bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification and Characterization of Novel Anti-MRSA Peptides Produced by Brevibacillus sp. SPR-20
Authors: Songnaka Nuttapon , Lertcanawanichakul Monthon , Hutapea Albert M. , Krobthong Sucheewin , Yingchutrakul Yodying , Atipairin Apichart
Published: December 2022

Methicillin-resistant Staphylococcus aureus (MRSA) is listed as a high-priority pathogen because its infection is associated with a high mortality rate. It is urgent to search for new agents to treat such an infection. Our previous study isolated a soil bacterium (Brevibacillus sp. SPR-20), showing the highest antimicrobial activity against S. aureus TISTR 517 and MRSA strains. The present study aimed to purify and characterize anti-MRSA substances produced by SPR-20. The result showed that five active substances (P1–P5) were found, and they were identified by LC-MS/MS that provided the peptide sequences of 14–15 residues. Circular dichroism showed that all peptides contained β-strand and disordered conformations as the major secondary structures. Only P1–P4 adopted more α-helix conformations when incubated with 50 mM SDS. These anti-MRSA peptides could inhibit S. aureus and MRSA in concentrations of 2–32 μg/mL. P1 (NH2-VVVNVLVKVLPPPVV-COOH) had the highest activity and was identified as a novel antimicrobial peptide (AMP). The stability study revealed that P1 was stable in response to temperature, proteolytic enzymes, surfactant, and pH. The electron micrograph showed that P1 induced bacterial membrane damage when treated at 1× MIC in the first hour of incubation. The killing kinetics of P1 was dependent on concentration and time. Mechanisms of P1 on tested pathogens involved membrane permeability, leakage of genetic material, and cell lysis. The P1 peptide at a concentration up to 32 μg/mL showed hemolysis of less than 10%, supporting its safety for human erythrocytes. This study provides promising anti-MRSA peptides that might be developed for effective antibiotics in the post-antibiotic era.
Root Bark Extract of Oroxylum indicum Vent. Inhibits Solid and Ascites Tumors and Prevents the Development of DMBA-Induced Skin Papilloma Formation
Authors: Menon Seema , Albaqami Jawaher J. , Hamdi Hamida , Lawrence Lincy , Divya Menon Kunnathully , Antony Liya , Padikkala Jose , Mathew Shaji E. , Narayanankutty Arunaksharan
Published: December 2022

Oroxylum indicum is a traditionally used plant in Ayurvedic and folk medicines. The plant is useful for the management of gastrointestinal diseases as well as skin diseases. In the present study, we analyzed the antitumor potential of O. indicum in Dalton’s lymphoma ascites tumor cells (DLA) and Ehrlich ascites carcinoma (EAC)-induced solid and ascites tumors. Further, the potential of O. indicum extract (OIM) on skin papilloma induction by dimethyl benz(a) anthracene (DMBA) and croton oil was evaluated. The chemical composition of the extract was analyzed using UPLC-Q-TOF-MS. The predominant compounds present in the extract were demethoxycentaureidin 7-O-rutinoside, isorhamnetin-3-O-rutinoside, baicalein-7-O-glucuronide, 5,6,7-trihydroxyflavone, 3-Hydroxy-3′,4′,5′-trimethoxyflavone, 5,7-dihydroxy-3-(4-methoxyphenyl) chromen-4-one, and 4′-Hydroxy-5,7-dimethoxyflavanone. Treatment with high-dose OIM enhanced the percentage of survival in ascites tumor-bearing mice by 34.97%. Likewise, high and low doses of OIM reduced the tumor volume in mice by 61.84% and 54.21%, respectively. Further, the skin papilloma formation was brought down by the administration of low- and high-dose groups of OIM (by 67.51% and 75.63%). Overall, the study concludes that the Oroxylum indicum root bark extract is a potentially active antitumor and anticancer agent.
Copper-Catalyzed Difluoroalkylation Reaction
Authors: Dong Dao-Qing , Yang Shao-Hui , Wu Pei , Wang Jin-Zhi , Min Ling-Hao , Yang Hao , Zhou Meng-Yu , Wei Ze-Hui , Ding Cai-Zhen , Wang Yan-Li , Gao Jia-Hui , Wang Shu-Jie , Wang Zu-Li
Published: December 2022

This review describes recent advances in copper-catalyzed difluoroalkylation reactions. The RCF2 radical is generally proposed in the mechanism of these reactions. At present, various types of copper-catalyzed difluoroalkylation reactions have been realized. According to their characteristics, we classify these difluoroalkylation reactions into three types.
Effect of IL-27, Teriflunomide and Retinoic Acid and Their Combinations on CD4+ T Regulatory T Cells—An In Vitro Study
Authors: Maślanka Tomasz
Published: December 2022

The principal goal of the study was to verify the concept of pharmacological induction of Foxp3+CD25+CD4+ T regulatory (Treg) cells which will additionally be characterized by a highly suppressive phenotype, i.e., by extensive CD25 and CD39 expression and IL-10 and TGF-β production. Stimulated and unstimulated murine lymphocytes were exposed to IL-27, teriflunomide (TER), and all trans retinoic acid (ATRA) alone and to their combinations. The study demonstrated that: (a) IL-27 alone induced CD39 expression on Treg cells and the generation of Tr1 cells; (b) TER alone induced Foxp3-expressing CD4+ T cells and up-regulated density of CD25 on these cells; TER also induced the ability of Treg cells to TGF-β production; (c) ATRA alone induced CD39 expression on Treg cells. The experiments revealed a strong superadditive effect between IL-27 and ATRA with respect to increasing CD39 expression on Treg cells. Moreover, IL-27 and ATRA in combination, but not alone, induced the ability of Treg cells to IL-10 production. However, the combination of IL-27, TER, and ATRA did not induce the generation of Treg cell subset with all described above features. This was due to the fact that TER abolished all listed above desired effects induced by IL-27 alone, ATRA alone, and their combination. IL-27 alone, ATRA alone, and their combination affected TER-induced effects to a lesser extent. Therefore, it can be concluded that in the aspect of pharmacological induction of Treg cells with a highly suppressive phenotype, the triple combination treatment with TER, IL-27, and ATRA does not provide any benefits over TER alone or dual combination including IL-27 and ATRA.
Resveratrol Ameliorates Fibrosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease via the Autophagy–Lysosome Pathway
Authors: Bao Lanxin , Ye Jing , Liu Nannan , Shao Yubao , Li Wenhao , Fan Xuefei , Zhao Dahai , Wang Hongzhi , Chen Xiaoyu
Published: December 2022

Interstitial lung disease associated with rheumatoid arthritis (RA-ILD) can lead to interstitial fibrosis and even lung failure as a complication of rheumatoid arthritis (RA), and there is currently no effective treatment and related basic research. Studies have found that resveratrol (Res) can improve the progression of RA by regulating autophagy, and increasing evidence supports the connection between autophagy and common interstitial lung disease (ILD). We explored changes in autophagy levels in fibrotic lungs in RA-ILD and found that the level of autophagy is enhanced in the early stage but inhibited in the late stage. However, resveratrol treatment improved the level of autophagy and reversed the inhibition of autophagy, and attenuated fibrosis. We created corresponding cell models that exhibited the same phenotypic changes as animal models; under the effect of resveratrol, the level of fibrosis changed accordingly, and the fusion process of lysosomes and autophagosomes in autophagy was liberated from the inhibition state. Resveratrol effects were reversed by the addition of the late autophagy inhibitor chloroquine. These results suggest that resveratrol attenuates pulmonary fibrosis, increases autophagic flux, and modulates the autophagy–lysosome pathway, and particularly it may work by improving the formation of autophagic lysosomes, which may be an effective treatment for induced RA-ILD.
O2 Carrier Myoglobin Also Exhibits β-Lactamase Activity That Is Regulated by the Heme Coordination State
Authors: Tang Shuai , Pan Ai-Qun , Wang Xiao-Juan , Gao Shu-Qin , Tan Xiang-Shi , Lin Ying-Wu
Published: December 2022

Heme proteins perform a variety of biological functions and also play significant roles in the field of bio-catalysis. The β-lactamase activity of heme proteins has rarely been reported. Herein, we found, for the first time, that myoglobin (Mb), an O2 carrier, also exhibits novel β-lactamase activity by catalyzing the hydrolysis of ampicillin. The catalytic proficiency ((kcat/KM)/kuncat) was determined to be 6.25 × 1010, which is much higher than the proficiency reported for designed metalloenzymes, although it is lower than that of natural β-lactamases. Moreover, we found that this activity could be regulated by an engineered disulfide bond, such as Cys46-Cys61 in F46C/L61C Mb or by the addition of imidazole to directly coordinate to the heme center. These results indicate that the heme active site is responsible for the β-lactamase activity of Mb. Therefore, the study suggests the potential of heme proteins acting as β-lactamases, which broadens the diversity of their catalytic functions.
Photocatalytic Oxidation of Carbon Monoxide Using Synergy of Redox-Separated Photocatalyst and Ozone
Authors: Weon Seunghyun
Published: December 2022

Separating the redox centers of photocatalysts is the most promising strategy to enhance photocatalytic oxidation efficiency. Herein, I investigate a site-selective loading of Pt on facet-engineered TiO2 to achieve carbon monoxide (CO) oxidation at room temperature. Spatially loaded Pt on {101} facets of TiO2 attracts photoinduced electrons efficiently. Thereby, oxygen dissociation is facilitated on the Pt surface, which is confirmed by enhanced oxidation of CO by 2.4 times compared to the benchmark of Pt/TiO2. The remaining holes on TiO2 can be utilized for the oxidation of various gaseous pollutants. Specifically, gaseous ozone, which is present in indoor and ambient air, is converted to a hydroxyl radical by reacting with the hole; thus, the poisoned Pt surface is continuously cleaned during the CO oxidation, as confirmed by in situ diffuse reflectance infrared transform spectroscopy. While randomly loaded Pt can act as recombination center, reducing photocatalytic activity, redox-separated photocatalyst enhances charge separation, boosting CO oxidation and catalyst regeneration via simultaneous ozone decomposition.
In Silico Evaluation and In Vitro Determination of Neuroprotective and MAO-B Inhibitory Effects of Pyrrole-Based Hydrazones: A Therapeutic Approach to Parkinson’s Disease
Authors: Kondeva-Burdina Magdalena , Mateev Emilio , Angelov Borislav , Tzankova Virginia , Georgieva Maya
Published: December 2022

Parkinson’s disease is a huge burden in modern medicinal practice. A serious drawback of current antiparkinsonian therapy is its symptomatic nature. This directed our investigations in the search for new more potent derivatives, affecting not only the loss of dopaminergic neurons but also the oxidative damage of neuronal cells. Thus in vitro neurotoxicity and neuroprotective analysis on a group of N-pyrrolyl hydrazide–hydrazones were performed. The neurotoxicity of the target derivatives was determined on a subcellular level in isolated rat synaptosomes, mitochondria and microsomes determining their effect on cellular vitality, GSH depletion and MDA production. The neuroprotective effects of the evaluated hydrazones were measured in three models of induced oxidative stress: 6-OHDA, t-BuOOH and Fe2+/AA-induced lipid peroxidation. Molecular docking simulations along with in vitro evaluation of MAO-B inhibitory potential of the target molecules were also performed. The results identified the ethyl 5-(4-bromophenyl)-1-(3-hydrazinyl-3-oxopropyl)-2-methyl-1H-pyrrole-3-carboxylate (12) as the most promising compound with the lowest neurotoxicity and highest neuroprotection on all evaluated parameters and inhibiting the hMAOB enzyme by 50%, comparable with the activity of the reference, Selegiline. The compatibility of the in silico and in vitro evaluations is a good prerequisite for these methods to be applied in future assessment of pyrrole-based compounds as anti-Parkinson agents.
A Novel Cathode Material Synthesis and Thermal Characterization of (1-x-y) LiCo1/3Ti1/3Fe1/3PO4, xLi2MnPO4, yLiFePO4 Composites for Lithium-Ion Batteries (LIBs)
Authors: Li Lu , Min Xin , Monajjemi Majid
Published: December 2022

Lithium-ion batteries are known for their high efficiency for storing electrical energy, especially for hybrid vehicles. In this research, the development of mixture composites in the cathode electrode of LIBs has been discussed and designed based on ternary solid solutions. We have given a novel synthesis and method preparation of cathode electrode materials to reduce costs while increasing the efficiency and simultaneity for the future of these technologies. The major problem in the LIBs is related to LiCoO2 as a popular cathode material that, although it has a high efficiency, is expensive and very toxic. Therefore, the usage of a lower weight of cobalt compared to the LiCoO2 cathode material is economically advantageous for this research. Several samples of the (1-x-y) LiCo1/3Ti1/3Fe1/3PO4 xLi2MnPO4 and yLiFePO4 system were synthesized via sol–gel experiments. Various stoichiometric amounts of the LiNO3, Li2MnPO4, Mn (Ac)2. 4H2O, Co (Ac)2.4H2O, Ti(NO3)2.6H2O and LiFePO4 have been used for several compositions of chrome, manganese, cobalt and titanium in 28 samples of (1-x-y) LiCo1/3Ti1/3Fe1/3PO4. By using thermal characterization, five samples have been selected due to their conditions in viewpoints of capacity and cyclability as well as activation energy, which is one of the major factors. These composites exhibited fairly consistent charge/discharge curves during the electrochemical testing. From the viewpoint of the physical and chemical properties, among these samples, the Li1.501Co0.389Ti0.055Fe0.055Mn0.501PO4 structure has a high efficiency compared to other compositions.
Studies on the Efficiency of Iron Release from Fe(III)-EDTA and Fe(III)-Cit and the Suitability of These Compounds for Tetracycline Degradation
Authors: Piotrowicz-Cieślak Agnieszka I. , Maciejczyk Maciej , Margas Małgorzata , Rydzyński Dariusz , Grajek Hanna , Michalczyk Dariusz J. , Wasilewski Janusz , Smyk Bogdan
Published: December 2022

Iron ions can be used to degrade tetracycline dispersed in nature. Studies of absorption and fluorescence spectra and quantum chemistry calculations showed that iron is more readily released from Fe(III)-citrate than from Fe(III)-EDTA, so Fe(III)-citrate (Fe(III)-Cit) is more suitable for tetracycline (TC) degradation. At 30 °C, a severe degradation of TC by Fe(III)-Cit occurred as early as after 3 days of incubation in the light, and after 5 days in the dark. In contrast, the degradation of TC by Fe(III)-EDTA proceeded very slowly in the dark. By the fifth day of incubation of TC with Fe(III)-Cit in darkness, the concentrations of the former compound dropped by 55% and 75%, at 20 °C and 30 °C, respectively. The decrease in tetracycline concentrations caused by Fe(III)-EDTA in darkness at the same temperatures was only 2% and 6%, respectively. Light increased the degradation rates of TC by Fe(III)-EDTA to 20% and 56% at 20 °C and 30 °C, respectively. The key role of the light in the degradation of tetracycline by Fe(III)-EDTA was thus demonstrated. The TC degradation reaction showed a second-order kinetics. The rate constants of Fe(III)-Cit-induced TC degradation at 20 °C and 30 °C in darkness were k = 4238 M−1day−1 and k = 11,330 M−1day−1, respectively, while for Fe(III)-EDTA were 55 M−1day−1 and 226 M−1day−1. In light, these constants were k = 15,440 M−1day−1 and k = 40,270 M−1day−1 for Fe(III)-Cit and k = 1012 M−1day−1 and 2050 M−1day−1 at 20 °C and 30 °C; respectively. A possible reason for the higher TC degradation rate caused by Fe(III)-Cit can be the result of its lower thermodynamical stability compared with Fe(III)-EDTA, which we confirmed with our quantum chemistry calculations. Two quantum chemistry calculations showed that the iron complex with EDTA is more stable (the free energy of the ensemble is 15.8 kcal/mol lower) than the iron complex with Cit; hence, Fe release from Fe(III)-EDTA is less effective.
Synthesis, Anti-Influenza H1N1 and Anti-Dengue Activity of A-Ring Modified Oleanonic Acid Polyamine Derivatives
Authors: Smirnova Irina , Petrova Anastasiya , Giniyatullina Gul’nara , Smirnova Anna , Volobueva Alexandrina , Pavlyukova Julia , Zarubaev Vladimir , Loc Tran Van , Tran Thi Phoung Thao , Hau Vu Thi Bich , Thuy Nguyen Thi Thu , Khine Myint Myint , Kazakova Oxana
Published: December 2022

A series of sixteen A-ring modified (2,3-indolo-, 2-benzylidene) oleanonic acid derivatives, holding some cyclic amines, linear polyamines and benzylaminocarboxamides at C28, has been synthesized and screened for antiviral activity against influenza A/PuertoRico/8/34 (H1N1) and Dengue virus serotypes of DENV-1, -2, -3, -4. It was found that 28-homopiperazine 2 and 3-N-phthalyl 22 amides of oleanonic acid demonstrated high potency with selectivity index SI 27 (IC50 21 μM) and 42 (IC50 12 μM). Oleanonic acid aminoethylpiperazine amide 6 and C-azepano-erythrodiol 23 appeared to be the most effective compounds against DENV-1 (IC50′s 67 and 107 μM) and -2 (IC50′s 86 and 68 μM correspondingly) serotypes.
Development of Phosphoramidite Reagents for the Synthesis of Base-Labile Oligonucleotides Modified with a Linear Aminoalkyl and Amino-PEG Linker at the 3′-End
Authors: Osawa Takashi , Ren Qin , Obika Satoshi
Published: December 2022

Oligonucleotides with an amino linker at the 3′-end are useful for the preparation of conjugated oligonucleotides. However, chemically modified nucleosides, which are unstable under basic conditions, cannot be incorporated into oligonucleotides using the conventional method entailing the preparation of oligonucleotides bearing a 3′-amino linker. Therefore, we designed Fmoc-protected phosphoramidites for the synthesis of base-labile oligonucleotides modified with a 3′-amino linker. The resultant phosphoramidites were then successfully incorporated into oligonucleotides bearing a 3′-amino linker. Various basic solutions were investigated for protecting group removal. All the protecting groups were removed by treating the oligonucleotides with 40% aqueous methylamine at room temperature for 2 h. Thus, the deprotection time and temperature were significantly reduced compared to the conventional conditions (28% NH3 aq., 55 °C, 17 h). In addition, the oligonucleotide protecting groups could be removed using a mild base (e.g., 50 mM potassium carbonate methanol solution). Furthermore, base-labile oligonucleotides bearing an amino linker at the 3′-end were successfully synthesized using the developed phosphoramidite reagents, highlighting the utility of our strategy.
The Use of Zidovudine Pharmacophore in Multi-Target-Directed Ligands for AIDS Therapy
Authors: Bianco Maria da Conceição Avelino Dias , Inacio Leite Debora , Silva Castelo Branco Frederico , Boechat Nubia , Uliassi Elisa , Bolognesi Maria Laura , Bastos Monica Macedo
Published: December 2022

The concept of polypharmacology embraces multiple drugs combined in a therapeutic regimen (drug combination or cocktail), fixed dose combinations (FDCs), and a single drug that binds to different targets (multi-target drug). A polypharmacology approach is widely applied in the treatment of acquired immunodeficiency syndrome (AIDS), providing life-saving therapies for millions of people living with HIV. Despite the success in viral load suppression and patient survival of combined antiretroviral therapy (cART), the development of new drugs has become imperative, owing to the emergence of resistant strains and poor adherence to cART. 3′-azido-2′,3′-dideoxythymidine, also known as azidothymidine or zidovudine (AZT), is a widely applied starting scaffold in the search for new compounds, due to its good antiretroviral activity. Through the medicinal chemistry tool of molecular hybridization, AZT has been included in the structure of several compounds allowing for the development of multi-target-directed ligands (MTDLs) as antiretrovirals. This review aims to systematically explore and critically discuss AZT-based compounds as potential MTDLs for the treatment of AIDS. The review findings allowed us to conclude that: (i) AZT hybrids are still worth exploring, as they may provide highly active compounds targeting different steps of the HIV-1 replication cycle; (ii) AZT is a good starting point for the preparation of co-drugs with enhanced cell permeability.
Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice
Authors: Motta Bruno Pereira , Pinheiro Camila Graça , Figueiredo Ingrid Delbone , Cardoso Felipe Nunes , Oliveira Juliana Oriel , Machado Rachel Temperani Amaral , da Silva Patrícia Bento , Chorilli Marlus , Brunetti Iguatemy Lourenço , Baviera Amanda Martins
Published: December 2022

Since lycopene has antioxidant activity, its combination with metformin may be useful to contrast diabetic complications related to oxidative stress. This study aimed to investigate the effects of metformin combined with lycopene on high-fat diet (HFD)-induced obese mice. Seventy-two C57BL-6J mice were divided into six groups: C (control diet-fed mice), H (HFD-fed mice for 17 weeks), H-V (HFD-fed mice treated with vehicle), H-M (HFD-fed mice treated with 50 mg/kg metformin), H-L (HFD-fed mice treated with 45 mg/kg lycopene), and H-ML (HFD-fed mice treated with 50 mg/kg metformin + 45 mg/kg lycopene). Treatments were administered for 8 weeks. Glucose tolerance, insulin sensitivity, fluorescent AGEs (advanced glycation end products), TBARS (thiobarbituric acid-reactive substances), and activities of antioxidant enzymes paraoxonase-1 (PON-1; plasma), superoxide dismutase, catalase and glutathione peroxidase (liver and kidneys) were determined. Metformin plus lycopene reduced body weight; improved insulin sensitivity and glucose tolerance; and decreased AGEs and TBARS in plasma, liver and kidneys. Combined therapy significantly increased the activities of antioxidant enzymes, mainly PON-1. Lycopene combined with metformin improved insulin resistance and glucose tolerance, and caused further increases in endogenous antioxidant defenses, arising as a promising therapeutic strategy for combating diabetic complications resulting from glycoxidative stress.
Molecularly Imprinted Methyl-Modified Hollow TiO2 Microspheres
Authors: Ferreira Vanessa R. A. , Azenha Manuel A. , Pereira Carlos M. , Silva António F.
Published: December 2022

The possibility of generating organically modified hollow TiO2 microspheres via a simple sol-gel synthesis was demonstrated for the first time in this work. A mixture of titania precursors, including an organically modified precursor, was used to obtain methyl-modified hollow TiO2 microspheres selective for bilirubin by the molecular imprinting technique (Methyl-HTM-MIM). Methyl-HTM-MIM were prepared by a sol-gel method using titanium (IV) isopropoxide (TTIP), and methyltitanium triisopropoxide (MTTIP) as precursors. Two ratios of titania precursors were tested (1/6 and 1/30 molMTTIP/molTTIP). With the characterization results obtained by the SEM and ATR-FTIR techniques, it was possible to establish that only the 1/30 molMTTIP/molTTIP ratio allowed for the preparation of hollow spheres with a reasonably homogeneous methylated-TiO2 shell. It was possible to obtain a certain degree of organization of the hybrid network, which increased with calcination temperatures. By adjusting isothermal adsorption models, imprinting parameters were determined, indicating that the new methylated microspheres presented greater selectivity for bilirubin than the totally inorganic hollow TiO2 microspheres. The effectiveness of the molecular imprinting technique was proven for the first time in an organically modified titania material, with imprinting factor values greater than 1.4, corresponding to a significant increase in the maximum adsorption capacity of the template represented by the molecularly imprinted microspheres. In summary, the results obtained with the new methyl-HTM-MIM open the possibility of exploring the application of these microspheres for selective sorption (separation or sensing, for example) or perhaps even for selective photocatalysis, particularly for the degradation of organic compounds.
Investigation into the Use of Encorafenib to Develop Potential PROTACs Directed against BRAFV600E Protein
Authors: Marini Elisabetta , Marino Marco , Gionfriddo Giulia , Maione Federica , Pandini Marta , Oddo Daniele , Giorgis Marta , Rolando Barbara , Blua Federica , Gastaldi Simone , Marchiò Serena , Kovachka Sandra , Spyrakis Francesca , Gianquinto Eleonora , Di Nicolantonio Federica , Bertinaria Massimo
Published: December 2022

BRAF is a serine/threonine kinase frequently mutated in human cancers. BRAFV600E mutated protein is targeted through the use of kinase inhibitors which are approved for the treatment of melanoma; however, their long-term efficacy is hampered by resistance mechanisms. The PROTAC-induced degradation of BRAFV600E has been proposed as an alternative strategy to avoid the onset of resistance. In this study, we designed a series of compounds where the BRAF kinase inhibitor encorafenib was conjugated to pomalidomide through different linkers. The synthesized compounds maintained their ability to inhibit the kinase activity of mutated BRAF with IC50 values in the 40–88 nM range. Selected compounds inhibited BRAFV600E signaling and cellular proliferation of A375 and Colo205 tumor cell lines. Compounds 10 and 11, the most active of the series, were not able to induce degradation of mutated BRAF. Docking and molecular dynamic studies, conducted in comparison with the efficient BRAF degrader P5B, suggest that a different orientation of the linker bearing the pomalidomide substructure, together with a decreased mobility of the solvent-exposed part of the conjugates, could explain this behavior.
Compensatory Transcriptional Response of Fischerella thermalis to Thermal Damage of the Photosynthetic Electron Transfer Chain
Authors: Vergara-Barros Pablo , Alcorta Jaime , Casanova-Katny Angélica , Nürnberg Dennis J. , Díez Beatriz
Published: December 2022

Key organisms in the environment, such as oxygenic photosynthetic primary producers (photosynthetic eukaryotes and cyanobacteria), are responsible for fixing most of the carbon globally. However, they are affected by environmental conditions, such as temperature, which in turn affect their distribution. Globally, the cyanobacterium Fischerella thermalis is one of the main primary producers in terrestrial hot springs with thermal gradients up to 60 °C, but the mechanisms by which F. thermalis maintains its photosynthetic activity at these high temperatures are not known. In this study, we used molecular approaches and bioinformatics, in addition to photophysiological analyses, to determine the genetic activity associated with the energy metabolism of F. thermalis both in situ and in high-temperature (40 °C to 65 °C) cultures. Our results show that photosynthesis of F. thermalis decays with temperature, while increased transcriptional activity of genes encoding photosystem II reaction center proteins, such as PsbA (D1), could help overcome thermal damage at up to 60 °C. We observed that F. thermalis tends to lose copies of the standard G4 D1 isoform while maintaining the recently described D1INT isoform, suggesting a preference for photoresistant isoforms in response to the thermal gradient. The transcriptional activity and metabolic characteristics of F. thermalis, as measured by metatranscriptomics, further suggest that carbon metabolism occurs in parallel with photosynthesis, thereby assisting in energy acquisition under high temperatures at which other photosynthetic organisms cannot survive. This study reveals that, to cope with the harsh conditions of hot springs, F. thermalis has several compensatory adaptations, and provides emerging evidence for mixotrophic metabolism as being potentially relevant to the thermotolerance of this species. Ultimately, this work increases our knowledge about thermal adaptation strategies of cyanobacteria.
[MII(H2dapsc)]-[Cr(CN)6] (M = Mn, Co) Chain and Trimer Complexes: Synthesis, Crystal Structure, Non-Covalent Interactions and Magnetic Properties
Authors: Sasnovskaya Valentina D. , Zorina Leokadiya V. , Simonov Sergey V. , Talantsev Artem D. , Yagubskii Eduard B.
Published: December 2022

Four new heterometallic complexes combining [MII(H2dapsc)]2+ cations with the chelating H2dapsc {2,6-diacetylpyridine-bis(semicarbazone)} Schiff base ligand and [Cr(CN)6]3− anion were synthesized: {[MII(H2dapsc)]CrIII(CN)6K(H2O)2.5(EtOH)0.5}n·1.2n(H2O), M = Mn (1) and Co (2), {[Mn(H2dapsc)]2Cr(CN)6(H2O)2}Cl·H2O (3) and {[Co(H2dapsc)]2Cr(CN)6(H2O)2}Cl·2EtOH·3H2O (4). In all the compounds, M(II) centers are seven-coordinated by N3O2 atoms of H2dapsc in the equatorial plane and N or O atoms of two apical –CN/water ligands. Crystals 1 and 2 are isostructural and contain infinite negatively charged chains of alternating [MII(H2dapsc)]2+ and [CrIII(CN)6]3− units linked by CN-bridges. Compounds 3 and 4 consist of centrosymmetric positively charged trimers in which two [MII(H2dapsc)]2+ cations are bound through one [CrIII(CN)6]3− anion. All structures are regulated by π-stacking of coplanar H2dapsc moieties as well as by an extensive net of hydrogen bonding. Adjacent chains in 1 and 2 interact also by coordination bonds via a pair of K+ ions. The compounds containing MnII (1, 3) and CoII (2, 4) show a significant difference in magnetic properties. The ac magnetic measurements revealed that complexes 1 and 3 behave as a spin glass and a field-induced single-molecule magnet, respectively, while 2 and 4 do not exhibit slow magnetic relaxation in zero and non-zero dc fields. The relationship between magnetic properties and non-covalent interactions in the structures 1–4 was traced.
Development of Novel Polypropylene Syntactic Foams Containing Paraffin Microcapsules for Thermal Energy Storage Applications
Authors: Galvagnini Francesco , Dorigato Andrea , Fambri Luca , Pegoretti Alessandro
Published: December 2022

polypropylene (PP) syntactic foams (SFs) containing hollow glass microspheres (HGMs) possess low density and elevated mechanical properties, which can be tuned according to the specific application. A possible way to improve their multifunctionality could be the incorporation of organic Phase Change Materials (PCMs), widely used for thermal energy storage (TES) applications. In the present work, a PCM constituted by encapsulated paraffin, having a melting temperature of 57 °C, was embedded in a compatibilized polypropylene SF by melt compounding and hot pressing at different relative amounts. The rheological, morphological, thermal, and mechanical properties of the prepared materials were systematically investigated. Rheological properties in the molten state were strongly affected by the introduction of both PCMs and HGMs. As expected, the introduction of HGMs reduced both the foam density and thermal conductivity, while the enthalpy of fusion (representing the TES capability) was proportional to the PCM concentration. The mechanical properties of these foams were improved by the incorporation of HGMs, while they were reduced by addition of PCMs. Therefore, the combination of PCMs and HGMs in a PP matrix generated multifunctional materials with tunable thermo-mechanical properties, with a wide range of applications in the automotive, oil, textile, electronics, and aerospace fields.
Characterization of New Egyptian Linseed Varieties and the Effects of Roasting on Their Pigments, Tocochromanols, Phytosterols, Omega-3 Fatty Acids, and Stability
Authors: Hassanein Minar , Abdel-Razek Adel , Afifi Sherine , Qian Ying , Radziejewska-Kubzdela Elżbieta , Siger Aleksander , Rudzińska Magdalena , Abo-Elwafa Ghada , Grygier Anna
Published: December 2022

The purpose of this study was to explore the effects of roasting linseeds on the pigment, lipid profile, bioactive components, and oxidative stability of the extracted oils. The linseed varieties Giza 11, Giza 12, Sakha 3, and Sakha 6 were roasted at 180 °C for 10 min, and the oils were extracted by cold pressing. The results showed that, after roasting, there was an increase in oil percentage and peroxide value, as well as small increases in p-anisidine and acid values. Roasting also caused an increase in chlorophyll content, while lutein and β-carotene tend to slightly decrease, except in the Giza 11 variety. The total phenolics content was markedly enhanced after roasting. Omega-3 fatty acids were not affected by the roasting process. The total amounts of tocochromanol were found to decrease in the Giza 12 and Sakha 6 varieties after roasting. Plastochromanol-8 increased in all varieties after roasting. The phytosterol composition was minimally affected by roasting. Roasting enhanced the stability of the extracted oils, increasing the induction period and decreasing EC50 values. These results may thus help to discriminate between the different linseed varieties and serve to recommend the use of roasting to enhance the oxidative stability of extracted oil.
Substituent-Dependent Divergent Synthesis of 2-(3-Amino-2,4-dicyanophenyl)pyrroles, Pyrrolyldienols and 3-Amino-1-acylethylidene-2-cyanopyrrolizines via Reaction of Acylethynylpyrroles with Malononitrile
Authors: Gotsko Maxim D. , Saliy Ivan V. , Ushakov Igor A. , Sobenina Lyubov N. , Trofimov Boris A.
Published: December 2022

An efficient method for the synthesis of pharmaceutically and high-tech prospective 2-(3-amino-2,4-dicyanophenyl)pyrroles (in up to 88% yield) via the reaction of easily available substituted acylethynylpyrroles with malononitrile has been developed. The reaction proceeds in the KOH/MeCN system at 0 °C for 2 h. In the case of 2-acylethynylpyrroles without substituents in the pyrrole ring, the reaction changes direction: instead of the target 2-(3-amino-2,4-dicyanophenyl)pyrroles, the unexpected formation of pyrrolyldienols and products of their intramolecular cyclization, 3-amino-1-acylethylidene-2-cyanopyrrolizines, is observed.
How to Identify Roast Defects in Coffee Beans Based on the Volatile Compound Profile
Authors: Rusinek Robert , Dobrzański Bohdan , Oniszczuk Anna , Gawrysiak-Witulska Marzena , Siger Aleksander , Karami Hamed , Ptaszyńska Aneta A. , Żytek Aleksandra , Kapela Krzysztof , Gancarz Marek
Published: December 2022

The aim of this study was to detect and identify the volatile compounds in coffee that was obtained in defect roast processes versus standard roasting and to determine the type and strength of the correlations between the roast defects and the volatile compound profile in roasted coffee beans. In order to achieve this goal, the process of coffee bean roasting was set to produce an underdeveloped coffee defect, an overdeveloped coffee defect, and defectless coffee. The “Typica” variety of Arabica coffee beans was used in this study. The study material originated from a plantation that is located at an altitude of 1400–2000 m a.s.l. in Huehuetenango Department, Guatemala. The analyses were carried out with the use of gas chromatography/mass spectrometry (GC–MS) and an electronic nose. This study revealed a correlation between the identified groups of volatile compounds and the following coffee roasting parameters: the time to the first crack, the drying time, and the mean temperatures of the coffee beans and the heating air. The electronic nose helped to identify the roast defects.
Paeoniflorin Protects against Acetaminophen-Induced Liver Injury in Mice via JNK Signaling Pathway
Authors: Deng Xinyu , Li Yubing , Li Xing , Zhang Zhenpeng , Dai Shu , Wu Hefei , Zhang Fangling , Hu Qichao , Chen Yuan , Zeng Jinhao , Ma Xiao
Published: December 2022

Background: Drug-induced liver injury (DILI), represented by acetaminophen (APAP), is a common cause of acute liver failure in clinics. Paeoniflorin (PF) has been proven to demonstrate a significant hepatoprotective effect. However, it is still unclear whether it can be a potential agent against hepatotoxicity induced by APAP. This study aimed to explore the preventive and therapeutic effects and mechanisms of PF on APAP-induced liver injury. Methods: Different doses of PF (50, 100, and 200 mg/kg) were given to C57BL/6 male mice for five consecutive days. After 12 h of APAP (250 mg/kg i.p.) treatment, blood and liver tissues were collected and isolated for detection. Results: The results showed that the therapeutic effects of PF on APAP mice were presented in the downregulation of the content of serum indices and significantly improved hepatic tissue edema and inflammatory infiltration. Meanwhile, PF reduces the level of the mitochondrial metabolic enzyme. Ulteriorly, it was found that PF has a downregulating effect on the apoptotic reaction and could inhibit the protein expression of CYP2E1/JNK signaling, which in turn reduces the damage of APAP. Conclusion: Our findings showed that PF acted as a protective agent against APAP-induced hepatotoxicity by inhibiting JNK-related signals, suggesting a novel insight into treating APAP-induced liver injury.
Hedgehog, Chamomile, and Multipetal Polymeric Structures on the Nanoparticle Surface: Computer Modelling
Authors: Saraev Zakhar R. , Lazutin Alexei A. , Vasilevskaya Valentina V.
Published: December 2022

A single spherical nanoparticle coated with a densely grafted layer of an amphiphilic homopolymer with identical A-graft-B monomer units was studied by means of coarse-grained molecular dynamics. In solvent, selectively poor for mainchain and good for pendant groups; the grafted macromolecules self-assemble into different structures to form a complex pattern on the nanoparticle surface. We distinguish hedgehog, multipetalar, chamomile, and densely structured shells and outline the area of their stability using visual analysis and calculate aggregation numbers and specially introduced order parameters, including the branching coefficient and relative orientation of monomer units. For the first time, the branching effect of splitting aggregates along with the distance to the grafting surface and preferred orientation of the monomer units with rearrangements of the dense compacted shell was described. The results explain the experimental data, are consistent with the analytical theory, and are the basis for the design of stimulus-sensitive matrix-free composite materials.
The Biodegradation of Indigo Carmine by Bacillus safensis HL3 Spore and Toxicity Analysis of the Degradation Products
Authors: Wang Chunlei , Wang Sijia , Zhang Jieru , Jiang Shumin , Cui Daizong , Sun Haiqiong , Liu Chengwei , Li Lili , Zhao Min
Published: December 2022

The aims of this article were to investigate Bacillus safensis HL3 spore for its capacity to degrade and detoxify indigo carmine and to provide an effective biological agent for the treatment of isatin dye wastewater. Bacillus safensis HL3 spore was found to decolorize indigo carmine by 97% in the presence of acetosyringone within 2 h. Significantly increased activities of spore laccase, intracellular tyrosinase, and lignin peroxidase upon exposure to indigo carmine were observed. The results of RT–qPCR also showed that the expression of laccase gene was significantly increased. The spore has the ability to degrade indigo carmine through oxidization. Furthermore, the pathway by which indigo carmine is degraded was investigated using liquid chromatography–mass spectrometry analysis to identify the biodegradation products. A detailed pathway of indigo carmine degradation by bacterial spores was proposed for the first time. Toxicity tests indicated that the biodegradation products of indigo carmine are non-toxic to Nicotiana tabacum seeds and are less hazardous to human erythrocytes than the original dye. Indigo carmine is a typical recalcitrant dye and severely jeopardizes human health. The results demonstrate the utility of the spore from Bacillus safensis HL3 for the degradation of indigo carmine and simultaneous reduction of its toxicity.
In Situ Fabrication of N-Doped ZnS/ZnO Composition for Enhanced Visible-Light Photocatalytic H2 Evolution Activity
Authors: Xiong Jinhua , Wang Xuxu , Wu Jinling , Han Jiaming , Lan Zhiyang , Fan Jianming
Published: December 2022

For achieving the goal of peaking carbon dioxide emissions and achieving carbon neutrality, developing hydrogen energy, the green and clean energy, shows a promising perspective for solving the energy and ecological issues. Herein, firstly, we used the hydrothermal method to synthesize the ZnS(en)0.5 as the precursor. Then, ZnS/ZnO composite was obtained by the in situ transformation of ZnS(en)0.5 with heat treatment under air atmosphere. The composition, optical property, morphology, and structural properties of the composite were characterized by X-ray photoemission spectroscopy (XPS), Ultraviolet-visible absorption spectra (Uv-vis Abs), Scanning electron microscopy (SEM) and Transmission electron microscopy image (TEM). Moreover, the content of ZnO in ZnS/ZnO was controlled via adjustment of the calcination times. The visible-light response of ZnS/ZnO originated from the in situ doping of N during the transformation of ZnS(en)0.5 to ZnS/ZnO under heat treatment, which was verified well by XPS. Photocatalytic hydrogen evolution experiments demonstrated that the sample of ZnS/ZnO-0.5 h with 6.9 wt% of ZnO had the best H2 evolution activity (1790 μmol/h/g) under visible light irradiation (λ > 400 nm), about 7.0 and 12.3 times that of the pure ZnS and ZnO, respectively. The enhanced activities of the ZnS/ZnO composites were ascribed to the intimated hetero-interface between components and efficient transfer of photo-generated electrons from ZnS to ZnO.
Polyoxygenated Terpenoids and Polyketides from the Roots of Flueggea virosa and Their Inhibitory Effect against SARS-CoV-2-Induced Inflammation
Authors: Cheng Ju-Chien , Chen Yi-Ju , Chuang Chi-Wen , Chao Ya-Hsuan , Huang Hui-Chi , Lin Chia-Chi , Chao Chih-Hua
Published: December 2022

Six new polyoxygenated terpenoids, podovirosanes A–F (1–6), and two known polyketides (7 and 8) were isolated from the roots of F. virosa. Their structures, along with absolute configurations, were deduced using spectroscopic analysis as well as computational calculations, including TDDFT calculation of ECD spectra and GIAO NMR calculations combined with DP4+ probability analysis. Compounds 2, 3, 5, and 8 were found to reduce the phosphorylation levels of NF-κB p65 in SARS-CoV-2 pseudovirus-stimulated PMA-differentiated THP-1 cells.
Behavior of PNIPAM Microgels in Different Organic Solvents
Authors: Komarova Galina A. , Kozhunova Elena Yu. , Potemkin Igor I.
Published: December 2022

In this research, we studied, in detail, the behavior of common PNIPAM microgels, obtained through surfactant-free precipitation polymerization, in a number of organic solvents. We showed that many of the selected solvents serve as good solvents for the PNIPAM microgels and that the size and architecture of the microgels depend on the solvent chosen. Expanding the range of solvents used for PNIPAM microgel incubation greatly enhances the possible routes for microparticle functionalization and modification, as well as the encapsulation of water-insoluble species. In this demonstration, we successfully encapsulated water-insoluble Sudan III dye in PNIPAM microgels and prepared the aqueous dispersions of such composite-colored microparticles.
Inhibition of Aflatoxin B1 Synthesis in Aspergillus flavus by Mate (Ilex paraguariensis), Rosemary (Rosmarinus officinalis) and Green Tea (Camellia sinensis) Extracts: Relation with Extract Antioxidant Capacity and Fungal Oxidative Stress Response Modulation
Authors: Al Khoury Anthony , El Khoury André , Rocher Ophélie , Hindieh Pamela , Puel Olivier , Maroun Richard G. , Atoui Ali , Bailly Jean-Denis
Published: December 2022

Plant extracts may represent an ecofriendly alternative to chemical fungicides to limit aflatoxin B1 (AFB1) contamination of foods and feeds. Mate (Ilex paraguariensis), rosemary (Romarinus officinalis) and green tea (Camellia sinensis) are well known for their beneficial properties, which are mainly related to their richness in bioactive phenolic compounds. AFB1 production is inhibited, with varying efficiency, by acetone/water extracts from these three plants. At 0.45 µg dry matter (DM)/mL of culture medium, mate and green tea extracts were able to completely inhibit AFB1 production in Aspergillus flavus, and rosemary extract completely blocked AFB1 biosynthesis at 3.6 µg DM/mL of culture medium. The anti-AFB1 capacity of the extracts correlated strongly with their phenolic content, but, surprisingly, no such correlation was evident with their antioxidative ability, which is consistent with the ineffectiveness of these extracts against fungal catalase activity. Anti-AFB1 activity correlated more strongly with the radical scavenging capacity of the extracts. This is consistent with the modulation of SOD induced by mate and green tea in Aspergillus flavus. Finally, rutin, a phenolic compound present in the three plants tested in this work, was shown to inhibit AFB1 synthesis and may be responsible for the anti-mycotoxin effect reported herein.
Rh-Catalyzed Cascade C-H Activation/Annulation of N-Hydroxybenzamides and Propargylic Acetates for Modular Access to Isoquinolones
Authors: Fang Taibei , Zhang Shiwen , Ye Qingqing , Kong Shuwen , Yang Tingting , Tang Kaijie , He Xinwei , Shang Yongjia
Published: December 2022

A sequential Rh(III)-catalyzed C-H activation/annulation of N-hydroxybenzamides with propargylic acetates leading to the formation of NH-free isoquinolones is described. This reaction proceeds through a sequential C-H activation/alkyne insertion/intramolecular annulation/N-O bond cleavage procedure, affording a broad spectrum of products with diverse substituents in moderate-to-excellent yields. Notably, this protocol features the simultaneous formation of two new C-C/C-N bonds and one heterocycle in one pot with the release of water as the sole byproduct.
Response Surface Optimization of Dispersive Solid-Phase Extraction Combined with HPLC for the Rapid Analysis of Multiple Coccidiostats in Feed
Authors: Tang Haolan , Liao Shudan , Yang Jian , Zhang Lilong , Tan Aijuan , Ou Deyuan , Lv Shiming , Song Xuqin
Published: December 2022

Since antimicrobials were banned as feed additives, coccidiostats with favorable anticoccidial action and growth promotion have been widely used in the breeding industry. The monitoring of coccidiostats in feed is necessary, while the current methods based on mass-spectrometer analysis have limited applicability and matrix effects could interfere with the results. Accordingly, in the present paper, a rapid analytical strategy for the simultaneous determination of six synthetic coccidiostats in feed using high-performance liquid chromatography coupled with diode-array detection was developed. Coccidiostats in chicken feeds were extracted with the trichloroacetic acid–acetonitrile solution. The cleanup was performed by dispersive solid-phase extraction after the optimization of the response surface methodology. The method exhibited good linearity for target coccidiostats within the range of 0.05~20 µg/mL. Recoveries for six compounds in fortified feed samples were from 67.2% to 107.2% with relative standard deviations less than 9.6%. The limit of detection was 0.2~0.3 mg/kg. The successful application of the method in commercial feed verified that it is effective and sensitive for the rapid determination of multiple coccidiostats in chicken feeds.