bluuebunny/crossref_metadata_2025 huggingface dataset:
Ore–Bearing Fluids of the Blagodatnoye Gold Deposit (Yenisei Ridge, Russia): Results of Fluid Inclusion and Isotopic Analyses
Authors: Shaparenko Elena , Gibsher Nadezhda , Tomilenko Anatoly , Sazonov Anatoly , Bul’bak Taras , Ryabukha Maria , Khomenko Margarita , Silyanov Sergey , Nekrasova Natalya , Petrova Marina
Published: October 2021

The Blagodatnoye deposit with 340 t gold reserves is one of the most productive mines in Russia. Modern methods of studying fluid inclusions were used to determine the properties of fluids that formed this deposit. A comprehensive study revealed that the Blagodatnoye gold deposit was formed between 120 and 350 °C and at 0.2–2.6 kbar, and from fluids with salinities ranging from 0.5 to 30 wt.% (NaCl–eq.). These fluids are: 1—water–carbon dioxide; 2—carbon dioxide–hydrocarbon; 3—highly saline aqueous. According to Raman spectroscopy and gas chromatography–mass spectrometry, ore–forming fluids contained H2O, CO2, hydrocarbons and oxygenated organic compounds, sulfonated, nitrogenated and halogenated compounds. Early oxidized water–carbon dioxide fluids formed barren associations of the deposit. Later reduced carbon dioxide–hydrocarbon fluids had a key role in the formation of gold-bearing quartz veins. The stable isotope data (δ34S = 0.8 to 21.3‰, δ13C = −2.8 to −20.9‰, 3He/4He = 0.14 ± 0.3 × 10–6) suggest the ore-forming fluids have a crustal source.
Protective Effects of 6-Shogaol, an Active Compound of Ginger, in a Murine Model of Cisplatin-Induced Acute Kidney Injury
Authors: Gwon Mi-Gyeong , Gu Hyemin , Leem Jaechan , Park Kwan-Kyu
Published: October 2021

Acute kidney injury (AKI) is a dose-limiting side effect of cisplatin therapy in cancer patients. However, effective therapies for cisplatin-induced AKI are not available. Oxidative stress, tubular cell death, and inflammation are known to be the major pathological processes of the disease. 6-Shogaol is a major component of ginger and exhibits anti-oxidative and anti-inflammatory effects. Accumulating evidence suggest that 6-shogaol may serve as a potential therapeutic agent for various inflammatory diseases. However, whether 6-shogaol exerts a protective effect on cisplatin-induced renal side effect has not yet been determined. The aim of this study was to evaluate the effect of 6-shogaol on cisplatin-induced AKI and to investigate its underlying mechanisms. An administration of 6-shogaol after cisplatin treatment ameliorated renal dysfunction and tubular injury, as shown by a reduction in serum levels of creatinine and blood urea nitrogen and an improvement in histological abnormalities. Mechanistically, 6-shogaol attenuated cisplatin-induced oxidative stress and modulated the renal expression of prooxidant and antioxidant enzymes. Apoptosis and necroptosis induced by cisplatin were also suppressed by 6-shogaol. Moreover, 6-shogaol inhibited cisplatin-induced cytokine production and immune cell infiltration. These results suggest that 6-shogaol exhibits therapeutic effects against cisplatin-induced AKI via the suppression of oxidative stress, tubular cell death, and inflammation.
Computational Approaches for the Design of Novel Anticancer Compounds Based on Pyrazolo[3,4-d]pyrimidine Derivatives as TRAP1 Inhibitor
Authors: Ali Amena , Abdellattif Magda H. , Ali Abuzer , AbuAli Ola , Shahbaaz Mohd , Ahsan Mohamed Jawed , Hussien Mostafa A.
Published: October 2021

In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R2 = 0.96 and Q2 = 0.57. Leave one out (LOO) cross-validation (R2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (−11.265, −10.532, −10.422, −10.827, −10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors
Exploring Gunnera tinctoria: From Nutritional and Anti-Tumoral Properties to Phytosome Development Following Structural Arrangement Based on Molecular Docking
Authors: Fathi Faezeh , Ebrahimi Samad N. , Valadão Ana I. G. , Andrade Nelson , Costa Anabela S. G. , Silva Cláudia , Fathi Alireza , Salehi Peyman , Martel Fátima , Alves Rita C. , Oliveira Maria Beatriz P. P.
Published: October 2021

Gunnera tinctoria, an underexplored invasive plant found in Azores, Portugal, was studied regarding its nutritional, antioxidant, and antitumoral properties. Higher antioxidant activity was found in baby leaves, followed by adult leaves and inflorescences. A phenolic fraction of the plant was enriched using adsorbent resin column chromatography (DiaionTM HP20LX, and Relite EXA90). Antitumoral effects were observed with the enriched fractions in breast (MCF-7) and pancreatic (AsPC-1) cancer cell lines, being more pronounced in the latter. To improve protection and membrane absorption rates of phenolic compounds, nano-phytosomes and cholesterol-conjugated phytosomes coated with natural polymers were loaded with the enriched fraction. The particles were characterized, and their physiochemical properties were evaluated and compared. All samples presented anionic charge and nanometer size in relation to the inner layer and micrometer size regarding the external layers. In addition, the molecular arrangement of phenolics within both types of phytosomes were studied for the first time by molecular docking. Polarity and molecular size were key factors on the molecular arrangement of the lipid bilayer. In conclusion, G. tinctoria showed to be an interesting source of nutrients and phenolic compounds with anti-tumoral potential. Moreover, phytosome loading with these compounds can increase their stability and bioavailability having in view future applications.
A Uniform Benchmark for Testing SsrA-Derived Degrons in the Escherichia coli ClpXP Degradation Pathway
Authors: Klimecka Maria Magdalena , Antosiewicz Anna , Izert Matylda Anna , Szybowska Patrycja Emanuela , Twardowski Piotr Krzysztof , Delaunay Clara , Górna Maria Wiktoria
Published: October 2021

The ssrA degron is commonly used in fusion proteins to control protein stability in bacteria or as an interaction module. These applications often rely on the modular activities of the ssrA tag in binding to the SspB adaptor and in engaging the ClpXP protease. However, a comparison of these activities for a substantial standard set of degron variants has not been conducted previously, which may hinder the development of new variants optimized exclusively for one application. Here, we strive to establish a benchmark that will facilitate the comparison of ssrA variants under uniform conditions. In our workflow, we included methods for expression and purification of ClpX, ClpP, SspB and eGFP-degrons, assays of ClpX ATPase activity, of eGFP-degron binding to SspB and for measuring eGFP-degron degradation in vitro and in vivo. Using uniform, precise and sensitive methods under the same conditions on a range of eGFP-degrons allowed us to determine subtle differences in their properties that can affect their potential applications. Our findings can serve as a reference and a resource for developing targeted protein degradation approaches.
1H NMR Study of the HCa2Nb3O10 Photocatalyst with Different Hydration Levels
Authors: Shelyapina Marina G. , Silyukov Oleg I. , Andronova Elizaveta A. , Nefedov Denis Y. , Antonenko Anastasiia O. , Missyul Alexander , Kurnosenko Sergei A. , Zvereva Irina A.
Published: October 2021

The photocatalytic activity of layered perovskite-like oxides in water splitting reaction is dependent on the hydration level and species located in the interlayer slab: simple or complex cations as well as hydrogen-bonded or non-hydrogen-bonded H2O. To study proton localization and dynamics in the HCa2Nb3O10·yH2O photocatalyst with different hydration levels (hydrated—α-form, dehydrated—γ-form, and intermediate—β-form), complementary Nuclear Magnetic Resonance (NMR) techniques were applied. 1H Magic Angle Spinning NMR evidences the presence of different proton containing species in the interlayer slab depending on the hydration level. For α-form, HCa2Nb3O10·1.6H2O, 1H MAS NMR spectra reveal H3O+. Its molecular motion parameters were determined from 1H spin-lattice relaxation time in the rotating frame (T1ρ) using the Kohlrausch-Williams-Watts (KWW) correlation function with stretching exponent β = 0.28: Ea=0.2102 eV, τ0=9.01 × 10−12 s. For the β-form, HCa2Nb3O10·0.8H2O, the only 1H NMR line is the result of an exchange between lattice and non-hydrogen-bonded water protons. T1ρ(1/T) indicates the presence of two characteristic points (224 and 176 K), at which proton dynamics change. The γ-form, HCa2Nb3O10·0.1H2O, contains bulk water and interlayer H+ in regular sites. 1H NMR spectra suggest two inequivalent cation positions. The parameters of the proton motion, found within the KWW model, are as follows: Ea=0.2178 eV, τ0=8.29 × 10−10 s.
Interfacial Compatibilization into PLA/Mg Composites for Improved In Vitro Bioactivity and Stem Cell Adhesion
Authors: Ben Abdeljawad Meriam , Carette Xavier , Argentati Chiara , Martino Sabata , Gonon Maurice-François , Odent Jérémy , Morena Francesco , Mincheva Rosica , Raquez Jean-Marie
Published: October 2021

The present work highlights the crucial role of the interfacial compatibilization on the design of polylactic acid (PLA)/Magnesium (Mg) composites for bone regeneration applications. In this regard, an amphiphilic poly(ethylene oxide-b-L,L-lactide) diblock copolymer with predefined composition was synthesised and used as a new interface to provide physical interactions between the metallic filler and the biopolymer matrix. This strategy allowed (i) overcoming the PLA/Mg interfacial adhesion weakness and (ii) modulating the composite hydrophilicity, bioactivity and biological behaviour. First, a full study of the influence of the copolymer incorporation on the morphological, wettability, thermal, thermo-mechanical and mechanical properties of PLA/Mg was investigated. Subsequently, the bioactivity was assessed during an in vitro degradation in simulated body fluid (SBF). Finally, biological studies with stem cells were carried out. The results showed an increase of the interfacial adhesion by the formation of a new interphase between the hydrophobic PLA matrix and the hydrophilic Mg filler. This interface stabilization was confirmed by a decrease in the damping factor (tanδ) following the copolymer addition. The latter also proves the beneficial effect of the composite hydrophilicity by selective surface localization of the hydrophilic PEO leading to a significant increase in the protein adsorption. Furthermore, hydroxyapatite was formed in bulk after 8 weeks of immersion in the SBF, suggesting that the bioactivity will be noticeably improved by the addition of the diblock copolymer. This ceramic could react as a natural bonding junction between the designed implant and the fractured bone during osteoregeneration. On the other hand, a slight decrease of the composite mechanical performances was noted.
Nitrogen-Based Linkers with a Mesitylene Core: Synthesis and Characterization
Authors: Bahrin Lucian Gabriel , Nicolescu Alina , Shova Sergiu , Marangoci Narcisa Laura , Birsa Lucian Mihail , Sarbu Laura Gabriela
Published: October 2021

Mesitylene was used as a core in seven new tritopic nitrogen containing linkers. Three of the linkers, each containing three nitrile groups, were obtained through Suzuki, Sonogashira and Heck-type coupling reactions. Next, these were converted to tetrazol-5-yl moieties by the cycloaddition of sodium azide to the nitrile functionalities. The last linker, containing three 1,2,3-triazol-4-yl moieties, was synthesized by the Huisgen cycloaddition of phenyl azide to the corresponding alkyne. The latter was obtained via a Corey–Fuchs reaction sequence from the previously reported formyl derivative. As the proof of concept for their potential in MOF design, one of the nitriles was used to build an Ag-based network.
Study on the CID Fragmentation Pathways of Deprotonated 4’-Monophosphoryl Lipid A
Authors: Aissa Ibrahim , Kilár Anikó , Dörnyei Ágnes
Published: October 2021

Lipid A, the membrane-bound phosphoglycolipid component of bacteria, is held responsible for the clinical syndrome of gram-negative sepsis. In this study, the fragmentation behavior of a set of synthetic lipid A derivatives was studied by electrospray ionization multistage mass spectrometry (ESI-MSn), in conjunction with tandem mass spectrometry (MS/MS), using low-energy collision-induced dissociation (CID). Genealogical insight about the fragmentation pathways of the deprotonated 4’-monophosphoryl lipid A structural analogs led to proposals of a number of alternative dissociation routes that have not been reported previously. Each of the fragment ions was interpreted using various possible mechanisms, consistent with the principles of reactions described in organic chemistry. Specifically, the hypothesized mechanisms are: (i) cleavage of the C-3 primary fatty acid leaves behind an epoxide group attached to the reducing sugar; (ii) cleavage of the C-3’ primary fatty acid (as an acid) generates a cyclic phosphate connected to the nonreducing sugar; (iii) cleavage of the C-2’ secondary fatty acid occurs both in acid and ketene forms; iv) the C-2 and C-2’ primary fatty acids are eliminated as an amide and ketene, respectively; (v) the 0,2A2 cross-ring fragment contains a four-membered ring (oxetanose); (vi) the 0,4A2 ion is consecutively formed from the 0,2A2 ion by retro-aldol, retro-cycloaddition, and transesterification; and (vii) formations of H2PO4− and PO3− are associated with the formation of sugar epoxide. An understanding of the relation between 0,2A2 and 0,4A2-type sugar fragments and the different cleavage mechanisms of the two ester-linked primary fatty acids is invaluable for distinguishing lipid A isomers with different locations of a single ester-linked fatty acid (i.e., at C-3 or C-3’). Thus, in addition to a better comprehension of lipid A fragmentation processes in mass spectrometers, our observations can be applied for a more precise elucidation of naturally occurring lipid A structures.
Surface Chemistry of Nanohybrids with Fumed Silica Functionalized by Polydimethylsiloxane/Dimethyl Carbonate Studied Using 1H, 13C, and 29Si Solid-State NMR Spectroscopy
Authors: Protsak Iryna S. , Morozov Yevhenii M. , Zhang Dong , Gun’ko Volodymyr M.
Published: October 2021

The investigation of molecular interactions between a silica surface and organic/inorganic polymers is crucial for deeper understanding of the dominant mechanisms of surface functionalization. In this work, attachment of various depolymerized polydimethylsiloxanes (PDMS) of different chain lengths, affected by dimethyl carbonate (DMC), to silica nanoparticles pretreated at different temperatures has been studied using 29Si, 1H, and 13C solid-state NMR spectroscopy. The results show that grafting of different modifier blends onto a preheated silica surface depends strongly on the specific surface area (SSA) linked to the silica nanoparticle size distributions affecting all textural characteristics. The pretreatment at 400 °C results in a greater degree of the modification of (i) A-150 (SSA = 150 m2/g) by PDMS-10/DMC and PDMS-1000/DMC blends; (ii) A-200 by PDMS-10/DMC and PDMS-100/DMC blends; and (iii) A-300 by PDMS-100/DMC and PDMS-1000/DMC blends. The spectral features observed using solid-state NMR spectroscopy suggest that the main surface products of the reactions of various depolymerized PDMS with pretreated nanosilica particles are the (CH3)3SiO-[(CH3)2SiO-]x fragments. The reactions occur with the siloxane bond breakage by DMC and replacing surface hydroxyls. Changes in the chemical shifts and line widths, as shown by solid-state NMR, provide novel information on the whole structure of functionalized nanosilica particles. This study highlights the major role of solid-state NMR spectroscopy for comprehensive characterization of functionalized solid surfaces.
Detection of Circulating Serum microRNA/Protein Complexes in ASD Using Functionalized Chips for an Atomic Force Microscope
Authors: Kaysheva Anna L. , Isaeva Arina I. , Pleshakova Tatyana O. , Shumov Ivan D. , Valueva Anastasia A. , Ershova Maria O. , Ivanova Irina A. , Ziborov Vadim S. , Iourov Ivan Y. , Vorsanova Svetlana G. , Ryabtsev Stepan V. , Archakov Alexander I. , Ivanov Yuri D.
Published: October 2021

MicroRNAs, which circulate in blood, are characterized by high diagnostic value; in biomedical research, they can be considered as candidate markers of various diseases. Mature microRNAs of glial cells and neurons can cross the blood–brain barrier and can be detected in the serum of patients with autism spectrum disorders (ASD) as components of macrovesicles, macromolecular protein and low-density lipoprotein particles. In our present study, we have proposed an approach, in which microRNAs in protein complexes can be concentrated on the surface of AFM chips with oligonucleotide molecular probes, specific against the target microRNAs. MicroRNAs, associated with the development of ASD in children, were selected as targets. The chips with immobilized molecular probes were incubated in serum samples of ASD patients and healthy volunteers. By atomic force microscopy (AFM), objects on the AFM chip surface have been revealed after incubation in the serum samples. The height of these objects amounted to 10 nm and 6 nm in the case of samples of ASD patients and healthy volunteers, respectively. MALDI-TOF-MS analysis of protein components on the chip surface allowed us to identify several cell proteins. These proteins are involved in the binding of nucleic acids (GBG10, RT24, RALYL), in the organization of proteasomes and nucleosomes (PSA4, NP1L4), and participate in the functioning of the channel of active potassium transport (KCNE5, KCNV2).
A Simple and Efficient Two-Dimensional High-Speed Counter-Current Chromatography Linear Gradient and Isocratic Elution Modes for the Preparative Separation of Coumarins from Roots of Toddalia asiatica (Linn.) Lam.
Authors: Ma Wenya , Ali Iftikhar , Li Yali , Hussain Hidayat , Zhao Huanzhu , Sun Xuan , Xie Lei , Cui Li , Wang Daijie
Published: October 2021

Toddalia asiatica (L.) Lam. (Rutaceae) has shown a broad spectrum of biological properties, such as anti-inflammatory, antioxidant, antimicrobial, anti-HIV, and anticancer properties. The present study is concerned with the separation of the main components with broad partition coefficients (KD values) from T. asiatica, using linear gradient high-speed counter-current chromatography (LGCCC) combined with an off-line two-dimensional (2D) mode. Similar to the binary gradient HPLC, the LGCCC mode is operated by the adjustment of the proportion between the mobile phase of 5:5:1:9 (v/v) (pump A) and 5:5:4.5:5.5 (v/v) (pump B) in an n-hexane/ethyl acetate/methanol/water solvent system. The off-line 2D-CCC mode was used in this study for the secondary separation of two similar KD value compounds with n-hexane/ethyl acetate/methanol/water (5:5:4:6, v/v). Notably, six coumarins, namely, tomentin (1), toddalolactone (2), 5,7,8-trimethoxycoumarin (3), mexoticin (4), isopimpinellin (5), and toddanone (6), were efficiently separated. The structures of the pure compounds were elucidated by spectral techniques and compared with the literature.
Establishing a New Link between Fuzzy Logic, Neuroscience, and Quantum Mechanics through Bayesian Probability: Perspectives in Artificial Intelligence and Unconventional Computing
Authors: Gentili Pier Luigi
Published: October 2021

Human interaction with the world is dominated by uncertainty. Probability theory is a valuable tool to face such uncertainty. According to the Bayesian definition, probabilities are personal beliefs. Experimental evidence supports the notion that human behavior is highly consistent with Bayesian probabilistic inference in both the sensory and motor and cognitive domain. All the higher-level psychophysical functions of our brain are believed to take the activities of interconnected and distributed networks of neurons in the neocortex as their physiological substrate. Neurons in the neocortex are organized in cortical columns that behave as fuzzy sets. Fuzzy sets theory has embraced uncertainty modeling when membership functions have been reinterpreted as possibility distributions. The terms of Bayes’ formula are conceivable as fuzzy sets and Bayes’ inference becomes a fuzzy inference. According to the QBism, quantum probabilities are also Bayesian. They are logical constructs rather than physical realities. It derives that the Born rule is nothing but a kind of Quantum Law of Total Probability. Wavefunctions and measurement operators are viewed epistemically. Both of them are similar to fuzzy sets. The new link that is established between fuzzy logic, neuroscience, and quantum mechanics through Bayesian probability could spark new ideas for the development of artificial intelligence and unconventional computing.
Longitudinal Bottom-Up Proteomics of Serum, Serum Extracellular Vesicles, and Cerebrospinal Fluid Reveals Candidate Biomarkers for Early Detection of Glioblastoma in a Murine Model
Authors: Greco Francesco , Anastasi Federica , Pardini Luca Fidia , Dilillo Marialaura , Vannini Eleonora , Baroncelli Laura , Caleo Matteo , McDonnell Liam A.
Published: October 2021

Glioblastoma Multiforme (GBM) is a brain tumor with a poor prognosis and low survival rates. GBM is diagnosed at an advanced stage, so little information is available on the early stage of the disease and few improvements have been made for earlier diagnosis. Longitudinal murine models are a promising platform for biomarker discovery as they allow access to the early stages of the disease. Nevertheless, their use in proteomics has been limited owing to the low sample amount that can be collected at each longitudinal time point. Here we used optimized microproteomics workflows to investigate longitudinal changes in the protein profile of serum, serum small extracellular vesicles (sEVs), and cerebrospinal fluid (CSF) in a GBM murine model. Baseline, pre-symptomatic, and symptomatic tumor stages were determined using non-invasive motor tests. Forty-four proteins displayed significant differences in signal intensities during GBM progression. Dysregulated proteins are involved in cell motility, cell growth, and angiogenesis. Most of the dysregulated proteins already exhibited a difference from baseline at the pre-symptomatic stage of the disease, suggesting that early effects of GBM might be detectable before symptom onset.
Biosynthesis, Characterization and Antibacterial Application of Novel Silver Nanoparticles against Drug Resistant Pathogenic Klebsiella pneumoniae and Salmonella Enteritidis
Authors: Huq Md. Amdadul , Akter Shahina
Published: October 2021

The present study highlights the biosynthesis of silver nanoparticles (AgNPs) using culture supernatant of Massilia sp. MAHUQ-52 as well as the antimicrobial application of synthesized AgNPs against multi-drug resistant pathogenic Klebsiella pneumoniae and Salmonella Enteritidis. Well-defined AgNPs formation occurred from the reaction mixture of cell-free supernatant and silver nitrate (AgNO3) solution within 48 h of incubation. UV-visible spectroscopy analysis showed a strong peak at 435 nm, which corresponds to the surface plasmon resonance of AgNPs. The synthesized AgNPs were characterized by FE-TEM, EDX, XRD, DLS and FT-IR. From FE-TEM analysis, it was found that most of the particles were spherical shape, and the size of synthesized nanoparticles (NPs) was 15–55 nm. EDX spectrum revealed a strong silver signal at 3 keV. XRD analysis determined the crystalline, pure, face-centered cubic AgNPs. FT-IR analysis identified various functional molecules that may be involved with the synthesis and stabilization of AgNPs. The antimicrobial activity of Massilia sp. MAHUQ-52 mediated synthesized AgNPs was determined using the disk diffusion method against K. pneumoniae and S. Enteritidis. Biosynthesized AgNPs showed strong antimicrobial activity against both K. pneumoniae and S. Enteritidis. The MICs of synthesized AgNPs against K. pneumoniae and S. Enteritidis were 12.5 and 25.0 μg/mL, respectively. The MBC of biosynthesized AgNPs against both pathogens was 50.0 μg/mL. From FE-SEM analysis, it was found that the AgNPs-treated cells showed morphological changes with irregular and damaged cell walls that culminated in cell death.
Selected Class of Enamides Bearing Nitro Functionality as Dual-Acting with Highly Selective Monoamine Oxidase-B and BACE1 Inhibitors
Authors: Venkidath Anusree , Oh Jong Min , Dev Sanal , Amin Elham , Rasheed Shebina P. , Vengamthodi Ajeesh , Gambacorta Nicola , Khames Ahmed , Abdelgawad Mohamed A. , George Ginson , Nicolotti Orazio , Kim Hoon , Mathew Bijo
Published: October 2021

A small series of nitro group-bearing enamides was designed, synthesized (NEA1–NEA5), and evaluated for their inhibitory profiles of monoamine oxidases (MAOs) and β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE1). Compounds NEA3 and NEA1 exhibited a more potent MAO-B inhibition (IC50 value = 0.0092 and 0.016 µM, respectively) than the standards (IC50 value = 0.11 and 0.14 µM, respectively, for lazabemide and pargyline). Moreover, NEA3 and NEA1 showed greater selectivity index (SI) values toward MAO-B over MAO-A (SI of >1652.2 and >2500.0, respectively). The inhibition and kinetics studies suggested that NEA3 and NEA1 are reversible and competitive inhibitors with Ki values of 0.013 ± 0.005 and 0.0049 ± 0.0002 µM, respectively, for MAO-B. In addition, both NEA3 and NEA1 showed efficient BACE1 inhibitions with IC50 values of 8.02 ± 0.13 and 8.21 ± 0.03 µM better than the standard quercetin value (13.40 ± 0.04 µM). The parallel artificial membrane permeability assay (PAMPA) method demonstrated that all the synthesized derivatives can cross the blood–brain barrier (BBB) successfully. Docking analyses were performed by employing an induced-fit docking approach in the GLIDE module of Schrodinger, and the results were in agreement with their in vitro inhibitory activities. The present study resulted in the discovery of potent dual inhibitors toward MAO-B and BACE1, and these lead compounds can be fruitfully explored for the generation of newer, clinically active agents for the treatment of neurodegenerative disorders.
Fatty Acids and Their Metal Salts: A Review of Their Infrared Spectra in Light of Their Presence in Cultural Heritage
Authors: Filopoulou Anna , Vlachou Sophia , Boyatzis Stamatis C.
Published: October 2021

In a cultural heritage context, fatty acids are usually found as breakdown products of lipid-containing organic remains in archaeological findings, binders in aged oil paintings, and additives in modern art-related materials. They may further interact with the ionic environment transforming into metal soaps, a process that has been recognized as a threat in aged paintings but has received less attention in archaeological objects. The investigation of the above related categories of materials with infrared spectroscopy can provide an overall picture of the organic components’ identity and demonstrate their condition and prehistory. The capability of investigating and distinguishing fatty acids and their metal soaps through their rich infrared features, such as the acidic carbonyl, the carboxylate shifts, the variable splits of alkyl chain stretching, bending, twisting, wagging, and rocking vibrations, as well as the hydroxyl peak envelopes and acid dimer bands, allows for their direct detailed characterization. This paper reviews the infrared spectra of selected saturated fatty monoacids and diacids, and their corresponding sodium, calcium, and zinc salts and, supported by newly recorded data, highlights the significance of their spectroscopic features.
Concise Large-Scale Synthesis of Tomatidine, A Potent Antibiotic Natural Product
Authors: Normandin Chad , Boudreault Pierre-Luc
Published: October 2021

Tomatidine has recently generated a lot of interest amongst the pharmacology, medicine, and biology fields of study, especially for its newfound activity as an antibiotic agent capable of targeting multiple strains of bacteria. In the light of its low natural abundance and high cost, an efficient and scalable multi-gram synthesis of tomatidine has been developed. This synthesis uses a Suzuki–Miyaura-type coupling reaction as a key step to graft an enantiopure F-ring side chain to the steroidal scaffold of the natural product, which was accessible from low-cost and commercially available diosgenin. A Lewis acid-mediated spiroketal opening followed by an azide substitution and reduction sequence is employed to generate the spiroaminoketal motif of the natural product. Overall, this synthesis produced 5.2 g in a single pass in 15 total steps and 15.2% yield using a methodology that is atom economical, scalable, and requires no flash chromatography purifications.
High Substitution Synthesis of Carboxymethyl Chitosan for Properties Improvement of Carboxymethyl Chitosan Films Depending on Particle Sizes
Authors: Thanakkasaranee Sarinthip , Jantanasakulwong Kittisak , Phimolsiripol Yuthana , Leksawasdi Noppol , Seesuriyachan Phisit , Chaiyaso Thanongsak , Jantrawut Pensak , Ruksiriwanich Warintorn , Rose Sommano Sarana , Punyodom Winita , Reungsang Alissara , Ngo Thi Minh Phuong , Thipchai Parichat , Tongdeesoontorn Wirongrong , Rachtanapun Pornchai
Published: October 2021

This study investigated the effect of chitosan particle sizes on the properties of carboxymethyl chitosan (CMCh) powders and films. Chitosan powders with different particle sizes (75, 125, 250, 450 and 850 µm) were used to synthesize the CMCh powders. The yield, degree of substitution (DS), and water solubility of the CMCh powders were then determined. The CMCh films prepared with CMCh based on chitosan with different particle sizes were fabricated by a solution casting technique. The water solubility, mechanical properties, and water vapor transmission rate (WVTR) of the CMCh films were measured. As the chitosan particle size decreased, the yield, DS, and water solubility of the synthesized CMCh powders increased. The increase in water solubility was due to an increase in the polarity of the CMCh powder, from a higher conversion of chitosan into CMCh. In addition, the higher conversion of chitosan was also related to a higher surface area in the substitution reaction provided by chitosan powder with a smaller particle size. As the particle size of chitosan decreased, the tensile strength, elongation at break, and WVTR of the CMCh films increased. This study demonstrated that a greater improvement in water solubility of the CMCh powders and films can be achieved by using chitosan powder with a smaller size.
Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound
Authors: Li Tsung-Ju , Lin Ting-Wei , Wu Shih-Pei , Chu Hsin-Tung , Kuo Yu-Hsuan , Chiou Jeng-Fong , Lu Long-Sheng , Chen Chin-Chu
Published: October 2021

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.
Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents
Authors: Maafi Negar , Mamun Abdullah Al , Janďourek Ondřej , Maříková Jana , Breiterová Kateřina , Diepoltová Adéla , Konečná Klára , Hošťálková Anna , Hulcová Daniela , Kuneš Jiří , Kohelová Eliška , Koutová Darja , Šafratová Marcela , Nováková Lucie , Cahlíková Lucie
Published: October 2021

The search for novel antimycobacterial drugs is a matter of urgency, since tuberculosis is still one of the top ten causes of death from a single infectious agent, killing more than 1.4 million people worldwide each year. Nine Amaryllidaceae alkaloids (AAs) of various structural types have been screened for their antimycobacterial activity. Unfortunately, all were considered inactive, and thus a pilot series of aromatic esters of galanthamine, 3-O-methylpancracine, vittatine and maritidine were synthesized to increase biological activity. The semisynthetic derivatives of AAs were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Ra and two other mycobacterial strains (M. aurum, M. smegmatis) using a modified Microplate Alamar Blue Assay. The most active compounds were also studied for their in vitro hepatotoxicity on the hepatocellular carcinoma cell line HepG2. In general, the derivatization of the original AAs was associated with a significant increase in antimycobacterial activity. Several pilot derivatives were identified as compounds with micromolar MICs against M. tuberculosis H37Ra. Two derivatives of galanthamine, 1i and 1r, were selected for further structure optimalization to increase the selectivity index.
Anticancer Effects of the Corchorus olitorius Aqueous Extract and Its Bioactive Compounds on Human Cancer Cell Lines
Authors: Tosoc John Paul Sese , Nuñeza Olga Macas , Sudha Thangirala , Darwish Noureldien H. E. , Mousa Shaker A.
Published: October 2021

Corchorus olitorius is a common, leafy vegetable locally known as “Saluyot” in the Philippines. Several studies have reported on its various pharmacological properties, such as antioxidant, anti-inflammatory, analgesic, and anticancer properties. However, little is known about its effects on angiogenesis. This study aimed to evaluate the anticancer properties, such as the antiproliferative, anti-angiogenic, and antitumor activities, of the C. olitorius aqueous extract (CO) and its bioactive compounds, chlorogenic acid (CGA) and isoquercetin (IQ), against human melanoma (A-375), gastric cancer (AGS), and pancreatic cancer (SUIT-2), using in vitro and in ovo biological assays. The detection and quantification of CGA and IQ in CO were achieved using LC-MS/MS analysis. The antiproliferative, anti-angiogenic, and antitumor activities of CO, CGA, and IQ against A-375, AGS, and SUIT-2 cancer cell lines were evaluated using MTT and CAM assays. CGA and IQ were confirmed to be present in CO. CO, CGA, and IQ significantly inhibited the proliferation of A-375, AGS, and SUIT-2 cancer cells in a dose-dependent manner after 48 h of treatment. Tumor angiogenesis (hemoglobin levels) of A-375 and AGS tumors was significantly inhibited by CO, CGA, IQ, and a CGA–IQ combination. The growth of implanted A-375 and AGS tumors was significantly reduced by CO, CGA, IQ, and a CGA–IQ combination, as measured in tumor weight. Our investigation provides new evidence to show that CO has promising anticancer effects on various types of human cancer cells. CO and its compounds are potential nutraceutical products that could be used for cancer treatment.
New Charge Transfer Complexes of K+-Channel-Blocker Drug (Amifampridine; AMFP) for Sensitive Detection; Solution Investigations and DFT Studies
Authors: Alghanmi Reem M. , Basha Maram T. , Soliman Saied M. , Alsaeedi Razan K.
Published: October 2021

UV–Vis spectroscopy was used to investigate two new charge transfer (CT) complexes formed between the K+-channel-blocker amifampridine (AMFP) drug and the two π-acceptors 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tetracyanoethylene (TCNE) in different solvents. The molecular composition of the new CT complexes was estimated using the continuous variations method and found to be 1:1 for both complexes. The formed CT complexes’ electronic spectra data were further employed for calculating the formation constants (KCT), molar extinction coefficients (εCT), and physical parameters at various temperatures, and the results demonstrated the high stability of both complexes. In addition, sensitive spectrophotometric methods for quantifying AMFP in its pure form were proposed and statistically validated. Furthermore, DFT calculations were used to predict the molecular structures of AMFP–DDQ and AMFP–TCNE complexes in CHCl3. TD-DFT calculations were also used to predict the electronic spectra of both complexes. A CT-based transition band (exp. 399 and 417 nm) for the AMFP–TCNE complex was calculated at 411.5 nm (f = 0.105, HOMO-1 → LUMO). The two absorption bands at 459 nm (calc. 426.9 nm, f = 0.054) and 584 nm (calc. 628.1 nm, f = 0.111) of the AMFP–DDQ complex were theoretically assigned to HOMO-1 → LUMO and HOMO → LUMO excitations, respectively.
Cajanin Suppresses Melanin Synthesis through Modulating MITF in Human Melanin-Producing Cells
Authors: Netcharoensirisuk Ponsawan , Umehara Kaoru , De-Eknamkul Wanchai , Chaotham Chatchai
Published: October 2021

Despite its classification as a non-life-threatening disease, increased skin pigmentation adversely affects quality of life and leads to loss of self-confidence. Until now, there are no recommended remedies with high efficacy and human safety for hyperpigmentation. This study aimed to investigate anti-melanogenic activity and underlying mechanism of cajanin, an isoflavonoid extracted from Dalbergia parviflora Roxb. (Leguminosae) in human melanin-producing cells. Culture with 50 μM cajanin for 48–72 h significantly suppressed proliferation in human melanoma MNT1 cells assessed via MTT viability assay. Interestingly, cajanin also efficiently diminished melanin content in MNT1 cells with the half maximum inhibitory concentration (IC50) at 77.47 ± 9.28 μM. Instead of direct inactivating enzymatic function of human tyrosinase, down-regulated mRNA and protein expression levels of MITF and downstream melanogenic enzymes, including tyrosinase, TRP-1 and Dct (TRP-2) were observed in MNT1 cells treated with 50 μM cajanin for 24–72 h. Correspondingly, treatment with cajanin modulated the signaling pathway of CREB and ERK which both regulate MITF expression level. Targeted suppression on MITF-related proteins in human melanin-producing cells strengthens the potential development of cajanin as an effective treatment for human hyperpigmented disorders.
Stable and Oriented Liquid Crystal Droplets Stabilized by Imidazolium Ionic Liquids
Authors: Ramou Efthymia , Rebordão Guilherme , Palma Susana I. C. J. , Roque Ana C. A.
Published: October 2021

Liquid crystals represent a fascinating intermediate state of matter, with dynamic yet organized molecular features and untapped opportunities in sensing. Several works report the use of liquid crystal droplets formed by microfluidics and stabilized by surfactants such as sodium dodecyl sulfate (SDS). In this work, we explore, for the first time, the potential of surface-active ionic liquids of the imidazolium family as surfactants to generate in high yield, stable and oriented liquid crystal droplets. Our results show that [C12MIM][Cl], in particular, yields stable, uniform and monodisperse droplets (diameter 74 ± 6 µm; PDI = 8%) with the liquid crystal in a radial configuration, even when compared with the standard SDS surfactant. These findings reveal an additional application for ionic liquids in the field of soft matter.
Fluorescent Liquid Tetrazines
Authors: Paradiz Dominguez Maximilian , Demirkurt Begüm , Grzelka Marion , Bonn Daniel , Galmiche Laurent , Audebert Pierre , Brouwer Albert M.
Published: October 2021

Tetrazines with branched alkoxy substituents are liquids at ambient temperature that despite the high chromophore density retain the bright orange fluorescence that is characteristic of this exceptional fluorophore. Here, we study the photophysical properties of a series of alkoxy-tetrazines in solution and as neat liquids. We also correlate the size of the alkoxy substituents with the viscosity of the liquids. We show using time-resolved spectroscopy that intersystem crossing is an important decay pathway competing with fluorescence, and that its rate is higher for 3,6-dialkoxy derivatives than for 3-chloro-6-alkoxytetrazines, explaining the higher fluorescence quantum yields for the latter. Quantum chemical calculations suggest that the difference in rate is due to the activation energy required to distort the tetrazine core such that the nπ*S1 and the higher-lying ππ*T2 states cross, at which point the spin-orbit coupling exceeding 10 cm−1 allows for efficient intersystem crossing to occur. Femtosecond time-resolved anisotropy studies in solution allow us to measure a positive relationship between the alkoxy chain lengths and their rotational correlation times, and studies in the neat liquids show a fast decay of the anisotropy consistent with fast exciton migration in the neat liquid films.
Anti-Herpes Simplex 1 Activity of Simmondsia chinensis (Jojoba) Wax
Authors: Tietel Zipora , Melamed Sarit , Eretz-Kdosha Noy , Guetta Ami , Gvirtz Raanan , Ogen-Shtern Navit , Dag Arnon , Cohen Guy
Published: October 2021

Jojoba (Simmondsia chinensis (Link) Schneider) wax is used for various dermatological and pharmaceutical applications. Several reports have previously shown beneficial properties of Jojoba wax and extracts, including antimicrobial activity. The current research aimed to elucidate the impact of Jojoba wax on skin residential bacterial (Staphylococcus aureus and Staphylococcus epidermidis), fungal (Malassezia furfur), and virus infection (herpes simplex 1; HSV-1). First, the capacity of four commercial wax preparations to attenuate their growth was evaluated. The results suggest that the growth of Staphylococcus aureus, Staphylococcus epidermidis, and Malassezia furfur was unaffected by Jojoba in pharmacologically relevant concentrations. However, the wax significantly attenuated HSV-1 plaque formation. Next, a complete dose–response analysis of four different Jojoba varieties (Benzioni, Shiloah, Hatzerim, and Sheva) revealed a similar anti-viral effect with high potency (EC50 of 0.96 ± 0.4 µg/mL) that blocked HSV-1 plaque formation. The antiviral activity of the wax was also confirmed by real-time PCR, as well as viral protein expression by immunohistochemical staining. Chemical characterization of the fatty acid and fatty alcohol composition was performed, showing high similarity between the wax of the investigated varieties. Lastly, our results demonstrate that the observed effects are independent of simmondsin, repeatedly associated with the medicinal impact of Jojoba wax, and that Jojoba wax presence is required to gain protection against HSV-1 infection. Collectively, our results support the use of Jojoba wax against HSV-1 skin infections.
Heavy Metals and Human Health: Possible Exposure Pathways and the Competition for Protein Binding Sites
Authors: Witkowska Danuta , Słowik Joanna , Chilicka Karolina
Published: October 2021

Heavy metals enter the human body through the gastrointestinal tract, skin, or via inhalation. Toxic metals have proven to be a major threat to human health, mostly because of their ability to cause membrane and DNA damage, and to perturb protein function and enzyme activity. These metals disturb native proteins’ functions by binding to free thiols or other functional groups, catalyzing the oxidation of amino acid side chains, perturbing protein folding, and/or displacing essential metal ions in enzymes. The review shows the physiological and biochemical effects of selected toxic metals interactions with proteins and enzymes. As environmental contamination by heavy metals is one of the most significant global problems, some detoxification strategies are also mentioned.
New 4-Aminoproline-Based Small Molecule Cyclopeptidomimetics as Potential Modulators of α4β1 Integrin
Authors: Sartori Andrea , Bugatti Kelly , Portioli Elisabetta , Baiula Monica , Casamassima Irene , Bruno Agostino , Bianchini Francesca , Curti Claudio , Zanardi Franca , Battistini Lucia
Published: October 2021

Integrin α4β1 belongs to the leukocyte integrin family and represents a therapeutic target of relevant interest given its primary role in mediating inflammation, autoimmune pathologies and cancer-related diseases. The focus of the present work is the design, synthesis and characterization of new peptidomimetic compounds that are potentially able to recognize α4β1 integrin and interfere with its function. To this aim, a collection of seven new cyclic peptidomimetics possessing both a 4-aminoproline (Amp) core scaffold grafted onto key α4β1-recognizing sequences and the (2-methylphenyl)ureido-phenylacetyl (MPUPA) appendage, was designed, with the support of molecular modeling studies. The new compounds were synthesized through SPPS procedures followed by in-solution cyclization maneuvers. The biological evaluation of the new cyclic ligands in cell adhesion assays on Jurkat cells revealed promising submicromolar agonist activity in one compound, namely, the c[Amp(MPUPA)Val-Asp-Leu] cyclopeptide. Further investigations will be necessary to complete the characterization of this class of compounds.
Bimetallic M–Cu (M = Ag, Au, Ni) Nanoparticles Supported on γAl2O3-CeO2 Synthesized by a Redox Method Applied in Wet Oxidation of Phenol in Aqueous Solution and Petroleum Refinery Wastewater
Authors: Guerra-Que Zenaida , Cortez-Elizalde Jorge , Pérez-Vidal Hermicenda , Arévalo-Pérez Juan C. , Silahua-Pavón Adib A. , Córdova-Pérez Gerardo E. , Cuauhtémoc-López Ignacio , Martínez-García Héctor , González-Díaz Anabel , Torres-Torres José Gilberto
Published: October 2021

Three bimetallic catalysts of the type M–Cu with M = Ag, Au and Ni supports were successfully prepared by a two-step synthesized method using Cu/Al2O3-CeO2 as the base monometallic catalyst. The nanocatalysts were characterized using X-ray diffraction (XRD), temperature-programmed reduction of H2 (H2-TPR), N2 adsorption-desorption, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM) and ultraviolet–visible spectroscopy with diffuse reflectance (DR-UV-Vis) techniques. This synthesized methodology allowed a close interaction between two metals on the support surface; therefore, it could have synthesized an efficient transition–noble mixture bimetallic nanostructure. Alloy formation through bimetallic nanoparticles (BNPs) of AgCuAlCe and AuCuAlCe was demonstrated by DR–UV–Vis, EDS, TEM and H2-TPR. Furthermore, in the case of AgCuAlCe and AuCuAlCe, improvements were observed in their reducibility, in contrast to NiCuAlCe. The addition of a noble metal over the monometallic copper-based catalyst drastically improved the phenol mineralization. The higher activity and selectivity to CO2 of the bimetallic gold–copper- and silver–copper-supported catalysts can be attributed to the alloy compound formation and the synergetic effect of the M–Cu interaction. Petroleum Refinery Wastewater (PRW) had a complex composition that affected the applied single CWAO treatment, rendering it inefficient.