Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme and one of the causes of tumor resistance to topoisomerase 1 inhibitors such as topotecan. Inhibitors of this Tdp1 in combination with topotecan may improve the effectiveness of therapy. In this work, we synthesized usnic acid derivatives, which are hybrids of its known derivatives - tumor sensitizers to topotecan. New compounds inhibit Tdp1 in the micromolar and submicromolar concentration range; some of them enhance the effect of topotecan on the metabolic activity of cells of various lines according to the MTT test. One of the new compounds (compound 7) not only sensitizes Krebs-2 and Lewis carcinomas of mice to the action of topotecan, but also normalizes the state of the peripheral blood of mice, which is disturbed in the presence of a tumor. Thus, the synthesized substances may be the prototype of a new class of additional therapy for cancer.

Chondrocytes maintain the normal morphological structure and physiological function of articular cartilage. However, the increased expression of inflammatory mediators and matrix-degrading enzymes in chondrocytes can promote ECM degradation, consequently disrupting the physiological function of articular cartilage and ultimately leading to the onset of osteoarthritis (OA). Usnic acid (UA), an extract derived from plants, possesses multiple bioactive properties including anti-inflammatory and antioxidant effects. Hence, this study aims to explore the molecular mechanisms underlying its protective effects in an in vitro simulated model of OA in rat chondrocytes. In vivo experiments encompassed three groups: Control, Model, and Usnic acid (50 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via ELISA assays. In this study, primary rat chondrocytes were employed as the experimental subject. After a 24-hour treatment period, culture supernatants, total RNA, total protein, and nuclear protein were extracted from the different chondrocyte groups. ELISA and qPCR methods were used to measure levels of IL-6, TNF-α, and PGE2. WB and qPCR were employed to assess levels of p65, p-p65, IκBα, p-IκBα, Nrf2, HO-1, NQO1 ADAMTS-4, MMP-1, MMP-3, MMP-13, INOS, COX-2, and COL2A1. IF analysis was performed to examine Nrf2, p-p65 and COL2A1. Results: (1) In vivo, intraperitoneal injection of usnic acid (50mg/kg) can alleviate pathological changes in articular cartilage and the levels of inflammatory and oxidative-related matrix in the serum. (2) UA reduced the level of inflammatory cytokines in IL-1β-induced chondrocytes supernatant. (3) UA can produce anti-inflammatory and antioxidant effects and inhibit chondrocytes matrix degradation through the Nrf2 and NF-κB pathways. (3) The mechanism by which UA exerts a protective role in chondrocytes is mediated by Nrf2 Conclusion: UA inhibits the expression of chondrocyte matrix degradation-related components through Nrf2 mediated Nrf2 pathway and NF-κB pathway, promotes the production of protective substances, and ultimately exerts a protective effect on chondrocytes.

Tdp1 and Tdp2 are DNA repair enzymes that repair DNA damages caused by various agents, including anticancer drugs. Thus, these enzymes resist anticancer therapy and could be the reasons of resistance to such widely used drugs as topotecan and etoposide. In the present work, we found compounds capable of inhibiting both enzymes among derivatives of (-)-usnic acid. Both (+)- and (-)-enantiomers of compounds act equally effectively against Tdp1, and only (-)-enantiomers inhibited Tdp2. Surprisingly, the compounds protect HEK293FT wild type cells from the cytotoxic effect of etoposide but potentiate it against Tdp2 knockout cells. We assume that the sensitizing effect of the compounds in the absence of Tdp2 is associated with effective inhibition of Tdp1, which could take over the functions of Tdp2.

In this paper, carbon nanotubes modified screen-printed electrode (CNTs/SPE) was prepared and the CNTs/SPE was employed for the electrochemical determination of antioxidant substance Chlorogenic acids (CGAs). A pair of well-defined redox peak of CGA was observed at the CNTs/SPE in 0.10 mol∙L^-1 acetic acid-sodium acetate buffer (pH 6.2) and electrode process is adsorption-controlled. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) method for the determination of CGA were proposed based on the CNTs/SPE. Under the optimal conditions, the proposed method exhibited linear ranges from 4.73×10^-7 to 4.45×10^-5 mol∙L^-1, the linear regression equation was Ipa(µA) = 4.1993 C (mol∙L^-1)+1.1039 (r = 0.9976) and the detection limit for CGA could reach 3.25×10^-6 mol∙L^-1. The recovery of matrine was 94.74~106.65% (RSD = 2.92%) in coffe beans. The proposed method is quick, sensitive, reliable, and can be used for the determination of CGA.

Human metapneumovirus is one of major causes of common cold among children, especially infants. Its key enzyme is RNA-dependent RNA-polymerase, which performs both replication and transcription, including capping and cap methylation. The goal of the work is to find possible inhibitors of RNA-dependent RNA-polymerase across the active compounds of Rosaceae plants. The candidates were selected by molecular docking to cap-transferring domain of RNA-polymerase (PDB ID: 4UCZ) in Autodock VINA. Among all the substances tested by docking, ellagic acid derivatives showed the most promising results (affinity values below -10 kcal/mol). Hence, they could be treated as possible candidate drugs against metapneumoviral infection after experimental examination. The main advantage of using these substances should be their low toxicity, which is quite uncommon for selective RNA polymerase inhibitors used in clinical practice. Occurrence of ellagic acid derivatives among the plants from Rosaceae family like raspberry could explain their effect during common cold.

Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, Oleanolic Acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized.A549 and SGC-7901 cells were used to screen the antitumor activity in vitro through the standard MTT method. The compounds, II₃, III₅ and Ⅳ_4, exhibited more potent cytotoxicity than positive drugs.

Ferulic acid has numerous beneficial effects for human health, which are frequently attributed to its antioxidant behavior. In this report many of them are reviewed and 185 new ferulic acid derivatives are computationally designed, using the CADMA-Chem protocol. For the later, the chemical space was sampled and evaluated. To that purpose selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes, directed related with the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and alpha-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directed related with the etiologies of Parkinson’s and Alzheimer’s diseases. They are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.

A variety of myricetin derivatives bearing ferulic acid amide scaffolds were designed and synthesized. The structures of all title compounds were determined by 1 H NMR, 13 C NMR, 19 F NMR and HRMS. Preliminary bioassays suggested that some of the target compounds exhibited remarkable antiviral activities. In particular, compound 4l possessed significant protection activity against tobacco mosaic virus (TMV), with an half maximal effective concentration (EC50) value of 196.11 μg/mL, which was better than commercial agent ningnamycin (447.92 μg/mL). Meanwhile, microscale thermophoresis (MST) indicated that compound 4l have strong binding capability to tobacco mosaic virus coat protein (TMV-CP) with dissociation constant (Kd) values of 0.34 μmol/L, which was better than ningnamycin (0.52 μmol/L). These results suggest that novel myricetin derivatives bearing ferulic acid amide scaffolds may be considered as an activator for antiviral agents.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

The aim of this work is research dedicated to the search for new bactericidal systems for use in cosmetic formulations, dermocosmetics, or the production of wound dressings. Over the last two decades chitosan due to its special biological activity, has become a highly indispensable biopolymer with very wide application possibilities. Literature reports on the antibacterial effects of chitosan are very diverse, but our research has shown that they can be successfully improved through chemical modification. Therefore, in this study, results on the synthesis of new Schiff bases chitosan – dCsSB-SFD and dCsSB-PCA obtained using two aldehydes: sodium 4-formylbenzene-1,3-disulfonate (SFD) and 2-pyridine carboxaldehyde (PCA) respectively. Chitosan derivatives synthesized in this way demonstrate stronger antimicrobial activity. Carrying out the procedure of grafting chitosan with a caproyl chain allowed obtaining compatible blends of chitosan derivatives with κ-carrageenan, which are stable hydrogels with a high swelling coefficient. Furthermore, covalently bounded PCL improved the solubility of obtained polymers in organic solvents. With this respect, the Schiff base-containing polymers obtained in this study, with special hydrogel and antimicrobial properties are very promising materials for the potential use as a controlled-release formulation of both, hydrophilic and hydrophobic drugs in cosmetic products for skin health.

Over the last decades, the increased incidence of metabolic disorders such as type 2 diabetes and obesity has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes was assessed by in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated by Lineweaver–Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 1.67–10.23 x 10-1 mmol/L). The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 1.62–5.19 x 10-1 mmol/L). Finally, PPC84, PPC89, and PPC101 also showed a potent inhibitory effect on α-glucosidase (IC50 of 0.51–3.53 x 10-1 mmol/L). PPC80 and PPC82 followed a non-competitive inhibition mechanism against pancreatic lipase, while PPC84 acted through competitive inhibition. The inhibition of pancreatic α-amylase by the derivatives was non-competitive, as well as for PPC84, PPC89 and PPC101 against α-glucosidase. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-kB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023) addressing their neuroprotective activity in vitro and in vivo.

Reactions of quinones with compounds containing an amino group can produce a wide variety of addition or substitution products that depend on reactivity of both quinone and amino derivative. 6,7-Dichloropyrido[1,2-a]benzimidazole-8,9-diones undergo selective nucleophilic substitution reaction with different benzohydrazides and α-hydroxy-p-quinone imine derivatives stabilized by strong intramolecular hydrogen bond were isolated. Synthesized compounds represent a combination of several structural motifs: benzimidazole core fused with α-hydroxy-p-quinone imine which contains a benzamido fragment. The protonation/deprotonation processes were investigated in a solution using UV-Vis spectroscopy and 1H NMR titration experiment. X-ray crystallography analysis revealed a set of weak non-covalent interactions such as intra- and intermolecular hydrogen bonds and π-π stacking. Additionally, the redox behavior of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its p-imino derivative was investigated in acidic and neutral environment using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as potential effective active electrode in aqueous electrolyte batteries, however further optimization is required.

This study reports a computational investigation on the antioxidant activity of five plant food benzoic acid derivatives, namely gallic acid (GA), para-hydroxybenzoic acid (PHBA), protocatechuic acid (PCA), syringic acid (SA), and vanillic acid (VA). Based on computed thermodynamics parameters, a detailed comparative debate is developed concerning their free radical scavenging activity in the gas phase and polar solutions (in water and methanol solvents). This discussion goes on to elucidate both the most preferred mechanism and the order of antioxidant activity for these molecules in each environment. Paradoxically, calculations using the harmonic oscillator model of aromaticity (HOMA) suggest that H abstraction radicals gain in stability as the central benzene ring loses in structural aromaticity. Finally, spin densities and fukui function f⁰ seem to be good indicators of the local reactivity of these compounds towards free radicals.

Cancer is a catchall term that refers to a collection of more than one chronic disease that can adversely affect the body, including the organs of the body. These diseases can be grouped together under the umbrella term "cancer." Cancer is a catch-all term that is used to refer to a number of different diseases. During the process of looking for new chemical entities, it was found that certain compounds with a basic nucleus of benzoic acid (BA) exhibit a remarkable anticancer potential. This was discovered while the researchers were looking for new chemical entities. In the sixteenth century, the aromatic chemical known as BA, which is also known as an aromatic carboxylic acid, was discovered. BA is also referred to as an aromatic carboxylic acid. When it comes to the chemical synthesis of a wide range of different active molecules, the utilization of a sizeable quantity of BA as a raw material is absolutely necessary. In addition to being present in a variety of other naturally occurring compounds, the BA moiety is the component that is responsible for the activity of the naturally occurring compounds vanillin, gallic acid, and syringic acid. In the synthesis of a wide variety of synthetic bioactive molecules, the BA scaffold is utilized as a building block. The drugs furosemide, bumetanide, benzocaine, tetracaine, and bexarotene are all examples of molecules that fall into this category. The scope of this review article allows for the discussion of a number of noteworthy and recent achievements of BA derivatives in terms of their effectiveness against cancer.

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield the Michael type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the reaction. The study of the variation of the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

1,3 Dipolar cycloaddition of imidazolidine derivatives containing exocyclic double bonds is a convenient method of creating spiro-conjugated molecules with the promising anticancer active. In this work, the derivatives of parabanic acid (2-thioxoimidazolidine-4,5-diones and 5-aryliminoimidazolidine-2,4-diones) were firstly investigated as dipolarophiles in the reactions with nitrile imines. The generation of nitrile imines was carried out either by the addition of tertiary amine to hydrazonoyl chlorides «drop by drop» or using recently proposed diffusion mixing technique, which led to ~5-15% increasing of target compounds yields. It was found that the addition of nitrile imines to C=S or C=N exocyclic double bonds led to 1,2,4-thiazolines or triazolines and occurred regioselectively in accordance to the ratio of FMO coefficients of reactants. The yield of the resulting spiro-compound depended on the presence of alkyl substituents in nitrile imine structure and was significantly decreases at the reactions with imines with strong electron donor or electron-withdrawing groups. Some of the obtained compounds showed reasonable in vitro cytotoxicity. IC50 values were calculated for HCT116 (colon cancer) cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test.

A number of chemical modifications were carried out in order to synthesize new compounds based on the triterpenoid betulonic acid. Triazolation reactions were carried out for the synthesis of new 1,2,3-triazole derivatives based on betulonic acid. Chemical changes were made on the carbonyl group at the C-3 position of the initial molecule and on the carboxyl and hydroxyl groups at the C-28 position. Chromatographic methods were used to separate and purify the formed products. Spectroscopic (NMR-, mass-) methods were used to establish the structure of synthesized compounds. As a result of the chemical transformations carried out, a number of new derivatives of betulonic acid were obtained. All synthesized compounds were tested for antimicrobial and cytotoxic activity. As a result, compounds with pronounced antimicrobial activity were identified.

The critical enzyme Dihydrofolate Reductase-Thymidylate Synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite's reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of novel anti-Leishmania chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family. We conducted a combined ligand/structure-based virtual screening to identify potential inhibitors against LmDHFR-TS. By consensus analysis of both approaches, we identified three compounds, i.e., lithospermic acid (237), diarctigenin (306), and isolappaol A (308), that exhibited a high probability of being inhibitors according to both approaches and were consequently classified as promising hits. Subsequently, we expanded the binding mode examination of these compounds within the active site of the test enzyme through molecular dynamics simulations, revealing a high degree of structural stability and minimal fluctuations in its tertiary structure. The in-silico predictions were then validated through in-vitro assays to examine the inhibitory capacity of the top-ranked naturally-occurring compounds against LmDHFR-TS recombinant protein. The test compounds effectively inhibited the enzyme with IC50 values ranging from 6.1 to 10.1 μM. In contrast, other common cinnamic acid derivatives (i.e., flavonoid glycosides) from the Asteraceae family, such as hesperidin, isovitexin 4′-O-glucoside, and rutin, exhibited low activity against this target. The selective index (SI) for all tested compounds was determined using HsDHFR, with moderate inhibitory effect. Among these hits, lignans 306 and 308 demonstrated the highest selectivity, displaying superior SI values compared to methotrexate, the reference inhibitor of DHFR-TS. Therefore, continued research into the anti-leishmanial potential of these C6C3-hybrid butyrolactone lignans may offer a brighter outlook for combating this neglected tropical disease.

One of the most interesting groups of fatty acid derivates is the group of conjugated fatty acids, from which the most researched are conjugated linoleic acid (CLA) and conjugated linolenic acid (CLNA), which are associated with countless health benefits. Sex pheromone mixture of some insect species, including tobacco horn-worm (Manduca sexta), are typical for the production of uncommon C16 long conjugated fatty acids with two and three conjugated double bonds, as opposed to C18 long CLA and CLNA. In this study, M. sexta desaturases MsexD2 and MsexD3 were expressed in multiple strains of Y. lipolytica with different genotypes. Experiments with supplementation of fatty acid methyl esters into the medium resulted in production of novel fatty acids. Using GCxGC-MS 20 new fatty acids with two or three double bonds were identified. Fatty acids with conjugated or isolated double bonds or combination of both were produced in trace amounts. Results of this study prove that Y. lipolytica is capable of synthesizing C16 conjugated fatty acids. Further genetic optimization of the Y. lipolytica genome and optimization of the fermentation process could lead to increased production of novel fatty acid derivatives with biotechnologically interesting properties.

We introduce a series of twisted donor-acceptor (D-A) carbazole-benzophenone based electroactive bipolar derivatives that were synthesized through the reaction of 4-fluorobenzophenone with various partially alkylated 3,3’-bicarbazoles. The comprehensive structural characterization of these compounds is provided. These amorphous materials exhibit suitable glass transition temperatures ranging from 57 to 102 °C and demonstrate high thermal stability, with decomposition temperatures reaching 400 °C. Moreover, the developed materials exhibit elevated photoluminescence quantum yields (PLQY) of up to 75.5% and favorable HOMO-LUMO levels, along with suitable triplet-singlet state energy values. Due to their good solubility and suitable film-forming properties, all the compounds were evaluated as blue emitters dispersed in 4,4’-bis(N-carbazolyl)-1,10-biphenyl (CBP) host for the fabrication of organic light-emitting diodes (OLEDs) in concentration dependent experiments. Among these experiments, the device containing 15 wt% of the guest 4-(9’-{2-ethylhexyl}-[3,3’]-bicarbazol-9-yl)benzophenone demonstrated the best characteristics, achieving maximum brightness of 3581 cd/m2, current efficiency of 5.7 cd/A, power efficiency of 4.1 lm/W and external quantum efficiency of 2.7%.

Resistance to the existing drugs and increasing numbers of diseases result in identifying new drug candidates with new forms of activity. Marine sources of alkylglycerols such as the liver oil Shark (SLO) mixture of certain species or rat fish (elasmobranch fishes) contain high levels of these compounds as a mixture of few species varying by length and unsaturation or saturation of the alkyl chain. They have multiple biological activities such as hematopoiesis stimulation, lowering radiotherapy-induced injuries, reducing tumor growth and improving vaccination efficiency. The synthesis of two Alkylglycerols (AKGs) containing at least one alkyne moiety in the alkyl chain has been reported. In this work, we describe the synthesis of others unknown AKGs based alkyne 1-O-(hexadec-11’-ynyl)-sn-glycerol 4 and 1-O-(octadec-9’-ynyl)-sn-glycerol 5 as analogues of bioactive ether lipids found in the SLO mixture.

(1) Background: The typical transporter protein, P-glycoprotein (P-gp), has been proven to be associated with multidrug resistance (MDR). Pyxinol and 24S-Pyxinol amino acid ester derivatives had been demonstrated to be promising P-gp inhibitors for reversal of tumor MDR in KBV cells, however, their roles in MDR reversal in other tumor-resistant cells are still unclear. (2) Methods: In the present study, we synthesized 40 amino acid ester derivatives of Pyxinol and 24S-Pyxinol. The MDR reversal effects of these derivatives were evaluated in A549/Tax, MCF-7/ADR, and HCT-8/VCR cells using the CCK-8 assay. Subsequently, western blot assay, intracellular Rhodamine123 (Rh123) accumulation assay and P-gp ATPase activity assay were utilized to investigate the effects of active compound on P-gp. Molecular docking was used to predict the possible binding patterns of active compound to P-gp. Moreover, based on UPLC-Q/TOF-MS cellular metabolomics technology to identify endogenous differential metabolites and metabolic pathways associated with tumor MDR effects of the active compound. (3) Results: The results of the CCK-8 assay showed that compounds 8, 14, 16, 17, 18, 23, 25, 34, 36, 37 exhibited strong MDR reversal effect in A549/Tax, MCF-7/ADR and HCT-8/VCR cells, which were screened by reversal fold (RF) greater than 5. Among them, 10 μM of derivative 37 (new compound) showed the outstanding activity (RF: 15.31) in reversing MDR in A549/Tax cells. Compound 37 could act as a substrate for P-gp and inhibit the efflux function of P-gp by competitively binding to the binding site of antitumor drugs. Meanwhile, the molecular docking results confirmed that compound 37 was identified to under-go high-affinity binding to the drug binding site of P-gp. In addition, 14 endogenous differential metabolites and 6 metabolic pathways involved closely associated with the reversal of tumor MDR effects of compound 37 were identified. (4) Conclusions: Overall, a new candidate compound 37 (24S-3-L-threonyl-Pyxinol) could be provided for reversing tumor MDR by this study.

Human mesenchymal stem cells (hMSCs) constitute of cells having potential of self-renewal and proliferation and are commonly isolated from bone marrow aspirates of large bones. The osteogenic potential of these stem cells has been extensively exploited by scientists during the last many years for the biological evaluation of synthetic scaffolds with applications in tissue engineering. Current work aimed to synthesize N-arylhydrazone derivatives of orotic acid and their evaluation as stimulators of human mesenchymal stem cells. Some of the analogs show good to moderate proliferation rate.

Based on DFT (density functional theory) using B3LYP/6-31G method, theoretical investigations applied to demonstrate the structural, electronic properties and stability of (N,Nˊ-(1,4-phenylene)bis(1,8-naphthalimide)) is more stable than the compound (N-(4-amino phenyl)1,8-naphthalimide) by (-1.2762 eV or -29.4299 Kcal.mol-1) depending on the values of HOMO, synthesis reaction of imide is spontaneous and endothermic at temperature 275˚C according to the values of ∆rS, ∆rG and ∆rH.

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether ARA metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and arachidonic acid (ARA) metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2, prostaglandin F2α, lipoxin A4, ±8(9)-EET, ±11(12)-EET, and ±8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (PLA2 and COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including IFN-γ, TGF-β1, IL-4, and IL-6. In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. In this study, we revealed the structure of the cecal flora of Wenchang chickens infected with S. Typhimurium and demonstrated that S. Typhimurium can mediate the onset and development of intestinal inflammation through the activation of the metabolic pathway of ARA cyclooxygenase in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

A novel investigation into the structure-function relationship was undertaken to enhance understanding of the mechanism of action of the vasoactive peptide angiotensin II (AngII) using unconventional substitutions such as AIB (α-aminobutyric acid), CHA (cyclohexylalanine acid), IAP (isonipecotic acid), TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amine-4-carboxylic acid) at position 3, and DMT (2,6-dimethyl-Tyrosine) at position 4. Biological potency assays were conducted on guinea pig ileum, and structural features were analyzed using circular dichroism (CD) and molecular dynamics (MD). CHA3-AngII and AIB3-AngII analogs retained some agonistic activity, whereas IAP3-AngII and TOAC3-AngII derivatives were inactive. CD results indicated low conformational flexibility for AIB3-AngII and CHA3-AngII, and greater conformational restrictions for IAP3-AngII and TOAC3-AngII, consistent with computational modeling analyses. DMT4-AngII exhibited significant agonistic activity compared to the inactive Phe4AngII. Molecular modeling suggested a potential interaction between the hydroxyl group of Tyr4 and the amide bond between positions 7 and 8. AngII showed greater conformational restriction compared to DMT4-AngII and Phe4-AngII, underscoring the importance of tyrosine at position 4.

Saikosaponin (SS) a is a compound with various pharmacological properties and easily degraded into SSb1 and SSg in acid condition. In present work another two new degradation products of SSa formed under acid hydrolytic condition were detected and isolated by analytical and semi-preparative liquid chromatography technology, furthermore their structures were characterized as hydroxyl-saikosaponin a and SSb2 by spectral analysis, which is not only essential in stability-indicating method development and validation but also could be used as a worst case to assess the analytical method performance of SSa. Moreover their structural transformation pathways were also proposed.

Our previous in vitro reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent antioxidant capacities as well as inhibitory activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including mainly ellagic acid, kaempferol and their derivatives. Nevertheless, few in vivo studies on antidiabetic activities of these phenolics were conducted. The present study investigated hypoglycemic effects with normal and diabetic rats being administrated orally without or with ECE at 200 and 800 mg/kg for 15 days. In normal rats, no significant differences were exhibited after ECE administration in body weight, fasting blood glucose level, levels of chelesterol, triglyceride, LDL and AST in serum, organ indexes, and levels of GSH and MDA in organs. In diabetic rats, the fasting blood glucose level, indexes of heart and liver, and levels of chelesterol and triglyceride in serum and MDA in heart tissue were significantly decreased. Moreover, HDL levels in serum and SOD activities in the four organs of diabetic rats were significantly improved after ECE administration at 800 mg/kg. Thus, in addition to inhibiting α-glucosidase, α-amylase and protein glycation reported previously, oak cups might contain novel dietary phytonutrients in preventing abnormal changes in blood glucose and lipid profile and attenuating oxidant stress in vivo. The results also implied that it is ellagic acid, kaempferol and their derivatives enriched in ECE that might play vital roles in managing type 1 as well as type 2 diabetes.

Elevated serum uric acid (sUA) is associated with risk of developing cardiovascular disease (CVD). Here, we examined the prognostic significance of sUA and exercise capacity in 411 Japanese adults (age, ≥65; mean, 81 years) hospitalized for worsening CVD. Mean sUA was significantly higher in the 23% of patients on an sUA-lowering agent than in those not. When the patients were stratified by sUA into three groups (7.0 mg/dL), the high sUA group had significantly worse peak VO2 and composite endpoint (rehospitalization due to worsening CVD and all-cause mortality) compared with low and moderate sUA groups (P < 0.001). When the patients were stratified by sUA into five groups (sUA 10.0 mg/dL), the incidence of the composite endpoint was significantly higher in the highest sUA group compared with that in the reference group, but only in women. Univariate Cox regression analysis, but not a multivariate analysis, indicated that sUA was significantly associated with the composite endpoint. Although sUA and exercise capacity may have some degree of prognostic significance in older patients with CVD, this significance may differ between men and women.

To better understand the shape memory materials and self-healing materials, a new series of liquid-crystalline shape memory polyurethane (LC-SMPU) composites, named SMPU-OOBAm, were successfully prepared by incorporating 4-octyldecyloxybenzoic acid (OOBA) into the PEG-based SMPU. The effect of OOBA on the structure, morphology and properties has been carefully investigated. The results demonstrate that SMPU-OOBAm have liquid crystalline properties, triple-shape memory properties and self-healing properties. The incorporated OOBA promotes the crystallizability of both soft and hard segments of SMPU, and the crystallization rate of the hard segment of SMPU decreases when the OOBA-content increases. Additionally, the SMPU-OOBAm forms a two-phase separated structure (SMPU phase and OOBA phase), and it shows two-step modulus changes upon heating. Therefore, the SMPU-OOBAm shows triple-shape memory behavior, and the shape recovery ratio decreases with an increase in the OOBA content. Finally, SMPU-OOBAm shows self-healing properties. The new mechanism can be ascribed to the heating-induced “bleeding” of OOBA in the liquid crystalline state and the subsequent re-crystallization upon cooling. This successful combination of liquid crystalline properties, triple-shape memory properties and self-healing properties make the SMPU-OOBAm composites with many promise applications in smart optical devices, smart electronic devices and smart sensors.

This paper investigates pseudo-polymorphism in 2-pyridylmethoxy derivatives of p-tert-butylcalix[4]arene (PyC4), p-tert-butyldihomooxa-calix[4]arenes (PyHOC4), and p-tert-butylhexahomotrioxacalix[3]arenes (PyHO3C3), presenting 11 crystal structures with 15 crystallographically independent molecules. The macrocycle of PyC4 is smaller and less flexible with respect to those of PyHOC4 and PyHO3C3 and in solution, the cone conformation of these three molecules exhibit different point symmetries: C4, Cs and C3, respectively. A correlation is observed between the macrocycle's structural rigidity and the number of pseudo-polymorphs formed. The more rigid PyC4 displays a higher number (6) of pseudo-polymorphs compared to PyHOC4 and PyHO3C3, which exhibit a smaller number of crystalline forms (3 and 2, respectively). The X-ray structures obtained show that the conformation of the macrorings is primarily influenced by the presence of an acetonitrile guest molecule within the cavity, with limited impact from crystal packing and intermolecular cocrystallized solvent molecules. Notably, both calix[4]arene derivatives produce host-guest complex with acetonitrile, while the most flexible and less aromatic PyHO3C3 do not give crystals with acetonitrile as guest. Intertwined 1D and 2D solvent channel networks were observed in the PyHOC4-hexane and in the PyHO3C3-H2O-MeOH crystal structures, respectively, while the other pseudopolymorphs of PyHOC4 and PyHO3C3 and all PyC4 crystal forms exhibit a closely packed crystal structures without open channels.

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

The paper presents a method to assess the effect of electrolyte additives on the energy capacity of Pb-acid batteries. The method applies to any chemically unreactive additive, including suspensions and gels. The approach is thermodynamically based and it leads to the definition of a region of admissible concentrations –the battery’s admissible range– where the battery can undergo an indefinite number of charge/discharge cycles without suffering permanent damage. An experimental procedure to determine this range is presented. The obtained results provide a way to assess the potential of electrolyte additives to improve the energy capacity of Pb-acid batteries. The same results also provide a means to determine the additive concentration that produces the maximum energy capacity increase of the battery. The paper closes with an example of application of the proposed approach to a practical case.

Background: Microscopic examination of acid-fast stained sputum smears for detecting mycobacterial acid-fast bacilli (AFB) remains the most economical and readily available method for laboratory diagnosis of tuberculosis (TB). However, this conventional approach has limitations, including low sensitivity and labor-intensive procedures. Methods: An automated microscopy system incorporating artificial intelligence (AI) and machine learning for AFB identification was evaluated. The study was conducted at an Infectious Disease Hospital in Jiangsu Province, China, utilizing an intelligent microscope system (TB-Scan, Wellgen Medical, Kaohsiung). A total of 1,000 sputum smears were included in the analysis, with the system capturing digital microscopic images and employing an image recognition model to automatically identify and classify AFB. Referee technicians provided the gold standard for discrepant results. Results: The automated system demonstrated an overall accuracy of 95.00% (950/1,000), sensitivity of 91.24% (177/194), and specificity of 95.91% (773/806). Notably, the system identified 21 smears as positive that were previously reported as negative, with referee technicians confirming 17 of these as true positive and retracting the test results accordingly. Recalculating the performance, the accuracy increased to 96.70% (967/1,000), sensitivity to 91.94% (194/211), and specificity to 97.97% (773/789), with a false negative rate of 8.06% (17/211) and a false positive rate of 2.03% (16/789). Conclusions: The incorporation of AI and machine learning into an automated microscopy system demonstrated the potential to enhance the sensitivity and efficiency of AFB detection in sputum smears compared to conventional manual microscopy. This approach holds promise for widespread application in TB diagnostics and potentially other fields requiring labor-intensive microscopic examination.

In this research, catalytic steam reforming acetic acid derived from the aqueous portion of bio-oil for hydrogen production was investigated by using different Ni/ATC (Attapulgite Clay) catalysts prepared by precipitation, impregnation and mechanical blending methods. The fresh and reduced catalysts were characterized by XRD, N₂ adsorption-desorption, TEM and H₂-TPR. The comprehensive results demonstrated that the interaction between active metallic Ni and ATC carrier was significantly improved in Ni/ATC catalyst prepared by precipitation method, and in which the mean Ni particle size was the smallest (~13 nm) resulted in the highest metal dispersion (7.5%). The catalytic performance of the three catalysts was evaluated through the process of steam reforming of acetic acid in a fixed-bed reactor under atmospheric pressure at two different temperatures, such as 550 ℃ and 650 ℃. Results showed that the Ni/ATC (PM-N/ATC) prepared by precipitation method, achieved the highest H₂ yield of ~82% and little lower acetic acid conversion efficiency of ~85% than that (~95%) of Ni/ATC (IM-NATC) prepared by impregnation method. In addition, the deactivation catalysts after reaction for 4 h were analyzed by XRD, TGA-DTG and TEM, which demonstrated that the catalyst deactivation was not caused by the amount of carbon deposition, but owed to the significant agglomeration and sintering of Ni particles in the carrier.

The term Conjugated Linoleic Acid (CLA) refers generically to a class of positional and geometric conjugated dienoic isomers of linoleic acid. Among the isomers of linoleic acid cis9, trans11-CLA (c9, t11-CLA) and trans10, cis12-CLA (t10, c12-CLA) are found to be bio-logically active isomers, and they occur naturally in milk, dairy products and meat from ruminants. In addition, some vegetables and some sea-foods have also been reported to contain CLA. Although the CLA levels in these natural sources are insufficient to confer the essential health benefits, anti-carcinogenic or anti-cancer effects are of current interest. In the rumen, CLA is an intermediate of isomerization and the biohydrogenation process of linoleic acid to stearic acid conducted by ruminal microorganisms. In addition to rumen bacteria, some other bacteria, such as Propionibacterium, Bifidobacterium and some lactic acid bacteria (LAB) are also capable of producing CLA. In this regard, Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) has demon-strated the ability to produce CLA isomers from linoleic acid by multiple enzymatic activi-ties, including hydration, dehydration, and isomerization. L. plantarum is one of the most versatile species of LAB and the bacterium is widely used in the food industry as a micro-bial food culture. The studies reviewed in this article reveal how, in the production of some fermented foods, the use of appropriate strains of L. plantarum, as a starter or additional culture, can be considered a critical factor in the design of new CLA-enriched functional foods.

Two interesting compounds such as quaternary ammonium lignin(QAL) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507) were synthesized as ionic liquids(QP-ILs) for the extraction of metal ions. The extraction behavior of Co(II) and Ni(II) from chloride solution was compared between QP-ILs and P507. The results showed that the extraction rates of Co(II) and Ni(II) in the two solutions varied with the extraction conditions, but QP-ILs has stronger extractability for cobalt than P507, while Ni is on the contrary. Under the same conditions, the Co/Ni separation performance(βCo/Ni) in QP-ILs is superior to that in p507. At pH4.0, 55℃, concentration of 20%, extraction time of 10 minutes, the βCo/Ni of QP-ILs reached to 2703, while that of P507 was only 164. In conclusion, QP-ILs was more efficient than P507 for separating Co from mixed solutions.

Cisplatin is a widely used anticancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas increased Bcl-2 expression. Moreover, in cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor interacting protein kinase (RIPK) and mixed lineage kinase domain like (MLKL) were identified. In vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted by co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anticancer adjuvant.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

The poly lactic acid (PLA) is one of the most used bio-derived thermoplastic polymers in 3D and 4D printing applications. The determination of PLA surface properties is of capital importance in 3D/4D printing technology. (1) Background: The surface thermodynamic properties of PLA polymer were determined by using the inverse gas chromatography (IGC) technique at infinite dilution. The determination of the retention volume of polar and non-polar molecules adsorbed on the PLA particles filling the column allowed us to obtain the dispersive, polar, and Lewis’s acid-base surface properties at different temperatures from 40 °C to 100 °C. (2) Methods: the applied surface method was based on our recent model that used the London dispersion equation and the new chromatographic parameter function of the deformation polarizability and the harmonic mean of the ionization energies of the PLA polymer and organic molecules. (3) Results: The application of this new method led to the determination of the dispersive and polar free surface energy of adsorption of molecules on the polymeric material, as well as the glass transition and the Lewis acid-base constants. (4) Conclusions: four interval temperatures were distinguished showing four zones of the variations of the surface properties of PLA as a function of the temperature before and after the glass transition.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR&gt;MTYR&gt;&gt;TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

β-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. β-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was also examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that β-lactams are inhibitors of hCA I, II and AChE. The K_i values of β-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that β-lactams (2a-k) inhibit both CA isoenzymes and AChE at low nanomolar concentrations.

Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties, including anti-inflammatory, antiviral and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures, but also new synthetic routes developed during the last years as well as promising therapeutic applications.

In agriculture, soil-borne fungal pathogens, especially Fusarium oxysporum strains, are posing a serious threat to efforts to achieve global food security. In the search for safer agrochemicals, silica nanoparticles (SiO2NPs) have recently been proposed as a new tool to alleviate pathogen damage including Fusarium wilt. Hollow mesoporous silica nanoparticles (HMSNs), a unique class of SiO2NPs, have been widely accepted as a desired pesticide carrier. However, their role in enhancing the disease resistance and the specific mechanism remain unknown. In this study, three sizes of HMSNs (19, 96 and 406 nm as HMSNs–19, HMSNs–96 and HMSNs–406, respectively) were synthesized and characterized to determine their effects on seed germination, seedling growth, and Fusarium oxysporum f. sp. phaseolus (FOP) suppression in cowpea roots by foliar spray using phenotypes, fresh biomass and disease progression as indicators. The results revealed that three HMSNs exhibited no adverse impacts on seed germination and tended to improve plant growth. Also, they exert their FOP suppression with a size- and concentration-dependent manner. HMSNs–406 possessed the best control effect at a concentration of 1000 mg/L showing an upto 40.00% decline in the disease severity. The Si(OH)4 control was also effective on FOP suppression at a lower concentration of 100 mg/L, whereas its higher concentrations exhibited obviously adverse impacts on FOP control, seed germination and plant growth. Moreover, we conformed that HMSNs posed their Fusarium wilt suppression in cowpea plant by activating SA (salicylic acid)-dependent SAR (systemic acquired resistance) responses rather than directly suppressing FOP. A higher level of SA content and elevated expression of its maker genes of PR-1 and PR-5 in HMSNs–406 treated cowpea roots provided substantial evidences of this mode of action. Other resistance-related genes, as well as defense-responsive enzymes, were also involved in the HMSNs-activated SAR pathway. Overall, for the first time, our results extended a new role of HMSNs as a potent elicitor to serve as a versatile alternative for plant disease protection of low cost, highly efficiency and sustainability.

The bilateral tempered fractional derivatives are introduced generalising previous works on the one-sided tempered fractional derivatives and the two-sided fractional derivatives. An analysis of the tempered Riesz potential is done and showed that it cannot be considered as a derivative.

Natural cytokinins are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of novel cytokinin analogs with alkyl substituents at various positions of the aromatic moiety, as well as with oxygen-containing groups, and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Two amino-linked compounds were anti-proliferative with the ability to act synergistically with doxorubicin, and two carbamate-based ones were cytoprotective. According to the molecular docking data, anti-proliferation was based on the A2AR and APRT inhibition and cytoprotection on the CDK2 inhibition. The obtained results are promising for the development of novel anti-cancer therapeutics.

This study investigated the effects of exogenous gibberellic acid (GA) treatments (elongating cluster + seedless + expanding, T1; seedless + expanding, T2; expanding, T3 and water, CK) on the content of sugars, organic acids, and endogenous hormones and sink strength.Results showed that T2 treatment displayed the highest fructose and glucose levels at 100 days after treatment (DAT), whereas its effect on tartaric acid, malic acid, and citric acid concentrations at 80 and 100 DAT was relatively weak. Under GA3 treatments, both GA3, IAA, and CTK contents increased, whereas ABA contents decreased at 1, 2, 4, 8, and 48 h. Analysis of sugar phloem unloading revealed that T2 treatment exhibited the highest values during softening and ripening stages. Our findings indicate that appropriate GA3 application can positively influence sink strength by regulating sink size and activity, including berry size enlargement, sugar phloem unloading and sugar accumulation in grape sink cells.

Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipopolysis group was introduced at the cordycepin N6 to improve the problem, Cordycepin derivatives(3a-4c) were synthesized, and biological evaluation of compounds were studied. In the study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with IC50 value of 27.566±0.52 μM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3, and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.

This study presented a novel and sustainable method for producing chitin nanocrystals (PA-ChNCs) using phosphoric acid hydrolysis. The produced PA-ChNCs were used as stabilizers for Pickering emulsions and their physicochemical properties as well as stabilization mechanisms were systematically investigated. The PA-ChNCs exhibited small particle sizes and high surface areas, enabling an effective adsorption at the oil/water interface, which prevented coalescence in Pickering emulsions. The particle size and surface charge PA-ChNCs were strongly pH-dependent, which were critical factors for stabilizing Pickering emulsions. The study showed that emulsions with higher O:W ratios (50%) exhibited larger droplets but greater viscosity, forming a stable gel-like matrix that was more stable than emulsions with other O:W ratios after storage for 30 days. Emulsions with higher PA-ChNCs concentrations (2.0 wt%) and higher pH values (pH 10) showed small droplets and high viscosity, leading to stable emulsions. This research contributes to the development of sustainable and effective emulsifiers for use in the food industry, making utilization of seafood waste in an eco-friendly manner possible. Overall, this study highlights the potential of using newly developed PA-ChNCs as stabilizers for Pickering emulsions in food products.

Owing to the growing concerns due to dwindling fossil fuel reserves, increasing energy demand and climate emergency, it is imperative to develop and deploy sustainable energy technologies to ensure future energy supply as well as transition to the net zero world. In this context, there is great potential in the biorefinery concept for supplying drop in biofuels in the form of biodiesel. Biodiesel as a fuel can certainly bridge the gap where electrification or the use of hydrogen is not feasible, for instance heavy vehicles, farm and marine transportation sector. However, biodiesel industry also leads to formation of large amount of crude glycerol as the byproduct. Crude glycerol due to presence of several impurities may not be a suitable feedstock for all high value products derived from glycerol but fits well with glycerol esterification for producing glycerol acetins, which have numerous applications. This review critically looks at the processes using nanostructured solid/liquid acid catalysts for glycerol esterification including the economic viability of the scale up.

This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

The paper discusses the mechanism of montmorillonite structure alteration and bentonites properties modification (on the example of samples from clay deposit Taganka, Kazakhstan) due to the thermochemical treatment (treatment with inorganic acid solutions at different temperatures, concentrations and reaction times). With the use of the suit of methods certain processes were distinguished: transformation of montmorillonite structure, which appears in the leaching of interlayer and octahedral cations, protonation of the interlayer and OH groups at octahedral sheets. Changes in the structure of the 2:1 layer of montmorillonite and its interlayer result in significant changes in the properties – reduction of cation exchange capacity and an increase of specific surface area. The results of the work showed that bentonite clays retain a significant portion of its adsorption properties even after the long term and intense thermochemical treatment (6M HNO3, 60°C, 108 hours)

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Monoterpenes as natural products are the subject of increased attention in the search for new pharmacological agents because of their numerous biological activities including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, vasodilating effects, etc. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing in experimental dementia and Parkinson’s disease effects. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive direction in experimental pharmacology and a promising approach to the therapy of various pathologies. Biologically active substances such as monoterpenes borneol, camphor, geraniol, pinene, and thymol, were used to synthesize compounds with different properties, including analgesic, anti-inflammatory, anticonvulsant, anti-depressant, anti-Alzheimer’s, anti-parkinsonian, antiviral and antibacterial (anti-tuberculosis). Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, conjugation of myrtenal with the known pharmacophore adamantane allows one to enhance some of its key properties. Myrtenal-adamantane derivatives exhibited a variety of beneficial properties – antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective, which are worth examining in more detail and at length.

Fractional calculus gained a lot of attention in the last couple of years. Researchers discovered that processes in various fields follow rather fractional dynamics than ordinary integer-ordered dynamics, meaning the corresponding differential equations feature non-integer valued derivatives. There are several arguments for why this is the case, one of them being that fractional derivatives’ inherit spatiotemporal memory and/or the ability to express complex naturally occurring phenomena. Another popular topic nowadays is machine learning, i.e., learning behavior and patterns from historical data. In our ever-changing world with ever-increasing amounts of data, machine learning is a powerful tool for data analysis, problem-solving, modeling, and prediction. It further provides many insights and discoveries in various scientific disciplines. As these two modern-day topics provide a lot of potential for combined approaches to describe complex dynamics, this article reviews combined approaches of fractional derivatives and machine learning from the past, puts them into context, and thus provides a list of possible combined approaches and the corresponding techniques. Note, however, that this article does not deal with neural networks, as there already is profound literature on neural networks and fractional calculus. We sorted past combined approaches from the literature into three categories, i.e., preprocessing, machine learning &amp; fractional dynamics, and optimization. The contributions of fractional derivatives to machine learning are manifold as they provide powerful preprocessing and feature augmentation techniques, can improve physically informed machine learning, and are capable of improving hyperparameter optimization. Thus, this article serves to motivate researchers dealing with data-based problems, to be specific machine learning practitioners, to adopt new tools and enhance their existing approaches.

A series of derivatives of trans-3-(2,4,6-trimethoxy phenyl)-4,5-dihydro isoxazolo-4,5-bis(aroylcarbohydrazide) and of trans-3-(2,4,6-trimethoxyphenyl)4,5-dihydroisoxazolo-4,5-bis[carbonyl-(4’phenyl)thiosemi- carbazide (9) were synthesized from trans-3-(2,4,6-trimethoxyphenyl)-4,5-dihydro-4,5-bis(hydrazenocarbonyl) Isoxazole (8). The structures of the Compounds were elucidated by elemental and spectral (IR, NMR, and MS) analysis. The compound 9 show activity against some bacterial species. Whereas, no activity was observed for compounds 10a, 10b and 10c against all bacterial species. The antioxidant activity of new compounds has been screened. Compound 9 showed higher antioxidant activity using the DPPH and ATBS method.

Wheat is widely grown in the Mediterranean region, where plants frequently face water shortages. Recently, more attention to rationalizing irrigation water has been increased due to the adoption of sustainable agricultural systems. Therefore, two field trials were conducted at the Agriculture Research Station of Nubaria, Egypt, in two consecutive seasons (2017/2018 and 2018/2019) to examine three irrigation regimes' effects, i.e., 60, 80, and 100% of crop evapotranspiration (ETc) combined with foliar ascorbic acid (AsA) or vitamin B2 (VB2) on yield and water productivity of wheat in two separate experiments. A split-plot design was used with three replicates. Irrigation treatments occupied the main plots, while the subplot in the first experiment was placed by ascorbic acid (AsA) and vitamin B2 in the second experiment. Results indicated that 100% ETc produced higher wheat yield and its attributes and insignificantly surpassed 80% ETc. Compared to the unsprayed plots, the foliar application of 6 mM ascorbic acid or 2.0 mM vitamin B2 significantly increased grain yield, components, and water use efficiency. The interaction between irrigation regimes (100% ETc or 80% ETc) and foliar application of 6.0 mM ascorbic acid or 2.0 mM vitamin B2 resulted in the highest values with no significant difference. Foliar application of ascorbic acid or vitamin B2 saved 20% of irrigation water while yielding a reduction that did not exceed 10%. The biplot graph of treatments x traits (TT) was a useful statistical tool for examining the impact of treatments on yield and its characteristics and identifying the links between these factors. Results suggest that riboflavin or ascorbic acid may have a potential role as an effective antioxidant for enhancing the tolerance for drought stress in wheat.

Although migraine belongs to the main causes of disability worldwide the mechanisms of its pathogenesis are poorly known, which is among the reasons that this disease is underdiagnosed and undertreated. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective markers of its occurrence and severity. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. Migraine patients displayed lower urinary levels of 5-HIAA and KYNA, but KYN and QA were enhanced as compared with the controls. Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios. Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score, monthly migraine, and monthly headache days. A negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be an easy-to-determine marker of migraine occurrence and severity and may contribute to the identification of migraine patients with depression.

Fruit cracking or splitting, a severe physiological disease that highly affects appearance and quality, compromise the commodity value of fruit and also causes huge economical losses to the producers of several fleshy fruit crops. The growth-promoting phytohormone gibberellic acid (GA) and growth-inhibiting phytohormone abscisic acid (ABA) antagonistically regulate numerous developmental processes throughout the plant life cycle. Homeostasis of endogenous GA and ABA play a significant role in the normal growth of fruits, and its imbalance may lead to the occurrence of cracking or splitting during the process of fruit growth, development, ripening and postharvest storage. The pathways of GA and ABA metabolism and signaling have been studied widely, and the major components were well characterized, which including the genes encoding major biosynthesis and catabolism enzymes and the key signaling components. Nevertheless, our knowledge of the mechanisms of GA and ABA governing fruit cracking is not comprehensive enough. In this review, we not only focus on the scenarios of effects of endogenous GA and ABA contents in the fruit and exogenous plant growth regulators GA and ABA treatments, but also endeavor to provide some genetic cues on the function of GA and ABA responsible for fruit cracking modulation. Information from this review aims to strengthen the understanding of potential molecular bases underlying GA and ABA in fruit cracking control and provide guidance in breeding of fruit cultivars with cracking-resistant ideotypes, and also make great theoretical significance in guiding the establishment of integrated prevention and control measures to fruit cracking or splitting.

Schiff bases attract research interest due to their applications in chemical synthesis and medicinal chemistry. In recent years, benitrobenrazide and benserazide containing imine moiety, have been synthesized and characterized as promising inhibitors of hexokinase 2 (HK2) an enzyme overexpressed in most cancer cells. Both compounds possess a common structural fragment, a 2,3,4-trihydroxybenzaldehyde moiety connected through hydrazone or hydrazine linker with acylated on N’-nitrogen atom by serine or 4-nitrobenzoic acid fragment. To avoid presence of toxicophoric nitro group in benitrobenrazide molecule we introduced common pharmacophores 4-fluorophenyl or 4-aminophenyl substituents. Modification of benserazide regards an introduction of other endogenous amino acids instead of serine. Herein we report the synthesis of benitrobenrazide and benserazide analogues and preliminary results of inhibitory activity against HK2 evoked by these structural changes. The derivatives contain a fluorine atom or amino group instead of a nitro group in BNB, exhibited the most potent inhibitory effects against HK2 at a concentration of 1 µM, with HK2 inhibition rates of 60% and 54%, respectively.

As a part of our ongoing effort in the search for promising antileishmanial agents based on the thiochroman scaffold, we prepared a series of substituted 2H-thiochromenes. Thirty-three compounds were evaluated against intracellular amastigotes forms of L. (V) panamensis. Twelve compounds were active with EC₅₀ values lower than 40 μM, and among those three compounds displayed the highest antileishmanial activity with EC₅₀ values below 10 uM. Cytotoxicity was determined against human U-937 macrophages; thus, compounds having electrophilic alkenes (α,β-unsaturated carbonyl, or nitriles) displayed the highest antileishmanial activity but also moderate to high cytotoxicities. Based on SAR analysis, compounds 8d and 10, which differ only in the hydroxy group at C4, were selected as the most promising compounds in this library because good antiparasitic activity and Selectivity Index.

Biomimetic materials are substances that replicate natural structures. There are several methods for producing such materials with highly developed surfaces from a wide range of polymers, but electrospinning is of particular interest due to its simplicity of implementation and the ability to modify the produced fibrous materials resembling structures found in living organisms. This study explores new biomimetic materials based on polyhydroxyalkanoates, specifically poly-3-hydroxybutyrate, modified with chlorophyll derivatives. The research investigates the impact of chlorophyll derivatives on the morphology, supramolecular structure, and key properties of nonwoven materials. The obtained results are of interest for the development of new biomimetic environmentally friendly materials for biomedicine with special properties.

A series of pyrazolopyrimidines derivatives 4– 11 were synthesized using 1-(6-(3-methoxyphenyl)-4-methylpyridazin-3-yl)-1H-pyrazolo [3,4-d] pyrimidin-4-amine 3 as a starting material. The detailed synthesis, structure assignments of the novel compounds based on chemical and spectroscopic evidence, spectroscopic data, pharmacological properties and molecular docking are reported. The pharmacological evaluation illustrated that many of these compounds have good analgesic, anti-inflammatory and antimicrobial activities.

A series of cysteine-based perfluoroaromatic (hexafluorobenzene (I) and decafluorobiphenyl (II) were synthesized and established as a chemoselective and available core to simple or more complex systems since small molecules to biomolecules with interesting properties. As proof of concept of the potential application of perfluorinated derivatives as non-cleavable linkers, some antibody-perfluorinated conjugates were prepared via thiol, demonstrating that the bioconjugation process doesn’t affect to the macromolecular entity. Besides, some molecular properties of synthesized compounds are evaluated using a combination of spectroscopic characterization (FT-IR and 19F-NMR chemical shifts) and theoretical calculations. Moreover, molecular Docking was also developed to predict cysteine-based hexafluorobenzene and decafluorobiphenyl derivatives’ affinity against topoisomerase Il and cyclooxygenase 2 (COX-2). The results suggested that mainly cysteine-based decafluorobiphenyl derivatives could be potential topoisomerase II α and COX-2 inhibitors, becoming potential anticancer agents and candidates for anti-inflammatory treatment.

This paper discusses the concept of fractional derivative with complex order from the application point of view. It is shown that a fractional derivative is hermitian, if and only if the order is real. The hermitian part of complex order derivatives behave like allpass filters with almost logarithmic phase.

The temperature effect plays an important role for an accurate determination of the polar free energy, polar thermodynamic parameters, and enthalpic and entropic Lewis’s acid base properties of oxides, polymers and composites polymers/oxides. The adsorption of polymers on other solid surfaces is crucial in many industrial applications, coatings, paints, catalysis, colloids and adhesion processes. (1) Background: Inverse gas chromatography at infinite was used for the physico-chemical characterization of solid substrates by determining the thermodynamic parameters of adsorption of model organic solvents on solid surfaces such as polymers, metallic oxides, carbon fibers, pharmaceutical or 3D/4D printing substrates. (2) Methods: A new method based on the London dispersion equation was applied with a new parameter associating the deformation po-larizability and the harmonic mean of the ionization energies of solvent. More accurate values of the dispersive and polar interaction energies of the various organic solvents adsorbed on PMMA in bulk phase and PMMA/silica at different recovery fractions were obtained as well as the Lewis acid-base parameters and the transition temperatures of the different composites. (3) Results: This new methodology gave very interesting results on the behavior of PMMA adsorbed on silica. An important effect of the temperature and the recovery fraction on the various physicochemical and thermodynamic properties was highlighted. The variations of all interaction parameters showed the presence of three transition temperatures for the different PMMA adsorbed on silica with the various coverage rates with a shift of these temperatures for a recovery fraction of 31% (4) Con-clusions: An important variation of the polar enthalpy and entropy of adsorption, the Lewis ac-id-base parameters and the intermolecular separation distance as a function of the temperature and the recovery fraction of PMMA on silica.

Hyperlipidemia is an identified risk factor for metabolic syndrome, obesity and cardiovascular complications characterized by elevated levels of lipids in blood. The present study aimed to inhibit HMG-CoA reductase with 15-oxoursolic acid through in-vivo and in-silico assessments. HFD-induced hyperlipidemia in rats was developed with a marked increase in total cholesterol (58.34 ± 0.21 mg/dl), triglycerides (45.45 ± 0.39 mg/dl), LDL-c (66.12 ± 0.10 mg/dl), VLDL-c (19.34 ± 0.16 mg/dl), and a decrease in HDL-c (10.34 ± 0.18 mg/dl). The oral administration of 15-oxoursolic acid at a concentration of 30 mg/Kg b.w significantly reduced the serum concentration of total cholesterol (42.65 ± 0.54 mg/dl), triglycerides (32.33 ± 0.16 mg/dl), LDL-c (50.34 ± 0.15 mg/dl) and VLDL-c (13.15 ± 0.45 mg/dl) respectively and an increased in the serum HDL-c (18.56 ± 0.34 mg/dl). 15-oxo ursolic acid also caused a decrease in the coronary risk index and atherogenic risk index. In-silico studies of 15-oxoursolic acid with HMG-CoA reductase showed significant interaction capability with binding energy (-9.26805 Kcal/mol). It is concluded that 15-oxoursolic acid could significantly reduce the total cholesterol, triglycerides and LDL levels in HFD-induced hyperlipidemia rats which might lead to new medication with significant hypolipidemic potential.

This work aims to introduce a novel concept: the Riesz-Dunkl fractional derivatives, within the context of Dunkl type operators. A particularly noteworthy revelation is that when a specific parameter $\kappa$ equals zero, the Riesz-Dunkl fractional derivative smoothly reduces to both the well-known Riesz fractional derivative and the fractional second-order derivative. Furthermore, we introduce a new concept: the fractional Sobolev space. This space is defined and characterized using the versatile framework of the Dunkl transform.

Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological aims, were presently tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues, and to assess calcium antagonism in comparison to amiodarone, lidocaine, procainamide, and quinidine. All compounds, but two, compared favorably with the reference drugs. Potent antiarrhythmic activity was observed for compounds (in increasing order) 4, 1, 6 and 5. The last compound N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase of threshold of ac-arrhythmia, and being devoid of antihypertensive activity against spontaneously hypertensive rats.

We propose a methodology for the quantification of model risk in the context of credit derivatives pricing and CVA, where the uncertain or unmodelled parameter is often the correlation between rates and credit. We take the rates model to be Hull-White (normal) and the credit model to be Black-Karasinski (lognormal). We show how highly accurate analytic pricing formulae, hitherto unpublished, can be derived for CDS and extended to address instruments with defaultable Libor flows which may in addition be capped and/or floored. We also consider the pricing of a contingent CDS with an interest rate swap underlying. We derive explicit expressions showing how to good accuracy the dependence of model prices on the uncertain parameter(s) can be captured in analytic formulae which are readily amenable to computation without recourse to Monte Carlo or lattice-based computation. In so doing, we take into account the impact on model calibration of the uncertain (or unmodelled) parameter.

Bile acids (BA) are classically known as an agent important in lipid absorption and cholesterol metabolism. Nowadays, BAs have been found to be involved in various cellular signaling pathways such as protein kinase cascades, cyclic AMP (cAMP) synthesis and calcium mobilization. In addition, they have also been shown to regulate glucose and energy homeostasis. Bile acids are ligands for several nuclear hormone receptors, including FXR. Recently, muscarinic receptor and TGR5, G-protein-coupled receptor (GPCR), have been suggested to play a role in bile acid activity which is independent of nuclear hormone receptors. Moreover, BAs have also been studied in other GPCR associated pathways, namely sphingosine-1-posphate and glucagon receptor. Hydrophobic bile acids have been proven to affect heart rate and its contraction. Elevated bile acids are associated with arrhythmias in adults and fetal heart. Altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase of serum bile acid concentrations. In contrast, the most hydrophilic BA known as ursodeoxycholic acid has been found beneficial in improving peripheral blood flow in chronic heart failure patients and protecting heart against reperfusion injury.

Two ferrocene derivatives, namely, 1,2-(tetramethylene)-ferrocene and 1,2,1’,2’-bis(tetramethylene)-ferrocene, were synthesized in a four-step reaction sequence starting from ferrocene. Friedel-Craft acylation of ferrocene with succinic anhydride gave mono- or bis(3-carboxypropinoyl)ferrocene depending on the stoichiometry of succinic anhydride. The reduction of the keto groups to methylene, followed by ring-closing using trifluoroacetic anhydride gave 1,2-(α-ketotetramethylene)-ferrocene or 1,2,1’,2’-bis(α-ketotetramethylene)ferrocene. The diastereomeric mixture of the latter diketones was separated by column chromatography, characterized by single-crystal X-ray analysis, and assigned their stereochemistry. Reduction of the keto groups to methylene under Clemmensen conditions gave homoannular mono- or bis(tetramethylene) ferrocene derivatives. The molecular structure of 1,2-(tetramethylene)-ferrocene revealed that the ipso carbon atoms of the cyclopentadienyl group are 0.023(3) Å farther away from Fe(II) compared to the remaining three carbon atoms. Both complexes exhibit lower half-wave oxidation potentials than ferrocene, possibly due to the electron-releasing effects of the tetramethylene bridges.

This research was devoted to study the effect of the tacticity of PMMA on the surface physicochemical properties such as the London dispersive component of the surface energy of the polymer, the polar and dispersive free energies, the Lewis’s acid-base surface parameters, and the Lewis acid and base surface energies of atactic, isotactic and syndiotactic PMMAs as a function of the temperature. Inverse gas chromatography (IGC) at infinite dilution was used to determine the surface thermodynamic properties of PMMA at different tacticities. The experimental values of the net retention time and volume of model organic molecules adsorbed on the atactic, isotactic and syndiotactic PMMAs, were obtained by IGC technique at infinite dilution. The London dispersion interaction energy was used for the separation of the polar and dispersive energy of the different n-alkanes and polar solvents adsorbed on the different PMMA surfaces. The London dispersive surface energy γ_s^d (T) of PMMAs was determined by applying the Hamieh thermal model that took into account the effect of the temperature on the surface area of adsorbed molecules. The obtained results showed non-linear variations of γ_s^d (T) of atactic, isotactic, and syndiotactic PMMAs with three maxima characterizing the three transition temperatures of PMMAs, T_g, T_g and T_(liq-liq) with a shift of these temperatures with the isotactic and syndiotactic PMMAs. It was showed that the polar interaction free energy ∆G_a^p (T) also showed the presence of the three above transition temperatures of the polymers. The study showed an important non-linearity variation of the different acid-base parameters in the various polymer surfaces proving the highest effect of the temperature and the tacticity on these parameters. The determination of the enthalpic and entropic Lewis’s acid-base parameters showed an amphoteric character for the different PMMAs. The basicity of the atactic PMMA was about four times larger than its acidity outside the neighborhood of the transition temperatures of the polymer. Whereas, the isotactic PMMA was about 2 to 2.5 times more basic than acid, while the syndiotactic PMMA exhibited the highest basicity by showing a surface 5 to 8 times more basic than acid. However, the Lewis acid-base parameters strongly depended on the temperature and sudden variations of these surface parameters were observed around the transition temperatures largely depending on the PMMA tacticity. The determination of the polar acid and base surface energies of the three PMMAs led to the same previous transition temperatures with an important effect of the tacticity of PMMA on the values of these acid-base surface energies.

Fine dust causes various disorders, including cardiovascular, neurological, renal, reproductive, motor, systemic, respiratory, and cancerous diseases. Therefore, it is necessary to study functional materials to prevent these problems. In this study we used various methods, including quantitative PCR, flow cytometry, ELISA, and Alizarin O staining, to study the beneficial effects of erucic acid against fine dust. Erucic acid and erucic acid-induced exosomes (EIE) strongly suppress the attenuation of osteocytic differentiation and inflammation induced by fine dust. Erucic acid effectively suppresses inflammation in fibroblasts exposed to fine dust. Notably, despite exposure to fine dust, EIE promoted osteocytic differentiation in adipose-derived stem cells (ASC) and osteogenesis in macrophages, in addition to phagocytosis. Dramatic upregulation of RunX2 and BMP7 by EIE indicates that it is a strong activator of osteocytic differentiation in ASC and protects them from the effects of fine dust. Moreover, EIE induces immune activity and acts as an osteogenic trigger for macrophages. Therefore, this study suggests the potential use of erucic acid and erucic acid-induced exosomes (EIE) as biomaterials to prevent environment-borne diseases.

The increase in fungal infections, accompanied by adverse effects and acquired resistance associated with the use of antifungal agents used for their clinical management, have facilitated the search for new substances with antifungal properties. Naphthoquinones have been investigated due to their multiple biological activities, including their significant antifungal potential. This study aimed at evaluating the antifungal potential of naphthoquinones against opportunistic fungi and dermatophytes and to assess the impact of a selected naphthoquinone on the formation of the cell wall, ergosterol membrane, and cellular membrane of Candida albicans ATCC 60193. Additionally, cytotoxicity in the MRC-(Medical Research Council-)5 cell lineage, Artemia salina, and tomato as well as arugula seeds was evaluated. The antifungal activity of four naphthoquinones was assessed using well-characterized fungal strains, the minimum inhibitory concentration (MIC) was determined applying the microdilution assay technique. Antifungal activity of the assessed naphthoquinones could be confirmed, particularly for 2,3-DBNQ (2,3-dibromo-1,4-naphthoquinone), which showed prominent antifungal activity (MIC of &lt;1.56 - 6.25 µg/mL) in all chosen test settings. However, its toxicity in MRC-5 cells (IC50 = 15.44 µM), a recorded 100% mortality in A. salina at a concentration of 50 µg/mL, as well as inhibition of 94.8% of the tomato seeds at a concentration of 400 µg/mL and inhibition of 64.1% of arugula seeds at a concentration of 200 µg/mL may limit hypothetical therapeutic applications. It was demonstrated that the likely mechanism of action of 2,3-DBNQ involves interfering with fungal membrane permeability, leading to increased leakage of nucleotides. This study adds to available knowledge on antifungal effects of naphthoquinones, especially of 2,3-DBNQ, against opportunistic yeasts and dermatophytes. However, the observed cytotoxicity in the MRC-5 cell lineage, A. salina, as well as tomato and arugula seeds highlights a need for further research to optimize the selectivity and safety profile of naphthoquinones like 2,3-DBNQ before potential clinical use may be assessed.

To study the feasibility and effect of compounding lignin and its derivatives to improve expansive soil, the physical properties, mechanical properties, and microstructure of the improved soil mixed with calcium lignosulfonate alone, calcium lignosulfonate and lignin fibers were investigated through indoor experiments and electron microscope scanning. Select samples with better performance for water stability tests, and discuss the improvement mechanism of expansive soil by combining macroscopic mechanical changes with microstructural characteristics. The research results show that the addition of calcium lignosulfonate can reduce the water content of the soil and enhance its strength of the soil. The overall performance is the best when the calcium lignosulfonate content is 3%. 3% calcium lignosulfonate compounded with 1.5% lignin fiber has the best all-around performance; the composite improved soil has a better pore-filling effect, the whole is more compact, and the connection between particles significantly enhances the strength, which greatly inhibits the development of cracks good water stability. Lignin and its derivatives compound improved expansive soil have better effect than traditional improvement methods, and have no pollution to the environment, which can provide a particular reference for engineering practice

To study the feasibility and effect of compounding lignin and its derivatives to improve expansive soil, the physical properties, mechanical properties, and microstructure of the improved soil mixed with calcium lignosulfonate alone, calcium lignosulfonate and lignin fibers were investigated through indoor experiments and electron microscope scanning. Select samples with better performance for water stability tests, and discuss the improvement mechanism of expansive soil by combining macroscopic mechanical changes with microstructural characteristics. The research results show that the addition of calcium lignosulfonate can reduce the water content of the soil and enhance its strength of the soil. The overall performance is the best when the calcium lignosulfonate content is 3%. 3% calcium lignosulfonate compounded with 1.5% lignin fiber has the best all-around performance; the composite improved soil has a better pore-filling effect, the whole is more compact, and the connection between particles significantly enhances the strength, which greatly inhibits the development of cracks good water stability. Lignin and its derivatives compound improved expansive soil have better effect than traditional improvement methods, and have no pollution to the environment, which can provide a particular reference for engineering practice.

A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds (3a-3i) exhibited significant clot lysis with respect to negative control and reference drug streptokinase (30,000 IU) while enhanced clotting time (CT) values were observed (130-342 sec) for these tested compounds than the standard drug heparin (110 sec.). High affinity towards 1NFY with greater docking score was observed for the compounds (3a, 3i, 3e, 3d and 3h) than the control ligand RPR200095. In addition, very good inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612-6270) with ACE values (–189.68 to –352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE –197.81 kcal/mol. In vitro, in vivo and in silico results proposed that these newly synthesized compounds can be used as anti-coagulant agents.

Research on retinoid-based cancer prevention, spurred by the effects of vitamin A deficiency on gastric cancer and subsequent clinical studies on digestive tract cancer, unveils novel avenues for chemoprevention. Acyclic retinoids like 4,5-didehydrogeranylgeranoic acid (4,5-didehydroGGA) emerged as potent agents against hepatocellular carcinoma (HCC), distinct from natural retinoids such as all-trans retinoic acid (ATRA). Mechanistic studies reveal GGA's unique induction of pyroptosis, a rapid cell death pathway, in HCC cells. GGA triggers mitochondrial superoxide hyperproduction and ER stress responses through Toll-like receptor 4 (TLR4) signaling and modulates autophagy, ultimately activating pyroptotic cell death in HCC cells. Unlike ATRA-induced apoptosis, GGA and palmitic acid (PA) induce pyroptosis, underscoring their distinct mechanisms. While all three fatty acids evoke mitochondrial dysfunction and ER stress responses, GGA and PA inhibit autophagy, leading to incomplete autophagic responses and pyroptosis, whereas ATRA promotes autophagic flux. In vivo experiments demonstrate GGA's potential as an anti-oncometabolite, inducing cell death selectively in tumor cells and thus suppressing liver cancer development. This review provides a comprehensive overview of the molecular mechanisms underlying GGA's anti-HCC effects and underscores its promising role in cancer prevention, highlighting its importance in HCC prevention.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

Background: Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Its serum concentration increases in cardiovascular disease (CVD). We hypothesized that DCA may affect hemodynamic parameters in rats. Methods: The concentration of DCA in systemic blood was measured with liquid chromatography coupled with mass spectrometry. Arterial blood pressure (BP), heart rate (HR) and echocardiographic parameters were evaluated in anesthetized, male, 3-4-month-old Sprague-Dawley rats administered intravenously (IV) or intracerebroventricularly (ICV) with investigated compounds. Mesenteric artery (MA) reactivity was tested ex vivo. Results: The baseline plasma concentration of DCA was 0.24 ± 0.03 mg/l. The oral antibiotic treatment produced a large decrease in the concentration. Administered IV, the compound increased BP and HR in a dose-dependent manner. DCA also increased heart contractility and cardiac output. None of the tested compounds: prazosin (an alpha-blocker), propranolol (beta-adrenolytic), atropine (muscarinic receptor antagonist), glibenclamide (K-ATP inhibitor) or DY 268 (FXR antagonist), glycyrrhetinic acid (11HSD2 inhibitor) significantly diminished the DCA-induced pressor effect. ICV infusion did not exert significant HR or BP changes. DCA relaxed MAs. Systemic vascular resistance did not change significantly. Conclusions: DCA increases BP by increasing cardiac output. As a bioactive gut bacteria-derived metabolite, DCA may co the interaction between gut microbiota and the host’s circulatory system.

We present synthetic experiments of lactic acid (LA) polycondensation to produce poly(lactic acid) (PLA), as well as kinetic modeling calculations that capture the polymer molecular weight increase with time, given the initial concentrations. Tin-octoate-catalyzed polycondensation of (D,L)- or L-lactic acid, was carried out in pre-dried toluene after azeotropic dehydration for 48-120 hours at 130-137 °C. The polymerization was optimized by varying lactic acid and catalyst concentrations as well as the temperature. Gel Permeation Chromatography was used to experimentally follow the evolution of molecular weights and the products were characterized by NMR, TGA, DSC and IR. Under optimal conditions, PLLA with weight-average molecular weight (Mw) of 161 kDa could be obtained. The rate equations that describe polycondensation kinetics were recast in a condensed form that allowed very fast numerical solution and calculation of the number-average molecular weight with time. Deviations with respect to the experiment were minimized in a least-squares fashion, to determine rate constants. The optimized kinetics parameters are shown to reproduce the experimental data accurately

DFT calculations on the photoisomerization reactions of pyridazine N-oxide derivatives are presented. The irradiation of 3,6-diphenylpyridazine N-oxide allowed to obtain the first excited singlet state that underwent to a ring opening reaction induced to the oxygen migration to the adjacent carbon atom, with the formation of a diazo derivative. This intermediate can give a ring closure reaction to give a pyrazole derivative, or, with a higher transition energy, it can lose nitrogen allowing the formation of 2,5-diphenylfuran. The irradiation of 3-phenylpyridazine N-oxide allowed the formation only of 2-phenylfuran. In this case, calculations allowed to explain this behavior. The first excited singlet state gave a photoisomerization reaction with the formation of the corresponding diazo intermediate. This intermediate could not be converted into the corresponding pyrazole derivative because it was converted into a N-formyl pyrazole never reported in literature. The only possible reaction is the loss of nitrogen and the formation of 2-phenylfuran.

Bipyridine and its related compounds are starting materials or precursors for a variety of valuable substances, such as biologically active molecules, ligands for catalysts, photosensitizers, viologens, and supramolecular architectures. Therefore, it is important to classify the synthesis methods and know their characteristics. Representative examples include the methods using homo- and heterocoupling of pyridine derivatives in the presence of catalyst. Because bipyridine compounds have a high ability to coordinate with metal centers, a decrease in catalytic activity and yield is often observed in the reaction system. To address this issue, the review provides insight into recent advances in bipyridine synthesis using metal complexes under both homogeneous and heterogeneous conditions. Moreover, the review also sheds light on strategies for bipyridine synthesis involving sulfur and phosphorous compounds. These alternative pathways offer promising avenues for overcoming challenges associated with traditional-catalyzed methods, providing a more comprehensive understanding of the synthesis landscape.

Breast cancer (BC) is the most common malignancy among women worldwide. In recent years, significant progress has been made in BC therapy. However, serious side effects resulting from the use of standard chemotherapeutic drugs, as well as the phenomenon of multidrug resistance (MDR), limit the effectiveness of approved therapies. Advanced research in the BC area is necessary to create more effective and safer forms of therapy to improve the outlook for individuals diagnosed with this aggressive neoplasm. For decades, plants and natural products with anti-cancer properties have been successfully utilized in treating various medical conditions. Anthracene derivatives are tricyclic secondary metabolites of natural origin that have been identified in plants, lichens, and fungi. They represent a few botanical families, e.g., Rhamnaceae, Rubia-ceae, Fabaceae, Polygonaceae, and others. The review comprehensively covers and analyzes the most recent advances in the anticancer activity of anthracene derivatives (emodin, aloe-emodin, hypericin, chrysophanol, rhein, and physcion) applied both individually, or in combination with other chemotherapeutic agents in in vitro and in vivo BC models.

An important parameter in the development of a new drug is the drug's affinity to the identified target (protein/enzyme). Predicting the ligand binding to the target (protein/enzyme) by molecular simulation would allow the synthesis to be restricted to the most promising compounds.A restricted hybrid HF-DFT calculation was performed in order to obtain the most stable conformer of each ligand and a series of DFT calculations using the B3LYP levels with 6-31G* basis set has been conducted. The docking studies of the quinolone compounds will be performed with the CLC Drug Discovery Workbench to identify and visualize the ligand-receptor interaction mode.

Terrestrial plant resources are becoming increasingly scarce; moreover, the development of science and technology has facilitated the exploration of marine ecosystems. We isolated and identified six novel (1–6) and six (7–12) known secondary metabolites of Alternaria sp MCCC 3A00467 by chromatographic and spectroscopic techniques and investigated their antitumor activities in human myeloma (U266), liver cancer (HepG2), and lung cancer (A549) cells by the MTT assay. Among these compounds, the new compounds 2, 3 and 4 exhibited excellent anticancer activities with IC₅₀ values of 21.98, 24.99 and 14.78 μg/mL, respectively. These compounds obtained from a marine source have the potential to be developed into novel anticancer drugs.

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date Alzheimer's and Parkinson's disease are the most common NDs. The risk of developing NDs increases dra-matically with age, and genetic and environmental factors can be crucial in their progression. The main feature of NDs is the abnormal presence of specific proteins that can lead to neuronal death, proteotoxic stress, and alteration of catabolic systems, which are major players in the processes of neurodegeneration and neuroinflammation. Despite research efforts to date, the therapies cur-rently in use for the treatment of NDs provide marginal therapeutic benefit, so the focus is now being direct toward the search of natural products that could be a valuable aid in combating these diseases, including the natural compound Andrographis paniculata (Ap) and especially its main constituent Andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap is capable to modulate neuroinflammatory and neurodegenerative responses, determining a reduction in inflammatory markers and oxidative stress in various NDs. Therefore, in this review we will focus on the molecular mechanisms through which Ap and Andro are able to modulate the processes of neurodegeneration and neuroinflammation that are major causes of neuronal death and cognitive decline.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavourable drugs properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use as inhalable formulations. Particulate-solid HA-VAN25 complex by spray drying from an aqueous dispersion was obtained. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern by X-ray was observed. The powder density, geometric size and morphology showed a suitable aerosolization and aerodynamic performance of the powder, indicating the capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 hours. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus, showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

Lignocellulosic biomass has garnered attention as an abundant and sustainable alternative energy source that can facilitate reliable and environmentally friendly energy generation. Energy security improves, and environmental impacts diminish when bioethanol, a biofuel produced via lignocellulose-based processes, is utilized. The lignocellulosic biomass of Thysanolaena latifolia has considerable potential as a bioethanol feedstock due to its high carbohydrate content (62.4 ± 0.7%). In this study, feedstock derived from T. latifolia was pretreated with various concentrations of H3PO4 to determine the ideal conditions for enzymatic hydrolysis to convert the feedstock to fermentable sugar. The findings revealed that hydrolysis efficiency and glucose recovery yields were substantially improved compared to those of the untreated sample. Pretreated samples were enzymatically digested to produce a liquid hydrolysate. This hydrolysate was fermented without detoxification using Saccharomyces cerevisiae TISTR 5339 to produce ethanol. The results indicated that T. latifolia biomass hydrolysate is a promising long-term carbon source for ethanol production from cellulosic biomass. Furthermore, the morphological and crystallographic characteristics of the treated T. latifolia biomass were influenced by H3PO4 concentration, as indicated by the SEM images, X-ray diffractogram patterns, and crystallinity index values. Therefore, utilizing T. latifolia feedstock to produce bioethanol can enhance bioenergy sustainability.

Visible-light photocatalysis, particularly in its application to organic synthesis, has experienced a big renaissance in the past decade. The rational design of new photocatalysts with designed and improved photocatalytic properties, that at the same time circumvents the necessity of using scarce and toxic transition metals, will predictably play a key role in photocatalysis in the next few years. Although free-base porphyrins were identified some years ago as a promising, easily accessible and easily tunable class of organic photoredox catalysts, a systematic study on the effect of the electronic nature and of the position of the substituents on both the ground-state and the excited-state redox potentials of these compounds is still lacking. We have prepared a set of known functionalized derivatives of meso-tetraphenyl porphyrin containing different substituents either in one of the meso-positions or at a beta-pyrrole carbon and we have determined their ground- and (singlet) excited-state redox potentials. This survey has led us to conclude that the introduction of a carbonyl group at the beta-pyrrolic position strongly increases the facility of the monoelectronic reduction of the porphyrin both in the ground state and in the singlet excited state. We have also prepared a second set of four previously unknown benzoyl derivatives of meso-tetraphenylporphyrin, and we have confirmed the validity of our conclusions.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Bile acids (BAs) and their signalling pathways have been identified as therapeutic targets for liver and metabolic diseases. We generated Cyp2c70-/- (KO) mice that are not able to convert chenodeoxycholic acid into rodent-specific muricholic acids (MCAs) and, hence, possess a more hydrophobic, human-like BA pool. Recently, we have shown that KO mice display cholangiopathic features with development of liver fibrosis. The aim of this study was to determine whether BA sequestration modulates liver pathology in Western type-diet (WTD)-fed KO mice. The BA sequestrant colesevelam was mixed into the WTD (2% w/w) of male Cyp2c70+/+ (WT) and KO mice and the effects were evaluated after 3 weeks of treatment. Colesevelam increased fecal BA excretion in WT and KO mice and reduced the hydrophobicity of biliary BAs in KO mice. Colesevelam ameliorated diet-induced hepatic steatosis in WT mice, whereas KO mice were resistant to diet-induced steatosis and BA sequestration had no additional effects on liver fat content. Total cholesterol concentrations in livers of colesevelam-treated WT and KO mice were significantly lower than those of untreated controls. Of particular note, colesevelam treatment normalized plasma levels of liver damage markers in KO mice and markedly decreased hepatic mRNA levels of fibrogenesis-related genes in KO mice. Lastly, colesevelam did not affect glucose excursions and insulin sensitivity in WT or KO mice. Our data show that BA sequestration ameliorates liver pathology in Cyp2c70-/- mice with a human-like bile acid composition without affecting insulin sensitivity.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

A new method for the synthesis of azido-propargyloxy derivatives of 1,3,5-triazine has been developed. The antibacterial activity against E. coli bacteria of propargyloxy substituted 1,3,5-triazines - 2,4,6-trispropargyloxy-1,3,5-triazine, 2-azido-4,6-bispropargyloxy-1,3,5-triazine and 2,4-diazido-6-propargyloxy-1,3,5-triazine and their hyperbranched polymers. It has been shown that the presence of an azide group in the compound directly affects the antibacterial activity. The cytotoxicity of these compounds against the M-HeLa, FetMSC and Vero cell lines was studied. The IC50 value was determined for low molecular weight compounds. It has been shown that hyperbranched polymers without azide groups don’t exhibit pronounced cytotoxicity and can be used in biomedical applications.

This comprehensive scientific review provides an in-depth analysis of both the natural compounds, pyrethrins, and their synthetic derivatives, pyrethroids, focusing on their classification, biosynthesis, mechanism of action, general and pharmaceutical uses, as well as their toxicity and environmental impact. Pyrethrins, derived from certain plant species, have long been recognized for their potent insecticidal properties. The review begins by examining the classification of pyrethrins and pyrethroids, elucidating their structural characteristics and unique features within the field of natural and synthetic compounds. The biosynthetic pathways responsible for producing pyrethrins in plants are discussed, highlighting the enzymatic reactions and genetic regulation involved. In addition, the synthesis of pyrethroid derivatives is explored, including both natural and synthetic sources and potential optimization strategies. Understanding the mechanisms of action by which pyrethrins and pyrethroids exert their insecticidal effects is a crucial aspect of this review. Complex interactions with the nervous systems of target organisms are examined, providing insights into their selective toxicity and modes of action. In addition, the various applications of these compounds are explored, from their use in agriculture for pest control to their incorporation into household insecticides and potential pharmaceutical applications. The review also critically evaluates the potential toxicity of pyrethrins and pyrethroids to human health. By consolidating current knowledge and research findings, this review provides a comprehensive understanding of the properties and applications of pyrethrins and pyrethroids, highlighting their benefits and risks, and the importance of responsible and sustainable use in various areas.