Development of a rapid screening method utilizing 2D LC for effect-directed analysis in the identification of environmental toxicants.

Effect-directed analysis (EDA) is a crucial tool in environmental toxicology, effectively integrating toxicity testing with chemical analysis. The conventional EDA approach, however, presents challenges such as significant solvent consumption, extended analysis time, labor intensity, and potential contamination risks. In response, we introduce an innovative alternative to the conventional EDA. This method utilizes the MTT bioassay and online two-dimensional liquid chromatography (2D LC) coupled with high-resolution mass spectrometry (HR-MS), significantly reducing the fractionation steps and leveraging the enhanced sensitivity of the bioassay and automated chemical analysis. In the chemical analysis phase, a switching valve interface is employed for comprehensive analysis. We tested the performance of both the conventional and our online 2D LC-based methods using a household product. Both methods identified the same number of toxicants in the sample. Our alternative EDA is 22.5 times faster than the conventional method, fully automated, and substantially reduces solvent consumption. This novel approach offers ease, cost-effectiveness, and represents a paradigm shift in EDA methodologies. By integrating a sensitive bioassay with online 2D LC, it not only enhances efficiency but also addresses the challenges associated with traditional methods, marking a significant advancement in environmental toxicology research.

Optimization, Metabolomic Analysis, Antioxidant Potential andDepigmenting Activity of Polyphenolic Compounds fromUnmature Ajwa Date Seeds (Phoenix dactylifera L.) Using Ultrasonic-Assisted Extraction.

This study sought to optimize the ultrasonic-assisted extraction of polyphenolic compounds from unmature Ajwa date seeds (UMS), conduct untargeted metabolite identification and assess antioxidant and depigmenting activities. Response surface methodology (RSM) utilizing the Box-Behnken design (BBD) and artificial neural network (ANN) modeling was applied to optimize extraction conditions, including the ethanol concentration, extraction temperature and time. The determined optimal conditions comprised the ethanol concentration (62.00%), extraction time (29.00 min), and extraction temperature (50 °C). Under these conditions, UMS exhibited total phenolic content (TPC) and total flavonoid content (TFC) values of 77.52 ± 1.55 mgGAE/g and 58.85 ± 1.12 mgCE/g, respectively, with low relative standard deviation (RSD%) and relative standard error (RSE%). High-resolution mass spectrometry analysis unveiled the presence of 104 secondary metabolites in UMS, encompassing phenols, flavonoids, sesquiterpenoids, lignans and fatty acids. Furthermore, UMS demonstrated robust antioxidant activities in various cell-free antioxidant assays, implicating engagement in both hydrogen atom transfer and single electron transfer mechanisms. Additionally, UMS effectively mitigated tert-butyl hydroperoxide (t-BHP)-induced cellular reactive oxygen species (ROS) generation in a concentration-dependent manner. Crucially, UMS showcased the ability to activate mitogen-activated protein kinases (MAPKs) and suppress key proteins including tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and -2) and microphthalmia-associated transcription factor (MITF), which associated melanin production in MNT-1 cell. In summary, this study not only optimized the extraction process for polyphenolic compounds from UMS but also elucidated its diverse secondary metabolite profile. The observed antioxidant and depigmenting activities underscore the promising applications of UMS in skincare formulations and pharmaceutical developments.

Biological activities, identification, method development, and validation for analysis of polyphenolic compounds in Nymphaea rubra flowers and leaves by UHPLC-Q-cIM-TOF-MS and UHPLC-TQ-MS.

INTRODUCTION: Nymphaea rubra belongs to the Nymphaea family and is regarded as a vegetable used in traditional medicine to cure several ailments. These species are rich in phenolic acid, flavonoids, and hydrolysable tannin. OBJECTIVE: This study aimed to assess the biological activities of Nymphaea rubra flowers (NRF) and leaves (NRL) by identifying and quantifying their polyphenolic compounds using ultra-performance liquid chromatography coupled to quadrupole cyclic ion mobility time-of-flight mass spectrometry (UHPLC-Q-cIM-TOF-MS) and triple quadrupole mass spectrometry (UHPLC-TQ-MS). METHODOLOGY: NRF and NRL powder was extracted with methanol and fractionated using hexane, ethylacetate, and water. Antioxidant and α-glucosidase, and tyrosinase enzyme inhibitory activities were evaluated. The polyphenolic components of NRF and NRL were identified and quantified using UHPLC-Q-cIM-TOF-MS and UHPLC-TQ-MS. The method was validated using linearity, precision, accuracy, limit of detection (LOD), and lower limit of quantification (LLOQ). RESULTS: Bioactive substances and antioxidants were highest in the ethylacetate fraction of flowers and leaves. Principal component analysis showed how solvent and plant components affect N. rubra's bioactivity and bioactive compound extraction. A total of 67 compounds were identified, and among them 21 significant polyphenols were quantified. Each calibration curve had R2 > 0.998. The LOD and LLOQ varied from 0.007 to 0.09 µg/mL and from 0.01 to 0.1 µg/mL, respectively. NRF contained a significant amount of gallic acid (10.1 mg/g), while NRL contained abundant pentagalloylglucose (2.8 mg/g). CONCLUSION: The developed method is simple, rapid, and selective for the identification and quantification of bioactive molecules. These findings provide a scientific basis for N. rubra's well-documented biological effects.

Enzymatic Activity and Amino Acids Production of Predominant Fungi from Traditional Meju during Soybean Fermentation.

To investigate the effect of the predominant fungal species from Korean traditional meju and doenjang on soybean fermentation, the enzymatic activity and amino acid production of twenty-two fungal strains were assessed through solid- and liquid-state soybean fermentation. Enzymatic activity analyses of solid-state fermented soybeans revealed different enzyme activities involving protease, leucine aminopeptidase (LAP), carboxypeptidase (CaP), glutaminase, γ-glutamyl transferase (GGT), and amylase, depending on the fungal species. These enzymatic activities significantly affected the amino acid profile throughout liquid-state fermentation. Strains belonging to Mucoromycota, including Lichtheimia, Mucor, Rhizomucor, and Rhizopus, produced smaller amounts of total amino acids and umami-producing amino acids, such as glutamic acid and aspartic acid, than strains belonging to Aspergillus subgenus circumdati. The genera Penicillium and Scopulariopsis produced large amounts of total amino acids and glutamic acid, suggesting that these genera play an essential role in producing umami and kokumi tastes in fermented soybean products. Strains belonging to Aspergillus subgenus circumdati, including A. oryzae, showed the highest amino acid content, including glutamic acid, suggesting the potential benefits of A. oryzae as a starter for soybean fermentation. This study showed the potential of traditional meju strains as starters for soybean fermentation. However, further analysis of processes such as the production of G-peptide for kokumi taste and volatile compounds for flavor and safety is needed.

Development and evaluation of a forensic nursing competency-based hybrid simulation education program: A quasi-experimental design.

AIM: This study aimed to develop and validate the effectiveness of a hybrid simulation education program designed to enhance the forensic nursing competency of emergency department nurses. BACKGROUND: Emergency nurses often bear the responsibility of conducting forensic nursing assessments and interventions, such as patient recognition and evidence collection, to safeguard patients' legal rights, given their frequent encounters with emergency department patients. Simulation methods have proven effective in training for forensic nursing care. However, there is still a need for the development of forensic nursing education using simulation methods. DESIGN: This study employed a one-group pre-test/post-test quasi-experimental design. A four-hour simulation education program was developed based on the analysis, design, development, implementation, and evaluation model, with a focus on enhancing forensic nursing competency. METHODS: Nurses with more than six months of clinical experience in the emergency department in South Korea were divided into an experimental group (n=23) and a baseline comparison group (n=24). Both groups completed self-evaluations of their forensic nursing competency through a survey. The experimental group underwent the simulation education program, and their forensic nursing performance was evaluated before and after the program. Following the training, participants completed a questionnaire to assess their forensic nursing competency and satisfaction with the program. RESULTS: The initial forensic nursing competency of the experimental and baseline comparison groups was found to be similar. However, the forensic nursing competency and performance of the experimental group exhibited significant improvement after the training. Regarding program evaluation, the average scores on a 5-point scale were as follows: theoretical lecture (4.79 SD 0.27), simulation education (4.78 SD 0.29), simulation design (4.42 SD 0.45), and satisfaction with the educational program (4.82 SD 0.28). CONCLUSIONS: The forensic nursing competency-based simulation education program herein improved the relevant competency and performance of emergency nurses.

Organometal Halide Perovskite-Based Photoelectrochemical Module Systems for Scalable Unassisted Solar Water Splitting.

Despite achievements in the remarkable photoelectrochemical (PEC) performance of photoelectrodes based on organometal halide perovskites (OHPs), the scaling up of small-scale OHP-based PEC systems to large-scale systems remains a great challenge for their practical application in solar water splitting. Significant resistive losses and intrinsic defects are major obstacles to the scaling up of OHP-based PEC systems, leading to the PEC performance degradation of large-scale OHP photoelectrodes. Herein, a scalable design of the OHP-based PEC systems by modularization of the optimized OHP photoelectrodes exhibiting a high solar-to-hydrogen conversion efficiency of 10.4% is suggested. As a proof-of-concept, the OHP-based PEC module achieves an optimal PEC performance by avoiding major obstacles in the scaling up of the OHP photoelectrodes. The constructed OHP module is composed of a total of 16 OHP photoelectrodes, and a photocurrent of 11.52 mA is achieved under natural sunlight without external bias. The successful operation of unassisted solar water splitting using the OHP module without external bias can provide insights into the design of scalable OHP-based PEC systems for future practical application and commercialization.

Profiling of Secondary Metabolites of Optimized Ripe Ajwa Date Pulp (Phoenix dactylifera L.) Using Response Surface Methodology and Artificial Neural Network.

The date palm (Phoenix dactylifera L.) is a popular edible fruit consumed all over the world and thought to cure several chronic diseases and afflictions. The profiling of the secondary metabolites of optimized ripe Ajwa date pulp (RADP) extracts is scarce. The aim of this study was to optimize the heat extraction (HE) of ripe Ajwa date pulp using response surface methodology (RSM) and artificial neural network (ANN) modeling to increase its polyphenolic content and antioxidant activity. A central composite design was used to optimize HE to achieve the maximum polyphenolic compounds and antioxidant activity of target responses as a function of ethanol concentration, extraction time, and extraction temperature. From RSM estimates, 75.00% ethanol and 3.7 h (extraction time), and 67 °C (extraction temperature) were the optimum conditions for generating total phenolic content (4.49 ± 1.02 mgGAE/g), total flavonoid content (3.31 ± 0.65 mgCAE/g), 2,2-diphenyl-1-picrylhydrazyl (11.10 ± 0.78 % of inhibition), and cupric-reducing antioxidant capacity (1.43 µM ascorbic acid equivalent). The good performance of the ANN was validated using statistical metrics. Seventy-one secondary metabolites, including thirteen new bioactive chemicals (hebitol II, 1,2-di-(syringoyl)-hexoside, naringin dihydrochalcone, erythron-guaiacylglycerol-ß-syringaresinol ether hexoside, erythron-1-(4'-O-hexoside-3,5-dimethoxyphenyl)-2-syrngaresinoxyl-propane-1,3-diol, 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid, linustatin and 1-deoxynojirimycin galactoside), were detected using high-resolution mass spectroscopy. The results revealed a significant concentration of phytoconstituents, making it an excellent contender for the pharmaceutical and food industries.

Identification and quantification of photodegradation products of disposed expanded polystyrene buoy used in aquaculture.

This study investigated the chemicals extracted from an EPS buoy used in aquaculture, which were subsequently collected from a recycling center. It was observed that the chemicals generated upon photodegradation make disposed buoys more toxic. Analysis of the extracted chemicals revealed the presence of 37 compounds, with four compounds quantitatively determined. Further analysis showed that the quantity of compounds dissolved in seawater was significantly higher than the amount remaining on the buoy surface. Based on the assumption that the buoy was exposed to sunlight for a year, it was estimated that 14.44 mg of the four compounds dissolved into the ocean. Given that South Korea used over 7 million EPS buoys, photodegraded EPS buoys are expected to represent a significant source of potentially hazardous chemicals.

Tyrosinase inhibitory activity of Sargassum fusiforme and characterisation of bioactive compounds.

INTRODUCTION: Sargassum fusiforme (Harvey) Setchell, also known as Tot (in Korean) and Hijiki (in Japanese), is widely consumed in Korea, Japan, and China due to its health promoting properties. However, the bioactive component behind the biological activity is still unknown. OBJECTIVES: We aimed to optimise the extraction conditions for achieving maximum tyrosinase inhibition activity by using two sophisticated statistical tools, that is, response surface methodology (RSM) and artificial neural network (ANN). Moreover, high-resolution mass spectrometry (HRMS) was used to tentatively identify the components, which are then further studied for molecular docking study using 2Y9X protein. METHODOLOGY: RSM central composite design was used to conduct extraction using microwave equipment, which was then compared to ANN. Electrospray ionisation tandem mass spectrometry (ESI-MS/MS) was used to tentatively identify bioactive components, which were then docked to the 2Y9X protein using AutoDock Vina and MolDock software. RESULTS: Maximum tyrosinase inhibition activity of 79.530% was achieved under optimised conditions of time: 3.27 min, temperature: 128.885°C, ethanol concentration: 42.13%, and microwave intensity: 577.84 W. Furthermore, 48 bioactive compounds were tentatively identified in optimised Sargassum fusiforme (OSF) extract, and among them, seven phenolics, five flavonoids, five lignans, six terpenes, and five sulfolipids and phospholipids were putatively reported for the first time in Sargassum fusiforme. Among 48 bioactive components, trifuhalol-A, diphlorethohydroxycarmalol, glycyrrhizin, and arctigenin exhibited higher binding energies for 2Y9X. CONCLUSION: Taken together, these findings suggest that OSF extract can be used as an effective skin-whitening source on a commercial level and could be used in topical formulations by replacing conventional drugs.

Photoelectrochemical Selective Oxidation of Glycerol to Glyceraldehyde with Bi-Based Metal-Organic-Framework-Decorated WO3 Photoanode.

The conversion of glycerol to high-value-added products via photoelectrochemical (PEC) oxidation has emerged as a promising approach for utilizing a sustainable and clean energy source with environmental and economic benefits. Moreover, the energy requirement for glycerol to produce hydrogen is lower than that for pure water splitting. In this study, we propose the use of WO3 nanostructures decorated with Bi-based metal-organic frameworks (Bi-MOFs) as the photoanode for glycerol oxidation with simultaneous hydrogen production. The WO3-based electrodes selectively converted glycerol to glyceraldehyde, a high-value-added product, with remarkable selectivity. The Bi-MOF-decorated WO3 nanorods enhanced the surface charge transfer and adsorption properties, thereby improving the photocurrent density and production rate (1.53 mA/cm2 and 257 mmol/m2·h at 0.8 VRHE). The photocurrent was maintained for 10 h, ensuring stable glycerol conversion. Furthermore, at 1.2 VRHE, the average production rate of glyceraldehyde reached 420 mmol/m2·h, with a selectivity of 93.6% between beneficial oxidized products over the photoelectrode. This study provides a practical approach for the conversion of glycerol to glyceraldehyde via the selective oxidation of WO3 nanostructures and demonstrates the potential of Bi-MOFs as a promising cocatalyst for PEC biomass valorization.

Concurrent induction of apoptosis and necroptosis in apigenin­treated malignant mesothelioma cells: Reversal of Warburg effect through Akt inhibition and p53 upregulation.

A high dependence on aerobic glycolysis, known as the Warburg effect, is one of the metabolic features exhibited by tumor cells. Therefore, targeting glycolysis is becoming a very promising strategy for the development of anticancer drugs. In the present study, it was investigated whether pre­adaptation of malignant mesothelioma (MM) cells to an acidic environment was associated with a metabolic shift to the Warburg phenotype in energy production, and whether apigenin targets acidosis­driven metabolic reprogramming. Cell viability, glycolytic activity, Annexin V­PE binding activity, reactive oxygen species (ROS) levels, mitochondrial membrane potential, ATP content, western blot analysis and spheroid viability were assessed in the present study. MM cells pre­adapted to lactic acid were resistant to the anticancer drug gemcitabine, increased Akt activation, downregulated p53 expression, and upregulated rate­limiting enzymes in glucose metabolism compared with their parental cells. Apigenin treatment increased cytotoxicity, Akt inactivation and p53 upregulation. Apigenin also reduced glucose uptake along with downregulation of key regulatory enzymes in glycolysis, increased ROS levels with loss of mitochondrial membrane potential, and downregulated the levels of complexes I, III and IV in the mitochondrial electron transport chain with intracellular ATP depletion, resulting in upregulation of molecules mediating apoptosis and necroptosis. Apigenin­induced alterations of cellular responses were similar to those of Akt inactivation by Ly294002. Overall, the present results provide mechanistic evidence supporting the anti­glycolytic and cytotoxic role of apigenin via inhibition of the PI3K/Akt signaling pathway and p53 upregulation.

Sudden Death Associated With Possible Flare-Ups of Multiple Sclerosis After COVID-19 Vaccination and Infection: A Case Report and Literature Review.

We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.

Ultrahigh dielectric permittivity in oxide ceramics by hydrogenation.

Boosting dielectric permittivity representing electrical polarizability of dielectric materials has been considered a keystone for achieving scientific breakthroughs as well as technological advances in various multifunctional devices. Here, we demonstrate sizable enhancements of low-frequency dielectric responses in oxygen-deficient oxide ceramics through specific treatments under humid environments. Ultrahigh dielectric permittivity (~5.2 × 106 at 1 Hz) is achieved by hydrogenation, when Ni-substituted BaTiO3 ceramics are exposed to high humidity. Intriguingly, thermal annealing can restore the dielectric on-state (exhibiting huge polarizability in the treated ceramics) to the initial dielectric off-state (displaying low polarizability of ~103 in the pristine ceramics after sintering). The conversion between these two dielectric states via the ambient environment-mediated treatments and the successive application of external stimuli allows us to realize reversible control of dielectric relaxation characteristics in oxide ceramics. Conceptually, our findings are of practical interest for applications to highly efficient dielectric-based humidity sensors.

Antioxidant, Tyrosinase, α-Glucosidase, and Elastase Enzyme Inhibition Activities of Optimized Unripe Ajwa Date Pulp (Phoenix dactylifera) Extracts by Response Surface Methodology.

The Ajwa date (Phoenix dactylifera L., Arecaceae family) is a popular edible fruit consumed all over the world. The profiling of the polyphenolic compounds of optimized unripe Ajwa date pulp (URADP) extracts is scarce. The aim of this study was to extract polyphenols from URADP as effectively as possible by using response surface methodology (RSM). A central composite design (CCD) was used to optimize the extraction conditions with respect to ethanol concentration, extraction time, and temperature and to achieve the maximum amount of polyphenolic compounds. High-resolution mass spectrometry was used to identify the URADP's polyphenolic compounds. The DPPH-, ABTS-radical scavenging, α-glucosidase, elastase and tyrosinase enzyme inhibition of optimized extracts of URADP was also evaluated. According to RSM, the highest amounts of TPC (24.25 ± 1.02 mgGAE/g) and TFC (23.98 ± 0.65 mgCAE/g) were obtained at 52% ethanol, 81 min time, and 63 °C. Seventy (70) secondary metabolites, including phenolic, flavonoids, fatty acids, and sugar, were discovered using high-resolution mass spectrometry. In addition, twelve (12) new phytoconstituents were identified for the first time in this plant. Optimized URADP extract showed inhibition of DPPH-radical (IC50 = 87.56 mg/mL), ABTS-radical (IC50 = 172.36 mg/mL), α-glucosidase (IC50 = 221.59 mg/mL), elastase (IC50 = 372.25 mg/mL) and tyrosinase (IC50 = 59.53 mg/mL) enzymes. The results revealed a significant amount of phytoconstituents, making it an excellent contender for the pharmaceutical and food industries.

Antioxidant Potential-Rich Betel Leaves (Piper betle L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In Vivo.

Each individual has a unique skin tone based on the types and quantities of melanin pigment, and oxidative stress is a key element in melanogenesis regulation. This research sought to understand the in vitro and in vivo antioxidant and depigmenting properties of betel leaves (Piper betle L.) extract (PBL) and the underlying mechanism. Ethyl acetate fractions of PBL (PBLA) demonstrated excellent phenolic content (342 ± 4.02 mgGAE/g) and strong DPPH, ABTS radicals, and nitric oxide (NO) scavenging activity with an IC50 value of 41.52 ± 1.02 µg/mL, 45.60 ± 0.56 µg/mL, and 51.42 ± 1.25 µg/mL, respectively. Contrarily, ethanolic extract of PBL (PBLE) showed potent mushroom, mice, and human tyrosinase inhibition activity (IC50 = 7.72 ± 0.98 µg/mL, 20.59 ± 0.83 µg/mL and 24.78 ± 0.56 µg/mL, respectively). According to gas chromatography-mass spectrometry, PBL is abundant in caryophyllene, eugenol, O-eugenol, 3-Allyl-6-methoxyphenyl acetate, and chavicol. An in vitro and in vivo investigation showed that PBLE suppressed tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and Trp-2), and microphthalmia-associated transcription factors (MITF), decreasing the formation of melanin in contrast to the untreated control. PBLE reduced the cyclic adenosine monophosphate (cAMP) response to an element-binding protein (CREB) phosphorylation by preventing the synthesis of cAMP. Additionally, it activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38), destroying Tyr and MITF and avoiding melanin production. Higher levels of microtubule-associated protein-light chain 3 (LC3-II), autophagy-related protein 5 (Atg5), Beclin 1, and lower levels of p62 demonstrate that PBLE exhibits significant anti-melanogenic effects via an autophagy-induction mechanism, both in vitro and in vivo. Additionally, PBLE significantly reduced the amount of lipid peroxidation while increasing the activity of several antioxidant enzymes in vivo, such as catalase, glutathione, superoxide dismutase, and thioredoxin. PBLE can therefore be employed in topical formulations as a potent skin-whitening agent.

Metabolite profiling of Nymphaea rubra (Burm. f.) flower extracts using cyclic ion mobility-mass spectrometry and their associated biological activities.

Nymphaea rubra flowers (NRF) are widely used as a food and in folk medicine throughout the subtropical regions due to their health-promoting characteristics. This study characterized the phytochemical composition of various extracts/fractions of NRF by establishing a quadrupole-cyclic ion mobility-time-of-flight (Q-cIM-TOF) mass spectrometry method in both positive and negative electrospray ionization modes. Over 100 phytoconstituents were tentatively identified, among which 53 phytochemicals belonging to phenolic acids, tannins, flavonoids, terpenoids, alkaloids, xanthones, and naphthopyrones have never been documented in NRF before. Moreover, the ethyl acetate fraction of NRF demonstrated strong antioxidant potential (IC50: 9.21 ± 0.47 µg/mL in DPPH assay and 13.65 ± 0.03 µg/mL in ABTS assay) and tyrosinase, α-glucosidase, and elastase inhibition (IC50: 10.58 ± 0.20, 2.48 ± 0.02, and 38.15 ± 0.25 µg/mL, respectively). The findings highlight the value of NRF as a source of functional components and broaden its potential applications in the food and nutraceutical industries.

Metabolite Profiling of Microwave-Assisted Sargassum fusiforme Extracts with Improved Antioxidant Activity Using Hybrid Response Surface Methodology and Artificial Neural Networking-Genetic Algorithm.

Sargassum fusiforme (SF) is a popular edible brown macroalga found in Korea, Japan, and China and is known for its health-promoting properties. In this study, we used two sophisticated models to obtain optimized conditions for high antioxidant activity and metabolite profiling using high-resolution mass spectrometry. A four-factor central composite design was used to optimize the microwave-assisted extraction and achieve the maximum antioxidant activities of DPPH (Y1: 28.01 % inhibition), ABTS (Y2: 36.07 % inhibition), TPC (Y3: 43.65 mg GAE/g), and TFC (Y4: 17.67 mg CAE/g), which were achieved under the optimized extraction conditions of X1: 47.67 %, X2: 2.96 min, X3: 139.54 °C, and X4: 600.00 W. Moreover, over 79 secondary metabolites were tentatively identified, of which 12 compounds were reported for the first time in SF, including five phenolic (isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate, 3,4-dihydroxyphenylglycol, scopoletin, caffeic acid 4-sulfate, and cinnamoyl glucose), two flavonoids (4',7-dihydroxyisoflavone and naringenin), three phlorotannins (diphlorethohydroxycarmalol, dibenzodioxin-1,3,6,8-tetraol, and fucophlorethol), and two other compounds (dihydroxyphenylalanine and 5-hydroxybenzofuran-2(3H)-one) being identified for the first time in optimized SF extract. These compounds may also be involved in improving the antioxidant potential of the extract. Therefore, optimized models can provide better estimates and predictive capabilities that would assist in finding new bioactive compounds with improved biological activities that can be further applied at a commercial level.

ERK1/2-Dependent Inhibition of Glycolysis in Curcumin-Induced Cytotoxicity of Prostate Carcinoma Cells.

Methods: Cell viability, glycolytic activity, Annexin V-PE binding activity, reactive oxygen species levels, mitochondrial membrane potential, ATP content, Western blot analysis, and spheroid viability were measured for this study. Results: Acidic pH-tolerant prostate cancer cells, PC-3AcT and DU145AcT, increased cytotoxicity with ERK1/2 inhibition in a curcumin concentration-dependent manner at concentrations that resulted in >90% cell viability in normal prostate epithelial HPrEC cells. ERK1/2 inhibition by curcumin and/or PD98059 suppressed cell growth, reduced glucose consumption, and downregulated the expression of key regulatory enzymes in glucose metabolism including hexokinases, phosphofructokinase, and pyruvate dehydrogenase. In addition, these compounds caused loss of mitochondrial membrane potential with increased intracellular ROS levels, decreased levels of complexes I, III, and IV in the mitochondrial electron transport chain, and cellular ATP depletion, leading to upregulation of marker proteins in apoptosis (cleaved caspase-3 and cleaved PARP) and necroptosis (p-MLKL and p-RIP3). The results of curcumin and/or PD98059 treatment in 3D cultures showed similar trends to those in 2D cultures. Conclusion: Taken together, the results provide mechanistic evidence for the antiglycolytic and cytotoxic roles of curcumin through inhibition of the MEK/ERK signaling pathway in prostate carcinoma cells preadapted to acidic conditions.

Terpenoid-Rich Extract of Dillenia indica L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress.

Insulin resistance (IR) plays a key role in the pathogenesis and clinical outcome of patients with multiple diseases and diabetes. In this study, we examined the antidiabetic effects of a terpenoid-rich extract from Dillenia indica L. bark (TRDI) in palmitic acid-induced insulin resistance (PA-IR) in C2C12 myotube and a streptozotocin (STZ)-induced diabetic mice model and explored the possible underlying mechanism. TRDI showed potential DPPH- and ABTS-radical scavenging effects with a half-maximal inhibitory concentration (IC50) value of 9.76 ± 0.50 µg/mL and 17.47 ± 1.31 µg/mL, respectively. Furthermore, TRDI strongly mitigated α-glucosidase activity with an IC50 value of 3.03 ± 1.01 µg/mL, which was 92-fold higher than the positive control, acarbose (IC50 = 279.49 ± µg/mL). TRDI stimulated the insulin receptor substrarte-1 (INS-1), downregulated phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (Akt) in both normal and PA-IR C2C12 cells as well as in STZ-induced diabetic mice, enhanced glucose transporter 4 (GLUT4) translocation to the plasma membrane (PM), and increased glucose absorption. Furthermore, TRDI administration significantly reduced PA-induced reactive oxygen species (ROS) formation in C2C12 cells and increased the protein level of numerous antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase-1 (GPx-1) and thioredoxin reductase (TrxR) both in vitro and in vivo. Furthermore, TRDI facilitated nuclear factor erythroid 2 related factor 2 (Nrf2) nuclear translocation and increased HO-1 expression in PA-IR C2C12 cells and STZ-induced diabetic mice. However, for the inhibition of Nrf2, TRDI failed to resist the effects of IR. Thus, this study provides new evidence to support the use of TRDI for diabetes treatment.

Nonvolatile Control of Metal-Insulator Transition in VO2 by Ferroelectric Gating.

Controlling phase transitions in correlated materials yields emergent functional properties, providing new aspects to future electronics and a fundamental understanding of condensed matter systems. With vanadium dioxide (VO2 ), a representative correlated material, an approach to control a metal-insulator transition (MIT) behavior is developed by employing a heteroepitaxial structure with a ferroelectric BiFeO3 (BFO) layer to modulate the interaction of correlated electrons. Owing to the defect-alleviated interfaces, the enhanced coupling between the correlated electrons and ferroelectric polarization is successfully demonstrated by showing a nonvolatile control of MIT of VO2 at room temperature. The ferroelectrically-tunable MIT can be realized through the Mott transistor (VO2 /BFO/SrRuO3 ) with a remanent polarization of 80 µC cm-2 , leading to a nonvolatile MIT behavior through the reversible electrical conductance with a large on/off ratio (≈102 ), long retention time (≈104 s), and high endurance (≈103 cycles). Furthermore, the structural phase transition of VO2 is corroborated by ferroelectric polarization through in situ Raman mapping analysis. This study provides novel design principles for heteroepitaxial correlated materials and innovative insight to modulate multifunctional properties.