bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Analysis of Plasmodium falciparum Dihydropteroate Synthase Variants Associated with Sulfadoxine Resistance Reveals Variant Distribution and Mechanisms of Resistance: A Computational-Based Study
Authors: Boateng Rita Afriyie , Myers-Hansen James L. , Dolling Nigel N. O. , Mensah Benedicta A. , Brodsky Elia , Mazumder Mohit , Ghansah Anita
Published: December 2022

The continual rise in sulfadoxine (SDX) resistance affects the therapeutic efficacy of sulfadoxine-pyrimethamine; therefore, careful monitoring will help guide its prolonged usage. Mutations in Plasmodium falciparum dihydropteroate synthase (Pfdhps) are being surveilled, based on their link with SDX resistance. However, there is a lack of continuous analyses and data on the potential effect of molecular markers on the Pfdhps structure and function. This study explored single-nucleotide polymorphisms (SNPs) in Pfdhps that were isolated in Africa and other countries, highlighting the regional distribution and its link with structure. In total, 6336 genomic sequences from 13 countries were subjected to SNPs, haplotypes, and structure-based analyses. The SNP analysis revealed that the key SDX resistance marker, A437G, was nearing fixation in all countries, peaking in Malawi. The mutation A613S was rare except in isolates from the Democratic Republic of Congo and Malawi. Molecular docking revealed a general loss of interactions when comparing mutant proteins to the wild-type protein. During MD simulations, SDX was released from the active site in mutants A581G and A613S before the end of run-time, whereas an unstable binding of SDX to mutant A613S and haplotype A437A/A581G/A613S was observed. Conformational changes in mutant A581G and the haplotypes A581G/A613S, A437G/A581G, and A437G/A581G/A613S were seen. The radius of gyration revealed an unfolding behavior for the A613S, K540E/A581G, and A437G/A581G systems. Overall, tracking such mutations by the continuous analysis of Pfdhps SNPs is encouraged. SNPs on the Pfdhps structure may cause protein–drug function loss, which could affect the applicability of SDX in preventing malaria in pregnant women and children.
Effects of Growth Period and Storage Methods on Primary Metabolite Contents and Antioxidant Activities of Morus alba L. Leaf
Authors: Hu Lei , Chen Dandan , Zhou Wei , Chen Xiaoyang , Zhang Qing
Published: December 2022

(1) Background: Mulberry leaves have been widely consumed due to their richness in bioactive substances and high antioxidant activity. The choice of storage method to ensure the quality of mulberry leaves is a challenge in the supply process. (2) Methods: The differences in primary metabolites of freeze-dried mulberry leaf powder after 30 days of storage under different storage conditions (i.e., vacuum or non-vacuum, 4 °C or room temperature) were investigated. (3) Results: A low temperature and vacuum had better preservation effects on the types and activity of the primary metabolites of mulberry leaves, with vacuum preservation being the best. However, the types of primary metabolites in mulberry leaves were significantly reduced after non-vacuum storage at room temperature compared to those with other storage methods. Among the metabolites detected, including dehydroascorbic acid, various phenolic acids, amino acids, lipids, and carbohydrates showed a significant decrease in their contents of more than 40%, and there was a significant increase in the contents of various compounds of the muconic acid biosynthetic pathway compared to those in other storage methods. Moreover, the antioxidant activity of mulberry leaves stored at room temperature under non-vacuum conditions was also significantly reduced. (4) Conclusions: Vacuum storage is the most ideal storage method for preserving mulberry leaves.
Analytical Methods for the Characterization of Vegetable Oils
Authors: Giacomino Agnese , Inaudi Paolo , Silletta Gessica , Diana Aleandro , Bertinetti Stefano , Gaggero Elisa , Malandrino Mery , Stilo Federico , Abollino Ornella
Published: December 2022

The determination of the authenticity of extra virgin olive oils (EVOOs) has become more interesting in recent years. Italy is the first country in Europe in terms of number of Protected Designation of Origin (PDO) oils, which connects consumers to a feeling of tradition and thus to higher quality standards. This work focused on the consideration of the inorganic content as a possible marker of EVOOs. Ten vegetable oils (VOs), eight Italian EVOOs and seven not Italian EVOOs were analyzed. After pretreatment by acid mineralization, Al, Ba, Ca, Cu, Fe, K, Li, Mg, Mn, Na, P, Sb, Se and Zn were determined by ICP-OES. The electrochemical properties of a selected group of EVOOs and other vegetal oils of different botanical origin were investigated by voltammetry. Carbon paste electrodes (CPEs) were prepared. The features observed in the voltammograms reflect the reactions of electroactive compounds, which are present in the oils. A chemometric treatment of the results was performed to assess the possibility to distinguish (i) the region of provenience considering the inorganic profile; and (ii) the plant species from which each oil was obtained on the basis of the current profile registered during voltammetric analysis. Inorganic composition seems to be a useful marker for the assessment of the geographical origin of an EVOO. The EVOO-CPEs voltammetry seems to have a good ability to distinguish the plant species of origin. This method could be useful to monitor the conservation status of the oils, as the redox profile is linked to the oxidative degradation state.
Therapeutic Potential of Flavonoids and Tannins in Management of Oral Infectious Diseases—A Review
Authors: Kováč Ján , Slobodníková Lívia , Trajčíková Eva , Rendeková Katarína , Mučaji Pavel , Sychrová Alice , Bittner Fialová Silvia
Published: December 2022

Medicinal plants are rich sources of valuable molecules with various profitable biological effects, including antimicrobial activity. The advantages of herbal products are their effectiveness, relative safety based on research or extended traditional use, and accessibility without prescription. Extensive and irrational usage of antibiotics since their discovery in 1928 has led to the increasing expiration of their effectiveness due to antibacterial resistance. Now, medical research is facing a big and challenging mission to find effective and safe antimicrobial therapies to replace inactive drugs. Over the years, one of the research fields that remained the most available is the area of natural products: medicinal plants and their metabolites, which could serve as active substances to fight against microbes or be considered as models in drug design. This review presents selected flavonoids (such as apigenin, quercetin, kaempferol, kurarinone, and morin) and tannins (including oligomeric proanthocyanidins, gallotannins, ellagitannins, catechins, and epigallocatechin gallate), but also medicinal plants rich in these compounds as potential therapeutic agents in oral infectious diseases based on traditional usages such as Agrimonia eupatoria L., Hamamelis virginiana L., Matricaria chamomilla L., Vaccinium myrtillus L., Quercus robur L., Rosa gallica L., Rubus idaeus L., or Potentilla erecta (L.). Some of the presented compounds and extracts are already successfully used to maintain oral health, as the main or additive ingredient of toothpastes or mouthwashes. Others are promising for further research or future applications.
Schiff Base in Ketoamine Form and Rh(η4-cod)-Schiff Base Complex with Z′ = 2 Structure from Pairwise C-H···Metallochelate-π Contacts
Authors: Enamullah Mohammed , Haque Imdadul , Resma Amina Khan , Woschko Dennis , Janiak Christoph
Published: December 2022

Condensation of 2-hydroxybenzaldehyde (salicylaldehyde) or 2-hydroxy-1-naphthaldehyde with 2-ethylaniline yields the Schiff base compound of (E)-2-(((2-ethylphenyl)imino)methyl)phenol (HL1) or (E)-1-(((2-ethylphenyl)imino)methyl)naphthalen-2-ol (HL2), which in turn react with the dinuclear complex of [Rh(η4-cod)(µ-O2CCH3)]2 (cod = cycloocta-1,5-diene) to afford the mononuclear (η4-cod){(E)-2-(((2-ethylphenyl)imino)methyl)phenolato-κ2N,O}rhodium(I), [Rh(η4-cod)(L1)] (1) or (η4-cod){(E)-1-(((2-ethylphenyl)imino)methyl)naphthalen-2-olato-κ2N,O}rhodium(I), [Rh(η4-cod)(L2)] (2) (L1 or L2 = deprotonated Schiff base ligand). The X-ray structure determination revealed that the HL2 exists in the solid state not as the usual (imine)N···H-O(phenol) form (enolamine form) but as the zwitterionic (imine)N-H+···–O(phenol) form (ketoamine form). 1H NMR spectra for HL2 in different solvents demonstrated the existence of keto-enol tautomerism (i.e., keto ⇆ enol equilibrium) in solution. The structure for 1 and 2 showed that the deprotonated Schiff base ligand coordinates to the Rh(η4-cod)-fragment as a six-membered N^O-chelate around the rhodium atom with a close-to-square-planar geometry. Two symmetry-independent molecules (with Rh1 and Rh2) were found in the asymmetric unit in 1 in a structure with Z’ = 2. The supramolecular packing in HL2 was organized by π-π and C-H···π contacts, while only two recognized C-H···π contacts were revealed in 1 and 2. Remarkably, there were reciprocal or pairwise C-H···π contacts between a pair of each of the symmetry-independent molecules in 1. This pairwise C-H contact to the Rh-N^O chelate (metalloaromatic) ring may be a reason for the two symmetry-independent molecules in 1. Differential scanning calorimetry (DSC) analyses revealed an irreversible phase transformation from the crystalline-solid to the isotropic-liquid phase and subsequently confirmed the thermal stability of the compounds. Absorption spectra in solution were explained by excited state properties from DFT/TD-DFT calculations.
Comprehensive Survey of Consensus Docking for High-Throughput Virtual Screening
Authors: Blanes-Mira Clara , Fernández-Aguado Pilar , de Andrés-López Jorge , Fernández-Carvajal Asia , Ferrer-Montiel Antonio , Fernández-Ballester Gregorio
Published: December 2022

The rapid advances of 3D techniques for the structural determination of proteins and the development of numerous computational methods and strategies have led to identifying highly active compounds in computer drug design. Molecular docking is a method widely used in high-throughput virtual screening campaigns to filter potential ligands targeted to proteins. A great variety of docking programs are currently available, which differ in the algorithms and approaches used to predict the binding mode and the affinity of the ligand. All programs heavily rely on scoring functions to accurately predict ligand binding affinity, and despite differences in performance, none of these docking programs is preferable to the others. To overcome this problem, consensus scoring methods improve the outcome of virtual screening by averaging the rank or score of individual molecules obtained from different docking programs. The successful application of consensus docking in high-throughput virtual screening highlights the need to optimize the predictive power of molecular docking methods.
Threonine Facilitates Cd Excretion by Increasing the Abundance of Gut Escherichia coli in Cd-Exposed Mice
Authors: Li Yongbin , Fang Zhijia , Zhou Xuewei , Gao Jian , Wang Jingwen , Huang Linru , Chen Yinyan , Sun Lijun , Deng Qi , Gooneratne Ravi
Published: December 2022

Cadmium (Cd) can easily enter the body through the food chain and threaten health since Cd pollution is prevalent in the environment. Gut microbiota is necessary for the reduction of metal ions. To reduce Cd-induced harmful impacts and Cd accumulation in the body, we investigated the effect of amino acids on gut microbiota and Cd excretion in (fecal Cd) Cd-exposed mice. The screening of 20 amino acids showed that threonine (Thr) effectively increased fecal Cd, and reduced Cd-induced intestinal structural damage. The abundance of Escherichia-Shigella genus and KF843036_g significantly increased after the oral administration of Thr. As the type species of the Escherichia-Shigella genus, Escherichia coli exhibited high similarity to KF843036_g species and significantly decreased Cd-induced gut damage. Cd contents in the liver, kidney, and gut of Cd-exposed mice were also significantly (p < 0.05) decreased after E. coli treatment, while the contents in the feces were increased. The results demonstrated the potential roles that gut E. coli might play in Thr-mediated Cd excretion in Cd-exposed mice. The findings may provide important data for better understanding the molecular biological mechanism of Thr in reducing Cd accumulation in the body.
Theoretical Investigation of Geometries and Bonding of Indium Hydrides in the In2Hx and In3Hy (x = 0–4,6; y = 0–5) Series
Authors: Pozdeev Anton S. , Rublev Pavel , Scheiner Steve , Boldyrev Alexander I.
Published: December 2022

Boron hydrides have been an object of intensive theoretical and experimental investigation for many decades due to their unusual and somewhat unique bonding patterns. Despite boron being a neighboring element to carbon, boron hydrides almost always form non-classical structures with multi-center bonds. However, we expect indium to form its interesting molecules with non-classical patterns, though such molecules still need to be extensively studied theoretically. In this work, we investigated indium hydrides of In2Hx (x = 0–4,6) and In3Hy (y = 0–5) series via DFT and ab initio quantum chemistry methods, performing a global minimum search, chemical bonding analysis, and studies of their thermodynamical stability. We found that the bonding pattern of indium hydrides differs from the classical structures composed of 1c-2e lone pairs and 2c-2e bonds and the bonding pattern of earlier investigated boron hydrides of the BnHn+2 series. The studied stoichiometries are characterized by multi-center bonds, aromaticity, and the tendency for indium to preserve the 1c-2e lone pair.
Voltammetric and Fluorimetric Studies of Dibenzoylmethane on Glassy Carbon Electrodes and Its Interaction with Tetrakis (3,5-Dicarboxyphenoxy) Cavitand Derivative
Authors: Kiss László , Nagymihály Zoltán , Kollár László , Kunsági-Máté Sándor
Published: December 2022

Due to the medical importance of dibenzoylmethane, one of the aims of the study was to find an appropriate packing material and a biologically friendly co-solvent to help its introduction into living systems. Accordingly, redox properties of dibenzoylmethane were investigated on glassy carbon electrodes in acetonitrile and in 1-propanol with cyclic voltammetry, and showed a diffusion-controlled process. In the anodic window, an oxidation peak appeared at around 1.9 V in both solvents. Cycling repeatedly between 0 and 2 V, the reproducibility of this peak was acceptable, but when extending the window to higher potentials, the electrode deactivated, obviously due to electrode material. The addition of the investigated tetrakis(3,5-dicarboxyphenoxy) cavitand did not significantly change the voltammograms. Further electrochemical experiments showed that the coexistence of water in acetonitrile and 1-propanol drastically reduces the solubility of dibenzoylmethane. Moreover, very rapid electrode deactivation occurred and this fact made the use of electrochemical methods complicated. Considering that both the cavitand and dibenzoylmethane are soluble in dimethyl sulfoxide, the interaction of these species was investigated and formation of stable complexes was detected. This observation was verified with fluorescence quenching studies. The mixture of water and dimethyl sulphoxide also dramatically improved the solubility of the cavitand–dibenzoylmethane complex at high excess of water. The addition of cavitand improved the solubility of dibenzoylmethane, a property which supports the application of dibenzoylmethane in therapy.
Inspection on the Mechanism of SARS-CoV-2 Inhibition by Penciclovir: A Molecular Dynamic Study
Authors: Giannetti Micaela , Mazzuca Claudia , Ripani Giorgio , Palleschi Antonio
Published: December 2022

In recent years, humanity has had to face a critical pandemic due to SARS-CoV-2. In the rapid search for effective drugs against this RNA-positive virus, the repurposing of already existing nucleotide/nucleoside analogs able to stop RNA replication by inhibiting the RNA-dependent RNA polymerase enzyme has been evaluated. In this process, a valid contribution has been the use of in silico experiments, which allow for a rapid evaluation of the possible effectiveness of the proposed drugs. Here we propose a molecular dynamic study to provide insight into the inhibition mechanism of Penciclovir, a nucleotide analog on the RNA-dependent RNA polymerase enzyme. Besides the presented results, in this article, for the first time, molecular dynamic simulations have been performed considering not only the RNA-dependent RNA polymerase protein, but also its cofactors (fundamental for RNA replication) and double-strand RNA.
A Nationwide Study of Residual Fate of Fluxapyroxad and Its Metabolites in Peanut Crops Across China: Assessment of Human Exposure Potential
Authors: Wang Xi , Chen Li , Ren Xin , Kang Shanshan , Li Wei , Chen Zenglong
Published: December 2022

Elaborating on the residual fate of fluxapyroxad and its metabolites based on their nationwide application was vital to protect the human population from their hazardous effects. In this study, a rapid and sensitive analytical method was developed to trace fluxapyroxad and two of its metabolites in peanut matrices using an ultrahigh chromatography method coupled with mass spectrometry (UHPLC–MS/MS) within 3.5 min. The occurrence, pharmacokinetic degradation and terminal magnitudes of fluxapyroxad were reflected in the original deposition of 8.41–38.15 mg/kg, half–lives of 2.5–8.6 d and final concentrations of 0.004–37.38 mg/kg in peanut straw. The total concentrations of fluxapyroxad in peanut straw (0.04–39.28 mg/kg) were significantly higher than those in peanut kernels (<0.001–0.005 mg/kg) and an obvious concentration effect was observed in fresh (0.01–11.56 mg/kg) compared dried peanut straw (0.04–38.97 mg/kg). Fluxapyroxad was demethylated to 3–(difluoromethyl)–N–(3′,4′,5′–trifluoro[1,1′–biphenyl]–2–yl)–1H–pyrazole–4–carboxamide (M700F008, 0.02–5.69 mg/kg) and further N–glycosylated to 3–(difluoromethyl)–1–(ß–D–glucopyranosyl)–N–(3′,4′,5′–triflurobipheny–2–yl)–1H–pyrzaole–4–carboxamide (M700F048, 0.04–39.28 mg/kg).The risk quotients of the total fluxapyroxad for the urban groups were significantly higher than those for the rural groups, and were both negatively correlated with the age of the groups, although both acute (ARfD%, 0.006–0.012%) and chronic (ADI%, 0.415–1.289%) risks are acceptable for the human population. The high-potential health risks of fluxapyroxad should be continuously emphasized for susceptible toddlers (1–3 years), especially those residing in urban areas.
Potential of Compounds Originating from the Nature to Act in Hepatocellular Carcinoma Therapy by Targeting the Tumor Immunosuppressive Microenvironment: A Review
Authors: Li Yunheng , Li Hui , He Qiaojun , Yang Xiaochun
Published: December 2022

Hepatocellular carcinoma (HCC), the most prevalent subtype of liver cancer, is the second main reason for cancer-related deaths worldwide. In recent decades, sufficient evidence supported that immunotherapy was a safe and effective treatment option for HCC. However, tolerance and frequent recurrence and metastasis occurred in patients after immunotherapy due to the complicated crosstalk in the tumor immunosuppressive microenvironment (TIME) in HCC. Therefore, elucidating the TIME in HCC and finding novel modulators to target TIME for attenuating immune suppression is critical to optimize immunotherapy. Recently, studies have shown the potentially immunoregulatory activities of natural compounds, characterized by multiple targets and pathways and low toxicity. In this review, we concluded the unique role of TIME in HCC. Moreover, we summarized evidence that supports the hypothesis of natural compounds to target TIME to improve immunotherapy. Furthermore, we discussed the comprehensive mechanisms of these natural compounds in the immunotherapy of HCC. Accordingly, we present a well-grounded review of the naturally occurring compounds in cancer immunotherapy, expecting to shed new light on discovering novel anti-HCC immunomodulatory drugs from natural sources.
A Novel Aptamer-Imprinted Polymer-Based Electrochemical Biosensor for the Detection of Lead in Aquatic Products
Authors: Zhu Nianxin , Liu Xinna , Peng Kaimin , Cao Hui , Yuan Min , Ye Tai , Wu Xiuxiu , Yin Fengqin , Yu Jinsong , Hao Liling , Xu Fei
Published: December 2022

Lead contamination in aquatic products is one of the main hazard factors. The aptasensor is a promising detection method for lead ion (Pb(II)) because of its selectivity, but it is easily affected by pH. The combination of ion-imprinted polymers(IIP) with aptamers may improve their stability in different pH conditions. This paper developed a novel electrochemical biosensor for Pb(II) detection by using aptamer-imprinted polymer as a recognition element. The glassy carbon electrode was modified with gold nanoparticles and aptamers. After the aptamer was induced by Pb(II) to form a G-quadruplex conformation, a chitosan-graphene oxide was electrodeposited and cross-linked with glutaraldehyde to form an imprint layer, improving the stability of the biosensor. Under the optimal experimental conditions, the current signal change (∆I) showed a linear correlation of the content of Pb(II) in the range of 0.1–2.0 μg/mL with a detection limit of 0.0796 μg/mL (S/N = 3). The biosensor also exhibited high selectivity for the determination of Pb(II) in the presence of other interfering metal ion. At the same time, the stability of the imprinted layer made the sensor applicable to the detection environment with a pH of 6.4–8.0. Moreover, the sensor was successfully applied to the detection of Pb(II) in mantis shrimp.
Molecular Dynamics and Chain Length of Edible Oil Using Low-Field Nuclear Magnetic Resonance
Authors: Jia Zijian , Liang Can
Published: December 2022

Nuclear magnetic resonance (NMR) techniques are widely used to identify pure substances and probe protein dynamics. Edible oil is a complex mixture composed of hydrocarbons, which have a wide range of molecular size distribution. In this research, low-field NMR (LF-NMR) relaxation characteristic data from various sample oils were analyzed. We also suggest a new method for predicting the size of edible oil molecules using LF-NMR relaxation time. According to the relative molecular mass, the carbon chain length and the transverse relaxation time of different sample oils, combined with oil viscosity and other factors, the relationship between carbon chain length and transverse relaxation time rate was analyzed. Various oils and fats in the mixed fluid were displayed, reflecting the composition information of different oils. We further studied the correlation between the rotation correlation time and the molecular information of oil molecules. The molecular composition of the resulting fluid determines its properties, such as viscosity and phase behavior. The results show that low-field NMR can obtain information on the composition, macromolecular aggregation and molecular dynamics of complex fluids. The measurements of grease in the free-fluid state show that the relaxation time can reflect the intrinsic properties of the fluid. It is shown that the composition characteristics and states of complex fluids can be measured using low-field nuclear magnetic resonance.
Encapsulating Calendula arvensis (Vaill.) L. Florets: UHPLC-HRMS Insights into Bioactive Compounds Preservation and Oral Bioaccessibility
Authors: Fiorentino Marika , Piccolella Simona , Gravina Claudia , Stinca Adriano , Esposito Assunta , Catauro Michelina , Pacifico Severina
Published: December 2022

Wild edible plants, once consumed in times of famine or for health purposes, today represent an interesting dietary supplement, aimed at enriching local dishes and/or formulating healthy nutraceutical products. In fact, the broad content of different, and diversely bioactive, specialized metabolites therein suggests new scenarios of use which, in order to be as functional as possible, must maximize the bioactivity of these compounds while preserving their chemistry. In this context, based on a recent investigation on the metabolic profile of the organs of Calendula arvensis that highlighted that florets are abundant in flavonol glycosides and triterpene saponins, the freeze-drying encapsulation of their alcoholic extract (FE) into maltodextrin (MD) was investigated. FE-MD chemical composition was evaluated using Fourier Transform InfraRed spectroscopy (FTIR), while ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) techniques were employed to unravel FE compound preservation also during in vitro simulated digestion. The establishment of H-bonds between FE compounds and MD hydroxyl groups was in line with FE-MD biocompatibility in Caco-2 cells, while in vitro digestion mostly affected structural integrity and/or diversity. Flavonol compounds underwent deglycosylation and demethylation, while deacylation, beyond oxidation, involved triterpene saponins, which massively preserve their aglycone core.
Some Novel Results Involving Prototypical Computation of Zagreb Polynomials and Indices for SiO4 Embedded in a Chain of Silicates
Authors: Tag El Din El Sayed M. , Sultan Faisal , Ghani Muhammad Usman , Liu Jia-Bao , Dehraj Sanaullah , Cancan Murat , Alharbi Fahad M. , Alhushaybari Abdullah
Published: December 2022

A topological index as a graph parameter was obtained mathematically from the graph’s topological structure. These indices are useful for measuring the various chemical characteristics of chemical compounds in the chemical graph theory. The number of atoms that surround an atom in the molecular structure of a chemical compound determines its valency. A significant number of valency-based molecular invariants have been proposed, which connect various physicochemical aspects of chemical compounds, such as vapour pressure, stability, elastic energy, and numerous others. Molecules are linked with numerical values in a molecular network, and topological indices are a term for these values. In theoretical chemistry, topological indices are frequently used to simulate the physicochemical characteristics of chemical molecules. Zagreb indices are commonly employed by mathematicians to determine the strain energy, melting point, boiling temperature, distortion, and stability of a chemical compound. The purpose of this study is to look at valency-based molecular invariants for SiO4 embedded in a silicate chain under various conditions. To obtain the outcomes, the approach of atom–bond partitioning according to atom valences was applied by using the application of spectral graph theory, and we obtained different tables of atom—bond partitions of SiO4. We obtained exact values of valency-based molecular invariants, notably the first Zagreb, the second Zagreb, the hyper-Zagreb, the modified Zagreb, the enhanced Zagreb, and the redefined Zagreb (first, second, and third). We also provide a graphical depiction of the results that explains the reliance of topological indices on the specified polynomial structure parameters.
Low-Temperature Toluene Oxidation on Fe-Containing Modified SBA-15 Materials
Authors: Trendafilova Ivalina , Ojeda Manuel , Andresen John M. , Ristić Alenka , Dimitrov Momtchil , Tušar Nataša Novak , Atanasova Genoveva , Popova Margarita
Published: December 2022

Transition metals as catalysts for total VOC oxidation at low temperatures (150–280 °C) are a big challenge nowadays. Therefore, iron-modified SBA-15, AlSBA-15, and ZrSBA-15 materials with 0.5 to 5.0 wt.% Fe loading were prepared and tested for toluene oxidation. It was found that increasing Fe loading significantly improved the rate of oxidation and lowered the temperature of achieving 100% removal of toluene from above 500 °C for the supports (AlSBA-15 and ZrSBA-15) to below 400 °C for 5FeZrSBA-15. The formation of finely dispersed iron oxide active sites with a particle size less than 5 nm was observed on all the SBA-15, AlSBA-15, and ZrSBA-15 supports. It was found that the surface properties of the mesoporous support due to the addition of Al or Zr predetermined the type of formed iron oxide species and their localization on the support surface. Fe-containing SBA-15 and AlSBA-15 showed activity in total toluene oxidation at higher temperatures (280–450 °C). However, 5 wt. % Fe-containing ZrSBA-15 showed excellent activity in the total oxidation of toluene as a model VOC at lower temperatures (150–380 °C) due to the synergistic effect of Fe-Zr and the presence of accessible and stable Fe2+/Fe3+ active sites.
The New Attempt at Modeling of the Three-Dimensional Geometry of the Epidermal Skin Layer and the Diffusion Processes of Nanomolecular Drug Carriers in Such Structures
Authors: Błaszczyk Mariola M. , Sęk Jerzy P.
Published: December 2022

Nanoparticles are presently considered the efficient carriers of medicals, cosmetics, and pharmaceuticals in the human organism. There is a lot of research carried out on the delivery of these materials in a non-invasive way. Such a method is very safe in times of global illnesses and pandemics. The most frequently investigated route is the approach to delivering nano-media through the skin as the result of diffusion processes. The stratum corneum, the outermost layer of skin, is the most resistive barrier to such a form of penetration. In this work, a new model is proposed to predict nanoparticles’ transport through this layer. It introduces the concept of the three-dimensional model of the stratum corneum, which allows to define the skin surface area from which diffusion occurs. This structure was replaced by the single capillary, resulting from theoretical considerations. Modeling of the diffusion process of nanoparticles as the result of Brownian motion in such a capillary was performed numerically using COMSOL Multiphysics package programs. Further, using the dimensions of such a capillary, a new model of diffusion was developed in which the parameters allow to determine the effective diffusion coefficient as a function of nanoparticle size and the viscosity of a liquid. As a result, the proposed models provide a new and efficient approach to the determination of the nano-molecules’ transport phenomena through the skin layer.
In Silico Identification of Anti-SARS-CoV-2 Medicinal Plants Using Cheminformatics and Machine Learning
Authors: Liang Jihao , Zheng Yang , Tong Xin , Yang Naixue , Dai Shaoxing
Published: December 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, is spreading rapidly and has caused hundreds of millions of infections and millions of deaths worldwide. Due to the lack of specific vaccines and effective treatments for COVID-19, there is an urgent need to identify effective drugs. Traditional Chinese medicine (TCM) is a valuable resource for identifying novel anti-SARS-CoV-2 drugs based on the important contribution of TCM and its potential benefits in COVID-19 treatment. Herein, we aimed to discover novel anti-SARS-CoV-2 compounds and medicinal plants from TCM by establishing a prediction method of anti-SARS-CoV-2 activity using machine learning methods. We first constructed a benchmark dataset from anti-SARS-CoV-2 bioactivity data collected from the ChEMBL database. Then, we established random forest (RF) and support vector machine (SVM) models that both achieved satisfactory predictive performance with AUC values of 0.90. By using this method, a total of 1011 active anti-SARS-CoV-2 compounds were predicted from the TCMSP database. Among these compounds, six compounds with highly potent activity were confirmed in the anti-SARS-CoV-2 experiments. The molecular fingerprint similarity analysis revealed that only 24 of the 1011 compounds have high similarity to the FDA-approved antiviral drugs, indicating that most of the compounds were structurally novel. Based on the predicted anti-SARS-CoV-2 compounds, we identified 74 anti-SARS-CoV-2 medicinal plants through enrichment analysis. The 74 plants are widely distributed in 68 genera and 43 families, 14 of which belong to antipyretic detoxicate plants. In summary, this study provided several medicinal plants with potential anti-SARS-CoV-2 activity, which offer an attractive starting point and a broader scope to mine for potentially novel anti-SARS-CoV-2 drugs.
Improving the Functional Performance of Date Seed Protein Concentrate by High-Intensity Ultrasonic Treatment
Authors: Kelany Mohamed , Yemiş Oktay
Published: December 2022

Date kernel is a plant-derived byproduct that has the potential to be converted into a high-value-added food ingredient, such as protein concentrate, in the food industry. Ultrasound, which is an alternative method for improving the functional properties of food proteins, is an effective physical treatment for modifying protein functionality. Solubility is the main criterion that primarily affects other functional properties of protein concentrates, such as emulsification, foaming, and water and oil binding. The aim of this study is to enhance the techno-functional performance of date seed protein concentrate (DSPC) by maximizing the solubility via a high-intensity ultrasound (HIUS) treatment at a fixed frequency of 20 kHz. The effect of ultrasonic homogenization under varying amplitudes and times (amplitude of 40, 60, and 80% for 5, 10, and 15 min, respectively) on the functional properties of the DSPC was investigated by using the response surface methodology (RSM). A face-centered central composite design (FC-CCD) revealed that the optimal process conditions of HIUS were at an amplitude of 80% for 15 min. The physicochemical and functional properties of the ultrasound-applied concentrate (DSPC-US) were determined under the optimum HIUS conditions, and then these properties of DSPC-US were compared to the native DSPC. The results showed that the solubility of all DSPC samples treated by HIUS was significantly (p < 0.05) higher than that of the native DSPC. In addition, emulsion activity/stability, foaming activity/stability, and oil-binding capacity increased after HIUS homogenization treatments, whereas the water-binding capacity decreased. These changes in the techno-functional properties of the DSPC-US were explained by the modification to the physicochemical structure of the DSPC (particle size, zeta potential, SDS-PAGE, SEM, FTIR, DSC, free SH content, surface hydrophobicity, and intrinsic emission). This work revealed that HIUS could be an effective treatment for enhancing the functional properties of date seed protein concentrate.
Neurotransmitters Regulation and Food Intake: The Role of Dietary Sources in Neurotransmission
Authors: Gasmi Amin , Nasreen Aniqa , Menzel Alain , Gasmi Benahmed Asma , Pivina Lyudmila , Noor Sàdaf , Peana Massimiliano , Chirumbolo Salvatore , Bjørklund Geir
Published: December 2022

Neurotransmitters (NTs) are biologically active chemicals, which mediate the electrochemical transmission between neurons. NTs control numerous organic functions particularly crucial for life, including movement, emotional responses, and the physical ability to feel pleasure and pain. These molecules are synthesized from simple, very common precursors. Many types of NTs have both excitatory and inhibitory effects. Neurotransmitters’ imbalance can cause many diseases and disorders, such as Parkinson’s disease, depression, insomnia, increased anxiety, memory loss, etc. Natural food sources containing NTs and/or their precursors would be a potential option to help maintain the balance of NTs to prevent brain and psychiatric disorders. The level of NTs could be influenced, therefore, by targeting dietary habits and nutritional regimens. The progressive implementation of nutritional approaches in clinical practice has made it necessary to infer more about some of the nutritional NTs in neuropsychiatry. However, the importance of the intake of nutritional NTs requires further understanding, since there are no prior significant studies about their bioavailability, clinical significance, and effects on nerve cells. Interventional strategies supported by evidence should be encouraged.
Antioxidant, Anti-Diabetic, Anti-Obesity, and Antihypertensive Properties of Protein Hydrolysate and Peptide Fractions from Black Sesame Cake
Authors: Chaipoot Supakit , Punfa Wanisa , Ounjaijean Sakaewan , Phongphisutthinant Rewat , Kulprachakarn Kanokwan , Parklak Wason , Phaworn Laddawan , Rotphet Pattrawan , Boonyapranai Kongsak
Published: December 2022

A low-value by-product of cold-pressed sesame oil is defatted black sesame cake (DBSC). The remaining protein and essential amino acids may be utilized as a renewable biological source to produce bioactive products. The bioactivities of the protein hydrolysate from black sesame cake and its peptide fractions were examined in this study for in vitro antioxidant activity and inhibition of DPP-IV, ACE, α-amylase, α-glucosidase, and pancreatic lipase. By using Flavourzyme to hydrolyze DBSC, followed by ultrafiltration, fractions with peptide sizes of <3, 3–10, and >10 kDa were obtained. According to the findings, the products of DBSC could neutralize free radicals and prevent ferric ion redox reactions. The highest inhibitory effects were shown with low Mw peptides (<3 kDa) against ACE, DPP-IV, α-amylase, and α-glucosidase. DBSC has demonstrated potential as a nutraceutical or functional ingredient for preventing and treating disorders associated with free radicals, such as diabetes, hypertension, and hyperglycemia.
Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains
Authors: Khan Farooq-Ahmad , Yaqoob Sana , Ali Shujaat , Tanveer Nimra , Wang Yan , Ashraf Sajda , Hasan Khwaja Ali , Khalifa Shaden A. M. , Shou Qiyang , Ul-Haq Zaheer , Jiang Zi-Hua , El-Seedi Hesham R.
Published: December 2022

The emergence of multidrug-resistant (MDR) pathogens and the gradual depletion of available antibiotics have exacerbated the need for novel antimicrobial agents with minimal toxicity. Herein, we report functionally substituted pyridine carbohydrazide with remarkable antimicrobial effect on multi-drug resistant strains. In the series, compound 6 had potent activity against four MDR strains of Candida spp., with minimum inhibitory concentration (MIC) values being in the range of 16–24 µg/mL and percentage inhibition up to 92.57%, which was exceptional when compared to broad-spectrum antifungal drug fluconazole (MIC = 20 µg/mL, 81.88% inhibition). Substitution of the octyl chain in 6 with a shorter butyl chain resulted in a significant anti-bacterial effect of 4 against Pseudomonas aeruginosa (ATCC 27853), the MIC value being 2-fold superior to the standard combination of ampicillin/cloxacillin. Time-kill kinetics assays were used to discern the efficacy and pharmacodynamics of the potent compounds. Further, hemolysis tests confirmed that both compounds had better safety profiles than the standard drugs. Besides, molecular docking simulations were used to further explore their mode of interaction with target proteins. Overall results suggest that these compounds have the potential to become promising antimicrobial drugs against MDR strains.
Clove Essential Oil and Its Main Constituent, Eugenol, as Potential Natural Antifungals against Candida spp. Alone or in Combination with Other Antimycotics Due to Synergistic Interactions
Authors: Biernasiuk Anna , Baj Tomasz , Malm Anna
Published: December 2022

The occurrence of candidiasis, including superficial infections, has recently increased dramatically, especially in immunocompromised patients. Their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. The aim of this study was to determine the antifungal effect of clove essential oil (CEO) and eugenol (EUG) towards both reference and clinical Candida spp. strains isolated from the oral cavity of patients with hematological malignancies, and to investigate their mode of action and the interactions in combination with the selected antimycotics. These studies were performed using the broth microdilution method, tests with sorbitol and ergosterol, and a checkerboard technique, respectively. The CEO and EUG showed activity against all Candida strains with a minimal inhibitory concentration (MIC) in the range of 0.25–2 mg/mL. It was also found that both natural products bind to ergosterol in the yeast cell membrane. Moreover, the interactions between CEO and EUG with several antimycotics—cetylpyridinium chloride, chlorhexidine, silver nitrate and triclosan—showed synergistic or additive effects in combination, except nystatin. This study confirms that the studied compounds appear to be a very promising group of phytopharmaceuticals used topically in the treatment of superficial candidiasis. However, this requires further studies in vivo.
Decrypting the Potential of Nanotechnology-Based Approaches as Cutting-Edge for Management of Hyperpigmentation Disorder
Authors: Singh Sukhbir , Sharma Neelam , Zahoor Ishrat , Behl Tapan , Antil Anita , Gupta Sumeet , Anwer Md Khalid , Mohan Syam , Bungau Simona Gabriela
Published: December 2022

The abundant synthesis and accretion of melanin inside skin can be caused by activation of melanogenic enzymes or increase in number of melanocytes. Melasma is defined as hyperpigmented bright or dark brown spots which are symmetrically distributed and have serrated and irregular borders. The three general categories of pigmentation pattern include centro facial pattern, malar pattern, and mandibular pattern. Exposure to UV rays, heat, use of cosmetics and photosensitizing drugs, female sex hormonal therapies, aberrant production of melanocyte stimulating hormone, and increasing aesthetic demands are factors which cause the development of melasma disease. This review gives a brief overview regarding the Fitzpatrick skin phototype classification system, life cycle of melanin, mechanism of action of anti-hyperpigmenting drugs, and existing pharmacotherapy strategies for the treatment of melasma. The objectives of this review are focused on role of cutting-edge nanotechnology-based strategies, such as lipid-based nanocarriers, i.e., lipid nanoparticles, microemulsions, nanoemulsions, liposomes, ethosomes, niosomes, transfersomes, aspasomes, invasomes penetration-enhancing vesicles; inorganic nanocarriers, i.e., gold nanoparticles and fullerenes; and polymer-based nanocarriers i.e., polymeric nanoparticles, polymerosomes, and polymeric micelles for the management of hyperpigmentation.
Clay-Catalyzed Ozonation of Organic Pollutants in Water and Toxicity on Lemna minor: Effects of Molecular Structure and Interactions
Authors: Foka Wembe Eric Noel , Benghafour Amina , Dewez David , Azzouz Abdelkrim
Published: December 2022

The use of clays as adsorbents and catalysts in the ozonation of organic pollutants (Atrazine, bis-Phenol A, Diazinon, and Diclofenac sodium) allowed simulating their natural oxidative degradation in clay soils and to evaluate the ecotoxicity of mixtures partially oxidized on the species Lemna minor, a biodiversity representative of plants in the aquatic environment. Kinetic data showed that the adsorption of organic pollutants on clay particles obeys the pseudo-second-order model, while the adsorption isotherms satisfactorily fit the Langmuir model. Adsorption reduces the dispersion of the organic pollutant in the environment and prolongs its persistence and its natural degradation probability. Measurements of the Zeta potential and particle size as a function of pH demonstrate that the catalytic activity of clay depends on its cation, its silica/alumina ratio, and therefore on its permanent and temporary ion exchange capacities. These factors seem to govern its delamination and dispersion in aqueous media, its hydrophilic-hydrophobic character, and its porosity. Tests conducted on Lemna minor in contact with ozonation mixtures revealed that the toxicity could be due to pH decrease and to the toxicity of the intermediates yielded. Ecotoxicity would depend on the structure of the organic molecules, the chemical composition of the clay surface and ozonation time, which determines the oxidation progress. These results are of great importance for further research because they allow concluding that the negative impact of the persistence of an organic molecule in clay-containing media depends on the type and composition of the very clay mineral.
Sequential Iron-Catalyzed C(sp2)–C(sp3) Cross-Coupling of Chlorobenzamides/Chemoselective Amide Reduction and Reductive Deuteration to Benzylic Alcohols
Authors: Bisz Elwira , Podchorodecka Pamela , Li Hengzhao , Ochędzan-Siodłak Wioletta , An Jie , Szostak Michal
Published: December 2022

Benzylic alcohols are among the most important intermediates in organic synthesis. Recently, the use of abundant metals has attracted significant attention due to the issues with the scarcity of platinum group metals. Herein, we report a sequential method for the synthesis of benzylic alcohols by a merger of iron catalyzed cross-coupling and highly chemoselective reduction of benzamides promoted by sodium dispersion in the presence of alcoholic donors. The method has been further extended to the synthesis of deuterated benzylic alcohols. The iron-catalyzed Kumada cross-coupling exploits the high stability of benzamide bonds, enabling challenging C(sp2)–C(sp3) cross-coupling with alkyl Grignard reagents that are prone to dimerization and β-hydride elimination. The subsequent sodium dispersion promoted reduction of carboxamides proceeds with full chemoselectivity for the C–N bond cleavage of the carbinolamine intermediate. The method provides access to valuable benzylic alcohols, including deuterium-labelled benzylic alcohols, which are widely used as synthetic intermediates and pharmacokinetic probes in organic synthesis and medicinal chemistry. The combination of two benign metals by complementary reaction mechanisms enables to exploit underexplored avenues for organic synthesis.