bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Diversity, LC-MS-MS Analysis and Potential Biological Activities of Brevibacillus laterosporus Extract
Authors: Zayed Muhammad , El-Garawani Islam M. , El-Sabbagh Sabha M. , Amr Bassem , Alsharif Sultan M. , Tayel Ahmed A. , AlAjmi Mohamed F. , Ibrahim Hasnaa M. S. , Shou Qiyang , Khalifa Shaden A. M. , El-Seedi Hesham R. , Elfeky Nora
Published: November 2022

Lake Mariout is Egypt’s degraded coastal marine habitat that encompasses a variety of wastes. The biodiversity and hard environmental conditions allow the co-existence of organisms with high resistance and rich metabolism, making them potential candidates for screening and isolating novel microbial strains. A bacterial isolate (BF202) cultured from the marine sediments of Alexandria’s Mariout Lake (Egypt) was tested for its antimicrobial and anticancer potential. The phylogenetic analysis of the isolated strain’s 16S rDNA and gyrB revealed that BF202 belongs to Brevibacillus laterosporus (B. laterosporus). Antibiosis of B. laterosporus was confirmed against microbial pathogens including Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, and Staphylococcus aureus. The highest antibacterial activity was detected on glucose peptone medium after 18 h of incubation at 35 °C, and at pH of 7.0 in the presence of mannose and ammonium carbonate as carbon and nitrogen sources, respectively. The cytotoxicity of the methanolic extract against breast cancer (MCF-7) and normal Vero cell lines, using the MTT test, revealed IC50 values of 7.93 and 23.79 µg/mL, respectively. To identify apoptotic and necrotic cells, a flow cytometric analysis using annexin V-FITC/PI dual-labeling was utilized and recorded a higher number of necrotic cells compared to apoptotic ones. Similarly, the cell cycle S-phase arrest was reported. The LC-MS-MS investigation of B. laterosporus extract and the molecular networking database analysis demonstrated five strategic diketopiperazine compounds with antimicrobial and anticancer activities. Taken together, this research shows that the crude extract of B. laterosporus might be an effective agent against drug-resistant bacteria and malignant disorders due to its richness in diketopiperazines.
CYP2C9 Polymorphism Influence in PK/PD Model of Naproxen and 6-O-Desmethylnaproxen in Oral Fluid
Authors: Oliveira Gabriela Moraes , Dionísio Thiago José , Siqueira-Sandrin Viviane Silva , Ferrari Leticia Alves de Lima , Bolani Bruna , Parisi Viviane Aparecida , Polanco Nelson Leonel Del Hierro , Colombini-Ishikiriama Bella Luna , Faria Flávio Augusto Cardoso , Santos Carlos Ferreira , Calvo Adriana Maria
Published: November 2022

Polymorphisms in CYP2C9 can significantly interfere with the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen. The present research aimed to study the PK/PD parameters of naproxen and its metabolite, 6-O-desmethylnaproxen, associated with allelic variations of CYP2C9. In our study, a rapid, selective, and sensitive Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method was developed and validated for the determination of naproxen and its main metabolite, 6-O-desmethylnaproxen, in oral fluid. Naproxen and its main metabolite were separated using a Shim-Pack XR-ODS 75L × 2.0 column and C18 pre-column at 40 °C using a mixture of methanol and 10 mM ammonium acetate (70:30, v/v), with an injection flow of 0.3 mL/min. The total analytical run time was 3 min. The volunteers, previously genotyped for CYP2C9 (16 ancestral—CYP2C9 *1 and 12 with the presence of polymorphism—CYP2C9 *2 or *3), had their oral fluids collected sequentially before and after taking a naproxen tablet (500 mg) at the following times: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72 and 96 h. Significant differences in the PK parameters (* p < 0.05) of naproxen in the oral fluid were: Vd/F (L): 98.86 (55.58–322.07) and 380.22 (261.84–1097.99); Kel (1/h): 0.84 (0.69–1.34) and 1.86 (1.09–4.06), in ancestral and mutated CYP2C9 *2 and/or *3, respectively. For 6-O-desmethylnaproxen, no PK parameters were significantly different between groups. The analysis of prostaglandin E2 (PGE2) proved to be effective and sensitive for PD parameters analysis and showed higher levels in the mutated group (p < 0.05). Both naproxen and its main metabolite, 6-O-desmethylnaproxen, and PGE2 in oral fluid can be effectively quantified using LC-MS/MS after a 500 mg oral dose of naproxen. Our method proved to be effective and sensitive to determine the lower limit of quantification of naproxen and its metabolite, 6-O-desmethylnaproxen, in oral fluid (2.4 ng/mL). All validation data, such as accuracy, precision, and repeatability intra- and inter-assay, were less than 15%. Allelic variations of CYP2C9 may be considered relevant in the PK of naproxen and its main metabolite, 6-O-desmethylnaproxen.
Antimicrobial Effectiveness of an Usnic-Acid-Containing Self-Decontaminating Coating on Underground Metro Surfaces in Athens
Authors: Maltezou Helena C. , Horefti Elina , Papamichalopoulos Nikolaos , Tseroni Maria , Ioannidis Anastasios , Angelakis Emmanouil , Chatzipanagiotou Stylianos
Published: November 2022

(1) Background: Surfaces have been implicated in the transmission of infections. We aimed to assess how effective an usnic-acid-containing self-decontaminating coating was on the surfaces of the Athens underground metro. (2) Methods: Two samples were collected from each of 60 surfaces of a station and a wagon before the application of the coating and 9 and 20 days after, and they were tested for bacteria, fungi, and SARS-CoV-2 using conventional microbiological and molecular methods. Bacteria and fungi growth were expressed in colony forming units (CFUs)/102cm2. (3) Results: Before the application of the coating, 50% of the samples tested positive for the targeted microbes: 91.7% for bacteria, 18.3% for fungi, and 8.3% for SARS-CoV-2. After nine days, 3.3% of the samples tested positive for bacteria and 6.6% after 20 days. The average amount of bacteria before the coating was applied was 8.5 CFU/102cm2 compared to 0 and 0 CFU/102cm2 after application (100% and 95% reduction); all samples collected after the application were negative for SARS-CoV-2 and fungi (100% reduction). (4) Conclusion: An usnic-acid-containing self-decontaminating coating was highly effective in eliminating bacterial, fungal, and SARS-CoV-2 contamination of surfaces in the underground metro.
Endocrine Disrupting Compounds (Nonylphenol and Bisphenol A)–Sources, Harmfulness and Laccase-Assisted Degradation in the Aquatic Environment
Authors: Gałązka Agnieszka , Jankiewicz Urszula
Published: November 2022

Environmental pollution with organic substances has become one of the world’s major problems. Although pollutants occur in the environment at concentrations ranging from nanograms to micrograms per liter, they can have a detrimental effect on species inhabiting aquatic environments. Endocrine disrupting compounds (EDCs) are a particularly dangerous group because they have estrogenic activity. Among EDCs, the alkylphenols commonly used in households deserve attention, from where they go to sewage treatment plants, and then to water reservoirs. New methods of wastewater treatment and removal of high concentrations of xenoestrogens from the aquatic environment are still being searched for. One promising approach is bioremediation, which uses living organisms such as fungi, bacteria, and plants to produce enzymes capable of breaking down organic pollutants. These enzymes include laccase, produced by white rot fungi. The ability of laccase to directly oxidize phenols and other aromatic compounds has become the focus of attention of researchers from around the world. Recent studies show the enormous potential of laccase application in processes such as detoxification and biodegradation of pollutants in natural and industrial wastes.
Enhanced Electron Uptake and Methane Production by Corrosive Methanogens during Electromethanogenesis
Authors: Mayer Florian , Sabel-Becker Björn , Holtmann Dirk
Published: November 2022

Electromethanogenesis is an interesting next-generation technology to produce methane from CO2 and electricity by using methanogens. Iron-corroding methanogens might be of special interest for that application due to their natural ability for electron uptake. Methanococcus maripaludis Mic1c10 and KA1 were tested in bioelectrochemical systems. Strain Mic1c10 showed a 120% higher current density and an 84% higher methane production rate (16.2 mmol m−2 d−2) than the non-corrosive strain Methanococcus maripaludis S2, which was identified earlier as the best methane producer under the same experimental conditions. Interestingly, strain KA1 also showed a 265% higher current density than strain S2. Deposits at the cathodes were detected and analyzed, which were not described earlier. A comparative genome analysis between the corrosive methanogen and the S2 strain enables new insights into proteins that are involved in enhanced electron transfer.
Simulating the Environmental Spread of SARS-CoV-2 via Cough and the Effect of Personal Mitigations
Authors: Bailey Claire , Johnson Paul , Moran Josh , Rosa Iwona , Brookes Jodi , Hall Samantha , Crook Brian
Published: November 2022

Background: A cough is known to transmit an aerosol cloud up to 2 m. During the COVID-19 pandemic of 2020 the United Kingdom’s National Health Service (NHS), other UK government agencies and the World Health Organization (WHO) advised people to cough into their elbows. It was thought that this would reduce viral spread and protect the public. However, there is limited peer reviewed evidence to support this. Objectives: To determine if cough related interventions reduce environmental contamination, protecting members of the public from infection. Methods: Scientists and engineers at the Health and Safety Executive (HSE) laboratory used a human cough simulator that provided a standardised cough challenge using a solution of simulated saliva and a SARS-CoV-2 surrogate virus; Phi6. Pseudomonas syringae settle plates were used to detect viable Phi6 virus following a simulated cough into a 4 × 4 m test chamber. The unimpeded pattern of contamination was compared to that when a hand or elbow was placed over the mouth during the cough. High speed back-lit video was also taken to visualise the aerosol dispersion. Results and Discussion: Viable virus spread up to 2 m from the origin of the cough outwards in a cloud. Recommended interventions, such as putting a hand or elbow in front of the mouth changed the pattern of cough aerosol dispersion. A hand deflected the cough to the side, protecting those in front from exposure, however it did not prevent environmental contamination. It also allowed for viral transfer from the hand to surfaces such as door handles. A balled fist in front of the mouth did not deflect the cough. Putting an elbow in front of the mouth deflected the aerosol cloud to above and below the elbow, but would not have protected any individuals standing in front. However, if the person coughed into a sleeved elbow more of the aerosol seemed to be absorbed. Coughing into a bare elbow still allowed for transfer to the environment if people touched the inside of their elbow soon after coughing. Conclusions: Interventions can change the environmental contamination pattern resulting from a human cough but may not reduce it greatly.
Report and Comparative Genomics of an NDM-5-Producing Escherichia coli in a Portuguese Hospital: Complex Class 1 Integrons as Important Players in blaNDM Spread
Authors: Tavares Rafael D. S. , Tacão Marta , Ramalheira Elmano , Ferreira Sónia , Henriques Isabel
Published: November 2022

Background: New Delhi metallo-beta-lactamase (NDM) has been spreading across the globe, but the causes of its success are poorly understood. We characterized a blaNDM-5-positive Escherichia coli strain from a Portuguese hospital and conducted comparative genomic analyses to understand the role of clonal background and horizontal gene transfer in blaNDM-5 dissemination. Methods: After blaNDM PCR screening and genome sequencing, Ec355340 was subjected to mating, transformation, and plasmid curing assays and MICs determination for several antibiotics. Comparison with data compiled from public databases was performed. Results: blaNDM-5 was in a complex integron co-located in a FIB-FII plasmid (pEc355340_NDM-5). The mating assays were unsuccessful, but plasmid transformation into a susceptible host led to resistance to all beta-lactams and to sulfamethoxazole-trimethoprim. The profile of virulence genes (n = 73) was compatible with extraintestinal pathogenesis. An analysis of genomes from public databases suggested that blaNDM-5 has rarely been associated with ST156 strains (such as Ec355340), while is has frequently been found on strains of the ST10 clonal complex. However, ST156 may play a role in the co-spreading of blaNDM and mcr genes. Regardless, comparative genomics confirmed the presence of blaNDM in similar complex integrons in plasmids (48/100 plasmids most similar to pEc355340_NDM-5) and ST156 genomes (20/41 blaNDM-positive genomes). Conclusions: blaNDM-5 and other blaNDM variants were more frequently associated to complex integrons than previously reported and, therefore, these platforms may be important drivers in their dissemination. The identification of blaNDM-5 for the first time in Portugal could be a game-changer in the current Portuguese antibiotic resistance scenario, as this gene encodes a higher-level resistance phenotype, and its spread may be facilitated due to the association with complex integrons.
Norepinephrine Effects on Uropathogenic Strains Virulence
Authors: Ignatova Nadezhda , Abidullina Alina , Streltsova Olga , Elagin Vadim , Kamensky Vladislav
Published: November 2022

The degree of virulence correlates with adhesion, biofilm formation, motility and the capacity to quickly colonize biological surfaces. The virulence of the bacteria that have colonized the urinary tract may be modified by substances dissolved in urine. One such substance is the norepinephrine (NE) hormone, which may be present in human urine, especially in times of stress and under changes in the activity of the renin-angiotensin-aldesterone system. In this work, we study the influence of NE on the biomass, biofilm formation, matrix production, adhesion, motility and metabolism of uropathogenic strains of E. coli and S. aureus. We used Congo red and gentian violet staining for detection of matrix and biomass formation, respectively. The optical density was measured by a multichannel spectrophotometer. The motility of bacterial cells was measured on semi-solid agar at 24 h and 48 h. The metabolic activity was analyzed by MTT assay. It was shown that the metabolic activity of E. coli was stimulated by NE, which led to the increasing synthesis of virulence factors such as biofilm production, adhesion, and motility. At the same time, NE did not activate the S. aureus strain’s metabolism and did not change its adhesion and motility. Thus, the virulence activity of uropathogenic E. coli may be modified by NE in urine.
Fungicolous Fungi on Pseudosclerotial Plates and Apothecia of Hymenoscyphus fraxineus and Their Biocontrol Potential
Authors: Kowalski Tadeusz , Bilański Piotr
Published: November 2022

In the present work, research tasks were carried out in the search for fungi with potential biocontrol possibilities in relation to the ash dieback pathogen, Hymenoscyphus fraxineus. In the years 2012–2021, dead petioles of F. excelsior and F. mandshurica were collected, on which morphological structures of H. fraxineus showed unusual symptoms of dying (apothecia) and signs of colonization by other fungi (pseudosclerotial plates). Based on morphological and molecular phylogenetic data, 18 fungal taxa were identified. Thirteen of them belong to Ascomycota: Clonostachys rosea, Cl. solani, Cordyceps sp., Minimidochium sp., Nemania diffusa, Fusarium sp., Pestalotiopsis sp., Trichoderma atroviride, T. harzianum, T. polysporum, T. rodmanii, T. tomentosum, Trichoderma sp., and five other taxa are represented by Basidiomycota: Corticiales sp., Cyathus olla, Efibula sp., Gymnopus sp. and Polyporales sp. In 108 dual cultures in vitro, three different types of interactions were distinguished: (i) physical colony contact (5.6%), (ii) presence of an inhibition zone between the colonies (0.9%), and (iii) copartner overgrowth of H. fraxineus colonies and partial or complete replacement of the pathogen (93.5%). In the dual cultures, various morphological deformations of H. fraxineus hyphae were observed: the development of apical or intercalary cytoplasmic extrusions, development of internal hyphae of the test fungi in pathogens’ hyphae, the deformation and disruption of significant sections of H. fraxineus hyphae via lysis and mycoparasitism, complete desolation of H. fraxineus cells and breakdown of hyphae into short fragments, and disappearing of pigment in the affected hyphae of H. fraxineus. The inoculation tests performed in vivo or in glass Petrie dishes showed that all the identified taxa were able to lead to pathological changes in H. fraxineus apothecia, and the mycelium of some of them completely covered pseudosclerotial plates of H. fraxineus. It was emphasized in the discussion that such activity of these fungi in forest stands may contribute to the reduction in the H. fraxineus inoculum reservoir.
Ultrathin Two-Dimensional Fe–Co Bimetallic Oxide Nanosheets for Separator Modification of Lithium–Sulfur Batteries
Authors: Pu Jun , Tan Yun , Wang Tao , Zhu Xiaomei , Fan Shanshan
Published: November 2022

The shuttle effect is understood to be the most significant issue that needs to be solved to improve the performance of lithium–sulfur batteries. In this study, ultrathin two-dimensional Fe–Co bimetallic oxide nanosheets were prepared using graphene as a template, which could rapidly catalyze the conversion of polysulfides and inhibit the shuttle effect. Additionally, such ultrathin nanostructures based on graphene provided sufficient active sites and fast diffusion pathways for lithium ions. Taking into account the aforementioned benefits, the ultrathin two-dimensional Fe–Co bimetallic oxide nanosheets modified separator assembled lithium–sulfur batteries delivered an incredible capacity of 1044.2 mAh g−1 at 1 C and retained an excellent reversible capacity of 859.4 mAh g−1 after 100 cycles. Even under high loading, it still achieved high area capacity and good cycle stability (92.6% capacity retention).
Interstellar Benzene Formation Mechanisms via Acetylene Cyclotrimerization Catalyzed by Fe+ Attached to Water Ice Clusters: Quantum Chemistry Calculation Study
Authors: Murakami Tatsuhiro , Takayanagi Toshiyuki
Published: November 2022

Benzene is the simplest building block of polycyclic aromatic hydrocarbons and has previously been found in the interstellar medium. Several barrierless reaction mechanisms for interstellar benzene formation that may operate under low-temperature and low-pressure conditions in the gas phase have been proposed. In this work, we studied different mechanisms for interstellar benzene formation based on acetylene cyclotrimerization catalyzed by Fe+ bound to solid water clusters through quantum chemistry calculations. We found that benzene is formed via a single-step process with one transition state from the three acetylene molecules on the Fe+(H2O)n (n = 1, 8, 10, 12 and 18) cluster surface. Moreover, the obtained mechanisms differed from those of single-atom catalysis, in which benzene is sequentially formed via multiple steps.
Mechanical Constraint Effect on DNA Persistence Length
Authors: Zhang Cheng-Yin , Zhang Neng-Hui
Published: November 2022

Persistence length is a significant criterion to characterize the semi-flexibility of DNA molecules. The mechanical constraints applied on DNA chains in new single-molecule experiments play a complex role in measuring DNA persistence length; however, there is a difficulty in quantitatively characterizing the mechanical constraint effects due to their complex interactions with electrostatic repulsions and thermal fluctuations. In this work, the classical buckling theory of Euler beam and Manning’s statistical theories of electrostatic force and thermal fluctuation force are combined for an isolated DNA fragment to formulate a quantitative model, which interprets the relationship between DNA persistence length and critical buckling length. Moreover, this relationship is further applied to identify the mechanical constraints in different DNA experiments by fitting the effective length factors of buckled fragments. Then, the mechanical constraint effects on DNA persistence lengths are explored. A good agreement among the results by theoretical models, previous experiments, and present molecular dynamics simulations demonstrates that the new superposition relationship including three constraint-dependent terms can effectively characterize changes in DNA persistence lengths with environmental conditions, and the strong constraint-environment coupling term dominates the significant changes of persistence lengths; via fitting effective length factors, the weakest mechanical constraints on DNAs in bulk experiments and stronger constraints on DNAs in single-molecule experiments are identified, respectively. Moreover, the consideration of DNA buckling provides a new perspective to examine the bendability of short-length DNA.
Cross-Linked Ionic Liquid Polymer for the Effective Removal of Ionic Dyes from Aqueous Systems: Investigation of Kinetics and Adsorption Isotherms
Authors: Reddy A. Vijaya Bhaskar , Rafiq Rehan , Ahmad Aqeel , Maulud Abdulhalim Shah , Moniruzzaman Muhammad
Published: November 2022

In the current study, we have synthesized an imidazolium based cross-linked polymer, namely, 1-vinyl-3-ethylimidazolium bis(trifluoromethylsulfonyl)imide (poly[veim][Tf2N]-TRIM) using trimethylolpropane trimethacrylate as cross linker, and demonstrated its efficiency for the removal of two extensively used ionic dyes—methylene blue and orange-II—from aqueous systems. The detailed characterization of the synthesized poly[veim][Tf2N]-TRIM was performed with the help of 1H NMR, TGA, FT-IR and FE-SEM analysis. The concentration of dyes in aqueous samples before and after the adsorption process was measured using an UV-vis spectrophotometer. The process parameters were optimised, and highest adsorption was obtained at a solution pH of 7.0, adsorbent dosage of 0.75 g/L, contact time of 7 h and dye concentrations of 100 mg/L and 5.0 mg/L for methylene blue and orange-II, respectively. The adsorption kinetics for orange-II and methylene blue were well described by pseudo-first-order and pseudo–second-order models, respectively. Meanwhile, the process of adsorption was best depicted by Langmuir isotherms for both the dyes. The highest monolayer adsorption capacities for methylene blue and orange-II were found to be 1212 mg/g and 126 mg/g, respectively. Overall, the synthesized cross-linked poly[veim][Tf2N]-TRIM effectively removed the selected ionic dyes from aqueous samples and provided >90% of adsorption efficiency after four cycles of adsorption. A possible adsorption mechanism between the synthesised polymeric adsorbent and proposed dyes is presented. It is further suggested that the proposed ionic liquid polymer adsorbent could effectively remove other ionic dyes and pollutants from contaminated aqueous systems.
Extraction, Purification, and Elucidation of Six Ginkgol Homologs from Ginkgo biloba Sarcotesta and Evaluation of Their Anticancer Activities
Authors: Li Fengnan , Boateng Isaac Duah , Yang Xiaoming , Li Yuanyuan
Published: November 2022

Ginkgols are active constituents from Ginkgo biloba L. (GB) and have pharmacological activities, such as antibacterial and antioxidant activities. In our previous report, only five ginkgols were separated. However, ginkgol C17:1 had two isomers, for which their separation, identification, and bioactivities have not yet been investigated. Hence, this research reports the successful isolation of six ginkgol homologs with alkyl substituents—C17:1-Δ12, C15:1-Δ8, C13:0, C17:2, C17:1-Δ10, and C15:0—for the first time using HPLC. This was followed by the identification of their chemical structures using Fourier transform infrared (FTIR), ultraviolet (UV), gas chromatography and mass spectrometry (GC-MS), carbon-13 nuclear magnetic resonance (13C-NMR), and proton nuclear magnetic resonance (1H-NMR) analysis. The results showed that two ginkgol isomers, C17:1-Δ12 and C17:1-Δ10, were obtained simultaneously from the ginkgol C17:1 mixture and identified entirely for the first time. That aside, the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay showed that the six ginkgol homologs possessed significant antiproliferation effects against HGC and HepG2 cells. Furthermore, the ginkgols with unsaturated side chains (C17:2, C15:1-Δ8, C17:1-Δ12, and C17:1-Δ10) exhibited more potent inhibitory effects than ginkgols with saturated side chains (C13:0, C15:0). In addition, unsaturated ginkgol C15:1-Δ8 showed the most potent cytotoxicity on HepG2 and HGC cells, of which the half-maximal inhibition concentrations (IC50) were 18.84 ± 2.58 and 13.15 ± 2.91 μM, respectively. The IC50 for HepG2 and HGC cells for the three unsaturated ginkgols (C17:1-Δ10, C17:2 and C17:1-Δ12) were ~59.97, ~60.82, and ~68.97 μM for HepG2 and ~30.97, ~33.81, and ~34.55 μM for HGC cells, respectively. Comparing the ginkgols’ structure–activity relations, the findings revealed that the position and number of the double bonds of the ginkgols with 17 side chain carbons in length had no significant difference in anticancer activity.
Inhibitory Effects of Selected Medicinal Plants on Bacterial Growth of Methicillin-Resistant Staphylococcus aureus
Authors: Jung In-Geun , Jeong Jae-Young , Yum Seung-Hoon , Hwang You-Jin
Published: November 2022

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to global public health due to its capacity of tolerate conventional antibiotics. Medicinal plants are traditionally used to treat infectious diseases caused by bacterial pathogens. In the present study, 16 medicinal plants were screened for antibacterial activities to preselect more effective species. Ethanol extracts of selected medicinal plants (Caesalpinia sappan L., Glycyrrhiza uralensis Fisch., Sanguisorba officinalis L., and Uncaria gambir Roxb) were partitioned successively with different solvents (n-hexane, chloroform, ethyl acetate, 1-butanol, and water). Disc diffusion assay and broth microdilution were performed to evaluate the antibacterial activities of plant extracts and fractions against Staphylococcus aureus strains. Furthermore, the cytotoxicity of the extracts and fractions was determined against the human hepatoma (HepG2) and human lung carcinoma (A549) cell lines using a trypan blue exclusion method. A few extracts and fractions showed significant inhibitory effects on the bacterial growth of all tested strains, including multidrug-resistance (MDR) clinical isolates. The ethyl acetate fraction of C. sappan had the most potent effects with minimum inhibitory/bactericidal concentrations (MIC/MBC) of 31.2/62.5 μg/mL and showed low cytotoxicity with over 90% cell viability in both cells. Our results suggest that medicinal plants have considerable potential as alternatives to conventional antibiotics.
High-Pressure Supercritical CO2 Pretreatment of Apple Orchard Waste for Carbohydrates Production Using Response Surface Methodology and Method Uncertainty Evaluation
Authors: Senila Lacrimioara , Scurtu Daniela Alexandra , Kovacs Eniko , Levei Erika Andrea , Cadar Oana , Becze Anca , Varaticeanu Cerasel
Published: November 2022

This study’s objective was to separate cellulose, hemicellulose, and lignin after high-pressure supercritical carbon dioxide pretreatment for further valorization. The study investigated the supercritical carbon dioxide pretreatment of apple orchard waste at temperatures of 160–200 °C, for 15–45 min, at a pressure of 10 MPa. Response Surface Methodology (RSM) was used to optimize the supercritical process and to improve its efficiency. The change of functional groups during different pretreatment conditions was examined by Fourier transform infrared (FTIR) spectroscopy. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) confirmed the structural changes in the biomass structure before and after pretreatment. A new ultra-high performance liquid chromatography (UHPLC) coupled with an evaporative light scattering detector (ELSD) method was developed and validated for the determination of carbohydrates in the liquid fraction that resulted after pretreatment. The estimated uncertainty of the method ranged from 16.9 to 20.8%. The pre-treatment of high-pressure supercritical CO2 appears to be an effective and promising technique for the recovery of sugars and secondary by-products without the use of toxic solvents.
Mechanochemical Approach towards Multi-Functionalized 1,2,3-Triazoles and Anti-Seizure Drug Rufinamide Analogs Using Copper Beads
Authors: Bhattacherjee Dhananjay , Kovalev Igor S. , Kopchuk Dmitry S. , Rahman Matiur , Santra Sougata , Zyryanov Grigory V. , Das Pralay , Purohit Rituraj , Rusinov Vladimir L. , Chupakhin Oleg N.
Published: November 2022

Highly regiospecific, copper-salt-free and neat conditions have been demonstrated for the 1,3-dipolar azide-alkyne cycloaddition (AAC) reactions under mechanochemical conditions. A group of structurally challenging alkynes and heterocyclic derivatives was efficiently implemented to achieve highly functionalized 1,4-disubstituted-1,2,3-triazoles in good to excellent yield by using the Cu beads without generation of unwanted byproducts. Furthermore, the high-speed ball milling (HSBM) strategy has also been extended to the synthesis of the commercially available pharmaceutical agent, Rufinamide, an antiepileptic drug (AED) and its analogues. The same strategy was also applied for the synthesis of the Cl-derivative of Rufinamide. Analysis of the single crystal XRD data of the triazole was also performed for the final structural confirmation. The Cu beads are easily recoverable from the reaction mixture and used for the further reactions without any special treatment.
Organocatalytic Enantioselective Michael Reaction of Aminomaleimides with Nitroolefins Catalyzed by Takemoto’s Catalyst
Authors: Mu Hongwen , Jin Yan , Zhao Rongrong , Wang Liming , Jin Ying
Published: November 2022

Known as electrophiles, maleimides are often used as acceptors in Michael additions to produce succinimides. However, reactions with maleimides as nucleophiles for enantioselective functionalization are only rarely performed. In this paper, a series of bifunctional Takemoto’s catalysts were used to organocatalyze the enantioselective Michael reaction of aminomaleimides with nitroolefins. The resulting products were obtained in good yields (76–86%) with up to 94% enantiomer excess (ee). The catalyst type and the substrate scope were broadened using this methodology.
Condensation of 4-Tert-butyl-2,6-dimethylbenzenesulfonamide with Glyoxal and Reaction Features: A New Process for Symmetric and Asymmetric Aromatic Sulfones
Authors: Paromov Artyom E. , Sysolyatin Sergey V. , Shchurova Irina A.
Published: November 2022

The synthesis of substituted aza- and oxaazaisowurtzitanes via direct condensation is challenging. The selection of starting ammonia derivatives is very limited. The important step in developing alternative synthetic routes to these compounds is a detailed study on their formation process. Here, we explored an acid-catalyzed condensation between 4-tert-butyl-2,6-dimethylbenzenesulfonamide and glyoxal in aqueous H2SO4, aqueous acetonitrile and acetone, and established some new processes hindering the condensation. In particular, an irreversible rearrangement of the condensation intermediate was found to proceed and be accompanied by the 1,2-hydride shift and by the formation of symmetric disulfanes and sulfanes. It has been shown for the first time that aldehydes may act as a reducing agent when disulfanes are generated from aromatic sulfonamides, as is experimentally proved. The condensation between 4-tert-butyl-2,6-dimethylbenzenesulfonamide and formaldehyde resulted in 1,3,5-tris((4-(tert-butyl)-2,6-dimethylphenyl)sulfonyl)-1,3,5-triazinane. It was examined if diimine could be synthesized from 4-tert-butyl-2,6-dimethylbenzenesulfonamide and glyoxal by the most common synthetic procedures for structurally similar imines. It has been discovered for the first time that the Friedel–Crafts reaction takes place between sulfonamide and the aromatic compound. A new synthetic strategy has been suggested herein that can reduce the stages in the synthesis of in-demand organic compounds of symmetric and asymmetric aromatic sulfones via the Brønsted acid-catalyzed Friedel–Crafts reaction, starting from aromatic sulfonamides and arenes activated towards an electrophilic attack.
Lipase-Catalyzed Phospha-Michael Addition Reactions under Mild Conditions
Authors: Xu Yuelin , Li Fengxi , Ma Jinglin , Li Jiapeng , Xie Hanqing , Wang Chunyu , Chen Peng , Wang Lei
Published: November 2022

Organophosphorus compounds are the core structure of many active natural products. The synthesis of these compounds is generally achieved by metal catalysis requiring specifically functionalized substrates or harsh conditions. Herein, we disclose the phospha-Michael addition reaction of biphenyphosphine oxide with various substituted β-nitrostyrenes or benzylidene malononitriles. This biocatalytic strategy provides a direct route for the synthesis of C-P bonds with good functional group compatibility and simple and practical operation. Under the optimal conditions (styrene (0.5 mmol), biphenyphosphine oxide (0.5 mmol), Novozym 435 (300 U), and EtOH (1 mL)), lipase leads to the formation of organophosphorus compounds in yields up to 94% at room temperature. Furthermore, we confirm the role of the catalytic triad of lipase in this phospha-Michael addition reaction. This new biocatalytic system will have broad applications in organic synthesis.
Analysis of Components and Properties of Extractives from Alnus cremastogyne Pods from Different Provenances
Authors: Chen Guoxi , Pan Fangya , Gao Yemei , Li Hao , Qin Xiaqing , Jiang Yongze , Qi Jinqiu , Xie Jiulong , Jia Shanshan
Published: November 2022

Chemical components with anti-oxidant, anti-inflammatory, and anti-cancer properties extracted from Alnus bark and leaves have been extensively studied. However, less attention has been paid to extractives from Alnus pods, which are mostly treated as waste. Here, extractives of Alnus cremastogyne pods from 12 provenances in Sichuan Province were studied for high value-added utilization of Alnus waste. The extractives were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS), Ultraviolet-visible spectroscopy (UV-Vis spectra), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity. A total of 58, 49, and 51 chemical components were found when the organic solvents of ethanol, petroleum ether, and ethyl acetate were used to collect extractives, respectively. These chemical components including Phytol, CIS-5,8,11,14,17-eicosapentaenoic acid, Germacrene D, Lupeol, and β-sitosterol, etc., have wide applications in the fields of pharmacy and cosmetics. Moreover, it was also found that extractives in ethanol and ethyl acetate had impressive UV resistance, especially for UV-C and UV-B blocking. The results showed that the maximum block ratio towards UV-C and UV-B could reach 99%. In addition, the ethanol extract showed good anti-oxidant activity with a maximum free radical scavenging rate of 96.19%. This comprehensive and systematic study on extractives from Alnus cremastogyne pods promotes the development of high-value utilization of Alnus components.
Protective Effect of Flavonoids against Methylglyoxal-Induced Oxidative Stress in PC-12 Neuroblastoma Cells and Its Structure–Activity Relationships
Authors: Zhang Danyang , Li Xia , He Xiaoshi , Xing Yan , Jiang Bo , Xiu Zhilong , Bao Yongming , Dong Yuesheng
Published: November 2022

Methylglyoxal-induced oxidative stress and cytotoxicity are the main factors causing neuronal death-related, diabetically induced memory impairment. Antioxidant and anti-apoptotic therapy are potential intervention strategies. In this study, 25 flavonoids with different substructures were assayed for protecting PC-12 cells from methylglyoxal-induced damage. A structure–activity relationship (SAR) analysis indicated that the absence of the double bond at C-2 and C-3, substitutions of the gallate group at the 3 position, the pyrogallol group at the B-ring, and the R configuration of the 3 position enhanced the protection of flavan-3-ols, and a hydroxyl substitution at the 4′ and meta-positions were important for the protection of flavonol. These SARs were further confirmed by molecular docking using the active site of the Keap1–Nrf2 complex as the receptor. The mechanistic study demonstrated that EGCG with the lowest EC50 protected the PC-12 cells from methylglyoxal-induced damage by reducing oxidative stress via the Nrf2/Keap1/HO-1 and Bcl-2/Bax signaling pathways. These results suggested that flavan-3-ols might be a potential dietary supplement for protection against diabetic encephalopathy.
Genistein Modified with 8-Prenyl Group Suppresses Osteoclast Activity Directly via Its Prototype but Not Metabolite by Gut Microbiota
Authors: Qiu Zuo-Cheng , Zhang Feng-Xiang , Hu Xue-Ling , Zhang Yang-Yang , Tang Zi-Ling , Zhang Jie , Yang Li , Wong Man-Sau , Chen Jia-Xu , Xiao Hui-Hui
Published: November 2022

Postmenopausal osteoporosis is a significant threat to human health globally. Genistein, a soy-derived isoflavone, is regarded as a promising anti-osteoporosis drug with the effects of promoting osteoblastogenesis and suppressing osteoclastogenesis. However, its oral bioavailability (6.8%) is limited by water solubility, intestinal permeability, and biotransformation. Fortunately, 8-prenelylated genistein (8PG), a derivative of genistein found in Erythrina Variegate, presented excellent predicted oral bioavailability (51.64%) with an improved osteoblastogenesis effect, although its effects on osteoclastogenesis and intestinal biotransformation were still unclear. In this study, an in vitro microbial transformation platform and UPLC-QTOF/MS analysis method were developed to explore the functional metabolites of 8PG. RANKL-induced RAW264.7 cells were utilized to evaluate the effects of 8PG on osteoclastogenesis. Our results showed that genistein was transformed into dihydrogenistein and 5-hydroxy equol, while 8PG metabolites were undetectable under the same conditions. The 8PG (10−6 M) was more potent in inhibiting osteoclastogenesis than genistein (10−5 M) and it down-regulated NFATC1, cSRC, MMP-9 and Cathepsin K. It was concluded that 8-prenyl plays an important role in influencing the osteoclast activity and intestinal biotransformation of 8PG, which provides evidence supporting the further development of 8PG as a good anti-osteoporosis agent.
A Computer Simulation Insight into the Formation of Apocarotenoids: Study of the Carotenoid Oxygenases BCO1 and BCO2 and Their Interaction with Putative Substrates
Authors: Martínez Anabela , Cantero Jorge , Meléndez-Martínez Antonio J. , Paulino Margot
Published: November 2022

Carotenoids are isoprenoid pigments, and sources of vitamin A in humans. The first metabolic pathway for their synthesis is mediated by the enzymes β,β-carotene-15,15′-dioxygenase (BCO1) and β,β-carotene-9′,10′-dioxygenase (BCO2), which cleave carotenoids into smaller compounds, called apocarotenoids. The objective of this study is to gain insight into the interaction of BCO1 and BCO2 with carotenoids, adding structural diversity and importance in the agro-food and/or health sectors. Homology modeling of BCO1 and BCO2, and the molecular dynamics of complexes with all carotenoids were performed. Interaction energy and structures were analyzed. For both enzymes, the general structure is conserved with a seven beta-sheet structure, and the β-carotene is positioned at an optimal distance from the catalytic center. Fe2+ forms in an octahedral coordination sphere with four perfectly conserved histidine residues. BCO1 finds stability in a structure in which the β-carotene is positioned ready for enzymatic catalysis at the 15–15′ bond, and BCO2 in positioning the bond to be cleaved (C9–C10) close to the active site. In BCO1 the carotenoids interact with only seven residues with aromatic rings, while the interaction of BCO2 is much more varied in terms of the type of interaction, with more residues of different chemical natures.
Resveratrol Analogues as Dual Inhibitors of Monoamine Oxidase B and Carbonic Anhydrase VII: A New Multi-Target Combination for Neurodegenerative Diseases?
Authors: Carradori Simone , Fantacuzzi Marialuigia , Ammazzalorso Alessandra , Angeli Andrea , De Filippis Barbara , Galati Salvatore , Petzer Anél , Petzer Jacobus P. , Poli Giulio , Tuccinardi Tiziano , Agamennone Mariangela , Supuran Claudiu T.
Published: November 2022

Neurodegenerative diseases (NDs) are described as multifactorial and progressive syndromes with compromised cognitive and behavioral functions. The multi-target-directed ligand (MTDL) strategy is a promising paradigm in drug discovery, potentially leading to new opportunities to manage such complex diseases. Here, we studied the dual ability of a set of resveratrol (RSV) analogs to inhibit two important targets involved in neurodegeneration. The stilbenols 1–9 were tested as inhibitors of the human monoamine oxidases (MAOs) and carbonic anhydrases (CAs). The studied compounds displayed moderate to excellent in vitro enzyme inhibitory activity against both enzymes at micromolar/nanomolar concentrations. Among them, the best compound 4 displayed potent and selective inhibition against the MAO-B isoform (IC50 MAO-A 0.43 µM vs. IC50 MAO-B 0.01 µM) with respect to the parent compound resveratrol (IC50 MAO-A 13.5 µM vs. IC50 MAO-B > 100 µM). It also demonstrated a selective inhibition activity against hCA VII (KI 0.7 µM vs. KI 4.3 µM for RSV). To evaluate the plausible binding mode of 1–9 within the two enzymes, molecular docking and dynamics studies were performed, revealing specific and significant interactions in the active sites of both targets. The new compounds are of pharmacological interest in view of their considerably reduced toxicity previously observed, their physicochemical and pharmacokinetic profiles, and their dual inhibitory ability. Compound 4 is noteworthy as a promising lead in the development of MAO and CA inhibitors with therapeutic potential in neuroprotection.
The Chemical Signatures of Water Extract of Zingiber officinale Rosc
Authors: Lu Fengying , Cai Hua , Li Saimei , Xie Wei , Sun Rongjin
Published: November 2022

Background: Ginger (Z. officinale Rosc.) is a common herb and is widely used as a diet-based or home therapy in traditional medicine worldwide. However, fresh ginger turns into dried ginger after kiln drying and shows a different treatment effect in clinical practice. Objective: To characterize the changes of major bioactive constituents in dried ginger after the processing of fresh ginger. Methods: A novel, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC–QTOF/MS) method was established to characterize the changes in the bioactive constituents of dried ginger. The novel strategy was split into two steps: firstly, the MS selected the most intense precursor ions of tandem MS; then, target MS/MS acquisition with different collision energies (10, 20, and 40 eV) was used to characterize the compound’s accurate MS/MS spectra and compare the MS/MS spectrum with the building MS reference library and reference standards. Result: Fifty-three compounds, including diarylheptanoids, gingerols, gingerodiols, gingerdiones, and shogaol-related compounds, were identified based on summarized fragmentation patterns. Fifteen out of fifty-three compounds were diarylheptanoids, which was different from fresh ginger. Conclusion: These identified compounds could be used to characterize the quality of dried ginger, pharmacologic studies should focus on diarylheptanoids explaining the different treatment effects between fresh ginger and dried ginger.
The Valence and Spin State Tuning of Iron(II/III) Porphyrazines with Bulky Pyrrolyl Periphery in Solution and Solid State
Authors: Koczorowski Tomasz , Szczolko Wojciech , Bakun Pawel , Wicher Barbara , Sobotta Lukasz , Gdaniec Maria , Teubert Anna , Mielcarek Jadwiga , Tykarska Ewa , Korecki Jozef , Burda Kvetoslava , Goslinski Tomasz
Published: November 2022

Iron(III) porphyrazines containing peripheral 2,5-dimethyl-, 2-methyl-5-phenyl-, and 2,3,5-triphenyl-1H-pyrrol-1-yl substituents were synthesized and subjected to physicochemical characterization. This was accomplished by high-resolution mass spectrometry, nuclear magnetic resonance (as diamagnetic Fe(II) derivatives), HPLC purity analysis, and UV-Vis spectroscopy, accompanied by the solvation study in dichloromethane and pyridine. X-ray structure analysis was performed for a single crystal of the previously obtained 2,5-diphenyl-substituted derivative of porphyrazine complex (5d). The octahedral geometries of iron cation, present in the porphyrazine core, influenced the packing mode of molecules in the crystals. Mössbauer studies, performed for solid samples of iron porphyrazines, indicated that low-spin reduced iron states might occupy low- or high-symmetry binding sites. It was found that the hyperfine parameters and the subsequent contribution of the iron cations depend on the number of phenyl groups surrounding the pyrrolyl moiety. For iron(II) porphyrazine 2,3,5-triphenylpyrrol-1-yl substituents (5b), a high-spin ferrous state fraction was observed. Temperature-dependent measurements showed that the freed rotation of the peripheral porphyrazine ligands and the increased flexibility of the macrocycle ring result in the Fe2+ ion being stabilized in a diamagnetic state at a binding site of high symmetry at room temperature in the solid state. This process is most probably stimulated by the range of collective motions of the polymeric ribbons consisting of iron(II) porphyrazines observed in the X-ray.
Neuroprotective Effect of Ginseng Fibrous Root Enzymatic Hydrolysate against Oxidative Stress
Authors: Zhu Yuhua , Wang Ziyan , Yu Shuxuan , Zhao Chong , Xu Baofeng , Liu Rui , Xu Li , Guo Yi
Published: November 2022

Oxidative stress is one of the potential causes of nervous system disease. Ginseng extract possesses excellent antioxidant activity; however, little research on the function of the ginseng fibrous root. This study aimed to investigate the neuroprotective effects of ginseng fibrous root to alleviate the pathogenesis of Alzheimer’s disease (AD) against oxidative stress. Ginseng fibrous root enzymatic hydrolysate (GFREH) was first prepared by digesting ginseng fibrous roots with alkaline protease. In vitro, the GFREH showed antioxidant activities in free radical scavenging mechanisms. With a cellular model of AD, GFREH inhibited the increase in Ca2+ levels and intracellular ROS content, maintained the balance of mitochondrial membrane potential, and relieved L-glutamic acid-induced neurotoxicity. In vivo, GFREH improved the survival rate of Caenorhabditis elegans (C. elegans) under oxidative stress, upregulated SOD-3 expression, and reduced reactive oxygen species (ROS) content. Therefore, our findings provide evidence for the alleviation effect of GFREH against oxidative stress in neuroprotection, which may accelerate the development of anti-Alzheimer’s drugs and treatments in the future.