ABSTRACT
Ovarian cancer is the leading cause of death from female gynecological cancers. Cisplatin (DDP) is a first-line drug for ovarian cancer treatment. Due to DDP resistance, there is an urgent need for novel therapeutic drugs with improved antitumor activity. AMPK-mediated metabolic regulatory pathways are related to tumor drug resistance. Our study aimed to determine the relationship between reversing DDP resistance with the anthraquinone derivative KA-4s and regulating AMPK energy metabolism in ovarian cancer. The results showed that KA-4s inhibited the proliferation of ovarian cancer cells. The combination of KA-4s with DDP effectively promoted drug-resistant ovarian cancer cell apoptosis and inhibited cell migration and invasion. Moreover, KA-4s decreased the intracellular ATP level and increased the calcium ion level, leading to AMPK phosphorylation. Further studies suggested that the AMPK signaling pathway may be involved in the mechanism through which KA-4s reduce drug resistance. KA-4s inhibited mitochondrial respiration and glycolysis; downregulated the glucose metabolism-related proteins GLUT1 and GLUT4; the lipid metabolism-related proteins SREBP1 and SCD1; and the drug resistance-related proteins P-gp, MRP1, and LRP. The inhibitory effect of KA-4s on GLUT1 was confirmed by the application of the GLUT1 inhibitor BAY-876. KA-4s combined with DDP significantly increased the expression of p-AMPK and reduced the expression of P-gp. In a xenograft model of ovarian cancer, treatment with KA-4s combined with DDP reduced energy metabolism and drug resistance, inducing tumor apoptosis. Consequently, KA-4s might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of treatment for ovarian cancer.
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This interdisciplinary study critically analyzes current research, establishing a profound connection between sea water, sea ice, sea temperature, and surface temperature through a 4D hyperchaotic Caputo fractional differential equation. Emphasizing the collective impact on climate, focusing on challenges from anthropogenic global warming, the study scrutinizes theoretical aspects, including existence and uniqueness. Two sliding mode controllers manage chaos in this 4D fractional system, assessed amid uncertainties and disruptions. The global stability of these controlled systems is also confirmed, considering both commensurate and non-commensurate 4D fractional order. To demonstrate the intricate chaotic motion within the system, we employ the Lyapunov exponent and Poincare sections. Numerical simulations are conducted by using the predictor-corrector method. The effects of surface temperature on chaotic dynamics are discussed. The crucial role of sea ice reflection in climate stability is highlighted in two scenarios. Correlation graphs, comparing model and observational data using the predictor-corrector method, enhance the proposed 4D hyperchaotic model's credibility. Subsequently, numerical simulations validate theoretical assertions about the controllers' influence. These controllers indicate which variable significantly contributes to controlling the chaos.
ABSTRACT
The main protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of Mpro inhibitor is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1a-h), dithiocarbamate-Cu(II) complexes (2a-hCu) and disulfide derivatives (2a-e, 2i) as potent inhibitors of Mpro, with IC50 value range of 0.09-0.72, 0.9-24.7 and 15.1-111 µM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1g may be a partial reversible inhibitor, while 2d and 2f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2d, 2f-Cu and 1g to Mpro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2f-Cu and 2d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2d and 1g exhibit low cytotoxicity, whereas 2f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.
ABSTRACT
Purpose: The present study aimed to develop a lipid nanoplatform, denoted as "BAL-PTX-LN", co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs. Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining. Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 µg/mL vs 31.722 µg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration. Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications.
Subject(s)
Lung Neoplasms , Paclitaxel , Paclitaxel/chemistry , Paclitaxel/pharmacokinetics , Paclitaxel/pharmacology , Paclitaxel/administration & dosage , Animals , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Humans , Flavonoids/chemistry , Flavonoids/pharmacology , Flavonoids/pharmacokinetics , Flavonoids/administration & dosage , Particle Size , Nanoparticles/chemistry , Mice , Liposomes/chemistry , Liposomes/pharmacokinetics , A549 Cells , Lipids/chemistry , Male , Mice, Inbred BALB C , Cell Line, Tumor , Drug Liberation , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Mice, Nude , Hemolysis/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/administration & dosageABSTRACT
Calcium ions are the second messenger playing as regulators for various cellular activities. Its spatiotemporal control is critical for various brain functions, including neuroplasticity, apoptosis, and cell death. The Endoplasmic Reticulum (ER) plays an important role in determining these spatiotemporal calcium dynamics. Stromal interaction molecule (STIM) - Orai channel on the membrane generates additional calcium flow, whereas other membrane fluxes contribute to cytosolic flux. Due to their anomalous character, we used the Caputo fractional differential operator to mimic these interactions in polar coordinates. Solutions were generated using hybrid integral transform methods to control the analytical approach. Using Green's function yielded a closed-form solution for Mittag-Leffler-type functions. This work emphasizes the significant relationship between calcium and various buffer levels in neurons. The differential transition simulation of a time derivative with space across different parameters indicated a decrease in calcium concentration. Anomalously low buffer levels exhibited the impact of Alzheimer's disease on calcium higher concentration, leading to the death of neurons. Additionally, the research introduces a method involving S100B, BAPTA, and calmodulin buffers to uphold optimal calcium levels within the neuronal cytosol. The applicability of this model with different buffer properties and parameters and memory impacts the calcium concentration with the neurological disorder.
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The electron extraction from perovskite/C60 interface plays a crucial role in influencing the photovoltaic performance of inverted perovskite solar cells (PSCs). Here, we develop a one-stone-for-three-birds strategy via employing a novel fullerene derivative bearing triple methyl acrylate groups (denoted as C60-TMA) as a multifunctional interfacial layer to optimize electron extraction at the perovskite/C60 interface. It is found that the C60-TMA not only passivates surface defects of perovskite via coordination interactions between C=O groups and Pb2+ cations but also bridge electron transfer between perovskite and C60. Moreover, it effectively induces the secondary grain growth of the perovskite film through strong bonding effect, and this phenomenon has never been observed in prior art reports on fullerene related studies. The combination of the above three upgrades enables improved perovskite film quality with increased grain size and enhanced crystallinity. With these advantages, C60-TMA treated PSC devices exhibit a much higher power conversion efficiency (PCE) of 24.89% than the control devices (23.66%). Besides, C60-TMA benefits improved thermal stability of PSC devices, retaining over 90% of its initial efficiency after aging at 85 °C for 1200 h, primarily due to the reinforced interfacial interactions and improved perovskite film quality.
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Kojic acid derivatives are useful in the cosmetics and pharmaceutical industries. The current investigation focuses on the search for a safe and environmentally friendly newer whole-cell biocatalyst for the synthesis of kojic acid derivative especially 2-amino-6-(hydroxymethyl)-8-oxo-4-phenyl-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile (APhCN). In this context, a total of six cultures were isolated from fecal samples of infants and subjected to probiotic characterization followed by screening as whole cell biocatalyst (WCB). In this multicomponent reaction, benzaldehyde, malononitrile, and kojic acid were used to synthesize APhCN at room temperature under aqueous conditions. The screening of potent whole cell biocatalyst (WCB) from isolated cultures was done by comparing reaction time and percent yield. The potent WCB gave a good yield of 95% within 15 h of time and hence further characterized biochemically and identified as Lentilactobacillus farraginis by using 16S rRNA gene sequencing. Lactobacilli having GRAS (generally regarded as safe) status and being able to carry out this transformation under moderate reaction conditions with easy recovery of both product and biocatalyst, it has the potential to replace some of the chemical catalytic methods.
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The five-year survival rate for patients with hepatocellular carcinoma (HCC) is only 20â¯%, highlighting the urgent need to identify new therapeutic targets and develop potential therapeutic options to improve patient prognosis. One promising approach is inhibiting autophagy as a strategy for HCC treatment. In this study, we established a virtual docking conformation of the autophagy promoter ULK1 binding XST-14 derivatives. Based on this conformation, we designed and synthesized four series of derivatives. By evaluating their affinity and anti-HCC effects, we confirmed that these compounds exert anti-HCC activity by inhibiting ULK1. The structure-activity relationship was summarized, with derivative A4 showing 10 times higher activity than XST-14 and superior efficacy to sorafenib against HCC. A4 has excellent effect on reducing tumor growth and enhancing sorafenib activity in HepG2 and HCCLM3 cells. Moreover, we verified the therapeutic effect of A4 in sorafenib-resistant HCC cells both in vivo and in vitro. These results suggest that inhibiting ULK1 to regulate autophagy may become a new treatment method for HCC and that A4 will be used as a lead drug for HCC in further research. Overall, A4 shows good drug safety and efficacy, offering hope for prolonging the survival of HCC patients.
Subject(s)
Antineoplastic Agents , Autophagy-Related Protein-1 Homolog , Autophagy , Carcinoma, Hepatocellular , Drug Design , Indoles , Liver Neoplasms , Molecular Docking Simulation , Protein Kinase Inhibitors , Sorafenib , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Autophagy-Related Protein-1 Homolog/antagonists & inhibitors , Autophagy-Related Protein-1 Homolog/metabolism , Indoles/pharmacology , Indoles/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Sorafenib/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Animals , Autophagy/drug effects , Hep G2 Cells , Mice, Nude , Cell Line, Tumor , Mice, Inbred BALB C , Xenograft Model Antitumor Assays , Mice , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/metabolism , Cell Proliferation/drug effectsABSTRACT
BODIPY-based chemosensors are widely used owing to merits like good selectivity, high fluorescence quantum yield, and excellent optical stability. As such, a pH-switchable hydrophilic fluorescent probe, BODIPY-PY-(SO3Na)2, was developed for detection of Fe3+ ion in aqueous solutions. BODIPY-PY-(SO3Na)2 revealed strong fluorescence intensity and was responsive to pH value in the range of 6.59-1.96. Additionally, BODIPY-PY-(SO3Na)2 showed good selectivity and sensitivity towards Fe3+. A good linear relationship for Fe3+ detection was obtained from 0.0 µM to 50.0 µM with low detecting limit of 6.34 nM at pH 6.59 and 2.36 nM at pH 4.32, respectively. The response to pH and detection of Fe3+ induced obvious multicolor changes. BODIPY-PY-(SO3Na)2 can also be utilized to quantitatively detect Fe3+ in real water sample. Different mechanisms of Fe3+ detection at investigated pH values were unraveled through relativistic density functional theory (DFT) calculations in BODIPY-PY-(SO3Na)2 and experiments of coexisting cations, anions and molecules. These results enabled us to gain a deeper understanding of the interactions between BODIPY-PY-(SO3Na)2 and Fe3+ and provide valuable fundamental information for design of efficient multicolor chemosensors for Fe3+ as well.
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We studied spectral properties of 1,N2-etheno-2-aminopurine after immobilization in poly (vinyl alcohol) films. The absorption spectrum of 1,N2-ε2APu consists of two peaks centered at 300 and 370 nm, and the fluorescence spectrum has maximum at about 460 nm. The fluorescence quantum efficiency is 62%. The fluorescence anisotropy reaches a value of 0.3 at longer wavelengths, while it is low at shorter wavelengths (corresponding to the second single excited state). The 1,N2-ε2APu has a relatively long fluorescence lifetime of about 16 ns and a noticeable room temperature phosphorescence with a lifetime of about 220 ms. A broad phosphorescence emission band (425-675 nm) is centered at about 530 nm and markedly overlaps with fluorescence at shorter wavelengths. Surprisingly, the phosphorescence excitation spectrum of 1,N2-ε2APu-doped poly (vinyl alcohol) film differs from the absorption and fluorescence excitation spectra. The strongest room temperature phosphorescence excitation is about 335 nm. At longer excitation wavelengths, above 450 nm, where fluorescence cannot be excited, a triplet excitation is still possible. The 1,N2-ε2APu phosphorescence anisotropy spectra confirm direct triplet state excitation. The ability to excite molecules at long wavelengths can find applications in the study of biological molecules that are unstable when excited at high energies.
Subject(s)
Luminescence , Polyvinyl Alcohol , Temperature , Polyvinyl Alcohol/chemistry , Spectrometry, Fluorescence , Luminescent Measurements , 2-Aminopurine/chemistry , Molecular StructureABSTRACT
This study explores the fractional form of modified Korteweg-de Vries-Kadomtsev-Petviashvili equation. This equation offers the physical description of how waves propagate and explains how nonlinearity and dispersion may lead to complex and fascinating wave phenomena arising in the diversity of fields like optical fibers, fluid dynamics, plasma waves, and shallow water waves. A variety of solutions in different shapes like bright, dark, singular, and combo solitary wave solutions have been extracted. Two recently developed integration tools known as generalized Arnous method and enhanced modified extended tanh-expansion method have been applied to secure the wave structures. Moreover, the physical significance of obtained solutions is meticulously analyzed by presenting a variety of graphs that illustrate the behaviour of the solutions for specific parameter values and a comprehensive investigation into the influence of the nonlinear parameter on the propagation of the solitary wave have been observed. Further, the governing equation is discussed for the qualitative analysis by the assistance of the Galilean transformation. Chaotic behavior is investigated by introducing a perturbed term in the dynamical system and presenting various analyses, including Poincare maps, time series, 2-dimensional 3-dimensional phase portraits. Moreover, chaotic attractor and sensitivity analysis are also observed. Our findings affirm the reliability of the applied techniques and suggest its potential application in future endeavours to uncover diverse and novel soliton solutions for other nonlinear evolution equations encountered in the realms of mathematical physics and engineering.
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Aim: The aim of the present study was to compare the clinical and radiographic success of amniotic membrane derivative (AMD), chitosan with mineral trioxide aggregate (C-MTA), diode laser (DL), and ferric sulfate (FS) as pulpotomy agents in human primary molars. Materials and methods: In this present study, pulpotomies were performed on 48 primary molars in 30 children aged between 4 and 8 years (12 teeth in each group). Following the pulpotomy procedure, teeth were evaluated clinically and radiographically at 1st, 3rd, 6th, and 9 monthly intervals. Results: After 9 months of follow-up, the clinical success was 91.6% for AMD and C-MTA and 83.3% for DL and FS. Radiographic success was 91.6, 91.6, 75, and 83.3% for AMD, C-MTA, DL, and FS groups, respectively. There is no statistically significant difference between the four groups (p > 0.05). Interpretation and conclusion: Results of our study showed that both AMD and C-MTA were equally successful compared to traditional agents like laser and ferric sulfate as pulpotomy agents. Clinical significance: Amniotic membrane derivative (AMD) and C-MTA are alternative biomimetic pulpotomy agents that can be used in pediatric primary tooth pulpotomies. How to cite this article: Lahoti VC, Lahoti P, Gundreddy LM, et al. Comparative Evaluation of Amniotic Membrane Derivative, Chitosan with Mineral Trioxide Aggregate, Diode Laser, and Ferric Sulfate as Pulpotomy Agents in Human Primary Molars: An In Vivo Study. Int J Clin Pediatr Dent 2024;17(2):153-157.
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The isothiourea derivative NT-1505 is known as a neuroprotector and cognition enhancer in animal models of neurodegenerative diseases. Bearing in mind possible relation of the NT-1505-mediated neuroprotection to mitochondrial uncoupling activity, here, we examine NT-1505 effects on mitochondria functioning. At concentrations starting from 10 µM, NT-1505 prevented Ca2+-induced mitochondrial swelling, similar to common uncouplers. Alongside the inhibition of the mitochondrial permeability transition, NT-1505 caused a decrease in mitochondrial membrane potential and an increase in respiration rate in both isolated mammalian mitochondria and cell cultures, which resulted in the reduction of energy-dependent Ca2+ uptake by mitochondria. Based on the oppositely directed effects of bovine serum albumin and palmitate, we suggest the involvement of fatty acids in the NT-1505-mediated mitochondrial uncoupling. In addition, we measured the induction of electrical current across planar bilayer lipid membrane upon the addition of NT-1505 to the bathing solution. Importantly, introduction of the palmitic acid into the lipid bilayer composition led to weak proton selectivity of the NT-1505-mediated BLM current. Thus, the present study revealed an ability of NT-1505 to cause moderate protonophoric uncoupling of mitochondria, which could contribute to the neuroprotective effect of this compound.
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Complexes [Cu(PI)2(H2O)](NO3)2 (1), [Cu(PBI)2(NO3)]NO3 (2), [Cu(TBI)2(NO3)]NO3 (3), [Cu(BBIP)2](ClO4)2 (4) and [Cu(BBIP)(CH3OH)(ClO4)2] (5) were synthesized from the reactions of Cu(II) salts with 2-(2'-pyridyl)imidazole (PI), (2-(2'-pyridyl)benzimidazole (PBI), 2-(4'-thiazolyl)-benzimidazole (TBI), 2,6-bis(benzimidazol-2-yl)-pyridine (BBIP), respectively. Their compositions and crystal structures were determined. Their in-vitro antitumor activities were screened on four cancer cell lines and one normal cell line (HL-7702) using cisplatin as the positive control. Complexes 2 and 4 show higher cytotoxicity than the other three complexes. The cytotoxicity of complex 2 are comparable to those for cisplatin, and the cytotoxicity for 4 are much higher than those for cisplatin. From a viewpoint of antitumor, 2 might be a nice choice on the tumor cell line of T24 because its IC50 values on T24 and HL-7702 are 15.03 ± 1.10 and 21.34 ± 0.35, respectively. Thus, a mechanistic study for complexes 2 and 4 on T24 cells was conducted. It revealed that they can reduce mitochondrial membrane potential and increase mitochondrial membrane permeability, resulting in increased intracellular ROS levels, Ca2+ inward flow, dysfunctional mitochondria and the eventual cell apoptosis. In conclusion, they can induce cell apoptosis through mitochondrial dysfunction. These findings could be useful in the development of new antitumor agents.
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Levofloxacin (LVX) is difficult to be naturally degraded by microorganisms in water, and its residues in water will pose significant risks to human health and ecological environment. In this study, Bi12O17Cl2 was used as the main body, Bi12O17Cl2/GO/Co3O4 composite photocatalyst was prepared by pyrolysis of zeolitic imidazolate framework-67 (ZIF-67) combined with in-situ precipitation method and used to degrade LVX. A sequence of characterizations shows that addition of Co3O4 and graphene oxide (GO) increases the visible light response range, improves the separation efficiency of photogenerated electrons and holes (e--h+) of photocatalyst, and thus improves the degradation efficiency of LVX. Under the optimal reaction conditions, the LVX degradation rate of Bi12O17Cl2/1.5GO/7.5Co3O4 can reach 91.2 % at 120 min, and its reaction rate constant is the largest (0.0151 min-1), which is 2.17, 13.14 and 1.53 times that of Bi12O17Cl2, Co3O4 and Bi12O17Cl2/7.5Co3O4, respectively, showing better photocatalytic performance. Simultaneously, the recycling stability of Bi12O17Cl2/1.5GO/7.5Co3O4 was also verified. The capture experiments and electron EPR test results showed that superoxide radicals (â¢O2-) and photogenerated holes (h+) were the primary active substances in the reaction process. Finally, combined with HPLC-MS results, the photocatalytic degradation pathway of LVX was derived. This work will provide a theoretical basis for the design of Metal Organic Frameworks (MOFs)-derivative modified Bi12O17Cl2-based photocatalysts.
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In this study, we introduce a novel iterative method combined with the Elzaki transformation to address a system of partial differential equations involving the Caputo derivative. The Elzaki transformation, known for its effectiveness in solving differential equations, is incorporated into the proposed iterative approach to enhance its efficiency. The system of partial differential equations under consideration is characterized by the presence of Caputo derivatives, which capture fractional order dynamics. The developed method aims to provide accurate and efficient solutions to this complex mathematical system, contributing to the broader understanding of fractional calculus applications in the context of partial differential equations. Through numerical experiments and comparisons, we demonstrate the efficacy of the proposed Elzaki-transform-based iterative method in handling the intricate dynamics inherent in the given system. The study not only showcases the versatility of the Elzaki transformation but also highlights the potential of the developed iterative technique for addressing similar problems in various scientific and engineering domains.
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Chitosan is a potentially suitable material for wound dressing, but is undesirably water-insoluble. Although chitosan can be modified to produce water-soluble derivatives, the best chitosan derivative for wound dressings remains unclear. The present study introduced three water-soluble chitosan derivatives, namely, carboxymethyl chitosan, quaternized chitosan (QCS), and carboxymethyl quaternized chitosan, and explored the physical properties, biochemical properties, and wound care effectiveness of films of these derivatives. The QCS-based film exhibited higher absorption ability, mechanical properties, water-vapor permeability, electroconductivity, and antioxidant capacity than the other films. Most importantly, the cationic quaternary ammonium groups facilitated the antibacterial activity (>95 %) and blood coagulant capacity of the QCS-based film. As this film also promoted wound healing, it presented as an ideal candidate for wound dressings.
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Combining rare earth elements with the halide perovskite structure offers valuable insights into designing nonlead (Pb) luminescent materials. However, most of these compositions tend to form zero-dimensional (0D) networks of metal-halide polyhedra, with higher-dimensional (1D, 2D, and 3D) structures receiving relatively less exploration. Herein, we present synthesis and optical properties of Cs3CeCl6·3H2O, characterized by its unique 1D crystal structure. The conduction band minimum of Cs3CeCl6·3H2O becomes less localized as a result of the increased structural dimension, making it possible for the materials to achieve an efficient electrical injection. For both Cs3CeCl6·3H2O single crystals and nanocrystals, we also observed remarkable luminescence with near-unity photoluminescence quantum yield and exceptional phase stability. Cs3CeCl6·3H2O single crystals demonstrate an X-ray scintillation light yield of 31900 photons/MeV, higher than that of commercial LuAG:Ce (22000 photons/MeV); electrically driven light-emitting diodes fabricated with Cs3CeCl6·3H2O nanocrystals yield the characteristic emission of Ce3+, indicating their potential use in next-generation violet-light-emitting devices.
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Formaldehyde (FA) is a carcinogen that is not only widespread in the environment, but is also produced endogenously by metabolic processes. In organisms, FA is converted to formic acid in a glutathione (GSH)-dependent manner by alcohol dehydrogenase 5 (ADH5). The abnormal accumulation of FA in the body can cause a variety of diseases, especially cognitive impairment leading to Alzheimer's disease (AD). In this study, melatonin derivative 6a (MD6a) markedly improved the survival and chemotactic performance of wild-type Caenorhabditis elegans exposed to high concentrations of FA. MD6a lowered FA levels in the nematodes by enhancing the release of covalently-bound GSH from S-hydroxymethyl-GSH in an adh-5-dependent manner. In addition, MD6a protected against mitochondrial dysfunction and cognitive impairment in beta-amyloid protein (Aß) transgenic nematodes by lowering endogenous FA levels and reducing Aß aggregation in an adh-5-dependent manner. Our findings suggest that MD6a detoxifies FA via ADH5 and protects against Aß toxicity by reducing endogenous FA levels in the C. elegans AD models. Thus, ADH5 might be a potential therapeutic target for FA toxicity and AD.
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This work presents an accurate and efficient method, for solving a two dimensional time-fractional Oldroyd-B fluid model. The proposed method couples the Laplace transform (LT) with a radial basis functions based local meshless method (LRBFM). The suggested numerical scheme first uses the LT which transform the given equation to an elliptic equation in LT space, and then it utilizes the LRBFM to solve transformed equation in LT space, and then the solution is converted back into the time domain via the improved Talbot's scheme. The local meshless methods are widely recognized for scattered data interpolation and for solving PDEs in complex shaped domains. The adaptability, simplicity, and ease of use are features that have led to the popularity of local meshless methods. The local meshless methods are easy and straightforward, they only requires to solve linear system of equations. The main objective of using the LT is to avoid the computation of costly convolution integral in time-fractional derivative and the effect of time stepping on accuracy and stability of numerical solution. The stability and the convergence of the proposed numerical scheme are discussed. Further, the Ulam-Hyers (UH) stability of the proposed model is discussed. The accuracy and efficiency of the suggested numerical approach have been demonstrated using numerical experiments on five different domains with regular nodes distribution.