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

Hordenine, a phenethylamine alkaloid, is found in a variety of plants and exhibits a broad array of biological activities and pharmacological properties, including anti-inflammatory and anti-fibrotic effects. However, the efficacy and underlying mechanisms of hordenine in treating ulcerative colitis (UC) remain unclear. To address this, we examined the therapeutic effects of hordenine on dextran sodium sulphate (DSS)-induced UC by comparing disease activity index (DAI), colon length, secretion of inflammatory factors, and degree of colonic histological lesions across diseased mice that were and were not treated with hordenine. We found that hordenine significantly reduced DAI and levels of pro-inflammatory factors, including interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α), and also alleviated colon tissue oedema, colonic lesions, inflammatory cells infiltration and decreased the number of goblet cells. Moreover, in vitro experiments showed that hordenine protected intestinal epithelial barrier function by increasing the expression of tight junction proteins including ZO-1 and occludin, while also promoting the healing of intestinal mucosa. Using immunohistochemistry and western blotting, we demonstrated that hordenine reduced the expression of sphingosine kinase 1 (SPHK1), sphingosine-1-phosphate receptor 1 (S1PR1), and ras-related C3 botulinum toxin substrate 1 (Rac1), and it inhibited the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in colon tissues. Thus, hordenine appears to be effective in UC treatment owing to pharmacological mechanisms that favor mucosal healing and the inhibition of SPHK-1/S1PR1/STAT3 signaling. Full article

2,3,5,6-Tetramethylpyrazine (TTMP) is an active ingredient of Ligusticum wallichii Franch. It can be used in medicine and food fields. In this study, Bacillus sp. TTMP20 was applied to produce TTMP using cane molasses as a carbon source. After pretreatment with phosphoric acid, 170 mL/L treated molasses, combined with 10 g/L yeast powder, 30 g/L tryptone and 30 g/L (NH₄)₂HPO₄ were used for fermentation. After 36 h, TTMP output reached the highest value of 208.8 mg/L. The yield of TTMP using phosphoric acid-treated molasses as carbon source was 145.59% higher than control. Under the sulfuric acid treatment process of molasses (150 g), the maximum yield of TTMP was 895.13 mg/L, which was 183.18% higher than that of untreated molasses (316.1 mg/L). This study demonstrated that molasses is a high-quality and inexpensive carbon source for the manufacture of TTMP, laying the groundwork for the future industrial production of TTMP. Full article

As a significant parameter in tuning the structure and performance of the boron-doped diamond (BDD), the thickness was focused on the mediation of the boron doping level and electrochemical properties. BDD films with different thicknesses were deposited on silicon wafers by the hot filament chemical vapor deposition (HFCVD) method. The surface morphology and composition of the BDD films were characterized by SEM and Raman, respectively. It was found that an increase in the BDD film thickness resulted in larger grain size, a reduced grain boundary, and a higher boron doping level. The electrochemical performance of the electrode equipped with the BDD film was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) in potassium ferricyanide. The results revealed that the thicker films exhibited a smaller peak potential difference, a lower charge transfer resistance, and a higher electron transfer rate. It was believed that the BDD film thickness-driven improvements of boron doping and electrochemical properties were mainly due to the columnar growth mode of CVD polycrystalline diamond film, which led to larger grain size and a lower grain boundary density with increasing film thickness. Full article

The hydrophobically associating polyacrylamide (HAPAM) is an important kind of water-soluble polymer, which is widely used as a rheology modifier in many fields. However, HAPAM products prepared in a traditional method show disadvantages including poor water solubility and the need for hydrocarbon solvents and appropriate surfactants, which lead to environmental pollution and increased costs. To solve these problems, we reported a novel kind of HAPAM “water-in-water” (w/w) emulsion and its solution properties. In this work, a series of cationic hydrophobic monomers with different alkyl chain lengths were synthesized and characterized. Then, HAPAM w/w emulsions were prepared by the aqueous dispersion polymerization of acrylamide, 2-methylacryloylxyethyl trimethyl ammonium chloride and a hydrophobic monomer. All these emulsions can be stored more than 6 months, showing excellent stability. An optical microscopy observation showed that the particle morphology and the particle size of the HAPAM emulsion were more regular and bigger than the emulsion without the hydrophobic monomer. The solubility tests showed that such HAPAM w/w emulsions have excellent solubility, which took no more than 180 s to dilute and achieve a homogeneous and clear solution. The rheology measurements showed that the HAPAM association increases with a hydrophobe concentration or the length of hydrophobic alkyl chains, resulting in better shear and temperature resistances. The total reduced viscosity was 124.42 mPa·s for cw101, 69.81 mPa·s for cw6-1, 55.38 mPa·s for cw8-0.25, 48.95 mPa·s for cw12-0.25 and 28 mPa·s for cw16-0.25 when the temperature increased from 30 °C to 90 °C. The cw8-2.0 that contains a 2 mol% hydrophobe monomer has the lowest value at 19.12 mPa·s due to the best association. Based on the excellent stability, solubility and rheological properties, we believe that these HAPAM w/w emulsions could find widespread applications. Full article

In East Africa, Dodonaea angustifolia (L.f.) is a well-known medicinal herb. Its leaf is primarily studied in light of its ethnobotanical use. In terms of phytochemistry and biological activity, its flower is not studied. In a prior study, our team looked into phytochemical screening, antioxidant activity, and total phenolic levels. This study aims to compare the profiles and biological activities of the leaf and flower samples of D. angustifolia and to present therapeutic alternatives. The leaf and flower sample powders were extracted with methanol using ultrasound-assisted extraction (UAE). HPTLC profile was obtained using CAMAG—HPTLC equipped with VisionCATS software. Antimicrobial agar well diffusion assay and minimum inhibition concentration (MIC) were determined. The leaf and flower extracts of D. angustifolia showed antibacterial activity with a MIC value of 20 µg/mL against Enterococcus faecalis and Listeria monocytogenes. Similarly, 40 µg/mL was found to be effective against Aspergillus flavus. D. angustifolia flower is a rich source of flavonoids and phenolic acids. Because of its antibacterial properties and profile, which are almost the same, the flower is emerging as a viable option for medicinal alternatives. 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

Microbial infections have always been a thorny problem. Multi-drug resistant (MDR) bacterial infections rendered the antibiotics commonly used in clinical treatment helpless. Nanomaterials based on aggregation-induced emission luminogens (AIEgens) recently made great progress in the fight against microbial infections. As a family of photosensitive antimicrobial materials, AIEgens enable the fluorescent tracing of microorganisms and the production of reactive oxygen (ROS) and/or heat upon light irradiation for photodynamic and photothermal treatments targeting microorganisms. The novel nanomaterials constructed by combining polymers, antibiotics, metal complexes, peptides, and other materials retain the excellent antimicrobial properties of AIEgens while giving other materials excellent properties, further enhancing the antimicrobial effect of the material. This paper reviews the research progress of AIEgen-based nanomaterials in the field of antimicrobial activity, focusing on the materials’ preparation and their related antimicrobial strategies. Finally, it concludes with an outlook on some of the problems and challenges still facing the field. Full article

The unusual and interesting architecture of the catalytic chamber of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) was recently explored using Cryogenic Electron Microscopy (Cryo-EM), which revealed the presence of two distinctive binding cavities within the catalytic chamber. In this report, first, we mapped out and fully characterized the variations between the two binding sites, BS1 and BS2, for significant differences in their amino acid architecture, size, volume, and hydrophobicity. This was followed by investigating the preferential binding of eight antiviral agents to each of the two binding sites, BS1 and BS2, to understand the fundamental factors that govern the preferential binding of each drug to each binding site. Results showed that, in general, hydrophobic drugs, such as remdesivir and sofosbuvir, bind better to both binding sites than relatively less hydrophobic drugs, such as alovudine, molnupiravir, zidovudine, favilavir, and ribavirin. However, suramin, which is a highly hydrophobic drug, unexpectedly showed overall weaker binding affinities in both binding sites when compared to other drugs. This unexpected observation may be attributed to its high binding solvation energy, which disfavors overall binding of suramin in both binding sites. On the other hand, hydrophobic drugs displayed higher binding affinities towards BS1 due to its higher hydrophobic architecture when compared to BS2, while less hydrophobic drugs did not show a significant difference in binding affinities in both binding sites. Analysis of binding energy contributions revealed that the most favorable components are the ΔE_ele, ΔE_vdw, and ΔG_gas, whereas ΔG_sol was unfavorable. The ΔE_ele and ΔG_gas for hydrophobic drugs were enough to balance the unfavorable ΔG_sol, leaving the ΔE_vdw to be the most determining factor of the total binding energy. The information presented in this report will provide guidelines for tailoring SARS-CoV-2 inhibitors with enhanced binding profiles. Full article

Aclacinomycin A (ACM-A) is an anthracycline antitumor agent widely used in clinical practice. The current industrial production of ACM-A relies primarily on chemical synthesis and microbial fermentation. However, chemical synthesis involves multiple reactions which give rise to high production costs and environmental pollution. Microbial fermentation is a sustainable strategy, yet the current fermentation yield is too low to satisfy market demand. Hence, strain improvement is highly desirable, and tremendous endeavors have been made to decipher biosynthesis pathways and modify key enzymes. In this review, we comprehensively describe the reported biosynthesis pathways, key enzymes, and, especially, catalytic mechanisms. In addition, we come up with strategies to uncover unknown enzymes and improve the activities of rate-limiting enzymes. Overall, this review aims to provide valuable insights for complete biosynthesis of ACM-A. 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

Pesticides can be found in beehives for several reasons, including contamination from surrounding crops or for their use by beekeepers, which poses a risk to bee ecosystems and consumers. Therefore, efficient and sensitive methods are needed for determining pesticide residues in bee products. In this study, a new analytical method has been developed and validated to determine seven acaricides (atrazine, chlorpyrifos, chlorfenvinphos, α-endosulfan, bromopropylate, coumaphos, and τ-fluvalinate) in bee pollen using gas chromatography coupled to mass spectrometry. After an optimization study, the best sample treatment was obtained when using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method employing an ethyl acetate and cyclohexane as the extractant mixture, and a mixture of salts for the clean-up step. A chromatographic analysis (<21 min) was performed in an Agilent DB-5MS column, and it was operated under programmed temperature conditions. The method was fully validated in terms of selectivity, limits of detection (0.2–3.1 µg kg⁻¹) and quantification (0.6–9.7 µg kg⁻¹), linearity, matrix effect (<20% in all cases), trueness (recoveries between 80% and 108%), and precision. Finally, the proposed method was applied to analyze commercial bee pollen samples, and some of the target pesticides (chlorfenvinphos, α-endosulfan, coumaphos, and τ-fluvalinate) were detected. Full article

This study aimed to systematically explore the chemical constituents of D. nobile and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of D. nobile were qualitatively analyzed, and the hypoglycemic compounds were quickly identified. Network pharmacological analysis and molecular docking technique were applied to assist in the elucidation of the hypoglycemic mechanisms of D. nobile. A type 2 diabetic mellitus (T2DM) rat model was established using the HFD and STZ method for in vivo experimental verification, and these T2DM rats were treated with D. nobile extract and D. nobile polysaccharide for two months by gavage. The results showed that a total of 39 chemical constituents of D. nobile, including alkaloids, bibenzyls, phenanthrenes and other types of compounds, were identified. D. nobile extract and D. nobile polysaccharide could significantly ameliorate the body weight, hyperglycemia, insulin resistance, dyslipidemia and morphological impairment of the liver and pancreas in the T2DM rats. α-Linolenic acid, dihydroconiferyl dihydro-p-coumarate, naringenin, trans-N-feruloyltyramine, gigantol, moscatilin, 4-O-methylpinosylvic acid, venlafaxine, nordendrobin and tristin were regarded as the key hypoglycemic compounds of D. nobile, along with the hypoglycemic effect on the PI3K-AKT signaling pathway, the insulin signaling pathway, the FOXO signaling pathway, the improvement of insulin resistance and the AGE-RAGE signaling pathway. The Western blotting experiment results confirmed that D. nobile activated the PI3K/AKT pathway and insulin signaling pathway, promoted glycogen synthesis via regulating the expression of glycogen synthase kinase 3 beta (GSK-3β) and glucose transporter 4 (GLUT4), and inhibited liver gluconeogenesis by regulating the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6pase) in the liver. The results suggested that the hypoglycemic mechanism of D. nobile might be associated with liver glycogen synthesis and gluconeogenesis, contributing to improving insulin resistance and abnormal glucose metabolism in the T2DM rats. Full article

We developed an integrated gas diffusion layer (GDL) for proton exchange membrane (PEM) fuel cells by growing carbon nanofibers (CNFs) in situ on carbon paper via the electro-polymerization of polyaniline (PANI) on carbon paper followed by a subsequent carbonization treatment process. The CNF/carbon paper showed a microporous structure and a significantly increased pore volume compared to commercial carbon paper. By utilizing this CNF/carbon paper in a PEM fuel cell, it was found that the cell with CNF/carbon paper had superior performance compared to the commercial GDL at both high and low humidity conditions, and its power density was as high as 1.21 W cm⁻² at 100% relative humidity, which is 26% higher than that of a conventional gas diffusion layer (0.9 W cm⁻²). The significant performance enhancement was attributed to a higher pore volume and porosity of the CNF/carbon paper, which improved gas diffusion in the GDL. In addition, the superior performance of the cell with CNF/carbon paper at low relative humidity demonstrated that it had better water retention than the commercial GDL. This study provides a novel and facile method for the surface modification of GDLs to improve the performance of PEM fuel cells. The CNF/carbon paper with a microporous structure has suitable hydrophobicity and lower through-plane resistance, which makes it promising as an advanced substrate for GDLs in fuel cell applications. Full article

The addition reaction of interelement compounds with heteroatom–heteroatom single bonds to unsaturated bonds under photoirradiation is an important method for the efficient and atom-economical construction of carbon–heteroatom bonds. However, in practice, the desired addition reaction is sometimes unable to proceed as expected due to the low efficiency of the desired addition reactions or the preferential polymerization of unsaturated compounds. In this study, by combining an interelement compound with homologous heteroatom compounds as a catalyst, we succeeded in suppressing the polymerization of the unsaturated compounds and in attaining a highly selective carbon–heteroatom bond formation through the desired addition reaction. In this paper, we have examined in detail whether such a “catalytic radical reaction” proceeds for unsaturated compounds and found that the dithiolation of some unsaturated compounds (i.e., vinylic ethers, styrenes, and isocyanides) could proceed with the assistance of (PhSe)₂ under light. The developed methods in this study are expected to have strong implications in the fields of radical chemistry, heteroatom chemistry, synthetic organic chemistry, and catalyst chemistry as atom-economical methods for carbon–heteroatom bond formation. Full article