The fruit of Rosa laevigata Michx. (FR), a traditional Chinese herb utilized for the treatment of a variety diseases, has notably diverse pharmacological activities including hepatoprotective, anti-oxidant, and anti-inflammatory effects. Despite ongoing research on illustrating the underlying anti-inflammatory mechanism of FR, the principal mechanism remained inadequately understood. In this study, we investigated in depth the molecular mechanism of the anti-inflammatory actions of the ethanol extract of FR (EFR) and its potential targets using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro. We showed that EFR effectively ameliorated the overproduction of inflammatory mediators and cytokines, as well as the expression of related genes. It was further demonstrated that LPS-induced activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) were significantly inhibited by pretreatment with EFR, accompanied by a concomitant decrease in the nuclear translocation of the p65 subunit of NF-κB and activator protein 1 (AP-1). In addition, EFR pretreatment potently prevented LPS-induced decreased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Our data also revealed that the activation of AMPK and subsequent inhibition of the mammalian target of the rapamycin (mTOR) signaling pathway was probably responsible for the inhibitory effect of EFR on LPS-induced inflammatory responses, evidenced by reverse changes observed under the condition of AMPK inactivation following co-treatment with the AMPK-specific inhibitor Compound C. Finally, the main components with an anti-inflammatory effect in EFR were identified as madecassic acid, ellagic acid, quinic acid, and procyanidin C1 by LC–MS and testified based on the inhibition of NO production and inflammatory mediator expression. Taken together, our results indicated that EFR was able to ameliorate inflammatory responses via the suppression of MAPKs/NF-κB signaling pathways following AMPK activation, suggesting the therapeutic potential of EFR for inflammatory diseases. Full article

Fibroblast growth factor receptors (FGFRs) play critical roles in the regulation of cell growth, differentiation, and proliferation. Specifically, FGFR2 gene amplification has been implicated in gastric and breast cancer. Pan-FGFR inhibitors often cause large toxic side effects, and the highly conserved ATP-binding pocket in the FGFR1/2/3 isoforms poses an immense challenge in designing selective FGFR2 inhibitors. Recently, an indazole-based inhibitor has been discovered that can selectively target FGFR2. However, the detailed mechanism involved in selective inhibition remains to be clarified. To this end, we performed extensive molecular dynamics simulations of the apo and inhibitor-bound systems along with multiple analyses, including Markov state models, principal component analysis, a cross-correlation matrix, binding free energy calculation, and community network analysis. Our results indicated that inhibitor binding induced the phosphate-binding loop (P-loop) of FGFR2 to switch from the open to the closed conformation. This effect enhanced extensive hydrophobic FGFR2-inhibitor contacts, contributing to inhibitor selectivity. Moreover, the key conformational intermediate states, dynamics, and driving forces of this transformation were uncovered. Overall, these findings not only provided a structural basis for understanding the closed P-loop conformation for therapeutic potential but also shed light on the design of selective inhibitors for treating specific types of cancer. Full article

The goal of accurately quantifying trace elements in ultrapure silicon carbide (SiC) with a purity target of 5N (99.999% purity) was addressed. The unsuitability of microwave-assisted acid digestion followed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis was proved to depend mainly on the contamination induced by memory effects of PTFE microwave vessels and by the purity levels of acids, even if highly pure ones were used in a clean environment. A new analytical protocol for the direct analysis of the solid material by laser ablation coupled with ICP-MS (LA-ICP-MS) was then exploited. Different samples were studied; the best results were obtained by embedding SiC (powders or grains) in epoxy resin. This technique has the great advantage of avoiding any source of external contamination, as grinding, pressing and sintering pretreatments are totally unnecessary. Two different laser wavelengths (266 and 193 nm) were tested, and best results were obtained with the 266 nm laser. The optimized protocol allows the determination of elements down to the sub-mg/kg level with a good accuracy level. Full article

Boron containing compounds (BCCs) aroused increasing interest in the scientific community due to their wide application as drugs in various fields. In order to design new compounds hopefully endowed with pharmacological activity and also investigate their conformational behavior, the support of computational studies is crucial. Nevertheless, the suitable molecular mechanics parameterization and the force fields needed to perform these simulations are not completely available for this class of molecules. In this paper, Amber force field parameters for phenyl-, benzyl-, benzylamino-, and methylamino-boronates, a group of boron-containing compounds involved in different branches of the medicinal chemistry, were created. The robustness of the obtained data was confirmed through molecular dynamics simulations on ligand/β-lactamases covalent complexes. The ligand torsional angles, populated over the trajectory frames, were confirmed by values found in the ligand geometries, located through optimizations at the DFT/B3LYP/6-31g(d) level, using water as a solvent. In summary, this study successfully provided a library of parameters, opening the possibility to perform molecular dynamics simulations of this class of boron-containing compounds. Full article

Alzheimer’s disease poses a global health concern with unmet demand requiring creative approaches to discover new medications. In this study, we investigated the chemical composition and the anticholinesterase activity of Aspergillus niveus Fv-er401 isolated from Foeniculum vulgare (Apiaceae) roots. Fifty-eight metabolites were identified using UHPLC-MS/MS analysis of the crude extract. The fungal extract showed acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory effects with IC₅₀ 53.44 ± 1.57 and 48.46 ± 0.41 µg/mL, respectively. Two known metabolites were isolated, terrequinone A and citrinin, showing moderate AChE and BuChE inhibitory activity using the Ellman’s method (IC₅₀ = 11.10 ± 0.38 µg/mL and 5.06 ± 0.15 µg/mL, respectively for AChE, and IC₅₀ 15.63 ± 1.27 µg/mL and 8.02 ± 0.08 µg/mL, respectively for BuChE). As evidenced by molecular docking, the isolated compounds and other structurally related metabolites identified by molecular networking had the required structural features for AChE and BuChE inhibition. Where varioxiranol G (−9.76 and −10.36 kcal/mol), penicitrinol B (−9.50 and −8.02 kcal/mol), dicitrinol A (−8.53 and −7.98 kcal/mol) and asterriquinone CT5 (−8.02 and −8.25 kcal/mol) showed better binding scores as AChE and BuChE inhibitors than the co-crystallized inhibitor (between −7.89 and 7.82 kcal/mol) making them promising candidates for the development of new drugs to treat Alzheimer’s. Full article

The convenient and highly compliant route for the delivery of active pharmaceutical ingredients is the tablet. A versatile platform of tablets is available for the delivery of therapeutic agents to the gastrointestinal tract. This study aimed to prepare gastro retentive drug delivery floating tablets of silymarin to improve its oral bioavailability and solubility. Hydroxypropyl methylcellulose (HPMCK4M and HPMCK15), Carbopol 934p and sodium bicarbonate were used as a matrix, floating enhancer and gas generating agent, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, in vitro drug release, in vivo floating behavior and in vivo pharmacokinetics. The drug–polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infrared (FTIR). The floating lag time of the formulation was within the prescribed limit (<2 min). The formulation showed good matrix integrity and retarded the release of drug for >12 h. The dissolution can be described by zero-order kinetics (r² = 0.979), with anomalous diffusion as the release mechanism (n = 0.65). An in vivo pharmacokinetic study showed that Cmax and AUC were increased by up to two times in comparison with the conventional dosage form. An in vivo imaging study showed that the tablet was present in the stomach for 12 h. It can be concluded from this study that the combined matrix system containing hydrophobic and hydrophilic polymers min imized the burst release of the drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only a hydrophilic matrix. An in vivo pharmacokinetic study elaborated that the bioavailability and solubility of silymarin were improved with an increased mean residence time. Full article

Metal-based aerogels have attracted numerous studies due to their unique physical, structural, thermal, and chemical properties. Utilizing aluminum waste, a novel, facile, environmentally friendly approach to aluminum-based aerogels is proposed. In this work, the aluminum-based aerogels produced do not use toxic chemicals unlike conventional aerogel production. Aluminum powder, with poly(acrylic acid) and carboxymethyl cellulose as binders, is converted into aluminum-based aerogels using the freeze-drying method. The aluminum-based aerogels have low density (0.08–0.12 g/cm³) and high porosity (93.83–95.68%). The thermal conductivity of the aerogels obtained is very low (0.038–0.045 W/m·K), comparable to other types of aerogels and commercial heat insulation materials. Additionally, the aerogels can withstand temperatures up to 1000 °C with less than 40% decomposition. The aerogels exhibited promising oil absorption properties with their absorption capacity of 9.8 g/g and 0.784 g/cm³. The Young’s modulus of the aerogels ranged from 70.6 kPa to 330.2 kPa. This study suggests that aluminum-based aerogels have potential in thermal insulation and oil absorption applications. Full article

Metabolic syndrome (MetS) is composed of central obesity, hyperglycemia, dyslipidemia and hypertension that increase an individual’s tendency to develop type 2 diabetes mellitus and cardiovascular diseases. Kelulut honey (KH) produced by stingless bee species has a rich phenolic profile. Recent studies have demonstrated that KH could suppress components of MetS, but its mechanisms of action are unknown. A total of 18 male Wistar rats were randomly divided into control rats (C group) (n = 6), MetS rats fed with a high carbohydrate high fat (HCHF) diet (HCHF group) (n = 6), and MetS rats fed with HCHF diet and treated with KH (HCHF + KH group) (n = 6). The HCHF + KH group received 1.0 g/kg/day KH via oral gavage from week 9 to 16 after HCHF diet initiation. Compared to the C group, the MetS group experienced a significant increase in body weight, body mass index, systolic (SBP) and diastolic blood pressure (DBP), serum triglyceride (TG) and leptin, as well as the area and perimeter of adipocyte cells at the end of the study. The MetS group also experienced a significant decrease in serum HDL levels versus the C group. KH supplementation reversed the changes in serum TG, HDL, leptin, adiponectin and corticosterone levels, SBP, DBP, as well as adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) level, area and perimeter at the end of the study. In addition, histological observations also showed that KH administration reduced fat deposition within hepatocytes, and prevented deterioration of pancreatic islet and renal glomerulus. In conclusion, KH is effective in preventing MetS by suppressing leptin, corticosterone and 11βHSD1 levels while elevating adiponectin levels. Full article

The purpose of this work is to significantly improve the vanadium grade of vanadium-bearing shale after flotation preconcentration, which is conducive to reducing the acid consumption and industrial costs in the subsequently enhanced acid leaching of vanadium. Vanadium concentrate from vanadium-bearing shale enriched by flotation is used for acid-leaching feed. The leaching effects of two kinds of acid-leaching systems were compared, and the mechanism of acid leaching on the mineral structure was also described. The difficulty of spontaneous reactions of vanadium-bearing minerals such as garnet in an acid-leaching system was studied through thermodynamics. Additionally, several characterization methods were used to evaluate the improvement of leaching performance. The addition of oxidants and fluorinating aids strengthens the acid-leaching process, which greatly destroys the structure of a garnet, which is conducive to the extraction of vanadium in a flotation concentrate. The leaching efficiency can reach 94.86%, and the acid consumption is also reduced. Through the mechanism study of the leaching system, it is expected that when the enhanced acid-leaching process is put into industrial production, the effective leaching of vanadium can be accurately controlled, and the difficulty of subsequent vanadium enrichment and purification can be reduced. Full article

Pullulan is a linear exopolysaccharide, produced in the fermentation media of Aureobasidium pullulans, with a variety of applications in the food and pharmaceutical industries. Pullulan derivatives have growing potential for biomedical applications, but the high cost of pullulan biofabrication currently restricts its commercial use. Better control over pullulan yield, molecular weight and melanin production by altering fermentation conditions could improve the economics. In this study, the effects of sugar and mineral salt stresses on the pullulan production of A. pullulans ATCC 42023 were examined in batch processes. The chemical structure of the recovered pullulan was characterized by FTIR and NMR spectroscopy, and the molecular weight distribution was obtained via SEC. Pullulan yield and melanin production varied when the conditions were adjusted, and pullulans with different molar masses were obtained. Higher-yield pullulan production and a lower polydispersity index were observed when CuSO₄ was added to the fermentation in comparison with the control and with the addition of sugars and other salts. Biofabrication of pullulan under stress conditions is a promising strategy to enhance biopolymer yield and to obtain pullulan with a targeted molecular weight. Full article

Ultrasound-assisted extraction (UAE) was applied to extract oil from blackberry (BB) seeds. The effect of UAE conditions on oil recovery and quality was investigated. Favorable experimental conditions (ultrasound intensity (UI), extraction temperature, and time) were investigated using response surface methodology (RSM). A Box–Behnken design was used to predict optimized conditions for BB seed oil extraction. These conditions were as follows: 13.77 W/cm² UI, 45 °C extraction temperature, and 15 min extraction time. The experimental value obtained for extraction efficiency under optimal conditions was 87 ± 0.34%, in good agreement with the optimized predicted value. UAE does not affect the oil composition and confers higher antioxidant values in BB seed oil in comparison with Soxhlet extraction. Full article

Optical spectroscopic analysis of the chemical composition of milk in its natural state is complicated by a complex colloidal structure, represented by differently sized fat and protein particles. The classical techniques of molecular spectroscopy in the visible, near-, and mid-infrared ranges carry only bulk chemical information about a sample, which usually undergoes a destructive preparation stage. The combination of Raman spectroscopy with confocal microscopy provides a unique opportunity to obtain a vibrational spectrum at any single point of the sample volume. In this study, scanning confocal Raman microscopy was applied for the first time to investigate the chemical microstructure of milk using samples of various compositions. The obtained hyperspectral images of selected planes in milk samples are represented by three-dimensional data arrays. Chemometric data analysis, in particular the method of multivariate curve resolution, has been used to extract the chemical information from complex partially overlaid spectral responses. The results obtained show the spatial distribution of the main chemical components, i.e., fat, protein, and lactose, in the milk samples under study using intuitive graphical maps. The proposed experimental and data analysis method can be used in an advanced chemical analysis of natural milk and products on its basis. Full article

This work aimed to evaluate the biological activities of 20 flavones (M1 to M20) and discuss their structure–activity relationships. In vitro assays were established to assess their numerous biological activities (anti-α-amylase, anti-acetylcholinesterase, anti-xanthine oxidase, anti-superoxide dismutase, and anticancer cell lines (HCT-116, MCF7, OVCAR-3, IGROV-1, and SKOV-3 cells lines)). An in silico docking study was also established in order to find the relationship between the chemical structure and the biological activities. In vitro tests revealed that M5 and M13 were the most active in terms of anti-α-amylase activity (IC₅₀ = 1.2 and 1.4 µM, respectively). M17 was an inhibitor of xanthine oxidase (XOD) and performed better than the reference (allopurinol), at IC₅₀ = 0.9 µM. M7 presented interesting anti-inflammatory (IC₅₀ = 38.5 µM), anti-supriode dismutase (anti-SOD) (IC₅₀ = 31.5 µM), and anti-acetylcholinesterase (IC₅₀ = 10.2 µM) activities. Those abilities were in concordance with its high scavenging activity in antioxidant ABTS and DPPH assays, at IC₅₀ = 6.3 and 5.2 µM, respectively. Selectivity was detected regarding cytotoxic activity for those flavones. M1 (IC₅₀ = 35.9 µM) was a specific inhibitor to the MCF7 cancer cell lines. M3 (IC₅₀ = 44.7 µM) and M15 (IC₅₀ = 45.6 µM) were particularly potent for the OVCAR-3 cell line. M14 (IC₅₀ = 4.6 µM) contributed more clearly to inhibiting the colon cancer cell line (HCT116). M7 (IC₅₀ = 15.6 µM) was especially active against the ovarian SKOV human cancer cell line. The results of the biological activities were supported by means of in silico molecular docking calculations. This investigation analyzed the contribution of the structure–activity of natural flavones in terms of their biological properties, which is important for their future application against diseases. Full article

Antibiotic water contamination is a growing environmental problem in the present day. As a result, water treatment is required for its reduction and elimination. Due to their important role in resolving this issue, photocatalysts have drawn a great deal of interest over the past few decades. When non-biodegradable organic matter is present in polluted water, the photo catalytic process, which is both environmentally friendly and an improved oxidation method, can be an effective means of remediation. In this regard, we report the successful synthesis of pure phased rare earth doped ZnO nanoparticles for tetracycline degradation. The prepared catalysts were systematically characterized for structural, optical, and magnetic properties. The optical band gap was tailored by rare earth doping, with redshift for Sm and Dy doped nanoparticles and blueshift for Nd doped ZnO nanoparticles. The analysis of photoluminescence spectra revealed information about the defect chemistry of all synthesised nanoparticles. Magnetic studies revealed that all synthesized diluted magnetic semiconductors exhibit room temperature ferromagnetism and can be employed for spintronic applications. Moreover, Dy doped ZnO nanoparticles were found to exhibit a maximum degradation efficiency of 74.19% for tetracycline (TCN) removal. The synthesized catalysts were also employed for the degradation of Malachite green (MG), and Crystal violet (CV) dyes. The maximum degradation efficiency achieved was 97.18% for MG and 98% for CV for Dy doped ZnO nanoparticles. The degradation mechanism involved has been discussed in view of the reactive species determined from scavenging experiments. Full article

Thyme is a colloquial term for number of aromatic species belonging to the genus Thymus L., known for their expressed biological activities and therefore used worldwide for seasoning and in folk medicine. In the present paper, the content of the total polyphenols (TP), total flavonoids (TF), and antioxidant capacity were assessed in the extracts of four traditionally used thyme species. Moreover, a comprehensive metabolomic study of thyme bioactive compounds was performed, and the obtained data were processed using multivariate statistical tests. The results clearly demonstrated the positive correlation between the content of the TP, TF, and antioxidant activity, and TF was more significant than TP. The findings revealed that four selected thyme species contained 528 secondary metabolites, including 289 flavonoids and 146 phenolic acids. Thymus marschallianus had a higher concentration of active ingredients, which improve its antioxidant capacity. Differentially accumulated metabolites were formed by complex pathways such as flavonoid, flavone, flavonol, isoflavonoid, and anthocyanin biosynthesis. Correlation analysis showed that 59 metabolites (including 28 flavonoids, 18 phenolic acids, and 7 terpenoid compounds) were significantly correlated with obtained values of the antioxidant capacity. The results suggested that selected thyme species exhibit a great diversity in antioxidant-related components, whereas flavonoids may be responsible for the high antioxidant capacity of all studied thyme species. The present study greatly expands our understanding of the complex phytochemical profiles and related applications of selected medicinal plants. Full article