bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome Characterization of Bacteriophage KPP-1, a Novel Member in the Subfamily Vequintavirinae, and Use of Its Endolysin for the Lysis of Multidrug-Resistant Klebsiella variicola In Vitro
Authors: Senevirathne Amal , Lee Jehee , De Zoysa Mahanama , Nikapitiya Chamilani
Published: January 2023

Multidrug-resistant members of the Klebsiella pneumoniae complex have become a threat to human lives and animals, including aquatic animals, owing to the limited choice of antimicrobial treatments. Bacteriophages are effective natural tools available to fight against multidrug-resistant bacteria. The bacteriophage KPP-1 was found to be strictly lytic against K. variicola, a multidrug-resistant isolate, producing clear plaques. The genome sequence analysis of KPP-1 revealed that it comprised 143,369 base pairs with 47% overall GC content. A total of 272 genes (forward 161, complementary 111) encode for 17 tRNAs and 255 open reading frames (ORFs). Among them, 32 ORFs could be functionally annotated using the National Center for Biotechnology Information (NCBI) Protein Basic Local Alignment Search Tool (BLASTp) algorithm while 223 were found to code for hypothetical proteins. Comparative genomic analysis revealed that the closest neighbor of KPP-1 can be found in the genus Mydovirus of the subfamily Vequintavirinae. KPP-1 not only markedly suppressed the growth of the host but also worked synergistically with ampicillin. Useful genes for pathogen control such as endolysin (locus tag: KPP_11591) were found to have activity against multidrug-resistant isolate of K. variicola. Further studies are necessary to develop a strategy to control the emerging pathogen K. variicola using bacteriophages such as KPP-1.
Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis
Authors: Lourenço Estela Mariana Guimarães , Di Iório Juliana Fortes , da Silva Fernanda , Fialho Felipe Leonardo Bley , Monteiro Melquisedeque Mateus , Beatriz Adilson , Perdomo Renata Trentin , Barbosa Euzébio Guimarães , Oses Jean Pierre , de Arruda Carla Cardozo Pinto , de Souza Júdice Wagner Alves , Rafique Jamal , de Lima Dênis Pires
Published: January 2023

Leishmaniasis is a neglected tropical disease, affecting more than 350 million people globally. However, there is currently no vaccine available against human leishmaniasis, and current treatment is hampered by high cost, side-effects, and painful administration routes. It has become a United Nations goal to end leishmaniasis epidemics by 2030, and multitarget drug strategy emerges as a promising alternative. Among the multitarget compounds, flavonoids are a renowned class of natural products, and a structurally diverse library can be prepared through organic synthesis, which can be tested for biological effectiveness. In this study, we synthesised 17 flavonoid analogues using a scalable, easy-to-reproduce, and inexpensive method. All synthesised compounds presented an impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y enzymes, which are highly expressed in the amastigote stage, the target form of the parasite. Compounds 3c, f12a, and f12b were found to be effective against all isoforms. Furthermore, their intermolecular interactions were also investigated through a molecular modelling study. These compounds were highly potent against the parasite and demonstrated low cytotoxic action against mammalian cells. These results are pioneering, representing an advance in the investigation of the mechanisms behind the antileishmanial action of flavonoid derivatives. Moreover, compounds have been shown to be promising leads for the design of other cysteine protease inhibitors for the treatment of leishmaniasis diseases.
Investigation into the Gaseous SO2 Attack on Sandstone in the Yungang Grottoes
Authors: Zhang Yue , Cao Cheng , Du Houmeng , Huang Jizhong , Guo Xiuwei , Luo Qingyang , Ren Jianguang
Published: January 2023

The Yungang Grottoes, with over 1500 years of history, have been subjected to air pollution since the last century. Field investigations have indicated that acid gases, particularly sulfur dioxide (SO2), have accumulated on the surface of the sculptures and caused various types of decay that reduce their artistic value. To shed new light on the gas–stone interaction process, artificially accelerated weathering was performed on local sandstone in the laboratory. In a specially developed test device, fresh specimens were exposed to gaseous SO2 under different relative humidity and temperature conditions. The physical, mineralogical, and chemical changes of Yungang sandstone were evaluated conjointly using destructive and non-destructive methods. The results show that after weathering, the luminosity of all specimens changed, with a slight alteration in hue toward yellow. The weight increased to various degrees during the aging cycles, which depended on both the accumulation of matter and the detachment of particles. Higher relative humidity and cyclic temperature fluctuations favored the dissolution of carbonates and the hydrolysis of feldspar in sandstone. The concentration of ions, especially dissolved Ca2+ and SO42−, increased considerably over time in the near-surface region of the specimens. A trace of newly formed gypsum was detected in some specimens at the end of the test. Knowing the synergistic impact of different climatic variables will make it possible to identify the mechanisms of the deterioration of sandstone in complex environments.
Trace Elements in Dental Enamel Can Be a Potential Factor of Advanced Tooth Wear
Authors: Zamojda Elzbieta , Orywal Karolina , Mroczko Barbara , Sierpinska Teresa
Published: January 2023

Enamel is the outermost layer of the tooth and has no ability to regenerate after tooth eruption. Its mineral composition is likely to be responsible for the enamel resistance to any agents that appear in oral cavity. The objective of this study was to compare the content of Ca, Mg, Zn and Cu in specific layers of healthy and worn tooth enamel. Three groups of dental enamel samples were analyzed. The amounts of Ca, Mg and Zn in the enamel bioptates were established using atomic absorption spectroscopy after an acid biopsy technique had been applied. The concentration of Cu was established using an electrothermic method with an AA spectrometer. The analysis was carried out using parametric tests (the Pearson’s linear correlation coefficient and the t-test for the correlation coefficient). Results: A statistically significant difference was confirmed between the mean amount of zinc in severely worn dentition and all the layers in vitro and in vivo. Strong positive relationships between magnesium and zinc contents were shown at some depths. A significant difference was registered between the amount of copper in the severely worn dentitions compared to the superficial layer of the healthy teeth in vitro and in vivo. Conclusion: It appears that zinc metabolism may play an important role in enamel formation and may influence enamel’s resistance to wear after tooth eruption.
Rare Earth Element Deposits in Mongolia
Authors: Dostal Jaroslav , Gerel Ochir
Published: January 2023

In Mongolia, rare earth element (REE) mineralization of economic significance is related either to the Mesozoic carbonatites or to the Paleozoic peralkaline granitoid rocks. Carbonatites occur as part of alkaline silicate-carbonatite complexes, which are composed mainly of nepheline syenites and equivalent volcanic rocks. The complexes were emplaced in the Gobi-Tien Shan rift zone in southern Mongolia where carbonatites usually form dikes, plugs or intruded into brecciated rocks. In mineralized carbonatites, REE occur mainly as fluorocarbonates (bastnäsite, synchysite, parisite) and apatite. Apatite is also present in the carbonatite-hosted apatite-magnetite (mostly altered to hematite) bodies. Alkaline silicate rocks and carbonatites show common geochemical features such as enrichment of light REE but relative depletion of Ti, Zr, Nb, Ta and Hf and similar Sr and Nd isotopic characteristics suggesting the involvement of the heterogeneous lithospheric mantle in the formation of both carbonatites and associated silicate rocks. Hydrothermal fluids of magmatic origin played an important role in the genesis of the carbonatite-hosted REE deposits. The REE mineralization associated with peralkaline felsic rocks (peralkaline granites, syenites and pegmatites) mainly occurs in Mongolian Altai in northwestern Mongolia. The mineralization is largely hosted in accessory minerals (mainly elpidite, monazite, xenotime, fluorocarbonates), which can reach percentage levels in mineralized zones. These rocks are the results of protracted fractional crystallization of the magma that led to an enrichment of REE, especially in the late stages of magma evolution. The primary magmatic mineralization was overprinted (remobilized and enriched) by late magmatic to hydrothermal fluids. The mineralization associated with peralkaline granitic rocks also contains significant concentrations of Zr, Nb, Th and U. There are promising occurrences of both types of rare earth mineralization in Mongolia and at present, three of them have already established significant economic potential. They are mineralization related to Mesozoic Mushgai Khudag and Khotgor carbonatites in southern Mongolia and to the Devonian Khalzan Buregtei peralkaline granites in northwestern Mongolia.
A Heterostructure Photoelectrode Based on Two-Dimensional Covalent Organic Framework Film Decorated TiO2 Nanotube Arrays for Enhanced Photoelectrochemical Hydrogen Generation
Authors: Zhang Yue , Li Yujie , Yu Jing , Sun Bing , Shang Hong
Published: January 2023

The well-defined heterostructure of the photocathode is desirable for photoelectrochemically producing hydrogen from aqueous solutions. Herein, enhanced heterostructures were fabricated based on typical stable covalent organic framework (TpPa-1) films and TiO2 nanotube arrays (NTAs) as a proof-of-concept model to tune the photoelectrochemical (PEC) hydrogen generation by tailoring the photoelectrode microstructure and interfacial charge transport. Ultrathin TpPa-1 films were uniformly grown on the surface of TiO2 NTAs via a solvothermal condensation of building blocks by tuning the monomer concentration. The Pt1@TpPa-1/TiO2-NTAs photoelectrode with single-atom Pt1 as a co-catalyst demonstrated improved visible-light response, enhanced photoconductance, lower onset potential, and decreased Tafel slope value for hydrogen evolution. The hydrogen evolution rate of the Pt1@TpPa-1/TiO2-NTAs photoelectrode was five times that of Pt1@TpPa-1 under AM 1.5 simulated sunlight irradiation and the bias voltage of 0 V. A lower overpotential was recorded as 77 mV@10 mA cm−2 and a higher photocurrent density as 1.63 mA cm−2. The hydrogen evolution performance of Pt1@TpPa-1/TiO2-NTAs photoelectrodes may benefit from the well-matched band structures, effective charge separation, lower interfacial resistance, abundant interfacial microstructural sites, and surficial hydrophilicity. This work may raise a promising way to design an efficient PEC system for hydrogen evolution by tuning well-defined heterojunctions and interfacial microstructures.
Electrolyte Design Strategies for Non-Aqueous High-Voltage Potassium-Based Batteries
Authors: Tan Hong , Lin Xiuyi
Published: January 2023

High-voltage potassium-based batteries are promising alternatives for lithium-ion batteries as next-generation energy storage devices. The stability and reversibility of such systems depend largely on the properties of the corresponding electrolytes. This review first presents major challenges for high-voltage electrolytes, such as electrolyte decomposition, parasitic side reactions, and current collector corrosion. Then, the state-of-the-art modification strategies for traditional ester and ether-based organic electrolytes are scrutinized and discussed, including high concentration, localized high concentration/weakly solvating strategy, multi-ion strategy, and addition of high-voltage additives. Besides, research advances of other promising electrolyte systems, such as potassium-based ionic liquids and solid-state-electrolytes are also summarized. Finally, prospective future research directions are proposed to further enhance the oxidative stability and non-corrosiveness of electrolytes for high-voltage potassium batteries.
Crystal Structure of Allantoinase from Escherichia coli BL21: A Molecular Insight into a Role of the Active Site Loops in Catalysis
Authors: Huang Yen-Hua , Yang Po-Chun , Lin En-Shyh , Ho Ya-Yeh , Peng Wei-Feng , Lu Hsin-Pin , Huang Chien-Chih , Huang Cheng-Yang
Published: January 2023

Allantoinase (ALLase; EC 3.5.2.5) possesses a binuclear metal center in which two metal ions are bridged by a posttranslationally carbamylated lysine. ALLase acts as a key enzyme for the biogenesis and degradation of ureides by catalyzing the conversion of allantoin into allantoate. Biochemically, ALLase belongs to the cyclic amidohydrolase family, which also includes dihydropyrimidinase, dihydroorotase, hydantoinase (HYDase), and imidase. Previously, the crystal structure of ALLase from Escherichia coli K-12 (EcALLase-K12) was reported; however, the two active site loops crucial for substrate binding were not determined. This situation would limit further docking and protein engineering experiments. Here, we solved the crystal structure of E. coli BL21 ALLase (EcALLase-BL21) at a resolution of 2.07 Å (PDB ID 8HFD) to obtain more information for structural analyses. The structure has a classic TIM barrel fold. As compared with the previous work, the two missed active site loops in EcALLase-K12 were clearly determined in our structure of EcALLase-BL21. EcALLase-BL21 shared active site similarity with HYDase, an important biocatalyst for industrial production of semisynthetic penicillin and cephalosporins. Based on this structural comparison, we discussed the functional role of the two active site loops in EcALLase-BL21 to better understand the substrate/inhibitor binding mechanism for further biotechnological and pharmaceutical applications.
Synthesis and Characterization of Novel Thiosalicylate-based Solid-Supported Ionic Liquid for Removal of Pb(II) Ions from Aqueous Solution
Authors: Kamaruddin Nur Anis Liyana , Taha Mohd Faisal , Wilfred Cecilia Devi
Published: January 2023

The main objectives of this study are to synthesize a new solid-supported ionic liquid (SSIL) that has a covalent bond between the solid support, i.e., activated silica gel, with thiosalicylate-based ionic liquid and to evaluate the performance of this new SSIL as an extractant, labelled as Si-TS-SSIL, and to remove Pb(II) ions from an aqueous solution. In this study, 1-methyl-3-(3-trimethoxysilylpropyl) imidazolium thiosalicylate ([MTMSPI][TS]) ionic liquid was synthesized and the formation of [MTMSPI][TS] was confirmed through structural analysis using NMR, FTIR, IC, TGA, and Karl Fischer Titration. The [MTMSPI][TS] ionic liquid was then chemically immobilized on activated silica gel to produce a new thiosalicylate-based solid-supported ionic liquid (Si-TS-SSIL). The formation of these covalent bonds on Si-TS-SSIL was confirmed by solid-state NMR analysis. Meanwhile, BET analysis was performed to study the surface area of the activated silica gel and the prepared Si-TS-SSIL (before and after washing with solvent) with the purpose to show that all physically immobilized [MTMSPI][TS] has been washed off from Si-TS-SSIL, leaving only chemically immobilized [MTMSPI][TS] on Si-TS-SSIL before proceeding with removal study. The removal study of Pb(II) ions from an aqueous solution was carried out using Si-TS-SSIL as an extractant, whereby the amount of Pb(II) ions removed was determined by AAS. In this removal study, the experiments were carried out at a fixed agitation speed (400 rpm) and fixed amount of Si-TS-SSIL (0.25 g), with different contact times ranging from 2 to 250 min at room temperature. The maximum removal capacity was found to be 8.37 mg/g. The kinetics study was well fitted with the pseudo-second order model. Meanwhile, for the isotherm study, the removal process of Pb(II) ions was well described by the Freundlich isotherm model, as this model exhibited a higher correlation coefficient (R2), i.e., 0.99, as compared to the Langmuir isotherm model.
Effect of Thermal Treatment on the Self-Assembly of Wheat Gluten Polypeptide
Authors: Liu Hao , Wang Jingxuan , Liu Mei , Zhang Xia , Liang Ying , Wang Jinshui
Published: January 2023

Self-assembled fibrillation of wheat gluten is a common phenomenon in the daily production and processing of wheat flour products. The driving forces for its formation and the factors that influence the morphology of fibrils have not been thoroughly investigated. In this study, the effect of three bonding changes (breaking hydrogen bonds, strengthening hydrophobic interactions, and SH-SS exchange reactions) on gluten polypeptide (GP) fibrillation was simulated by adjusting the heating temperature (room temperature (RT), 45 °C, 65 °C, and 95 °C). The results showed that the breakage of hydrogen bonds could induce conformational transitions in GPs and help to excite fibrillation in GPs. Strengthened hydrophobic interactions significantly contributed to the fibrillation of GPs. Covalent crosslinks generated by SH-SS exchange reactions might also promote the fibrillation of GPs. GPs with different degrees of hydrolysis (4.0%, 6.0%, and 10.0%, represented by DH 4, DH 6, and DH 10, respectively) presented different extents of fibrillation, with DH 10 GPs having a higher propensity to fibrillation than DH 4 and DH 6 GPs. The results of Fourier’s transform infrared spectroscopy indicated that hydrophobic interactions drive the transition from a random coil and α-helix to a β-sheet. In addition, hydrophobic interactions also drive the intermolecular polymerization of GPs, resulting in larger molecular weight aggregates. The morphology presented by transmission electron microscopy showed that the greater the DH, the stronger the tendency for the worm-like aggregation of GPs.
Scalable Synthesis of TRPV1 Antagonist Bipyridinyl Benzimidazole Derivative via the Suzuki–Miyaura Reaction and Selective SeO2 Oxidation
Authors: Lee Joon-Hwan , Kim Jiduck , Kim Hakwon
Published: January 2023

In this study, a kilogram-scale synthesis of a potent TRPV1 antagonist, 1, is described. To synthesize bipyridinyl benzimidazole derivative 1, we have developed a scalable Suzuki–Miyaura reaction capable of providing a key intermediate, 6′-methyl-3-(trifluoromethyl)-2,3′-bipyridine 4, on a kilogram scale. Then, unlike the existing oxidation reaction pathway, two synthetic routes that can be applied to mass production of bipyridinyl carboxylic acid intermediate 5 or aldehyde intermediate 6 were developed by appropriately controlling the oxidation reaction using a selenium dioxide oxidizing agent. Using our developed synthetic procedure, which includes Suzuki–Miyaura coupling, selective selenium dioxide oxidation, and benzimidazole formation, multi-kilogram-scale bi-pyridinyl benzimidazole derivative 1 can be synthesized.
Structure and Formation of Z-DNA and Z-RNA
Authors: Krall Jeffrey B. , Nichols Parker J. , Henen Morkos A. , Vicens Quentin , Vögeli Beat
Published: January 2023

Despite structural differences between the right-handed conformations of A-RNA and B-DNA, both nucleic acids adopt very similar, left-handed Z-conformations. In contrast to their structural similarities and sequence preferences, RNA and DNA exhibit differences in their ability to adopt the Z-conformation regarding their hydration shells, the chemical modifications that promote the Z-conformation, and the structure of junctions connecting them to right-handed segments. In this review, we highlight the structural and chemical properties of both Z-DNA and Z-RNA and delve into the potential factors that contribute to both their similarities and differences. While Z-DNA has been extensively studied, there is a gap of knowledge when it comes to Z-RNA. Where such information is lacking, we try and extend the principles of Z-DNA stability and formation to Z-RNA, considering the inherent differences of the nucleic acids.
DEML: Drug Synergy and Interaction Prediction Using Ensemble-Based Multi-Task Learning
Authors: Wang Zhongming , Dong Jiahui , Wu Lianlian , Dai Chong , Wang Jing , Wen Yuqi , Zhang Yixin , Yang Xiaoxi , He Song , Bo Xiaochen
Published: January 2023

Synergistic drug combinations have demonstrated effective therapeutic effects in cancer treatment. Deep learning methods accelerate identification of novel drug combinations by reducing the search space. However, potential adverse drug–drug interactions (DDIs), which may increase the risks for combination therapy, cannot be detected by existing computational synergy prediction methods. We propose DEML, an ensemble-based multi-task neural network, for the simultaneous optimization of five synergy regression prediction tasks, synergy classification, and DDI classification tasks. DEML uses chemical and transcriptomics information as inputs. DEML adapts the novel hybrid ensemble layer structure to construct higher order representation using different perspectives. The task-specific fusion layer of DEML joins representations for each task using a gating mechanism. For the Loewe synergy prediction task, DEML overperforms the state-of-the-art synergy prediction method with an improvement of 7.8% and 13.2% for the root mean squared error and the R2 correlation coefficient. Owing to soft parameter sharing and ensemble learning, DEML alleviates the multi-task learning ‘seesaw effect’ problem and shows no performance loss on other tasks. DEML has a superior ability to predict drug pairs with high confidence and less adverse DDIs. DEML provides a promising way to guideline novel combination therapy strategies for cancer treatment.
Analytical Method Development of Benzisothiazolinone, a Biocide, Using LC–MS/MS and a Pharmacokinetic Application in Rat Biological Matrices
Authors: Jo Seong Jun , Huang Zhouchi , Lee Chae Bin , Chae Soon Uk , Bae Soo Hyeon , Bae Soo Kyung
Published: January 2023

Benzisothiazolinone (BIT), a biocide widely used as a preservative in household cleaning and personal care products, is cytotoxic to lung cells and a known skin allergen in humans, which highlights the importance of assessing its toxicity and pharmacokinetics. In this study, a simple, sensitive, and accurate LC–MS/MS method for the quantification of BIT in rat plasma, urine, or tissue homogenates (50 μL) using phenacetin as an internal standard was developed and validated. Samples were extracted with ethyl acetate and separated using a Kinetex phenyl–hexyl column (100 × 2.1 mm, 2.6 μm) with isocratic 0.1% formic acid in methanol and distilled water over a run time of 6 min. Positive electrospray ionization with multiple reaction monitoring transitions of m/z 152.2 > 134.1 for BIT and 180.2 > 110.1 for phenacetin was used for quantification. This assay achieved good linearity in the calibration ranges of 2–2000 ng/mL (plasma and urine) and 10–1000 ng/mL (tissue homogenates), with r ≥ 0.9929. All validation parameters met the acceptance criteria. BIT pharmacokinetics was evaluated via an intravenous and dermal application. This is the first study that evaluated BIT pharmacokinetics in rats, providing insights into the relationship between BIT exposure and toxicity and a basis for future risk assessment studies in humans.
Light Increases Astaxanthin Absorbance in Acetone Solution through Isomerization Reactions
Authors: Virchenko Oleksandr , Stefánsson Tryggvi
Published: January 2023

Astaxanthin quantitative analysis is prone to high variability between laboratories. This study aimed to assess the effect of light on the spectrometric and high-performance liquid chromatography (HPLC) measurements of astaxanthin. The experiment was performed on four Haematococcus pluvialis-derived astaxanthin-rich oleoresin samples with different carotenoid matrices that were analyzed by UV/Vis spectrometry and HPLC according to the United States Pharmacopoeia (USP) monograph. Each sample was dissolved in acetone in three types of flasks: amber glass wrapped with aluminium foil, uncovered amber glass, and transparent glass. Thus, the acetone solutions were either in light-proof flasks or exposed to ambient light. The measurements were taken within four hours (spectrometry) or three hours (HPLC) from the moment of oleoresin dissolution in acetone to investigate the dynamics of changes in the recorded values. The results confirm the logarithmic growth of astaxanthin absorbance by 8–11% (UV/Vis) and 7–17% (HPLC) after 3 h of light exposure. The changes were different in the samples with different carotenoid matrices; for instance, light had the least effect on the USP reference standard sample. The increase in absorbance was accompanied with the change of isomeric distribution, namely a reduction of 13Z and an increase of All-E and 9Z astaxanthin. The greater HPLC values’ elevation was related not only to the increase of astaxanthin absorbance, but also to light-dependent degradation of internal standard apocarotenal. The findings confirm a poor robustness of the conventional analytical procedure for astaxanthin quantitation and a necessity for method revision and harmonization to improve its reproducibility.
Cyclodextrin Metal-Organic Framework as a Broad-Spectrum Potential Delivery Vehicle for the Gasotransmitters
Authors: Liao Li-Guo , Ke Duo , Li Guo-Chen , Zhang Sheng , Li Bang-Jing
Published: January 2023

The important role of gasotransmitters in physiology and pathophysiology suggest employing gasotransmitters for biomedical treatment. Unfortunately, the difficulty in storage and controlled delivery of these gaseous molecules hindered the development of effective gasotransmitters-based therapies. The design of a safe, facile, and wide-scale method to delivery multiple gasotransmitters is a great challenge. Herein, we use an ultrasonic assisted preparation γ-cyclodextrin metal organic framework (γ-CD-MOF) as a broad-spectrum delivery vehicle for various gasotransmitters, such as SO2, NO, and H2S. The release rate of gasotransmitters could be tuned by modifying the γ-CD-MOF with different Pluronics. The biological relevance of the exogenous gasotransmitters produced by this method is evidenced by the DNA cleavage ability and the anti-inflammatory effects. Furthermore, the γ-CD-MOF composed of food-grade γ-CD and nontoxic metal salts shows good biocompatibility and particle size (180 nm). Therefore, γ-CD-MOF is expected to be an excellent tool for the study of co-delivery and cooperative therapy of gasotransmitters.
Electroreductively Induced Radicals for Organic Synthesis
Authors: Xiang Huaming , He Jinyu , Qian Weifeng , Qiu Mingqiang , Xu Hao , Duan Wenxi , Ouyang Yanyan , Wang Yanzhao , Zhu Cuiju
Published: January 2023

Organic electrochemistry has attracted tremendous interest within the novel sustainable methodologies that have not only reduced the undesired byproducts, but also utilized cleaner and renewable energy sources. Particularly, oxidative electrochemistry has gained major attention. On the contrary, reductive electrolysis remains an underexplored research direction. In this context, we discuss advances in transition-metal-free cathodically generated radicals for selective organic transformations since 2016. We highlight the electroreductive reaction of alkyl radicals, aryl radicals, acyl radicals, silyl radicals, fluorosulfonyl radicals and trifluoromethoxyl radicals.
Carotenoid Content and Profiles of Pumpkin Products and By-Products
Authors: Ninčević Grassino Antonela , Rimac Brnčić Suzana , Badanjak Sabolović Marija , Šic Žlabur Jana , Marović Roko , Brnčić Mladen
Published: January 2023

The goal of this review is to provide an overview of the current findings on the major carotenoids and their content in pumpkin products and by-products. The content of total carotenoids and the composition of carotenoids in pumpkins depend mainly on the species and cultivar, pedoclimatic conditions, the part of the plant (pulp, peel or seed), extraction procedures and the type of solvent used for extraction. The major carotenoids identified in pumpkins were β-carotene, α-carotene, lutein and zeaxanthin. β-Carotene is the major carotenoid in most pumpkin species. The number and content of total carotenoids are higher when minor carotenoids and ester forms are considered. The use of carotenoids in the development of functional foods has been the topic of many versatile studies in recent years, as they add significant value to foods associated with numerous health benefits. In view of this, pumpkin and pumpkin by-products can serve as a valuable source of carotenoids.
Galectin-1 Used in Assisted Reproduction—Embryo Safety and Toxicology Studies
Authors: Roncoletta Marcelo , de Sales Nathali Adrielli Agassi , Rey Fernando Sebastian Baldi , Ferraz Guilherme Camargo , Morani Erika da Silva Carvalho
Published: January 2023

Galectin-1 has been cited as a mediator involved in preventing early embryonic death in mammals and is implicated in maternal–fetal tolerance. Galectin-1 is also a reasonable tool to improve fertility in assisted reproduction procedures. As recommended in the ICH guidelines (S5-R2 and S6-R1) and based on bioethical concerns, we chose bovine embryos (BE) to assess in vitro embryo development as part of a larger reproductive safety and toxicology study in progress. The design considered in vitro embryo development using rHGAL-1 supplementations (in three different concentrations) of the in vitro embryo culture (IVP) media. Based on procedures for the commercial in vitro production of BE using oocytes aspirated from slaughterhouse ovaries, rHGAL-1 supplementation was performed in two experiments: In Experiment 1 on oocyte maturation, involving IVM medium supplementation, and in Experiment 2 on culture step IVC, involving supplementation with an SOF medium. IVP commercial procedures were used, with three IVP replicates per experiment, and the oocytes we distributed into four groups of treatment (one control group and three different dosages of rHGAL-1 to supplement both IVM and SOF media using 2, 20, and 40 µg·mL−1, respectively. A total of 967 (Experiment 1) and 1213 (Experiment 2) oocytes were aspirated and submitted to the IVP procedure. There was no damage to the in vitro bovine embryo growth when considering cleavage percentage (%CLE), blastocyst development (Bl, Bx, Bh, and B) at Days 7 and 8, or an amount of rHGAL-1 supplementation ≤20 µg·mL−1. The immunohistochemistry assay with D8 embryos cultivated using rHGAL-1 supplementation on the culture medium (SOF medium) demonstrated the presence of exogenous GAL-1 distributed in mass cell and trophoblastic cells, and the profile observed was dependent on exogenous supplementation, which was most evident in hatched embryos. The findings confirmed the use of a reasonable amount of rHGAL-1 for in vitro embryonic development and would make the use of rHGAL-1 in assisted reproduction in humans more reliable and safer. Even though it was not the objective of the study, we verified that supplementation with 2 µg·mL−1 significantly improved some of the evaluated parameters of embryonic development (%BlD7, %BD7, %BlD8, %BhD8, and %BD8).
Soluble Guanylyl Cyclase Activators—Promising Therapeutic Option in the Pharmacotherapy of Heart Failure and Pulmonary Hypertension
Authors: Grześk Grzegorz , Witczyńska Adrianna , Węglarz Magdalena , Wołowiec Łukasz , Nowaczyk Jacek , Grześk Elżbieta , Nowaczyk Alicja
Published: January 2023

Endogenous nitric oxide (NO)-dependent vascular relaxation plays a leading role in the homeostasis of the cardiovascular, pulmonary, and vascular systems and organs, such as the kidneys, brain, and liver. The mechanism of the intracellular action of NO in blood vessels involves the stimulation of the activity of the soluble cytosolic form of guanylyl cyclase (soluble guanylyl cyclase, sGC), increasing the level of cyclic 3′-5′—guanosine monophosphate (cGMP) in smooth muscle and subsequent vasodilation. In recent years, a new group of drugs, soluble guanylyl cyclase stimulators, has found its way into clinical practice. Based on the CHEST-1 and PATENT-1 trials, riociguat was introduced into clinical practice for treating chronic thromboembolic pulmonary hypertension (CTEPH). In January 2021, the FDA approved the use of another drug, vericiguat, for the treatment of heart failure.
Anti-Inflammatory, Anti-Bacterial, and Anti-Fungal Activity of Oligomeric Proanthocyanidins and Extracts Obtained from Lignocellulosic Agricultural Waste
Authors: Andersone Anna , Janceva Sarmite , Lauberte Liga , Ramata-Stunda Anna , Nikolajeva Vizma , Zaharova Natalija , Rieksts Gints , Telysheva Galina
Published: January 2023

It has now been proven that many pathogens that cause infections and inflammation gradually mutate and become resistant to antibiotics. Chemically synthesized drugs treating inflammation most often only affect symptoms, but side effects could lead to the failure of human organs’ functionality. On the other hand, plant-derived natural compounds have a long-term healing effect. It was shown that sea buckthorn (SBT) twigs are a rich source of biologically active compounds, including oligomeric proanthocyanidins (PACs). This study aimed to assess the anti-pathogenic and anti-inflammatory activity of water/ethanol extracts and PACs obtained from the lignocellulosic biomass of eight SBT cultivars. The anti-pathogenic activity of extracts and PACs was studied against pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Bacillus cereus and fungus Candida albicans in 96-well plates by the two-fold serial broth microdilution method. The anti-bacterial activity of purified PACs was 4 and 10 times higher than for water and water/ethanol extracts, respectively, but the extracts had higher anti-fungal activity. Purified PACs showed the ability to reduce IL-8 and IL-6 secretion from poly-I:C-stimulated peripheral blood mononuclear cells. For the extracts and PACs of SBT cultivar ‘Maria Bruvele’ in the concentration range 0.0313–4.0 mg/mL, no toxic effect was observed.
Synthesis of Mono- and Polyazole Hybrids Based on Polyfluoroflavones
Authors: Panova Mariya A. , Shcherbakov Konstantin V. , Zhilina Ekaterina F. , Burgart Yanina V. , Saloutin Victor I.
Published: January 2023

The possibility of functionalization of 2-(polyfluorophenyl)-4H-chromen-4-ones, with them having different numbers of fluorine atoms, with 1,2,4-triazole or imidazole under conditions of base-promoted nucleophilic aromatic substitution has been shown. A high selectivity of mono-substitution was found with the use of an azole (1.5 equiv.)/NaOBut(1.5 equiv.)/MeCN system. The structural features of fluorinated mono(azolyl)-substituted flavones in crystals were established using XRD analysis. The ability of penta- and tetrafluoroflavones to form persubstituted products with triazole under azole (6 equiv.)/NaOBut(6 equiv.)/DMF conditions was found in contrast to similar transformations with imidazole. On the basis of mono(azolyl)-containing polyfluoroflavones in reactions with triazole and pyrazole, polynuclear hybrid compounds containing various azole fragments were obtained. For poly(pyrazolyl)-substituted flavones, green emission in the solid state under UV-irradiation was found, and for some derivatives, weak fungistatic activity was found.
Enhancement of Electromagnetic Wave Shielding Effectiveness by the Incorporation of Carbon Nanofibers–Carbon Microcoils Hybrid into Commercial Carbon Paste for Heating Films
Authors: Kang Gi-Hwan , Kim Sung-Hoon , Kang Ji-Hun , Lim Junwoo , Yoo Myeong Ho , Kim Yi Tae
Published: January 2023

Carbon microcoils (CMCs) were formed on stainless steel substrates using C2H2 + SF6 gas flows in a thermal chemical vapor deposition (CVD) system. The manipulation of the SF6 gas flow rate and the SF6 gas flow injection time was carried out to obtain controllable CMC geometries. The change in CMC geometry, especially CMC diameter as a function of SF6 gas flow injection time, was remarkable. In addition, the incorporation of H2 gas into the C2H2 + SF6 gas flow system with cyclic SF6 gas flow caused the formation of the hybrid of carbon nanofibers–carbon microcoils (CNFs–CMCs). The hybrid of CNFs–CMCs was composed of numerous small-sized CNFs, which formed on the CMCs surfaces. The electromagnetic wave shielding effectiveness (SE) of the heating film, made by the hybrids of CNFs–CMCs incorporated carbon paste film, was investigated across operating frequencies in the 1.5–40 GHz range. It was compared to heating films made from commercial carbon paste or the controllable CMCs incorporated carbon paste. Although the electrical conductivity of the native commercial carbon paste was lowered by both the incorporation of the CMCs and the hybrids of CNFs–CMCs, the total SE values of the manufactured heating film increased following the incorporation of these materials. Considering the thickness of the heating film, the presently measured values rank highly among the previously reported total SE values. This dramatic improvement in the total SE values was mainly ascribed to the intrinsic characteristics of CMC and/or the hybrid of CNFs–CMCs contributing to the absorption shielding route of electromagnetic waves.
Inhibitory Effects of 2-Aminoethoxydiphenyl Borate (2-APB) on Three KV1 Channel Currents
Authors: Zhao Wei , Pan Lanying , Stalin Antony , Xu Jianwei , Wu Liren , Ke Xianfu , Chen Yuan
Published: January 2023

2-Aminoethoxydiphenyl borate (2-APB), a boron-containing compound, is a multitarget compound with potential as a drug precursor and exerts various effects in systems of the human body. Ion channels are among the reported targets of 2-APB. The effects of 2-APB on voltage-gated potassium channels (KV) have been reported, but the types of KV channels that 2-APB inhibits and the inhibitory mechanism remain unknown. In this paper, we discovered that 2-APB acted as an inhibitor of three representative human KV1 channels. 2-APB significantly blocked A-type Kv channel KV1.4 in a concentration-dependent manner, with an IC50 of 67.3 μM, while it inhibited the delayed outward rectifier channels KV1.2 and KV1.3, with IC50s of 310.4 μM and 454.9 μM, respectively. Further studies on KV1.4 showed that V549, T551, A553, and L554 at the cavity region and N-terminal played significant roles in 2-APB’s effects on the KV1.4 channel. The results also indicated the importance of fast inactivation gating in determining the different effects of 2-APB on three channels. Interestingly, a current facilitation phenomenon by a short prepulse after 2-APB application was discovered for the first time. The docked modeling revealed that 2-APB could form hydrogen bonds with different sites in the cavity region of three channels, and the inhibition constants showed a similar trend to the experimental results. These findings revealed new molecular targets of 2-APB and demonstrated that 2-APB’s effects on KV1 channels might be part of the reason for the diverse bioactivities of 2-APB in the human body and in animal models of human disease.
Hesperidin Methyl Chalcone Reduces the Arthritis Caused by TiO2 in Mice: Targeting Inflammation, Oxidative Stress, Cytokine Production, and Nociceptor Sensory Neuron Activation
Authors: Artero Nayara A. , Manchope Marília F. , Carvalho Thacyana T. , Saraiva-Santos Telma , Bertozzi Mariana M. , Carneiro Jessica A. , Franciosi Anelise , Dionisio Amanda M. , Zaninelli Tiago H. , Fattori Victor , Ferraz Camila R. , Piva Maiara , Mizokami Sandra S. , Camilios-Neto Doumit , Casagrande Rubia , Verri Waldiceu A.
Published: January 2023

Arthroplasty is an orthopedic surgical procedure that replaces a dysfunctional joint by an orthopedic prosthesis, thereby restoring joint function. Upon the use of the joint prosthesis, a wearing process begins, which releases components such as titanium dioxide (TiO2) that trigger an immune response in the periprosthetic tissue, leading to arthritis, arthroplasty failure, and the need for revision. Flavonoids belong to a class of natural polyphenolic compounds that possess antioxidant and anti-inflammatory activities. Hesperidin methyl chalcone’s (HMC) analgesic, anti-inflammatory, and antioxidant effects have been investigated in some models, but its activity against the arthritis caused by prosthesis-wearing molecules, such as TiO2, has not been investigated. Mice were treated with HMC (100 mg/kg, intraperitoneally (i.p.)) 24 h after intra-articular injection of 3 mg/joint of TiO2, which was used to induce chronic arthritis. HMC inhibited mechanical hyperalgesia, thermal hyperalgesia, joint edema, leukocyte recruitment, and oxidative stress in the knee joint (alterations in gp91phox, GSH, superoxide anion, and lipid peroxidation) and in recruited leukocytes (total reactive oxygen species and GSH); reduced patellar proteoglycan degradation; and decreased pro-inflammatory cytokine production. HMC also reduced the activation of nociceptor-sensory TRPV1+ and TRPA1+ neurons. These effects occurred without renal, hepatic, or gastric damage. Thus, HMC reduces arthritis triggered by TiO2, a component released upon wearing of prosthesis.
Chiral Separation, Configuration Confirmation and Bioactivity Determination of the Stereoisomers of Hesperidin and Narirutin in Citrus reticulata Blanco
Authors: Jiang Bingtong , Cao Sirong , Zhang Jiayu , Wang Zhaokun
Published: January 2023

Hesperidin and narirutin are a class of flavanone glycosides, which are the main active constituents in Citrus reticulata Blanco. In the present study, a chiral HPLC-UV method with amylose tris(3,5-dimethylphenylcarbamate) as a stationary phase under a normal-phase mode was used to achieve the stereoselective separation of the C-2 diastereomers of hesperidin and narirutin simultaneously. The single epimer was then successfully prepared by applying semi-preparative chromatography, whose absolute configuration (R/S) was characterized by combining the experimental electronic circular dichroism (ECD) detection with time-dependent density functional theory (TDDFT) calculations. The epimer composition of these two chiral flavanone glycosides in Citrus reticulata Blanco was then determined, which was found to be slightly different in the herbs from different production regions. The anti-inflammatory activity of each prepared single epimer was further evaluated, and some differences between one pair of epimers of hesperidin and narirutin were observed, which suggested that the presence of different epimers should be considered in the quality evaluation and control of natural medicine.
How the Position of Substitution Affects Intermolecular Bonding in Halogen Derivatives of Carboranes: Crystal Structures of 1,2,3- and 8,9,12-Triiodo- and 8,9,12-Tribromo ortho-Carboranes
Authors: Suponitsky Kyrill Yu. , Anufriev Sergey A. , Sivaev Igor B.
Published: January 2023

The crystal structures of two isomeric triiodo derivatives of ortho-carborane containing substituents in the three most electron-withdrawing positions of the carborane cage, 1,2,3-I3-1,2-C2B10H9, and the three most electron-donating positions, 8,9,12-I3-1,2-C2B10H9, as well as the crystal structure of 8,9,12-Br3-1,2-C2B10H9, were determined by single-crystal X-ray diffraction. In the structure of 1,2,3-I3-1,2-C2B10H9, an iodine atom attached to the boron atom (position 3) donates its lone pairs simultaneously to the σ-holes of both iodine atoms attached to the carbon atoms (positions 1 and 2) with the I⋯I distance of 3.554(2) Å and the C-I⋯I and B-I⋯I angles of 169.2(2)° and 92.2(2)°, respectively. The structure is additionally stabilized by a few B-H⋯I-shortened contacts. In the structure of 8,9,12-I3-1,2-C2B10H9, the I⋯I contacts of type II are very weak (the I⋯I distance is 4.268(4) Å, the B8-I8⋯I12 and B12-I12⋯I8 angles are 130.2(3)° and 92.2(3)°) and can only be regarded as dihalogen bonds formally. In comparison with the latter, the structure of 8,9,12-Br3-1,2-C2B10H9 demonstrates both similarities and differences. No Br⋯Br contacts of type II are observed, while there are two Br⋯Br halogen bonds of type I.
Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats
Authors: Hussain Sohail , Ashafaq Mohammad , Alshahrani Saeed , Bokar Ibrahim A. M. , Siddiqui Rahimullah , Alam Mohammad Intakhab , Taha Manal Mohamed Elhassan , Almoshari Yosif , Alqahtani Saad S. , Ahmed Rayan A. , Jali Abdulmajeed M. , Qadri Marwa
Published: January 2023

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1β, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.
Correction: Thang et al. Effects of Different Colored LEDs on the Enhancement of Biologically Active Ingredients in Callus Cultures of Gynura procumbens (Lour.) Merr. Molecules 2019, 24, 4336
Authors: Lian Thang Tung , Moe Myat Myat , Kim Yong Ju , Bang Keuk Soo
Published: January 2023

There were some errors in the original publication [...]
Polyoxypregnane Glycosides from Root of Marsdenia tenacissima and Inhibited Nitric Oxide Levels in LPS Stimulated RAW 264.7 Cells
Authors: Na Zhi , Gongpan Pianchou , Fan Qingfei
Published: January 2023

Six new polyoxypregnane glycosides, marstenacisside F1–F3 (1–3), G1–G2 (4–5) and H1 (6), as well as 3-O-β-D-glucopyranosyl-(1→4)-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-11α,12β-di-O-benzoyl-tenacigenin B (7), were isolated from the roots of Marsdenia tenacissima. Their structures were established by an extensive interpretation of their 1D and 2D NMR and HRESIMS data. Compounds 1–7 were tenacigenin B derivatives with an oligosaccharide chain at C-3. This was the first time that compound 7 had been isolated from the title plant and its 1H and 13C NMR data were reported. Compounds 4 and 5 were the first examples of C21 steroid glycoside bearing unique β-glucopyranosyl-(1→4)-β-glucopyranose sugar moiety. All the isolated compounds were evaluated for anti-inflammatory activity by inhibiting nitric oxide (NO) production in the lipopolysaccharide-induced RAW 264.7 cells. The results showed that marstenacisside F1 and F2 exhibited significant NO inhibitory activity with an inhibition rate of 48.19 ± 4.14% and 70.33 ± 5.39%, respectively, at 40 μM, approximately equal to the positive control (L-NMMA, 68.03 ± 0.72%).