolytes, and other inactive components. Making use of these biodegradable materials to design a SSS enables the technology to sustain for a very long time since biodegradable materials are not only environment friendly but also, they show relatively high performance. This review focuses on recent progress of different biodegradable electrodes, and electrolytes along with their properties, electrochemical performance and biodegradable capabilities for SSS have been analyzed and provides a concise summary enabling readers to understand the importance of biodegradable materials and to narrow down the research in a more rational way.

2D MXenes Nanosheets for Advanced Energy Conversion and Storage Devices: Recent Advances and Future Prospects.

Since the initial MXenes were discovered in 2011, several MXene compositions constructed using combinations of various transition metals have been developed. MXenes are ideal candidates for different applications in energy conversion and storage, because of their unique and interesting characteristics, which included good electrical conductivity, hydrophilicity, and simplicity of large-scale synthesis. Herein, we study the current developments in two-dimensional (2D) MXene nanosheets for energy storage and conversion technologies. First, we discuss the introduction to energy storage and conversion devices. Later, we emphasized on 2D MXenes and some specific properties of MXenes. Subsequently, research advances in MXene-based electrode materials for energy storage such as supercapacitors and rechargeable batteries is summarized. We provide the relevant energy storage processes, common challenges, and potential approaches to an acceptable solution for 2D MXene-based energy storage. In addition, recent advances for MXenes used in energy conversion devices like solar cells, fuel cells and catalysis is also summarized. Finally, the future prospective of growing MXene-based energy conversion and storage are highlighted.

Gamma-Irradiated Gum Arabic Grafted with 2-Hydroxyethyl Methacrylate: A Novel Superabsorbent Polymer for Controlled Folic Acid Release.

This study explores the synthesis and characterization of superabsorbent hydrogels derived from chemically modified gum Arabic, designed for controlled folic acid release. The synthesis involves a two-step process: carboxymethylation followed by grafting with 2-hydroxyethyl methacrylate via gamma irradiation. The resulting hydrogels exhibit enhanced mechanical strength and controlled diffusivity, essential for nutrient delivery systems. Key factors such as copolymer composition and irradiation dose are investigated, affecting the synthesis process. Systematic studies of swelling behaviors reveal that the hydrogel achieves a maximum swelling of 888.1% at 40 °C. The hydrogels are loaded with folic acid, and in vitro, sustained release profiles are examined under various pH conditions. The maximum release of 83.3% is observed after 24 h at pH 7.0, following a Korsmeyer-Peppas release mechanism. Different characterization techniques, confirm the successful synthesis and unique properties of the superabsorbent hydrogels. Rheological behavior analysis, scanning electron microscopy, and biocompatibility assessments provide a comprehensive understanding of the hydrogel structures. Gamma irradiation ensures a homogeneous network structure, crucial for optimal swelling behavior and mechanical properties. This research highlights the potential of eco-friendly biopolymer hydrogels in precise drug delivery applications, leveraging the safety and process control benefits of gamma irradiation.

Coastal Flood risk assessment using ensemble multi-criteria decision-making with machine learning approaches.

Coastal areas are at a higher risk of flooding, and novel changes in the climate are induced to raise the sea level. Flood acceleration and frequency have increased recently because of unplanned infrastructural conveniences and anthropogenic activities. Therefore, the assessment of flood susceptibility mapping is considered the most significant flood management model. In this paper, flood susceptibility identification is performed by applying the innovative Multi-criteria decision-making model (MCDM) called Analytical Hierarchy Process (AHP) by ensembles with Support vector machine (AHP-SVM) and Decision Tree (AHP-DT). This model combines two Representation concentration pathway (RCP) scenarios such as RCP 2.6 & RCP 8.5. The factors influencing the coastal flooding in Bandar Abbas, Iran, identified through Flood susceptibility mapping. Multi-criteria decision-making (MCDM) has been applied to evaluate the Coastal flood conditioning factors, and ensemble machine learning (ML) approaches are employed for Coastal risk factor (CRF) prediction and classification. The statistical variances are measured through Friedman and Wilcoxon signed rank tests and statistical metrics such as Accuracy, sensitivity, and specificity. Among the models, AHP-DT obtained an improved AUC value of ROC as 0.95. After applying the ML models, the northern and western park of Raidak Basin River recognises very low and low flood susceptibility because of their topographic characteristics. The eastern part of the middle section fell very high and high CFSM. Observed from this result analysis, the people living nearer to the coastline are distributed by the low to medium exposure in the region of the west and middle of the considered study area. The results of this study can help decision-makers take necessary risk reduction approaches in the high-risk flooding zones of the coastal system.

Diagnostic Evaluation of Polycythemia Vera at High Altitude.

BACKGROUND: Polycythemia is a common medical problem, frequently acquired and reactive to secondary conditions. High-altitude-associated hypoxia contributes to the greater prevalence of polycythemia at altitude. Primary clonal polycythemia vera (PV), even though it is rare, requires a different therapeutic approach. Suspicion of PV usually drives the diagnostic workup of polycythemia. METHODS: In this retrospective lab record study, we collected all JAK2 tests requested over a three-year period. We analyzed requests that were made for the evaluation of polycythemia. Complete blood count (CBC) and imaging of the abdomen were collected. RESULTS: Out of 208 total requests, 136 were for the purpose of polycythemia evaluation. JAK2 mutation was positive (confirming the presence of PV) in 22 (16.7%) cases. PV patients have the usual demographics reported elsewhere. Additionally, PV patients exhibit distinct hemogram results featuring leukocytosis, thrombocytosis, and hypochromic microcytic red blood cells (RBCs) related to the associated iron deficiency. CONCLUSIONS: Many patients with polycythemia at altitude might be unnecessarily considered for an evaluation of PV, if hemoglobin/hematocrit is the sole deciding criterion. PV patients have a distinct CBC pattern that can be exploited to better select patients with polycythemia for further evaluation and thus reduce unnecessary workups.

Electronic cigarette vapor disrupts key metabolic pathways in human lung epithelial cells.

The steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative stress and increased inflammation. Concurrently, the integrity of cellular metabolism is essential for cellular homeostasis and mitigation of toxic insults. However, the effects of EC on cellular metabolism remain largely unknown. In this study, we investigated the metabolic changes induced by EC in human lung epithelial cells (A549) using an untargeted metabolomics approach. A549 cells were exposed to increasing EC vapor extract concentrations, and cell viability, oxidative stress, and metabolomic changes were assessed. Our findings show that ECs induce cell death and increase oxidative stress in a concentration-dependent manner. Metabolomic studies demonstrated that ECs induce unique metabolic changes in key cellular metabolic pathways. Our results revealed that exposure to ECs induced clear segregation in metabolic responses which is driven significantly by number of essential metabolites such as aminoacids, fatty acids, glutathione, and pyruvate. Interstingly, our metabolomics results showed that each concentration of ECs induced unqiues pattern of metabolic changes, suggesting the complexity of ECs induced cytotoxcity. Disrupted metabolites were linked to essential cellular pathways, such as fatty acid biosynthesis, as well as glutathione, pyruvate, nicotinate and nicotinamide, and amino acid metabolisms. These results highlight the potential adverse effects of ECs on cellular metabolism and emphasize the need for further research to fully understand the long-term consequences of EC use. Overall, this study demonstrates that ECs not only induce cell death and oxidative stress but also disrupt cellular metabolism in A549 lung epithelial cells.

Hierarchical NiCo@NiOOH@CoMoO4 Core-Shell Heterostructure on Carbon Cloth for High-Performance Asymmetric Supercapacitors.

The fabrication of low-cost, effective, and highly integrated nanostructured materials through simple and reproducible methods for high-energy-density supercapacitors is highly desirable. Herein, an activated carbon cloth (ACC) is designed as the functional scaffold for supercapacitors and treated hydrothermally to deposit NiCo nanoneedles working as internal core, followed by a dip-dry coating of NiOOH nanoflakes core-shell and uniform hydrothermal deposition of CoMoO4 nanosheets serving as an external shell. The structured core-shell heterostructure ACC@NiCo@NiOOH@CoMoO4 electrode resulted in exceptional specific areal capacitance of 2920 mF cm-2 and exceptional cycling stability for 10 000 cycles. Moreover, the fabricated electrode is developed into an asymmetric supercapacitor which demonstrates excellent areal capacitance, energy density, and power density within the broad potential window of 1.7 V with a cycling life of 92.4% after 10 000 charge-discharge cycles, which reflects excellent cycle life. The distinctive core-shell structure, highly conductive substrate, and synergetic effect of coated material results in more electrochemical active sites and flanges for effective electrons and ion transportation. This unique technique provides a new perspective for cost-efficient supercapacitor applications.

High pressure CO2 adsorption onto Malaysian Mukah-Balingian coals: Adsorption isotherms, thermodynamic and kinetic investigations.

CO2 sequestration into coalbed seams is one of the practical routes for mitigating CO2 emissions. The adsorption mechanisms of CO2 onto Malaysian coals, however, are not yet investigated. In this research CO2 adsorption isotherms were first performed on dry and wet Mukah-Balingian coal samples at temperatures ranging from 300 to 348 K and pressures up to 6 MPa using volumetric technique. The dry S1 coal showed the highest CO2 adsorption capacity of 1.3 mmol g-1, at 300 K and 6 MPa among the other coal samples. The experimental results of CO2 adsorption were investigated using adsorption isotherms, thermodynamics, and kinetic models. Nonlinear analysis has been employed to investigate the data of CO2 adsorption onto coal samples via three parameter isotherm equilibrium models, namely Redlich Peterson, Koble Corrigan, Toth, Sips, and Hill, and four parameter equilibrium model, namely Jensen Seaton. The results of adsorption isotherm suggested that the Jensen Seaton model described the experimental data well. Gibb's free energy change values are negative, suggesting that CO2 adsorption onto the coal occurred randomly. Enthalpy change values in the negative range established that CO2 adsorption onto coal is an exothermic mechanism. Webber's pore-diffusion model, in particular, demonstrated that pore-diffusion was the main controlling stage in CO2 adsorption onto coal matrix. The activation energy of the coals was calculated to be below -13 kJ mol-1, indicating that adsorption of CO2 onto coals occurred through physisorption. The results demonstrate that CO2 adsorption onto coal matrix is favorable, spontaneous, and the adsorbed CO2 molecules accumulate more onto coal matrix. The observations of this investigation have significant implications for a more accurate measurement of CO2 injection into Malaysian coalbed seams.

Mud Ring Optimization Algorithm with Deep Learning Model for Disease Diagnosis on ECG Monitoring System.

Due to the tremendous growth of the Internet of Things (IoT), sensing technologies, and wearables, the quality of medical services has been enhanced, and it has shifted from standard medical-based health services to real time. Commonly, the sensors can be combined as numerous clinical devices to store the biosignals generated by the physiological actions of the human body. Meanwhile, a familiar method with a noninvasive and rapid biomedical electrocardiogram (ECG) signal can be used to diagnose and examine cardiovascular disease (CVD). As the growing number of patients is destroying the classification outcome because of major changes in the ECG signal patterns among numerous patients, computer-assisted automatic diagnostic tools are needed for ECG signal classification. Therefore, this study presents a mud ring optimization technique with a deep learning-based ECG signal classification (MROA-DLECGSC) technique. The presented MROA-DLECGSC approach recognizes the presence of heart disease using ECG signals. To accomplish this, the MROA-DLECGSC technique initially preprocessed the ECG signals to transform them into a uniform format. In addition, the Stacked Autoencoder Topographic Map (SAETM) approach was utilized for the classification of ECG signals to identify the presence of CVDs. Finally, the MROA was applied as a hyperparameter optimizer, which assisted in accomplishing enhanced performance. The experimental outcomes of the MROA-DLECGSC algorithm were tested on the benchmark database, and the results show the better performance of the MROA-DLECGSC methodology compared to other recent algorithms.

Leveraging Metaheuristic Unequal Clustering for Hotspot Elimination in Energy-Aware Wireless Sensor Networks.

Wireless sensor networks (WSNs) are becoming a significant technology for ubiquitous living and continue to be involved in active research because of their varied applications. Energy awareness will be a critical design problem in WSNs. Clustering is a widespread energy-efficient method and grants several benefits such as scalability, energy efficiency, less delay, and lifetime, but it results in hotspot issues. To solve this, unequal clustering (UC) has been presented. In UC, the size of the cluster differs with the distance to the base station (BS). This paper devises an improved tuna-swarm-algorithm-based unequal clustering for hotspot elimination (ITSA-UCHSE) technique in an energy-aware WSN. The ITSA-UCHSE technique intends to resolve the hotspot problem and uneven energy dissipation in the WSN. In this study, the ITSA is derived from the use of a tent chaotic map with the traditional TSA. In addition, the ITSA-UCHSE technique computes a fitness value based on energy and distance metrics. Moreover, the cluster size determination via the ITSA-UCHSE technique helps to address the hotspot issue. To demonstrate the enhanced performance of the ITSA-UCHSE approach, a series of simulation analyses were conducted. The simulation values stated that the ITSA-UCHSE algorithm has reached improved results over other models.

The Exposure to Lead (Pb) Exacerbates Immunological Abnormalities in BTBR T+ Itpr3tf/J Mice through the Regulation of Signaling Pathways Relevant to T Cells.

Autism spectrum disorder (ASD) is a common neurodevelopmental illness characterized by abnormal social interactions, communication difficulties, and repetitive and limited behaviors or interests. The BTBR T+ Itpr3tf/J (BTBR) mice have been used extensively to research the ASD-like phenotype. Lead (Pb) is a hazardous chemical linked to organ damage in the human body. It is regarded as one of the most common metal exposure sources and has been connected to the development of neurological abnormalities. We used flow cytometry to investigate the molecular mechanism behind the effect of Pb exposure on subsets of CD4+ T cells in the spleen expressing IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Furthermore, using RT-PCR, we studied the effect of Pb on the expression of numerous genes in brain tissue, including IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, AhR, IL-10, and Foxp3. Pb exposure increased the population of CD4+IFN-γ+, CD4+T-bet+, CD4+STAT1+, CD4+STAT4+, CD4+IL-9+, CD4+IRF4+, CD4+IL-22+, and CD4+AhR+ cells in BTBR mice. In contrast, CD4+IL-10+ and CD4+Foxp3+ cells were downregulated in the spleen cells of Pb-exposed BTBR mice compared to those treated with vehicle. Furthermore, Pb exposure led to a significant increase in IFN-γ, T-bet, STAT1, STAT4, IL-9, IRF4, IL-22, and AhR mRNA expression in BTBR mice. In contrast, IL-10 and Foxp3 mRNA expression was significantly lower in those treated with the vehicle. Our data suggest that Pb exposure exacerbates immunological dysfunctions associated with ASD. These data imply that Pb exposure may increase the risk of ASD.

Histamine H4 Receptor Antagonist Ameliorates the Progression of Experimental Autoimmune Encephalomyelitis via Regulation of T-Cell Imbalance.

Multiple sclerosis (MS) is a degenerative condition characterized by immune-mediated attacks on the central nervous system (CNS), resulting in demyelination and recurring T-cell responses. The histamine H4 receptor (H4R) is mainly expressed in cellular populations and plays a vital role in inflammation and immunological responses. The role of H4R in neurons of the CNS has recently been revealed. However, the precise role of H4R in neuronal function remains inadequately understood. The objective of this work was to investigate the impact of JNJ 10191584 (JNJ), a highly effective and specific H4R antagonist, on the development of experimental autoimmune encephalomyelitis (EAE) and to gain insight into the underlying mechanism involved. In this study, we examined the potential impact of JNJ therapy on the course of EAE in SJL/J mice. EAE mice were administered an oral dose of JNJ at a concentration of 6 mg/kg once a day, starting from day 10 and continuing until day 42. Afterward, the mice's clinical scores were assessed. In this study, we conducted additional research to examine the impact of JNJ on several types of immune cells, specifically Th1 (IFN-γ and T-bet), Th9 (IL-9 and IRF4), Th17 (IL-17A and RORγt), and regulatory T (Tregs; Foxp3 and TGF-ß1) cells in the spleen. In this study, we further investigated the impact of JNJ on the mRNA expression levels of IFN-γ, T-bet, IL-9, IRF4, IL-17A, RORγt, Foxp3, and TGF-ß1 in the brain. Daily treatment of JNJ effectively reduced the development of EAE in mice. The percentages of CD4+IFN-γ+, CD4+T-bet+, CD4+IL-9+, CD4+IRF4+, CD4+IL-17A+, and CD4+RORγt+ cells were shown to decrease, whereas the percentages of CD4+TGF-ß1+ and CD4+Foxp3+ cells were observed to increase in EAE mice treated with JNJ. Therefore, the HR4 antagonist positively affected the course of EAE by modulating the signaling of transcription factors. The identified results include possible ramifications in the context of MS treatment.

Comparing the safety and effectiveness of various umbilical cord milking techniques and delayed cord clamping in full-term and preterm infants: A systematic review and meta-analysis.

We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical cord milking (UCM) and delayed cord clamping (DCC) in both full-term and preterm infants. A comprehensive search through various databases aimed to compare UCM and DCC studies until May 2nd, 2023. Cochrane and NIH tools assessed RCTs and cohorts, respectively. Meta-analysis employed Review Manager 5.4 software, calculating MD and RR with 95% CIs for continuous and dichotomous data. We included 20 studies with a total of 5189 infants. Regarding preterm infants, hematocrit level showed no significant difference between intact Umbilical Cord Milking (iUCM) compared to DCC (MD = -0.24, 95% CI [-1.11, 0.64]). Moreover, Neonatal death incidence was significantly higher with the UCM technique in comparison to DCC (RR = 1.28, 95% CI [1.01 to 1.62]). Regarding term and late preterm infants, Hematocrit level showed no significant difference between the iUCM or cUCM techniques compared to DCC (MD = 0.21, 95% CI [-1.28 to 1.69]), (MD = 0.96, 95% CI [-1.02 to 2.95]), respectively. UCM led to a higher risk of neonatal death in preterm infants compared to DCC. However, the incidence of polycythemia was lower in the UCM group. Additionally, UCM was associated with higher rates of severe IVH events. Based on these findings, DCC may be preferred due to its lower incidence of severe IVH and neonatal death.

Nous comparons l'hématocrite, l'hémoglobine, le besoin de transfusion, la photothérapie récurrente, le taux de bilirubine sérique et la ferritine sérique à différentes périodes pour la traite du cordon ombilical (UCM) et le clampage retardé du cordon (DCC) chez les nourrissons nés à terme et prématurés. Une recherche complète dans diverses bases de données visait à comparer les études UCM et DCC jusqu'au 2 mai 2023. Les outils Cochrane et NIH ont évalué les ECR et les cohortes, respectivement. La méta-analyse a utilisé le logiciel Review Manager 5.4, calculant le MD et le RR avec des IC à 95 % pour les données continues et dichotomiques. Nous avons inclus 20 études portant sur un total de 5 189 nourrissons. Concernant les nourrissons prématurés, le niveau d'hématocrite n'a montré aucune différence significative entre la traite du cordon ombilical intact (iUCM) et la DCC (DM = -0,24, IC à 95 % [-1,11, 0,64]). De plus, l'incidence des décès néonatals était significativement plus élevée avec la technique UCM qu'avec la technique DCC (RR = 1,28, IC à 95 % [1,01 à 1,62]). Concernant les nourrissons à terme et peu prématurés, le niveau = 0,21, IC à 95 % [-1,28 à 1,69]), (DM = 0,96, IC à 95 % [-1,02 à 2,95]), respectivement. L'UCM a entraîné un risque plus élevé de décès néonatal chez les nourrissons prématurés par rapport au DCC. Cependant, l'incidence de la polyglobulie était plus faible dans le groupe UCM. De plus, l'UCM était associée à des taux plus élevés d'événements IVH graves. Sur la base de ces résultats, le DCC peut être préféré en raison de sa plus faible incidence d'IVH grave et de décès néonatals. d'hématocrite n'a montré aucune différence significative entre les techniques iUCM ou cUCM par rapport à la technique DCC (DM.

Development of novel indolin-2-one derivative incorporating thiazole moiety as DHFR and quorum sensing inhibitors: Synthesis, antimicrobial, and antibiofilm activities with molecular modelling study.

Nowadays, it's imperative to develop novel antimicrobial agents active against both drug-sensitive and drug-resistant bacterial infections with favorable profiles as high efficacy, low toxicity, and short therapy duration. Accordingly, a series of new thiazolo-indolin-2-one derivatives were synthesized based on acid and base catalyzed condensation or reaction of thiosemicarbazone 8 with different electrophilic reagents. The structure of the new compounds was confirmed based on elemental analysis and spectral data. Based on the MIC results, the most active thiazolo-indoline derivatives 2, 4, 7a, and 12 exhibited promising antibacterial activity against gram-positive and gram-negative bacteria with weak to moderate antifungal activities. Surprisingly, the N-(thiazol-2-yl)benzenesulfonamide derivative 4 was found to be most active on antibiofilm activity against both S. aureus (ATCC 29213) with BIC50 (1.95 ± 0.01 µg/mL), while 5-(2-oxoindolin-3-ylidene)-thiazol-4(5H)-one derivative 7a exhibited the strongest antibiofilm activity against P. aeruginosa pathogens with BIC50 (3.9 ± 0.16 µg/mL). Further, the thiazole derivatives 2, 4 and 12 exhibited a significant inhibition activity against the fsr system in a dose-dependent manner without affecting bacterial growth. The target derivatives behaved synergistic and additively effect against MDR p. aeruginosa, and thiazole derivative 12 exhibited a high synergistic effect with most tested antibiotics except Cefepime with FIC value ranging between 0.249 and 1.0, reducing their MICs. Interestingly, the 3-(2-(4-thiazol-2-yl)hydrazono)indolin-2-one derivative 12 displayed the highest selectivity to DHFR inhibitory with IC50 value 40.71 ± 1.86 nM superior to those of the reference Methotrexate. Finally, in silico molecular modeling simulation, some physicochemical properties and toxicity predictions were performed for the most active derivatives.

Key Electronic, Linear and Nonlinear Optical Properties of Designed Disubstituted Quinoline with Carbazole Compounds.

Organic materials development, especially in terms of nonlinear optical (NLO) performance, has become progressively more significant owing to their rising and promising applications in potential photonic devices. Organic moieties such as carbazole and quinoline play a vital role in charge transfer applications in optoelectronics. This study reports and characterizes the donor-acceptor-donor-π-acceptor (D-A-D-π-A) configured novel designed compounds, namely, Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1. We further analyze the structure-property relationship between the quinoline-carbazole compounds for which density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed at the B3LYP/6-311G(d,p) level to obtain the optimized geometries, natural bonding orbital (NBO), NLO analysis, electronic properties, and absorption spectra of all mentioned compounds. The computed values of λmax, 364, 360, and 361 nm for Q3, Q4, and Q5 show good agreement of their experimental values: 349, 347, and 323 nm, respectively. The designed compounds (Q3D1-Q5D1) exhibited a smaller energy gap with a maximum redshift than the reference molecules (Q3-Q5), which govern their promising NLO behavior. The NBO evaluation revealed that the extended hyperconjugation stabilizes these systems and caused a promising NLO response. The dipole polarizabilities and hyperpolarizability (ß) values of Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1 exceed those of the reference Q3, Q4, and Q5 molecules. These data suggest that the NLO active compounds, Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1, may find their place in future hi-tech optical devices.

Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease.

BACKGROUND: Chronic alcohol consumption is a significant cause of liver disease worldwide. Several biochemical mechanisms have been linked to the initiation and progression of alcoholic liver disease (ALD) such as oxidative stress, inflammation, and metabolic dysregulation, including the disruption of NAD+/NADH. Indeed, an ethanol-mediated reduction in hepatic NAD+ levels is thought to be one factor underlying ethanol-induced steatosis, oxidative stress, steatohepatitis, insulin resistance, and inhibition of gluconeogenesis. Therefore, we applied a NAD+ boosting supplement to investigate alterations in the pathogenesis of early-stage ALD. METHODS: To examine the impact of NAD+ therapy on the early stages of ALD, we utilized nicotinamide mononucleotide (NMN) at 500 mg/kg intraperitoneal injection every other day, for the duration of a Lieber-DeCarli 6-week chronic ethanol model in mice. Numerous strategies were employed to characterize the effect of NMN therapy, including the integration of RNA-seq, immunoblotting, and metabolomics analysis. RESULTS: Our findings reveal that NMN therapy increased hepatic NAD+ levels, prevented an ethanol-induced increase in plasma ALT and AST, and changed the expression of 25% of the genes that were modulated by ethanol metabolism. These genes were associated with a number of pathways including the MAPK pathway. Interestingly, our analysis revealed that NMN treatment normalized Erk1/2 signaling and prevented an induction of Atf3 overexpression. CONCLUSIONS: These findings reveal previously unreported mechanisms by which NMN supplementation alters hepatic gene expression and protein pathways to impact ethanol hepatotoxicity in an early-stage murine model of ALD. Overall, our data suggest further research is needed to fully characterize treatment paradigms and biochemical implications of NAD+-based interventions.

Synthesis, Structure Study, First-Principles Investigations and Luminescence Properties of Europium and Terbium Complexes.

The synthesis of 1-benzyl-2-((2-Aminoethyl) amino)-5-oxopyrrolidine-3,4-diyl diacetate (boad), an oxopyrrolidine type ligand; designed to coordinate lanthanides (Eu3+ and Tb3+) to get luminescent material. The target complexes showed good photoluminescence properties, which indicate that this type of compound can be used as sensitizers having luminescence for the green (Tb3+) and red (Eu3+) emission. The obtained results revealed that sensitizer efficiency can be improved by adding ligands like acac (Eu(acac)3, which has also enhanced the luminescence quantum output and period for Eu3+ ions. The ground state geometries were developed by using density functional theory at B3LYP/6-31G** level. The charge transfer analysis and electronic properties were performed. The Europium and Terbium complexes formation with boad ligand was explored based on molecular electrostatic potential, MDC-q charges, and frontier molecular orbitals (FMOs) analysis.

Quantifying Competition among Mitochondrial Protein Acylation Events Induced by Ethanol Metabolism.

Mitochondrial dysfunction is one of many key factors in the etiology of alcoholic liver disease (ALD). Lysine acetylation is known to regulate numerous mitochondrial metabolic pathways, and recent reports demonstrate that alcohol-induced protein acylation negatively impacts these processes. To identify regulatory mechanisms attributed to alcohol-induced protein post-translational modifications, we employed a model of alcohol consumption within the context of wild type (WT), sirtuin 3 knockout (SIRT3 KO), and sirtuin 5 knockout (SIRT5 KO) mice to manipulate hepatic mitochondrial protein acylation. Mitochondrial fractions were examined by label-free quantitative HPLC-MS/MS to reveal competition between lysine acetylation and succinylation. A class of proteins defined as "differential acyl switching proteins" demonstrate select sensitivity to alcohol-induced protein acylation. A number of these proteins reveal saturated lysine-site occupancy, suggesting a significant level of differential stoichiometry in the setting of ethanol consumption. We hypothesize that ethanol downregulates numerous mitochondrial metabolic pathways through differential acyl switching proteins. Data are available via ProteomeXchange with identifier PXD012089.

Microwave synthesis of novel halogenated ß-enaminonitriles linked 9-bromo-1H-benzo[f]chromene moieties: Induces cell cycle arrest and apoptosis in human cancer cells via dual inhibition of topoisomerase I and II.

A novel series of halogenated ß-enaminonitriles (4a-m), linked 9-bromo-1H-benzo[f]-hromene moieties, were synthesized via microwave irradiation and were predestined for their cytotoxic activity versus three cancer cell lines, namely: MCF-7, HCT-116, and HepG-2. Several of the tested compounds showed high growth inhibitory activities versus the tumor cell lines. Particularly, compounds 4c, 4d, 4f, 4h, 4j, 4l, and 4m demonstrated superior antitumor activities against the aforementioned cell lines. Moreover, the apoptosis process in all the tested cells was induced by compounds 4c, 4d, 4h, 4l, and 4m, as observed by the Annexin V/PI double staining flow cytometric assay. The DNA flow, cytometric analysis revealed that these compounds prompted cell cycle arrest at the G2/M phases. Furthermore, the topoisomerase catalytic activity assays indicated that these compounds inhibited both the topoisomerase I and II enzymes.

Antiproliferative effect, cell cycle arrest and apoptosis generation of novel synthesized anticancer heterocyclic derivatives based 4H-benzo[h]chromene.

Novel ß-enaminonitrile/ester compounds (4, 6) and an imidate of 4 (9) were utilized as key scaffolds for the synthesis of newly 2-substituted 4H-benzo[h]chromene (7, 8, 10, 11, 13, 14) and 7H-benzo[h]chromeno[2,3-d]pyrimidine derivatives (15-19). The spectral data confirmed the successful isolation of the desired compounds. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer cell line (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2), while doxorubicin, vinblastine, and colchicine were utilized as standard references drugs. Some of the examined compounds displayed high growth inhibitory activity against the three different cell lines. For example, the aminoimino derivative (18) exhibited excellent antitumor activity versus all cancer cell lines with IC50 values = 0.45 µg/mL, 0.7 µg/mL, and 1.7 µg/mL. Among the tested molecules, compounds 9, 15, and 18 were selected for further study regarding their effects on cell cycle analysis, apoptosis assay, caspase 3/7 activity, and DNA fragmentation. We found that these three potent cytotoxic compounds induce cell cycle arrest at the S and G2/M phases, which causes apoptosis. Furthermore, these compounds significantly inhibit the invasion and migration of the different tested cancer cells. Finally, the SAR survey highlighted the antitumor activity of the new molecules that was remarkably influenced by the hydrophilicity of substituent as well the fused rings at certain positions.