Molecules, Volume 28, Issue 14 (July-2 2023) – 331 articles

This research presents a novel, eco-friendly, vortex-assisted liquid–liquid microextraction (VALLME) approach, integrating hydrophobic deep eutectic solvents (DESs) with HPLC for the identification and quantification of nine specific flavonoids in Shanxi aged vinegar (SAV). The parameters of DES-VALLME, including the ratio of trioctylmethylammonium chloride to 1,4-butanediol (1:6), DES volume (150 μL), vortex duration (5 min), the concentration of NaCl (0.40 g), and centrifugation time (10 min), were optimized to achieve the maximum extraction efficiency of target substances. Under these optimal conditions, quantitative analyses performed via HPLC demonstrated a broad linear range of 0.20–50.00 μg/mL and correlation coefficients (r²) greater than 0.9944 for all nine calibration curves. The limits of detection (LOD) and limits of quantitation (LOQ) were 0.09–0.18 μg/mL and 0.30–0.60 μg/mL, respectively, ensuring high sensitivity. The relative standard deviations for intra-day and inter-day variability were within the acceptable range, 2.34–3.77% and 3.04–4.96%, respectively, demonstrating the method’s reliability. The recovery rates ranged from 85.97% to 108.11%, underscoring the method’s precision. This technique exhibited a significant enrichment effect (enrichment factor: 43 to 296) on SAV flavonoids. Notably, the eco-friendliness of this procedure was evaluated using the Analytical Eco-Scale, Green Analytical Procedure Index, and Analytical Greenness Metric. The results suggested that this technique is a viable green alternative to traditional flavonoid determination methods in SAV. In summary, this novel method provides a theoretical basis for assessing flavonoid content in SAV samples and tracing SAV products. This contribution has significant implications for enhancing analytical techniques in food chemistry and environmental science and the sustainable development of the food industry. Full article

The performance of lead-acid batteries could be significantly increased by incorporating carbon materials into the negative electrodes. In this study, a modified carbon material developed via a simple high-temperature calcination method was employed as a negative electrode additive, and we have named it as follows: N-doped chitosan-derived carbon (NCC). The performance of this material was compared with a control battery containing activated carbon (AC). X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy were engaged in analyzing the crystal structure and morphology of the material. Afterwards, the electrochemical and battery performance was examined through cyclic voltammetry (CV), linear voltammetry (LSV) and constant current charge-discharge testing. Markedly, the electrode plate containing 1 wt.% NCC indicates the highest specific capacity (106.48 F g⁻¹) as compared to the control battery, which is 1.56 times higher than the AC electrode plate and 4.75 times higher than the blank electrode plate. The linear voltammetry shows that the hydrogen precipitation current density of the 1 wt.% NCC electrode plate is only −0.028 A cm⁻², a much higher value than that of the AC electrode plate. In addition, the simulated battery containing 1 wt.% NCC has a cycle life of 4324 cycles, which is 2.36 times longer than that of the same amount of additive AC battery (1834 cycles) and 5.34 times longer than that of the blank battery (809 cycles). In summary, NCC carbon has the advantage of extending the life of lead-acid batteries, rendering it a promising candidate for lead-acid battery additives. Full article

Lignocellulosic biomasses have a complex and compact structure, requiring physical and/or chemical pretreatments to produce glucose before hydrolysis. Mathematical modeling of enzymatic hydrolysis highlights the interactions between cellulases and cellulose, evaluating the factors contributing to reactor scale-up and conversion rates. Furthermore, this study evaluated the influence of two pretreatments (hydrothermal and organosolv) on the kinetics of enzymatic hydrolysis of sugarcane bagasse. The kinetic parameters of the model were estimated using the Pikaia genetic algorithm with data from the experimental profiles of cellulose, cellobiose, glucose, and xylose. The model considered the phenomenon of non-productive adsorption of cellulase on lignin and inhibition of cellulase by xylose. Moreover, it included the behavior of cellulase adsorption on the substrate throughout hydrolysis and kinetic equations for obtaining xylose from xylanase-catalyzed hydrolysis of xylan. The model for both pretreatments was experimentally validated with bagasse concentration at 10% w/v. The Plackett–Burman design identified 17 kinetic parameters as significant in the behavior of process variables. In this way, the modeling and parameter estimation methodology obtained a good fit from the experimental data and a more comprehensive model. Full article

Sedatives promote calmness or sleepiness during surgery or severely stressful events. In addition, depression is a mental health issue that negatively affects emotional well-being. A group of drugs called anti-depressants is used to treat major depressive illnesses. The aim of the present work was to evaluate the effects of quercetin (QUR) and linalool (LIN) on thiopental sodium (TS)-induced sleeping mice and to investigate the combined effects of these compounds using a conventional co-treatment strategy and in silico studies. For this, the TS-induced sleeping mice were monitored to compare the occurrence, latency, and duration of the sleep-in response to QUR (10, 25, 50 mg/kg), LIN (10, 25, 50 mg/kg), and diazepam (DZP, 3 mg/kg, i.p.). Moreover, an in silico investigation was undertaken to assess this study’s putative modulatory sedation mechanism. For this, we observed the ability of test and standard medications to interact with various gamma-aminobutyric acid A receptor (GABA_A) subunits. Results revealed that QUR and LIN cause dose-dependent antidepressant-like and sedative-like effects in animals, respectively. In addition, QUR-50 mg/kg and LIN-50 mg/kg and/or DZP-3 mg/kg combined were associated with an increased latency period and reduced sleeping times in animals. Results of the in silico studies demonstrated that QUR has better binding interaction with GABA_A α3, β1, and γ2 subunits when compared with DZP, whereas LIN showed moderate affinity with the GABA_A receptor. Taken together, the sleep duration of LIN and DZP is opposed by QUR in TS-induced sleeping mice, suggesting that QUR may be responsible for providing sedation-antagonizing effects through the GABAergic interaction pathway. Full article

A catalyst-free aza-Michael addition/C(sp³)-O bond formation tandem reaction of substituted amino ferrocenes with quinone esters was developed, which provided a green and efficient strategy for the construction of a C(sp³)-O bond from C(sp³)-H, and a series of N-ferrocene-substituted benzodihydrooxazoles were smoothly produced in moderate to excellent yields (up to >99% yield). The mechanism experiments showed that quinone esters performed as both substrate and oxidant. The salient features of this transformation include good functional group tolerance, broad substrate scope and mild conditions. Full article

Alzheimer’s disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial origin, current targeted treatments have only managed to reduce or control symptoms, and to date, only two drugs are close to being able to halt its progression. For decades, natural compounds produced by living organisms have been at the forefront of research for new therapies. Mushrooms, which are well-known for their nutritional and medicinal properties, have also been studied for their potential use in the treatment of AD. Natural products derived from mushrooms have shown to be beneficial in several AD-related mechanisms, including the inhibition of acetylcholinesterase (AChE) and β-secretase (BACE 1); the prevention of amyloid beta (Aβ) aggregation and neurotoxicity; and the prevention of Tau expression and aggregation, as well as antioxidant and anti-inflammatory potential. Several studies in the literature relate mushrooms to neurodegenerative diseases. However, to the best of our knowledge, there is no publication that summarizes only AD data. In this context, this review aims to link the therapeutic potential of mushrooms to AD by compiling the anti-AD potential of different mushroom extracts or isolated compounds, targeting known AD-related mechanisms. Full article

Metal-organic frameworks—through the use of creative synthetic designs—could produce MOF materials with excellent porosity, stability, particle microstructures, and conductivity, and their inherent characteristics—including their porosity and controllable structure—may result in an immense number of prospects for energy storage. In this paper, a nanosphere-like NiCo-MOF was effectively manufactured via an ultra-fast microwave technique. Additionally, the ideal synthesis conditions of the NiCo-MOF were investigated by adjusting the microwave output power and microwave reaction time. Under the reaction conditions of a 600 W microwave and a 210 s microwave reaction time, the NiCo-MOF exhibited an excellent capacitance of 1348 F/g at a current density of 1 A/g and an 86.1% capacity retention rate at 10 A/g. In addition, self-assembled NiCo-MOF/AC asymmetric capacitors showed a splendid energy density of 46.6 Wh/kg and a power density of 8000 W/kg. Full article

Eriobotrya japonica (loquat tree) has been used in traditional medicine to treat respiratory ailments, inflammation, and skin diseases; however, its potential antidepressant-like effects have not been extensively investigated. In this study, we evaluated the antidepressant-like effects of E. japonica fruit extract (EJFE) in a mouse model of corticosterone (CORT)-induced depression. An HPLC analysis revealed that chlorogenic acid (CGA) is the major compound in EJFE. Male ICR mice (5weeks-old) were injected with CORT (40 mg/kg, intraperitoneally) once daily for 21 days to induce depressive-like behaviors. Various behavioral tests, including the open field test, rotarod test, elevated plus maze (EPM), passive avoidance test (PAT), tail suspension test (TST), and forced swim test (FST), were conducted 1 h after the oral administration of EJFE at different doses (30, 100, and 300 mg/kg) and CGA (30 mg/kg). High-dose EJFE and CGA significantly alleviated CORT-induced depressive-like behaviors, as indicated by the reduced immobility times in the TST and FST. A decrease in the step-through latency time in the PAT, without an effect on locomotor activity, suggested an improvement in cognitive function. Moreover, EJFE- and CGA-treated mice exhibited significantly reduced anxiety-like behaviors in the EPM. Our results imply the promising potential of EJFE containing CGA as a therapeutic candidate for depression. Full article

The demand of plant production product use has increased because of the current system of citrus production, which prioritizes high agricultural yields. Therefore, the monitoring of pesticide residues in citrus fruits and other agricultural products and their impacts on human health and food security are of great concern. This study aims to determine multi-class pesticides including highly polar residues in satsuma mandarins. A total of 226 mandarin samples were collected over three consecutive harvesting years from 2019 to 2021 in the Izmir region of Turkey. Targeted compounds included pesticides and metabolites with European Union (EU) regulatory levels, plus other non-approved residues and highly polar compounds. The residues excluding highly polar substances were analyzed by applying the quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction and liquid chromatography–triple quadrupole mass spectrometry (LC-MS/MS) determination for 434 analytes and gas chromatography–triple quadrupole mass spectrometry (GC-MS/MS) determination for 71 analytes. For six highly polar pesticides, sample preparation was based on Quick Polar Pesticides (QuPPe) extraction. The polar residues were determined by LC-MS/MS using internal standards. Forty different residues, including two highly polar substances, were recorded in mandarin samples through three harvesting years. In 8.4% of the samples, no quantifiable residues were detected, whereas 207 samples contained at least one residue. The maximum residue level (MRL) exceedances were recorded for 22.1% of the samples. The two most frequently found pesticides were phosphonic acid and spirotetramat, with an incidence rate of 48.7% and 46.5%, respectively. The concentration of phosphonic acid and spirotetramat in mandarin samples varied from 0.026 to 39.386 mg kg⁻¹ and from 0.010 to 1.485 mg kg⁻¹, respectively. The results will enable researchers and regulatory authorities to assess the extent of pesticide presence, identify potential risks, and take necessary measures to ensure the safety of satsuma mandarins for consumers. Full article

Tumor immunotherapy, compared with other treatment strategies, has the notable advantage of a long-term therapeutic effect for preventing metastasis and the recurrence of tumors, thus holding great potential for the future of advanced tumor therapy. However, due to the poor water solubility of immune modulators and immune escape properties of tumor cells, the treatment efficiency of immunotherapy is usually significantly reduced. Cyclodextrin (CD) has been repeatedly highlighted to be probably one of the most investigated building units for cancer therapy due to its elegant integration of an internal hydrophobic hollow cavity and an external hydrophilic outer surface. The application of CD for immunotherapy provides new opportunities for overcoming the aforementioned obstacles. However, there are few published reviews, to our knowledge, summarizing the use of CD for cancer immunotherapy. For this purpose, this paper provides a comprehensive summary on the application of CD for immunotherapy with an emphasis on the role, function, and reported strategies of CD in mediating immunotherapy. This review summarizes the research progress made in using CD for tumor immunotherapy, which will facilitate the generation of various CD-based immunotherapeutic delivery systems with superior anticancer efficacy. Full article

A chitosan/poly(vinyl alcohol)-stabilized copper nanoparticle (CP@Cu NPs) was used as a heterogeneous catalyst for the borylation of α, β-unsaturated ketones, MBH alcohols, and MBH esters in mild conditions. This catalyst not only demonstrated remarkable efficiency in synthesizing organoboron compounds but also still maintained excellent reactivity and stability even after seven recycled uses of the catalyst. This methodology provides a gentle and efficient approach to synthesize the organoboron compounds by efficiently constructing carbon–boron bonds. Full article

To study the use of partial or total potassium bicarbonate (PBC) to replace sodium tripolyphosphate (STPP) on reduced-phosphate silver carp batters, all the batters were composed of silver carp surimi, pork back fat, ice water, spices, sugar, and sodium chloride. Therein, the sample of T1 contained 4 g/kg STPP; T2 contained 1 g/kg PBC, 3 g/kg STPP; T3 contained 2 g/kg PBC, 2 g/kg STPP; T4 contained 3 g/kg PBC, 1 g/kg STPP; T5 contained 4 g/kg PBC, and they were all produced using a bowl chopper. The changes in pH, whiteness, water- and oil-holding capacity, gel and rheological properties, as well as protein conformation were investigated. The pH, cooking yield, water- and oil-holding capacity, texture properties, and the G′ values at 90 °C of the reduced-phosphate silver carp batters with PBC significantly increased (p < 0.05) compared to the sample without PBC. Due to the increasing pH and enhanced ion strength, more β-sheet and β-turns structures were formed. Furthermore, by increasing PBC, the pH significantly increased (p < 0.05) and the cooked silver carp batters became darkened. Meanwhile, more CO₂ was generated, which destroyed the gel structure, leading the water- and oil-holding capacity, texture properties, and G′ values at 90 °C to be increased and then decreased. Overall, using PBC partial as a substitute of STPP enables reduced-phosphate silver carp batter to have better gel characteristics and water-holding capacity by increasing its pH and changing its rheology characteristic and protein conformation. Full article

Following the successful experimental synthesis of single-layer metallic 1T-TaS₂ and semiconducting 2H-MoS₂, 2H-WSe₂, we perform a first-principles study to investigate the electronic and interfacial features of metal/semiconductor 1T-TaS₂/2H-MoS₂ and 1T-TaS₂/2H-WSe₂ van der Waals heterostructures (vdWHs) contact. We show that 1T-TaS₂/2H-MoS₂ and 1T-TaS₂/2H-WSe₂ form n-type Schottky contact (n-ShC type) and p-type Schottky contact (p-ShC type) with ultralow Schottky barrier height (SBH), respectively. This indicates that 1T-TaS₂ can be considered as an effective metal contact with high charge injection efficiency for 2H-MoS₂, 2H-WSe₂ semiconductors. In addition, the electronic structure and interfacial properties of 1T-TaS₂/2H-MoS₂ and 1T-TaS₂/2H-WSe₂ van der Waals heterostructures can be transformed from n-type to p-type Schottky contact through the effect of layer spacing and the electric field. At the same time, the transition from Schottky contact to Ohmic contact can also occur by relying on the electric field and different interlayer spacing. Our results may provide a new approach for photoelectric application design based on metal/semiconductor 1T-TaS₂/2H-MoS₂ and 1T-TaS₂/2H-WSe₂ van der Waals heterostructures. Full article

Matrix acidification is one of the most effective stimulations to dissolve scales and remove damage in carbonate reservoirs. However, existing acid systems are difficult to dissolve organic and inorganic scales simultaneously, and complex multi-stage alternative injection often introduces new precipitation and damages the reservoir. Here, based on the retardation ability of emulsified acid and the stable structure of microemulsion, an oil-phase solvent was preferably selected, and the surfactant and cosurfactant were optimized to prepare an acid-in-oil type microemulsion acid capable of dissolving both organic and inorganic scales and high solubilizing for hydrochloric acid. Based on the rotating disc experiment, scale dissolution experiment and acid driving experiment, the acid-rock reaction kinetics, scale dissolution ability and acidizing and plugging removal performance of microemulsion acid in a carbonate reservoir were systematically studied and compared. The results show that Solvesso 150 (aromatic solvent) has the advantages of low toxicity, high flash point and high-scale dissolving ability. At NP−4: OP−10: A (cosurfactant) = 3:3:4, the microemulsion acid system has the strongest ability to solubilize hydrochloric acid and can solve the problem of low H⁺ concentration. The particle size of microemulsion acid is smaller compared to emulsified acid. At 60 °C, the mass transfer coefficient of microemulsion acid is 3.2 × 10⁻⁸ cm²/s, which is one order of magnitude less than that of emulsified acid. Microemulsion acid shows good solubility performance in dissolving organic and inorganic scales, and the comprehensive solubility of mixed scales can reach 98.28%. The stronger scale solubilization ability and lower acid-rock reaction rate enable microemulsion acid to form a thin and straight main wormhole, thus enhancing the acidizing and plugging removal effect. This study can solve the problem of poor hydrochloric acid solubilization ability of microemulsion acid to a certain extent, which provides theoretical and data support for the research and development of microemulsion acid and the efficient plugging removal technology for carbonate reservoirs. Full article

Diabetic nephropathy (DN) contributes to increased morbidity and mortality among patients with diabetes and presents a considerable global health challenge. However, reliable biomarkers of DN have not yet been established. Phosphorylated proteins are crucial for disease progression. However, their diagnostic potential remains unexplored. In this study, we used ultra-high-sensitivity quantitative phosphoproteomics to identify phosphoproteins in urinary extracellular vesicles (uEVs) as potential biomarkers of DN. We detected 233 phosphopeptides within the uEVs, with 47 phosphoproteins exhibiting significant alterations in patients with DN compared to those in patients with diabetes. From these phosphoproteins, we selected phosphorylated aquaporin-2 (p-AQP2[S256]) and phosphorylated glycogen synthase kinase-3β (p-GSK3β[Y216]) for validation, as they were significantly overrepresented in pathway analyses and previously implicated in DN pathogenesis. Both phosphoproteins were successfully confirmed through Phos-tag western blotting in uEVs and immunohistochemistry staining in kidney sections, suggesting that phosphoprotein alterations in uEVs reflect corresponding changes within the kidney and their potential as candidate biomarkers for DN. Our research proposes the utilization of phosphoproteins in uEVs as a liquid biopsy, presenting a highly feasible diagnostic tool for kidney disease. Full article

Fluorescent nanoprobes show similar fluorescence properties to traditional organic dyes, but the addition of nanotechnology accurately controls the size, shape, chemical composition, and surface chemistry of the nanoprobes with unique characteristics and properties, such as bright luminescence, high photostability, and strong biocompatibility. For example, modifying aptamers or antibodies on a fluorescent nanoprobe provides high selectivity and specificity for different objects to be tested. Fluorescence intensity, life, and other parameters of targets can be changed by different sensing mechanisms based on the unique structural and optical characteristics of fluorescent nanoprobes. What’s more, the detection of fluorescent nanoprobes is cost-saving, simple, and offers great advantages in rapid food detection. Sensing mechanisms of fluorescent nanoprobes were introduced in this paper, focusing on the application progress in pesticide residues, veterinary drug residues, heavy metals, microbes, mycotoxins, and other substances in food safety detection in recent years. A brief outlook for future development was provided as well. Full article

Neuropilin 1 (NRP1), a cell-surface co-receptor of a number of growth factors and other signaling molecules, has long been the focus of attention due to its association with the development and the progression of several types of cancer. For example, the KDKPPR peptide has recently been combined with a photosensitizer and a contrast agent to bind NRP1 for the detection and treatment by photodynamic therapy of glioblastoma, an aggressive brain cancer. The main therapeutic target is a pocket of the fragment b1 of NRP1 (NRP1-b1), in which vascular endothelial growth factors (VEGFs) bind. In the crystal packing of native human NRP1-b1, the VEGF-binding site is obstructed by a crystallographic symmetry neighbor protein, which prevents the binding of ligands. Six charged amino acids located at the protein surface were mutated to allow the protein to form a new crystal packing. The structure of the mutated fragment b1 complexed with the KDKPPR peptide was determined by X-ray crystallography. The variant crystallized in a new crystal form with the VEGF-binding cleft exposed to the solvent and, as expected, filled by the C-terminal moiety of the peptide. The atomic interactions were analyzed using new approaches based on a multipolar electron density model. Among other things, these methods indicated the role played by Asp320 and Glu348 in the electrostatic steering of the ligand in its binding site. Molecular dynamics simulations were carried out to further analyze the peptide binding and motion of the wild-type and mutant proteins. The simulations revealed that specific loops interacting with the peptide exhibited mobility in both the unbound and bound forms. Full article

4-Hydroxyphenylacetate-3-hydroxylase (4HPA3H; EC 1.14.14.9) is a heterodimeric flavin-dependent monooxygenase complex that catalyzes the ortho-hydroxylation of resveratrol to produce piceatannol. Piceatannol has various health benefits and valuable applications in food, medicine, and cosmetics. Enhancing the catalytic activity of 4HPA3H toward resveratrol has the potential to benefit piceatannol production. In this study, the critical amino acid residues in the substrate pocket of 4HPA3H that affect its activity toward resveratrol were identified using semi-rational engineering. Two key amino acid sites (I157 and A211) were discovered and the simultaneous “best” mutant I157L/A211D enabled catalytic efficiency (Kcat/Km—resveratrol) to increase by a factor of 4.7-fold. Molecular dynamics simulations indicated that the increased flexibility of the 4HPA3H substrate pocket has the potential to improve the catalytic activity of the enzyme toward resveratrol. On this basis, we produced 3.78 mM piceatannol by using the mutant I157L/A211D whole cells. In this study, we successfully developed a highly active 4HPA3H variant for the hydroxylation of resveratrol to piceatannol. Full article

Most machine learning (ML) models produce black box predictions that are difficult, if not impossible, to understand. In pharmaceutical research, black box predictions work against the acceptance of ML models for guiding experimental work. Hence, there is increasing interest in approaches for explainable ML, which is a part of explainable artificial intelligence (XAI), to better understand prediction outcomes. Herein, we have devised a test system for the rationalization of multiclass compound activity prediction models that combines two approaches from XAI for feature relevance or importance analysis, including counterfactuals (CFs) and Shapley additive explanations (SHAP). For compounds with different single- and dual-target activities, we identified small compound modifications that induce feature changes inverting class label predictions. In combination with feature mapping, CFs and SHAP value calculations provide chemically intuitive explanations for model decisions. Full article

“Undruggable” targets such as KRAS are particularly challenging in the development of drugs. We devised a novel chemical knockdown strategy, CANDDY (Chemical knockdown with Affinity aNd Degradation DYnamics) technology, which promotes protein degradation using small molecules (CANDDY molecules) that are conjugated to a degradation tag (CANDDY tag) modified from proteasome inhibitors. We demonstrated that CANDDY tags allowed for direct proteasomal target degradation independent of ubiquitination. We synthesized a KRAS-degrading CANDDY molecule, TUS-007, which induced degradation in KRAS mutants (G12D and G12V) and wild-type KRAS. We confirmed the tumor suppression effect of TUS-007 in subcutaneous xenograft models of human colon cells (KRAS G12V) with intraperitoneal administrations and in orthotopic xenograft models of human pancreatic cells (KRAS G12D) with oral administrations. Thus, CANDDY technology has the potential to therapeutically target previously undruggable proteins, providing a simpler and more practical drug targeting approach and avoiding the difficulties in matchmaking between the E3 enzyme and the target. Full article

Oxidative stress induces the adaptive response and alteration of energy metabolism across human cell types. Dermal fibroblasts shift their energy system to overload anaerobic glycolysis when exposed to sub-lethal hydrogen peroxide (H₂O₂). However, oxidative stress levels in the cells can be depleted by antioxidants, and such cellular changes can therefore be modulated. The present study aimed to investigate the modulatory effect of rosmarinic acid (a polyphenol antioxidant) against H₂O₂-induced reactive oxygen species (ROS) and the glycolytic adaptive response in fibroblasts. The results showed that H₂O₂ caused a significant ROS increase in the cells, and pre-treatment with rosmarinic acid (5–50 µM) decreased ROS significantly in the presence of glutathione. Rosmarinic acid modulated the adaptive response in H₂O₂-treated cells by decreasing glucose consumption and lactate production. The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway. Several glycolytic enzymes, including hexokinase-2 (HK-2), phosphofructokinase-2 (PFK-2), and lactate dehydrogenase A (LDHA), were downregulated in cells treated with rosmarinic acid. Furthermore, the key antioxidant enzymes: glutathione-disulfide reductase (GSR), glutathione peroxidase-1 (GPx-1), and peroxiredoxin-1 (Prx-1) and redox protein thioredoxin-1 (Trx-1) were upregulated in treated cells compared to control cells. To sum up, the rosmarinic acid could be used as an antioxidant against H₂O₂-induced adaptive responses in fibroblasts by modulating glucose metabolism, glycolytic genes, and GSH production. The present work indicates that rosmarinic acid holds promise in cell-based research applications for combating ROS and enhancing dermal fibroblast health. Full article

MSN8C, an analog of mansonone E, has been identified as a novel catalytic inhibitor of human DNA topoisomerase II that induces tumor regression and differs from VP-16(etoposide). Treatment with MSN8C showed significant antiproliferative activity against eleven human tumor cell lines in vitro. It was particularly effective against the HL-60/MX2 cell line, which is resistant to Topo II poisons. The resistance factor (RF) of MSN8C for Topo II in HL-60/MX2 versus HL-60 was 1.7, much lower than that of traditional Topo II poisons. Furthermore, in light of its potent antitumor efficacy and low toxicity, as demonstrated in the A549 tumor xenograft model, MSN8C has been identified as a promising candidate for antitumor applications. Full article

Lithium-oxygen batteries have attracted considerable attention in the past several years due to their ultra-high theoretical energy density. However, there are still many serious issues that must be addressed before considering practical applications, including the sluggish oxygen redox kinetics, the limited capacity far from the theoretical value, and the poor cycle stability. This study proposes a surface modification strategy that can enhance the catalytic activity by loading Fe₃C particles on carbon fibers, and the microstructure of Fe₃C particle-modified carbon fibers is studied by multiple materials characterization methods. Experiments and density functional theory (DFT) calculations show that the discharge products on the Fe₃C carbon fiber (Fe₃C-CF) cathode are mainly Li_2−xO₂. Fe₃C-CF exhibits high catalytic ability based on its promotion of the formation/decomposition processes of Li_2−xO₂. Consequently, the well-designed electrode catalyst exhibits a large specific capacity of 17,653.1 mAh g⁻¹ and an excellent cyclability of 263 cycles at a current of 200 mA g⁻¹. Full article

Ultrasonic (US) maltreatment was performed before the vacuum far-infrared drying (VFID) of Codonopsis pilosula (CP) slices to investigate the effects of different US parameters on the drying characteristics and nutrients of CP slices. The grey correlation method with relative correlation degree (r_i) as the evaluation measure was used to construct a model for the evaluation of the pretreatment quality of CP and to determine the optimal pretreatment conditions. The results showed that with the increase in US frequency and power, the drying rate increased. Under the conditions of US power of 180 W, frequency of 60 kHz and a pre-treatment time of 30 min, the drying time reduced by 28.6%. The contents of polysaccharide and syringin in dried CP slices pretreated by US increased by 14.7% and 62.0%, respectively, compared to the non-pre-treated samples, while the total flavonoid content decreased by 10.0%. In terms of colour, pretreatment had a certain protective effect on the red colour of dried products. The highest relative correlation (0.574) and the best overall quality of performance were observed at 180 W, 60 kHz and 30 min. Overall, US technology is suitable for the pretreatment processing of CP, which is of great significance to the drying of CP. Full article

Chitooligosaccharide (COS) is a natural product from the ocean, and while many studies have reported its important role in metabolic diseases, no study has systematically elaborated the anti-obesity effect and mechanism of COS. Herein, COSM (MW ≤ 3000 Da) was administered to diet-induced obese mice by oral gavage once daily for eight weeks. The results show that COSM administration reduced body weight; slowed weight gain; reduced serum Glu, insulin, NEFA, TC, TG, and LDL-C levels; increased serum HSL and HDL-C levels; improved inflammation; and reduced lipid droplet size in adipose tissue. Further lipidomic analysis of adipose tissue revealed that 31 lipid species are considered to be underlying lipid biomarkers in COS therapy. These lipids are mainly enriched in pathways involving insulin resistance, thermogenesis, cholesterol metabolism, glyceride metabolism and cyclic adenosine monophosphate (cAMP), which sheds light on the weight loss mechanism of COS. The Western blot assay demonstrated that COSM intervention can improve insulin resistance, inhibit de novo synthesis, and promote thermogenesis and β-oxidation in mitochondria by the AMPK pathway, thereby alleviating high-fat diet-induced obesity. In short, our study can provide a more comprehensive direction for the application of COS in obesity based on molecular markers. Full article

Various host systems have been employed to increase the yield of recombinant proteins. However, some recombinant proteins were successfully produced at high yields but with no functional activities. To achieve both high protein yield and high activities, molecular biological strategies have been continuously developed. This work describes the effect of signal peptide (SP) and co-expression of molecular chaperones on the production of active recombinant protein in Escherichia coli. Extracellular enzymes from Bacillus subtilis, including β-1,4-xylanase, β-1,4-glucanase, and β-mannanase constructed with and without their signal peptides and intracellular enzymes from Pseudomonas stutzeri ST201, including benzoylformate decarboxylase (BFDC), benzaldehyde dehydrogenase (BADH), and d-phenylglycine aminotransferase (d-PhgAT) were cloned and overexpressed in E. coli BL21(DE3). Co-expression of molecular chaperones with all enzymes studied was also investigated. Yields of β-1,4-xylanase (Xyn), β-1,4-glucanase (Cel), and β-mannanase (Man), when constructed without their N-terminal signal peptides, increased 1112.61-, 1.75-, and 1.12-fold, respectively, compared to those of spXyn, spCel, and spMan, when constructed with their signal peptides. For the natural intracellular enzymes, the chaperones, GroEL-GroES complex, increased yields of active BFDC, BADH, and d-PhgAT, up to 1.31-, 4.94- and 37.93-fold, respectively, and also increased yields of Man and Xyn up to 1.53- and 3.46-fold, respectively, while other chaperones including DnaK-DnaJ-GrpE and Trigger factor (Tf) showed variable effects with these enzymes. This study successfully cloned and overexpressed extracellular and intracellular enzymes in E. coli BL21(DE3). When the signal peptide regions of the secretory enzymes were removed, yields of active enzymes were higher than those with intact signal peptides. In addition, a higher yield of active enzymes was obtained, in general, when these enzymes were co-expressed with appropriate chaperones. Therefore, E. coli can produce cytoplasmic and secretory enzymes effectively if only the enzyme coding sequence without its signal peptide is used and appropriate chaperones are co-expressed to assist in correct folding. Full article

High-ash coal, also known as low-grade coal, has becomes a viable alternative in recent years to high-quality coal because available resources have become increasingly scarce due to extensive mining activity. This work aims to provide a comprehensive understanding of the structural characteristics of high-ash coal and construct a plausible molecular structure to elucidate its chemical reactivity in future applications. Its properties were investigated using Solid-state ¹³C nuclear magnetic resonance (¹³C NMR), X-ray photoelectron spectroscopy analysis (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). The molecular structure was constructed and validated using Material Studio, LAMMPS Software Package, and MATLAB program. The characterization results revealed that high-ash coal contains 72.15% aromatic carbon, significantly surpassing the percentage of aliphatic carbon (27.85%). The ratio of bridgehead carbon to peripheral aromatic carbon was calculated as 0.67, indicating that the pentacene is the main carbon skeleton form in the high-ash coal structure. Furthermore, oxygen-containing functional groups presented as C=O/O–C–O, C–O, and COO– within the structure along with pyridine and pyrrolic structures. Consequently, the molecular structure comprises pentacene with aliphatic carbon chains, such as methylene, that connect the benzene rings and form a three-dimensional network. The results of a simulated IR spectrum and contact angle simulation aligned with the experimental results, validating the molecular structure of high-ash coal. The chemical formula for the high-ash coal model was determined as C₂₀₃H₁₈₉N₇O₆₁S with a molecular weight of 3734.79. Full article

Aging is a major risk factor for Alzheimer’s disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems^® to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood–brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models. Full article

Diosmin is used to relieve chronic venous disease (CVD) symptoms. This study aimed to investigate the anti-inflammatory and antioxidant effects of diosmetin-3-O-β-d-glucuronide, the major metabolite of diosmin, using human skin explants. The explants were exposed to substance P (inflammation model) or UVB irradiation (oxidative model) and to five diosmetin-3-O-β-d-glucuronide concentrations. Inflammation was evaluated through interleukin-8 (IL-8) secretion measurements and capillary dilation observation, and oxidation was evaluated by measuring the hydrogen peroxide levels and observing cyclobutane pyrimidine dimers (CPDs). In substance-P-exposed explants, diosmetin-3-O-β-d-glucuronide induced a significant decrease in IL-8 secretions, with a maximal effect at 2700 pg/mL (−49.6%), and it reduced the proportion of dilated capillaries and the mean luminal cross-sectional area (p < 0.0001 at all tested concentrations), indicating a vasoconstrictive effect. In UVB-irradiated fragments, diosmetin-3-O-β-d-glucuronide induced a significant decrease in hydrogen peroxide production and in the number of CPD-positive cells, reaching a maximal effect at the concentration of 2700 pg/mL (−48.6% and −52.0%, respectively). Diosmetin-3-O-β-d-glucuronide induced anti-inflammatory and antioxidant responses, with the maximal effect being reached at 2700 pg/mL and corresponding to the peak plasma concentration estimated after the oral intake of 600 mg of diosmin, the daily dose usually recommended for the treatment of CVD. These ex vivo findings suggest a protective role of diosmetin-3-O-β-d-glucuronide against inflammatory and oxidative stress affecting the vascular system in CVD pathophysiology. Full article

An environmentally friendly pore size-controlled, superhydrophobic polylactic acid (PLA) membrane was successfully prepared by a simpler freeze solidification phase separation method (FSPS) and solution impregnation, which has application prospects in the field of oil–water separation. The pore size and structure of the membrane were adjusted by different solvent ratios and solution impregnation ratios. The PLA-FSPS membrane after solution impregnation (S-PLA-FSPS) had the characteristics of uniform pore size, superhydrophobicity and super lipophilicity, its surface roughness Ra was 338 nm, and the contact angle to water was 151°. The S-PLA-FSPS membrane was used for the oil–water separation. The membrane oil flux reached 16,084 L·m⁻²·h⁻¹, and the water separation efficiency was 99.7%, which was much higher than that of other oil–water separation materials. In addition, the S-PLA-FSPS membrane could also be applied for the adsorption and removal of oil slicks and underwater heavy oil. The S-PLA-FSPS membrane has great application potential in the field of oil–water separation. Full article