bluuebunny/crossref_metadata_2025 huggingface dataset:
The Methionine 549 and Leucine 552 Residues of Friedelin Synthase from Maytenus ilicifolia Are Important for Substrate Binding Specificity
Authors: Mazzeu Bruna F. , Souza-Moreira Tatiana M. , Oliveira Andrew A. , Remlinger Melissa , Felippe Lidiane G. , Valentini Sandro R. , Guido Rafael V. C. , Zanelli Cleslei F. , Furlan Maysa
Published: November 2021

Friedelin, a pentacyclic triterpene found in the leaves of the Celastraceae species, demonstrates numerous biological activities and is a precursor of quinonemethide triterpenes, which are promising antitumoral agents. Friedelin is biosynthesized from the cyclization of 2,3-oxidosqualene, involving a series of rearrangements to form a ketone by deprotonation of the hydroxylated intermediate, without the aid of an oxidoreductase enzyme. Mutagenesis studies among oxidosqualene cyclases (OSCs) have demonstrated the influence of amino acid residues on rearrangements during substrate cyclization: loss of catalytic activity, stabilization, rearrangement control or specificity changing. In the present study, friedelin synthase from Maytenus ilicifolia (Celastraceae) was expressed heterologously in Saccharomyces cerevisiae. Site-directed mutagenesis studies were performed by replacing phenylalanine with tryptophan at position 473 (Phe473Trp), methionine with serine at position 549 (Met549Ser) and leucine with phenylalanine at position 552 (Leu552Phe). Mutation Phe473Trp led to a total loss of function; mutants Met549Ser and Leu552Phe interfered with the enzyme specificity leading to enhanced friedelin production, in addition to α-amyrin and β-amyrin. Hence, these data showed that methionine 549 and leucine 552 are important residues for the function of this synthase.
Source Indication and Geochemical Significance of Sedimentary Organic Matters from the Xisha Area, the South China Sea
Authors: Li Yan , Zhou Qian-Zhi , Xu Xiang-Po , Fang Yun-Xin , Liu Jin-Zhong , Wang Jiang-Hai
Published: November 2021

Although various geochemical and geophysical investigations have already indicated a great resource potential in the Xisha area of the South China Sea, the origin of organic matter and molecular evidence for tracing the migration of hydrocarbons from deep petroleum reservoirs are still lacking. In this study, systematic organic geochemical analyses, including bulk organic matter parameters and lipid biomarkers were performed for deep sediments from two cores. The C/N ratios and δ13C and δ15N values of organic matter in most of the samples, together with the maxima of short-chain n-alkanoic acids and mid-chain n-alkanols, high abundances of monounsaturated fatty acids C18:1ω9 and C22:1ω13, jointly indicate the dominance of marine organic matter. n-Alkanes in sediments from core GMGS4-XH-W06B are characterized by small unresolved complex mixture (UCMs) humps, high odd/even predominance (OEP) and carbon preference index (CPI) values, clearly exhibiting characteristics of modern sediments. However, the sediments for core GMGS4-XH-W03B are featured with big UCMs, associated with OEP and CPI values around 1.0, showing signatures of petroleum hydrocarbons from high maturity sources. Considering the geologic background, the biomarker signatures are solid evidence for indicating the existence of underlying petroleum reservoirs, and may provide the valuable information for assessing the hydrocarbon resources in the Xisha area.
Low-Dimensional Architectures in Isomeric cis-PtCl2{Ph2PCH2N(Ar)CH2PPh2} Complexes Using Regioselective-N(Aryl)-Group Manipulation
Authors: De’Ath Peter , Elsegood Mark R. J. , Sanchez-Ballester Noelia M. , Smith Martin B.
Published: November 2021

The solid-state behaviour of two series of isomeric, phenol-substituted, aminomethylphosphines, as the free ligands and bound to PtII, have been extensively studied using single crystal X-ray crystallography. In the first library, isomeric diphosphines of the type Ph2PCH2N(Ar)CH2PPh2 [1a–e; Ar = C6H3(Me)(OH)] and, in the second library, amide-functionalised, isomeric ligands Ph2PCH2N{CH2C(O)NH(Ar)}CH2PPh2 [2a–e; Ar = C6H3(Me)(OH)], were synthesised by reaction of Ph2PCH2OH and the appropriate amine in CH3OH, and isolated as colourless solids or oils in good yield. The non-methyl, substituted diphosphines Ph2PCH2N{CH2C(O)NH(Ar)}CH2PPh2 [2f, Ar = 3-C6H4(OH); 2g, Ar = 4-C6H4(OH)] and Ph2PCH2N(Ar)CH2PPh2 [3, Ar = 3-C6H4(OH)] were also prepared for comparative purposes. Reactions of 1a–e, 2a–g, or 3 with PtCl2(η4-cod) afforded the corresponding square-planar complexes 4a–e, 5a–g, and 6 in good to high isolated yields. All new compounds were characterised using a range of spectroscopic (1H, 31P{1H}, FT–IR) and analytical techniques. Single crystal X-ray structures have been determined for 1a, 1b∙CH3OH, 2f∙CH3OH, 2g, 3, 4b∙(CH3)2SO, 4c∙CHCl3, 4d∙½Et2O, 4e∙½CHCl3∙½CH3OH, 5a∙½Et2O, 5b, 5c∙¼H2O, 5d∙Et2O, and 6∙(CH3)2SO. The free phenolic group in 1b∙CH3OH, 2f∙CH3OH,2g, 4b∙(CH3)2SO, 5a∙½Et2O, 5c∙¼H2O, and 6∙(CH3)2SO exhibits various intra- or intermolecular O–H∙∙∙X (X = O, N, P, Cl) hydrogen contacts leading to different packing arrangements.
Molecular Insights into Binding Mode and Interactions of Structure-Based Virtually Screened Inhibitors for Pseudomonas aeruginosa Multiple Virulence Factor Regulator (MvfR)
Authors: Almihyawi Raed A. H. , Al-Hasani Halah M. H. , Jassim Tabarak Sabah , Muhseen Ziyad Tariq , Zhang Sitong , Chen Guang
Published: November 2021

Multi-drug resistance (MDR) bacterial pathogens pose a threat to global health and warrant the discovery of new therapeutic molecules, particularly those that can neutralize their virulence and stop the evolution of new resistant mechanisms. The superbug nosocomial pathogen, Pseudomonas aeruginosa, uses a multiple virulence factor regulator (MvfR) to regulate the expression of multiple virulence proteins during acute and persistent infections. The present study targeted MvfR with the intention of designing novel anti-virulent compounds, which will function in two ways: first, they will block the virulence and pathogenesis P. aeruginosa by disrupting the quorum-sensing network of the bacteria, and second, they will stop the evolution of new resistant mechanisms. A structure-based virtual screening (SBVS) method was used to screen druglike compounds from the Asinex antibacterial library (~5968 molecules) and the comprehensive marine natural products database (CMNPD) (~32 thousand compounds), against the ligand-binding domain (LBD) of MvfR, to identify molecules that show high binding potential for the relevant pocket. In this way, two compounds were identified: Top-1 (4-((carbamoyloxy)methyl)-10,10-dihydroxy-2,6-diiminiodecahydropyrrolo[1,2-c]purin-9-yl sulfate) and Top-2 (10,10-dihydroxy-2,6-diiminio-4-(((sulfonatocarbamoyl)oxy)methyl)decahydropyrrolo[1,2-c]purin-9-yl sulfate), in contrast to the co-crystallized M64 control. Both of the screened leads were found to show deep pocket binding and interactions with several key residues through a network of hydrophobic and hydrophilic interactions. The docking results were validated by a long run of 200 ns of molecular dynamics simulation and MM-PB/GBSA binding free energies. All of these analyses confirmed the presence of strong complex formation and rigorous intermolecular interactions. An additional analysis of normal mode entropy and a WaterSwap assay were also performed to complement the aforementioned studies. Lastly, the compounds were found to show an acceptable range of pharmacokinetic properties, making both compounds potential candidates for further experimental studies to decipher their real biological potency.
Novel Triterpenoids from Cassia fistula Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats
Authors: Indu Sabapathy , Vijayalakshmi Periyasamy , Selvaraj Jayaraman , Rajalakshmi Manikkam
Published: November 2021

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (p < 0.05). Plasma insulin (p < 0.0001)/C-peptide (p < 0.0006), tissue glycogen (p < 0.0034), glycogen phosphorylase (p < 0.005), glucose 6-phosphatase (p < 0.0001) and lipid markers were significantly increased (p < 0.0001) in diabetic rats, whereas glucokinase (p < 0.0047), glycogen synthase (p < 0.003), glucose oxidation (p < 0.001), GLUT4 mRNA (p < 0.0463), GLUT4 protein (p < 0.0475) and the insulin-signaling molecules IR mRNA (p < 0.0195), IR protein (p < 0.0001), IRS-1 mRNA (p < 0.0478), p-IRS-1Tyr612 (p < 0.0185), Akt mRNA (p < 0.0394), p–AktSer473 (p < 0.0162), GLUT4 mRNA (p < 0.0463) and GLUT4 (p < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1–C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1–C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.
Structural Requirements of 1-(2-Pyridinyl)-5-pyrazolones for Disproportionation of Boronic Acids
Authors: Cho Joungmo , Sadu Venkata Subbaiah , Han Yohan , Bae Yunsoo , Lee Hwajeong , Lee Kee-In
Published: November 2021

We observed an unusual formation of four-coordinate boron(III) complexes from the reaction of 1-(2-pyridinyl)-5-pyrazolone derivatives with arylboronic acids in the basic media. The exact mechanism is not clear; however, the use of unprotected boronic acid and the presence of a bidentate ligand appeared to be the key structural requirements for the transformation. The results suggest that base-promoted disproportionation of arylboronic acid with the assistance of the [N,O]-bidentate ligation of 1-(2-pyridinyl)-5-pyrazolone should take place and facilitate the formation of pyrazole diarylborinate. Experiments to obtain a deeper understanding of its mechanism are currently underway.
Synthesis and Fungicidal Activity of Hydrated Geranylated Phenols against Botrytis cinerea
Authors: Soto Mauricio , Estevez-Braun Ana , Amesty Ángel , Kluepfel Julia , Restrepo Susana , Diaz Katy , Espinoza Luis , Olea Andrés F. , Taborga Lautaro
Published: November 2021

Botrytis cinerea is a ubiquitous fungus that affects hundreds of plants, resulting in economic losses to the horticulture and fruit industry. The search for new antifungal agents is a matter of current interest. Thus, in this work a series of geranylated phenols in which the side alkyl chain has been hydrated have been synthesized, and their activity against B. cinerea has been evaluated. The coupling of phenol and geraniol has been accomplished under microwave irradiation obtaining the highest reaction yields in the shortest reaction times. Hydration of the side chain was carried out in dioxane with p-toluenesulfonic acid polymer-bound as the catalyst. All synthesized compounds were tested against B. cinerea using the growth inhibition assay and EC50 values were determined. The results show that activity depends on the number and nature of functional groups in the phenol ring and hydration degree of the geranyl chain. The most active compound is 1,4-dihydroquinone with one hydroxyl group attached at the end of the alkyl chain. Results from a molecular docking study suggest that hydroxyl groups in the phenol ring and alkyl chain are important in the binding of compounds to the active site, and that the experimental antifungal activity correlates with the number of H-bond that can be formed in the binding site.
Panchromatic Fluorescence Emission from Thienosquaraines Dyes: White Light Electrofluorochromic Devices
Authors: Corrente Giuseppina Anna , Parisi Francesco , Maltese Vito , Cospito Sante , Imbardelli Daniela , La Deda Massimo , Beneduci Amerigo
Published: November 2021

Electrofluorochromic devices (EFCDs) that allow the modulation of the light emitted by electroactive fluorophores are very attractive in the research field of optoelectronics. Here, the electrofluorochromic behaviour of a series of squaraine dyes was studied for the first time. In solutions, all compounds are photoluminescent with maxima located in the range 665–690 nm, characterized by quantum yields ranging from 30% to 4.1%. Squaraines were incorporated in a polymer gel used as an active layer in all-in-one gel switchable EFCDs. An aggregation induced quenching occurs in the gel phase, causing a significant decrease in the emission quantum yield in the device. However, the squaraines containing the thieno groups (thienosquaraines, TSQs) show a panchromatic emission and their electrofluorochromism allows the tuning of the fluorescence intensity from 500 nm to the near infrared. Indeed, the application of a potential difference to the device induces a reversible quenching of their emission that is significantly higher and occurs at shorter switching times for TSQs-based devices compared to the reference squaraine dye (DIBSQ). Interestingly, the TSQs fluorescence spectral profile becomes more structured under voltage, and this could be explained by the shift of the aggregates/monomer equilibrium toward the monomeric species, due to electrochemical oxidation, which causes the disassembling of aggregates. This effect may be used to modulate the colour of the fluorescence light emitted by a device and paves the way for conceiving new electrofluorochromic materials based on this mechanism.
Non-Chemical Treatments for the Pre- and Post-Harvest Elicitation of Defense Mechanisms in the Fungi–Avocado Pathosystem
Authors: Herrera-González Juan Antonio , Bautista-Baños Silvia , Serrano Mario , Romanazzi Gianfranco , Gutiérrez-Martínez Porfirio
Published: November 2021

The greatest challenge for the avocado (Persea americana Miller) industry is to maintain the quality of the fruit to meet consumer requirements. Anthracnose is considered the most important disease in this industry, and it is caused by different species of the genus Colletotrichum, although other pathogens can be equally important. The defense mechanisms that fruit naturally uses can be triggered in response to the attack of pathogenic microorganisms and also by the application of exogenous elicitors in the form of GRAS compounds. The elicitors are recognized by receptors called PRRs, which are proteins located on the avocado fruit cell surface that have high affinity and specificity for PAMPs, MAMPs, and DAMPs. The activation of defense-signaling pathways depends on ethylene, salicylic, and jasmonic acids, and it occurs hours or days after PTI activation. These defense mechanisms aim to drive the pathogen to death. The application of essential oils, antagonists, volatile compounds, chitosan and silicon has been documented in vitro and on avocado fruit, showing some of them to have elicitor and fungicidal effects that are reflected in the postharvest quality of the fruit and a lower incidence of diseases. The main focus of these studies has been on anthracnose diseases. This review presents the most relevant advances in the use of natural compounds with antifungal and elicitor effects in plant tissues.
Anti-Osteoporotic Effects of n-trans-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling
Authors: Lim Hyung Jin , Park Eun-Jae , Won Yeong-Seon , Bak Seon Gyeong , Cheong Sun Hee , Lee Seung Woong , Lee Soyoung , Lee Seung-Jae , Rho Mun-Chual
Published: November 2021

Osteoporosis is characterized by the deterioration of bone structures and decreased bone mass, leading to an increased risk of fracture. Estrogen deficiency in postmenopausal women and aging are major factors of osteoporosis and are some of the reasons for reduced quality of life. In this study, we investigated the effects of n-trans-hibiscusamide (NHA) and its derivative 4-O-(E)-feruloyl-N-(E)-hibiscusamide (HAD) on receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL)-induced osteoclast differentiation and an ovariectomized osteoporosis mouse model. NHA and HAD significantly inhibited the differentiation of osteoclasts from bone marrow-derived macrophages (BMMs) and the expression of osteoclast differentiation-related genes. At the molecular level, NHA and HAD significantly downregulated the phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules. However, Akt and NF-κB phosphorylation was inhibited only after NHA or HAD treatment. In the ovariectomy (OVX)-induced osteoporosis model, both NHA and HAD effectively improved trabecular bone structure. C-terminal telopeptide (CTX), a bone resorption marker, and RANKL, an osteoclast stimulation factor, were significantly reduced by NHA and HAD. The tartrate-resistant acid phosphatase (TRAP)-stained area, which indicates the osteoclast area, was also decreased by these compounds. These results show the potential of NHA and HAD as therapeutic agents for osteoporosis.
Mild Copper-Catalyzed, l-Proline-Promoted Cross-Coupling of Methyl 3-Amino-1-benzothiophene-2-carboxylate
Authors: Kederienė Vilija , Jaglinskaitė Indrė , Voznikaitė Paulina , Rousseau Jolanta , Rollin Patrick , Šačkus Algirdas , Tatibouët Arnaud
Published: November 2021

Cu-catalyzed N-arylation is a useful tool for the chemical modification of aromatic heterocycles. Herein, an efficient carbon–nitrogen cross-coupling of methyl 3-amino-1-benzothiophene-2-carboxylate with a range of (hetero)aryl iodides using CuI, l-proline and Cs2CO3 in dioxane at moderate temperature is described. The procedure is an extremely general, relatively cheap, and experimentally simple way to afford the N-substituted products in moderate to high yields. The structures of the new heterocyclic compounds were confirmed by NMR spectroscopy and HRMS investigation.
Determination of N-Acetyl-l-cysteine Ethyl Ester (NACET) by Flow Injection Analysis and Spectrophotometric Detection Using Different Thiol-Sensitive Ligands
Authors: Kukoc-Modun Lea , Kraljević Tomislav , Tsikas Dimitrios , Radić Njegomir , Modun Darko
Published: November 2021

A new flow injection spectrophotometric method for the determination of N-acetyl-l-cysteine ethyl ester (NACET) was developed and validated. The method is based on the reduction of Cu(II)-ligand complexes to chromophoric Cu(I)-ligand complexes with the analyte. The studied ligands were neocuproine (NCN), bicinchoninic acid (BCA) and bathocuproine disulfonic acid (BCS). The absorbance of the Cu(I)-ligand complex was measured at 458, 562 and 483 nm for the reactions of NACET with NCN, BCA and BCS, respectively. The method was validated in terms of linear dynamic range, limit of detection and quantitation, accuracy, selectivity, and precision. Experimental conditions were optimized by a univariate method, yielding linear calibration curves in a concentration range from 2.0 × 10−6 mol L−1 to 2.0 × 10−4 mol L−1 using NCN; 2.0 × 10−6 mol L−1 to 1.0 × 10−4 mol L−1 using BCA and 6.0 × 10−7 mol L−1 to 1.2 × 10−4 mol L−1 using BCS. The achieved analytical frequency was 90 h−1 for all three ligands. The method was successfully employed for NACET determination in pharmaceutical preparations, indicating that this FIA method fulfilled all the essential demands for the determination of NACET in quality control laboratories, as it combined low instrument and reagent costs with a high sampling rate.
Region-Specific Biomarkers and Their Mechanisms in the Treatment of Lung Adenocarcinoma: A Study of Panax quinquefolius from Wendeng, China
Authors: Zhang Xuanming , Han Liwen , Li Peihai , Zhang Shanshan , Zhang Mengqi , Li Xiaobin , Chu Jie , Wang Lizhen , Tu Pengfei , Zhang Yun , Liu Kechun
Published: November 2021

Panax quinquefolius, a popular medicinal herb, has been cultivated in China for many years. In this work, the region-specific profiles of metabolites in P. quinquefolius from Wendeng was investigated using liquid-chromatography–quadrupole–time-of-flight-(LC–Q–TOF)-based metabolomics analysis. The three most abundant biomarkers, identified as ginsenoside Rb3, notoginsenoside R1, and ginsenoside Rc, were the representative chemical components employed in the network pharmacology analysis. In addition, molecular docking and western blotting analyses revealed that the three compounds were effective binding ligands with Hsp90α, resulting in the inactivation of SRC and PI3K kinase, which eventually led to the inactivation of the Akt and ERK pathways and lung cancer suppression. The outcomes obtained herein demonstrated the intriguing chemical characteristics and potential functional activities of P. quinquefolius from Wendeng.
Well-Orientation Strategy Biosynthesis of Cefuroxime-Silver Nanoantibiotic for Reinforced Biodentine™ and Its Dental Application against Streptococcus mutans
Authors: Gad El-Rab Sanaa M. F. , Ashour Amal A. , Basha Sakeenabi , Alyamani Amal Ahmed , Felemban Nayef H. , Enan Enas Tawfik
Published: November 2021

Dental caries results from the bacterial pathogen Streptococcus mutans (S. mutans) and is the maximum critical reason for caries formation. Consequently, the present study aims to evaluate the antibacterial activity of a newly synthesized nanoantibiotic–Biodentine formulation. The silver nanoparticles (ROE-AgNPs) were biosynthesized from the usage of Rosmarinus officinalis L. extract (ROE) and conjugated with cefuroxime to form Cefuroxime-ROE-AgNPs. Using Biodentine™ (BIOD), five groups of dental materials were prepared, in which Group A included conventional BIOD, Group B included BIOD with ROE-AgNPs, Groups C and D included BIOD with Cefuroxime-ROE-AgNPs at concentrations of 0.5% and 1.5% cefuroxime, respectively, and Group E included BIOD with 1.5% cefuroxime. The synthesized ROE-AgNPs or Cefuroxime-ROE-AgNPs were characterized for conjugating efficiency, morphology, particle size, and in vitro release. Minimum inhibitory concentration (MIC) of the cefuroxime, ROE-AgNPs, and Cefuroxime-ROE-AgNPs were additionally evaluated against cefuroxime resistant S. mutans, which furthered antibacterial efficacy of the five groups of dental materials. The UV-Visible spectrum showed the ROE-AgNPs or Cefuroxime-ROE-AgNPs peaks and their formation displayed through transmission electron microscopy (TEM), X-ray diffraction (XRD) pattern, and Fourier transforms infrared (FTIR) analysis. The end result of Cefuroxime-ROE-AgNPs showed conjugating efficiency up to 79%. Cefuroxime-ROE-AgNPs displayed the highest antibacterial efficacy against S. mutans as compared to cefuroxime or ROE-AgNPs alone. Moreover, the MIC of ROE-AgNPs and Cefuroxime-ROE-AgNPs was detected against S. mutans to be 25 and 8.5 μg/mL, respectively. Consequently, Cefuroxime-ROE-AgNPs displayed that a decrease in the MIC reached to more than three-fold less than MIC of ROE-AgNPs on the tested strain. Moreover, Cefuroxime-ROE-AgNPs/BIOD was employed as a novel dental material that showed maximum antimicrobial activity. Groups C and D of novel materials showed inhibitory zones of 19 and 26 mm, respectively, against S. mutans and showed high antimicrobial rates of 85.78% and 91.17%, respectively. These data reinforce the utility of conjugating cefuroxime with ROE-AgNPs to retrieve its efficiency against resistant S. mutant. Moreover, the nanoantibiotic delivered an advantageous antibacterial effect to BIOD, and this may open the door for future conjugation therapy of dental materials against bacteria that cause dental caries.
Therapeutic Screening of Herbal Remedies for the Management of Diabetes
Authors: Balbaa Mahmoud , El-Zeftawy Marwa , Abdulmalek Shaymaa A.
Published: November 2021

The study of diabetes mellitus (DM) patterns illustrates increasingly important facts. Most importantly, they include oxidative stress, inflammation, and cellular death. Up to now, there is a shortage of drug therapies for DM, and the discovery and the development of novel therapeutics for this disease are crucial. Medicinal plants are being used more and more as an alternative and natural cure for the disease. Consequently, the objective of this review was to examine the latest results on the effectiveness and protection of natural plants in the management of DM as adjuvant drugs for diabetes and its complex concomitant diseases.
Distigmasterol-Modified Acylglycerols as New Structured Lipids—Synthesis, Identification and Cytotoxicity
Authors: Rudzińska Magdalena , Grudniewska Aleksandra , Chojnacka Anna , Gładkowski Witold , Maciejewska Gabriela , Olejnik Anna , Kowalska Katarzyna
Published: November 2021

Plant sterols, also referred as phytosterols, have been known as bioactive compounds which have cholesterol-lowering properties in human blood. It has been established that a diet rich in plant sterols or their esters alleviates cardiovascular diseases (CVD), and also may inhibit breast, colon and lung carcinogenesis. Phytosterols, in their free and esterified forms, are prone to thermo-oxidative degradation, where time and temperature affect the level of degradation. Looking for new derivatives of phytosterols with high thermo-oxidative stability for application in foods, our idea was to obtain novel structured acylglycerols in which two fatty acid parts are replaced by stigmasterol residues. In this work, asymmetric (1,2- and 2,3-) distigmasterol-modified acylglycerols (dStigMAs) were synthesized by the covalent attachment of stigmasterol residues to sn-1 and sn-2 or sn-2 and sn-3 positions of 3-palmitoyl-sn-glycerol or 1-oleoyl-sn-glycerol, respectively, using a succinate or carbonate linker. The chemical structures of the synthesized compounds were identified by NMR, HR-MS, and IR data. Moreover, the cytotoxicity of the obtained compounds was determined. The dStigMAs possessing a carbonate linker showed potent cytotoxicity to cells isolated from the small intestine and colon epithelium and liver, whereas the opposite results were obtained for compounds containing a succinate linker.
Syntheses and Characterization of the First Cycloheptatrienyl Transition-Metal Complexes with a M-CF3 Bond
Authors: Lampropoulos Christos , Rashad Gabriel , Douvris Chris
Published: November 2021

The organometallic chemistry of metal complexes with organocyclic ligands of higher than five hapticity is much more lacking than the chemistry of metal complexes with η5-cyclopentadienyl ligands, which has been explored in considerable depth, resulting in novel advances. The main reason for this is stability. In particular, reports indicate that (η7-C7H7)MLn complexes are considerably less stable than analogous (η5-C5H5)MLn. In perfluoroalkyl metal chemistry, there is currently no reported (η7-C7H7)MLn derivative, whereas a number of alkylated ones are known and important conclusions have been drawn about their stability. Responding to this void, and using Morrison’s trifluoromethylating reagent, the present study reports the synthesis and characterization of the first cycloheptatrienyl molybdenum complexes bearing the trifluoromethyl moiety; (η7-C7H7)Mo(CO)2CF3 (I), and (η7-C7H7)Mo(CO)(PMe3)CF3 (II) and discusses their low thermal instability.
Multicomponent Synthesis of 2-(2,4-Diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonic Acids in DMSO
Authors: Ryzhkova Yuliya E. , Elinson Michail N. , Maslov Oleg I. , Fakhrutdinov Artem N.
Published: November 2021

Dimethyl sulfoxide is a widely used solvent in organic synthesis and in the pharmaceutical industry because of its low cost, stability, and low toxicity. Multicomponent reactions are an advanced approach that has become an efficient, economical, and eco-friendly substitute for the conventional sequential multi-step synthesis of various biologically active compounds. This approach was adopted for the synthesis of previously unknown 2-(2,4-diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonic acids via transformation of salicylaldehydes, malononitrile dimer, and malonic acid. It was shown that the use of DMSO at room temperature makes it possible to synthesize previously unavailable compounds. The investigation of the reaction mechanism using 1H-NMR monitoring made it possible to confirm the proposed mechanism of the transformation. The structure of synthesized 5H-chromeno[2,3-b]pyridines was confirmed by 2D-NMR spectroscopy.
Encapsulation of α-Pinene in Delivery Systems Based on Liposomes and Cyclodextrins
Authors: Hammoud Zahraa , Kayouka Maya , Trifan Adriana , Sieniawska Elwira , Jemâa Jouda Mediouni Ben , Elaissari Abdelhamid , Greige-Gerges Hélène
Published: November 2021

The essential oil component α-pinene has multiple biological activities. However, its application is limited owing to its volatility, low aqueous solubility, and chemical instability. For the aim of improving its physicochemical properties, α-pinene was encapsulated in conventional liposomes (CLs) and drug-in-cyclodextrin-in-liposomes (DCLs). Hydroxypropyl-β-cyclodextrin/α-pinene (HP-β-CD/α-pinene) inclusion complexes were prepared in aqueous solution, and the optimal solubilization of α-pinene occurred at HP-β-CD:α-pinene molar ratio of 7.5:1. The ethanol-injection method was applied to produce different formulations using saturated (Phospholipon 90H) or unsaturated (Lipoid S100) phospholipids in combination with cholesterol. The size, the phospholipid and cholesterol incorporation rates, the encapsulation efficiency (EE), and the loading rate (LR) of α-pinene were determined, and the storage stability of liposomes was assessed. The results showed that α-pinene was efficiently entrapped in CLs and DCLs with high EE values. Moreover, Lipoid S100 CLs displayed the highest LR (22.9 ± 2.2%) of α-pinene compared to the other formulations. Both carrier systems HP-β-CD/α-pinene inclusion complex and Lipoid S100 CLs presented a gradual release of α-pinene. Furthermore, the DPPH radical scavenging activity of α-pinene was maintained upon encapsulation in Lipoid S100 CLs. Finally, it was found that all formulations were stable after three months of storage at 4 °C.
Stable Field Emission from Vertically Oriented SiC Nanoarrays
Authors: Xiao Jianfeng , Zhao Jiuzhou , Liu Guanjiang , Cole Mattew Thomas , Zhou Shenghan , Chen Ke , Liu Xinchuan , Li Zhenjun , Li Chi , Dai Qing
Published: November 2021

Silicon carbide (SiC) nanostructure is a type of promising field emitter due to high breakdown field strength, high thermal conductivity, low electron affinity, and high electron mobility. However, the fabrication of the SiC nanotips array is difficult due to its chemical inertness. Here we report a simple, industry-familiar reactive ion etching to fabricate well-aligned, vertically orientated SiC nanoarrays on 4H-SiC wafers. The as-synthesized nanoarrays had tapered base angles >60°, and were vertically oriented with a high packing density >107 mm−2 and high-aspect ratios of approximately 35. As a result of its high geometry uniformity—5% length variation and 10% diameter variation, the field emitter array showed typical turn-on fields of 4.3 V μm−1 and a high field-enhancement factor of ~1260. The 8 h current emission stability displayed a mean current fluctuation of 1.9 ± 1%, revealing excellent current emission stability. The as-synthesized emitters demonstrate competitive emission performance that highlights their potential in a variety of vacuum electronics applications. This study provides a new route to realizing scalable field electron emitter production.
Synthesis of Fullerenes from a Nonaromatic Chloroform through a Newly Developed Ultrahigh-Temperature Flash Vacuum Pyrolysis Apparatus
Authors: Zhang Hong-Gang , Zhuo Ya-Qi , Zhang Xiao-Min , Zhang Leng , Xu Piao-Yang , Tian Han-Rui , Lin Shui-Chao , Zhang Qianyan , Xie Su-Yuan , Zheng Lan-Sun
Published: November 2021

The flash vacuum pyrolysis (FVP) technique is useful for preparing curved polycyclic aromatic compounds (PAHs) and caged nanocarbon molecules, such as the well-known corannulene and fullerene C60. However, the operating temperature of the traditional FVP apparatus is limited to ~1250 °C, which is not sufficient to overcome the high energy barriers of some reactions. Herein, we report an ultrahigh-temperature FVP (UT-FVP) apparatus with a controllable operating temperature of up to 2500 °C to synthesize fullerene C60 from a nonaromatic single carbon reactant, i.e., chloroform, at 1350 °C or above. Fullerene C60 cannot be obtained from CHCl3 using the traditional FVP apparatus because of the limitation of the reaction temperature. The significant improvements in the UT-FVP apparatus, compared to the traditional FVP apparatus, were the replacement of the quartz tube with a graphite tube and the direct heating of the graphite tube by impedance heating instead of indirect heating of the quartz tube using an electric furnace. Because of the higher temperature range, UT-FVP can not only synthesize fullerene C60 from single carbon nonaromatic reactants but sublimate some high-molecular-weight compounds to synthesize larger curved PAHs in the future.
Potential Relevance of Bioactive Peptides in Sports Nutrition
Authors: König Daniel , Kohl Jan , Jerger Simon , Centner Christoph
Published: November 2021

Bioactive peptides are physiologically active peptides mostly derived from proteins following gastrointestinal digestion, fermentation or hydrolysis by proteolytic enzymes. It has been shown that bioactive peptides can be resorbed in their intact form and have repeatedly been shown to have a positive effect on health-related parameters such as hypertension, dyslipoproteinemia, inflammation and oxidative stress. In recent years, there has been increasing evidence that biologically active peptides could also play an important role in sports nutrition. Current studies have shown that bioactive peptides could have a positive impact on changes in body composition and muscular performance, reduce muscle damage following exercise and induce beneficial adaptions within the connective tissue. In the following overview, potential mechanisms as well as possible limitations regarding the sports-related effect of bioactive peptides and their potential mechanisms are presented and discussed. In addition, practical applications will be discussed on how bioactive peptides can be integrated into a nutritional approach in sports to enhance athletic performance as well as prevent injuries and improve the rehabilitation process.
Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study
Authors: Irvin Marguerite R. , Montasser May E. , Kind Tobias , Fan Sili , Barupal Dinesh K. , Patki Amit , Tanner Rikki M. , Armstrong Nicole D. , Ryan Kathleen A. , Claas Steven A. , O’Connell Jeffrey R. , Tiwari Hemant K. , Arnett Donna K.
Published: November 2021

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10−8/132 = 4 × 10−10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p < 8.0 × 10−7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p < 3.3 × 10−3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal.
Chronic Recurrent Multifocal Osteomyelitis Associated with Crohn Disease: A Potential Role of Exclusion Diet? Comment on Starz et al. The Modification of the Gut Microbiota via Selected Specific Diets in Patients with Crohn’s Disease. Nutrients 2021, 13, 2125
Authors: Cantarelli Erika , Baccelli Francesco , Simonini Gabriele , Alvisi Patrizia
Published: November 2021

The efficacy of diet and its influence on gut microbiome composition has been largely demonstrated in inflammatory bowel disease (IBD). Little is known about its potential in the management of extraintestinal manifestations. We report a successful application of Crohn disease exclusion diet (CDED) in association with infliximab and methotrexate, as salvage therapy in a child affected by chronic recurrent multifocal osteomyelitis (CRMO) and Crohn disease (CD) resistant to optimized therapy. Both intestinal and bone symptoms remitted after the application of CDED. Diet may have acted on common microbic inciting agents that trigger both intestinal and bone inflammation, supporting the role of microbiota in the pathogenesis of IBD-associated extraintestinal manifestations. Our experience suggests the potential benefit of CDED in association with combined therapy in resistant patients affected by CD and extraintestinal manifestations.
Albumin Substitution in Decompensated Liver Cirrhosis: Don’t Forget Zinc
Authors: Grüngreiff Kurt , Gottstein Thomas , Reinhold Dirk , Blindauer Claudia A.
Published: November 2021

Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2–4 years after the first diagnosis of ascites. Albumin is an important tool in the therapy of cirrhotic ascites. By virtue of its oncotic properties, it reduces the risk of cardiovascular dysfunction after paracentesis. Treatment with albumin also counteracts the development of hepatorenal syndrome and spontaneous bacterial peritonitis. More recently, the positive impact of long-term albumin supplementation in liver disease, based on its pleiotropic non-oncotic activities, has been recognized. These include transport of endo- and exogenous substances, anti-inflammatory, antioxidant and immunomodulatory activities, and stabilizing effects on the endothelium. Besides the growing recognition that effective albumin therapy requires adjustment of the plasma level to normal physiological values, the search for substances with adjuvant activities is becoming increasingly important. More than 75% of patients with decompensated liver cirrhosis do not only present with hypoalbuminemia but also with zinc deficiency. There is a close relationship between albumin and the essential trace element zinc. First and foremost, albumin is the main carrier of zinc in plasma, and is hence critical for systemic distribution of zinc. In this review, we discuss important functions of albumin in the context of metabolic, immunological, oxidative, transport, and distribution processes, alongside crucial functions and effects of zinc and their mutual dependencies. In particular, we focus on the major role of chronic inflammatory processes in pathogenesis and progression of liver cirrhosis and how albumin therapy and zinc supplementation may affect these processes.
Effects of Vitamin D in Post-Exercise Muscle Recovery. A Systematic Review and Meta-Analysis
Authors: Bello Hugo J. , Caballero-García Alberto , Pérez-Valdecantos Daniel , Roche Enrique , Noriega David C. , Córdova-Martínez Alfredo
Published: November 2021

Vitamin D is a key micronutrient modulating function and health in skeletal muscle. Therefore, we sought to systematically review the role of vitamin D in muscle recovery. A search in different databases (PubMed/MEDLINE, WOS, Google Scholar, and Scopus) was carried out following PRISMA® and PICOS. The search period was from inception to April 2020. Changes in post-exercise muscle damage were quantified comparing experimental group vs. placebo in each study by using number of participants, standardized mean difference (SMD), and standard error of the SMD. Hedges’s g was used to calculate the SMDs for each study group and biased by the inverse of variance that allows calculating an overall effect and the 95% confidence interval (CI). The net vitamin D supplementation effect was calculated by subtracting the placebo SMD from SMD of the experimental group. The DerSimonian and Laird method was used as a random effect model, taking into account that the effect of vitamin D on muscular damage may vary according to the dose administered and additional moderators. Six studies were selected. In conclusion, regarding circulating levels of muscle biomarkers and additional limitations of the studies, it cannot be concluded that vitamin D supplementation exerts an effect in post-exercise muscle recovery. Likely, the anti-inflammatory action of vitamin D is quicker than the recovery of tissue structure and function. This aspect is pending verification in future research.
Nutrient Density as a Dimension of Dietary Quality: Findings of the Nutrient Density Approach in a Multi-Center Evaluation
Authors: Vossenaar Marieke , Solomons Noel W. , Muslimatun Siti , Faber Mieke , García Olga P. , Monterrosa Eva , van Zutphen Kesso Gabrielle , Kraemer Klaus
Published: November 2021

The nutrient adequacy of a diet is typically assessed by comparing estimated nutrient intakes with established average nutrient requirements; this approach does not consider total energy consumed. In this multinational survey investigation in Indonesia, Mexico, and South Africa, we explore the applications of the “critical nutrient-density approach”—which brings energy requirements into the equation—in the context of public health epidemiology. We conducted 24 h dietary recalls in convenience samples of normal-weight (BMI 18.5–25 kg/m2) or obese (BMI > 30 kg/m2), low-income women in three settings (n = 290). Dietary adequacy was assessed both in absolute terms and using the nutrient density approach. No significant differences in energy and nutrient intakes were observed between normal-weight and obese women within any of the three samples (p > 0.05). Both the cut-point method (% of EAR) and critical nutrient density approach revealed a high probability of inadequate intakes for several micronutrients but with poor concordance between the two methods. We conclude that it may often require some approximate estimate of the habitual energy intake from an empirical source to apply a true critical nutrient density reference for a population or subgroup. This will logically signify that there would be more “problem nutrients” in the diets examined with this nutrient density approach, and efforts toward improved food selection or food- or biofortification will frequently be indicated.
Plant-Based Formulas and Liquid Feedings for Infants and Toddlers
Authors: Vandenplas Yvan , De Mulder Nele , De Greef Elisabeth , Huysentruyt Koen
Published: November 2021

Exclusive breastfeeding is the recommended feeding for all infants. Recent research has focused on the importance of balanced feeding during the first 1000 days, starting at conception with a balanced diet of the pregnant woman, up to the age of two years. The following step, a balanced diet after the age of two years is a challenge, as the dietary intake becomes more diversified. The role of young-child formula in this process is debated. This paper discusses the use of planted-based drinks, since they are a valuable and progressively more popular alternative for cow’s milk, if nutritionally adapted to the requirements of toddlers. Plant-based drinks are per definition lactose free.
Enhanced Eating Competence Is Associated with Improved Diet Quality and Cardiometabolic Profile in Finnish Adults with Increased Risk of Type 2 Diabetes
Authors: Aittola Kirsikka , Karhunen Leila , Männikkö Reija , Järvelä-Reijonen Elina , Mikkonen Santtu , Absetz Pilvikki , Kolehmainen Marjukka , Schwab Ursula , Harjumaa Marja , Lindström Jaana , Lakka Timo , Tilles-Tirkkonen Tanja , Pihlajamäki Jussi
Published: November 2021

Eating competence (EC) is characterized by positive attitudes towards food and eating, having regular meals, eating a variety of foods, and internally regulated eating. We investigated the associations of changes in EC with changes in lifestyle, anthropometrics and biomarkers of glucose and lipid metabolism in 2291 adults at increased risk of type 2 diabetes as part of the StopDia study conducted in primary healthcare. EC and diet quality were assessed with validated digital questionnaires. During the intervention, the participants received either (1) the digital lifestyle intervention, (2) the combined digital and face-to-face group-based lifestyle intervention, or (3) standard care. EC increased among the participants independent of the intervention type. Increase in EC was associated with an increase in diet quality, high-density lipoprotein (HDL) cholesterol, and with a decrease in body mass index and waist circumference, regardless of baseline EC. Of the subdomains of EC, the contextual skills, food acceptance and eating attitudes were associated with various of these changes. Our results thus suggest that EC could be a potential target in lifestyle interventions aiming to improve the cardiometabolic health of people at type 2 diabetes risk.
Dietary Patterns and Weight Status in Italian Preschoolers with Autism Spectrum Disorder and Typically Developing Children
Authors: Raspini Benedetta , Prosperi Margherita , Guiducci Letizia , Santocchi Elisa , Tancredi Raffaella , Calderoni Sara , Morales Maria Aurora , Morelli Mariangela , Simione Meg , Fiechtner Lauren , Muratori Filippo , Cena Hellas
Published: November 2021

Atypical eating habits are more common in children with autism spectrum disorders (ASD) than typically developing (TD) peers. Feeding problems may lead to the double burden of specific nutrient deficiencies and excessive weight gain, with a consequent increase in obesity prevalence. The dietary intake of Italian preschoolers with ASD compared to their TD peers and the impact of their dietary choices on their weight status and relationship to food selectivity (FS) were investigated. Dietary patterns and their associations with body mass index (BMI) were evaluated in 65 children with ASD and 82 peers with TD aged 1.3–6.4 years. Eating habits were assessed with a modified version of a parent-rated semi-quantitative Food Frequency Questionnaire. Moreover, the prevalence of FS and possible links with dietary patterns and BMI were investigated in the ASD group. Children with ASD consumed significantly higher amounts of simple sugars, processed and ultra-processed carbohydrates, both low- and high-fat animal proteins, and lower amounts of vegetables and fruits compared to peers with TD. The obesity rate was 1.5% in children with TD and more than fourfold (6.2%) in children with ASD, although the difference between groups was not statistically significant. FS was significantly more frequent in children with ASD than in peers with TD. Children with ASD and FS showed significantly lower annual intakes of vegetable proteins and fiber (considered essential nutrients for a healthy diet) than children with ASD without FS. Our results showed that children with ASD showed different dietary habits than those with TD, with the higher consumption of energy-dense foods and lower amounts of food-sourced fibers, which could place them at increased risk to develop overweight, obesity, and micronutrient deficiencies later in life.