bluuebunny/crossref_metadata_2025 huggingface dataset:
New Drimane Sesquiterpenes and Polyketides from Marine-Derived Fungus Penicillium sp. TW58-16 and Their Anti-Inflammatory and α-Glucosidase Inhibitory Effects
Authors: Gou Xiaoshuang , Tian Danmei , Wei Jihua , Ma Yihan , Zhang Yixue , Chen Mei , Ding Wenjuan , Wu Bin , Tang Jinshan
Published: July 2021

Marine fungi-derived natural products represent an excellent reservoir for the discovery of novel lead compounds with biological activities. Here, we report the identification of two new drimane sesquiterpenes (1 and 2) and six new polyketides (3–8), together with 10 known compounds (9–18), from a marine-derived fungus Penicillium sp. TW58-16. The planar structures of these compounds were elucidated by extensive 1D and 2D NMR, which was supported by HR-ESI-MS data. The absolute configurations of these compounds were determined by experimental and calculated electronic circular dichroism (ECD), and their optical rotations compared with those reported. Evaluation of the anti-inflammatory activity of compounds 1–18 revealed that compound 5 significantly inhibited the release of nitric oxide (NO) induced by lipopolysaccharide (LPS) in RAW264.7 cells, correlating with the inhibition of expression of inducible nitric oxide synthase (iNOS). In addition, we revealed that compounds 1, 3–6, 14, 16, and 18 showed strong α-glucosidase inhibitory effects with inhibition rates of 35.4%, 73.2%, 55.6%, 74.4%, 32.0%, 36.9%, 88.0%, and 91.1%, respectively, which were comparable with or even better than that of the positive control, acarbose. Together, our results illustrate the potential of discovering new marine-based therapeutic agents against inflammation and diabetes mellitus.
Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model
Authors: Alsaidi Sahar , Cornejal Nadjet , Mahoney Oneil , Melo Claudia , Verma Neeharika , Bonnaire Thierry , Chang Theresa , O’Keefe Barry R. , Sailer James , Zydowsky Thomas M. , Teleshova Natalia , Romero José A. Fernández
Published: July 2021

Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC50/EC50) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC50 between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC50 between 0.2 and 3.8 µg/mL; combination index <1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2.
Stability of Domoic Acid in 50% Methanol Extracts and Raw Fecal Material from Bowhead Whales (Balaena mysticetus)
Authors: Bowers Emily K. , Stimmelmayr Raphaela , Lefebvre Kathi A.
Published: July 2021

Domoic acid (DA), the toxin causing amnesic shellfish poisoning (ASP), is produced globally by some diatoms in the genus Pseudo-nitzschia. DA has been detected in several marine mammal species in the Alaskan Arctic, raising health concerns for marine mammals and subsistence communities dependent upon them. Gastrointestinal matrices are routinely used to detect Harmful Algal Bloom (HAB) toxin presence in marine mammals, yet DA stability has only been studied extensively in shellfish-related matrices. To address this knowledge gap, we quantified DA in bowhead whale fecal samples at multiple time points for two groups: (1) 50% methanol extracts from feces, and (2) raw feces stored in several conditions. DA concentrations decreased to 70 ± 7.1% of time zero (T0) in the 50% methanol extracts after 2 weeks, but remained steady until the final time point at 5 weeks (66 ± 5.7% T0). In contrast, DA concentrations were stable or increased in raw fecal material after 8 weeks of freezer storage (−20 °C), at room temperature (RT) in the dark, or refrigerated at 1 °C. DA concentrations in raw feces stored in an incubator (37 °C) or at RT in the light decreased to 77 ± 2.8% and 90 ± 15.0% T0 at 8 weeks, respectively. Evaporation during storage of raw fecal material is a likely cause of the increased DA concentrations observed over time with the highest increase to 126 ± 7.6% T0 after 3.2 years of frozen storage. These results provide valuable information for developing appropriate sample storage procedures for marine mammal fecal samples.
Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique
Authors: Mohamed Osama G. , Dorandish Sadaf , Lindow Rebecca , Steltz Megan , Shoukat Ifrah , Shoukat Maira , Chehade Hussein , Baghdadi Sara , McAlister-Raeburn Madelaine , Kamal Asad , Abebe Dawit , Ali Khaled , Ivy Chelsey , Antonova Maria , Schultz Pamela , Angell Michael , Clemans Daniel , Friebe Timothy , Sherman David , Casper Anne M. , Price Paul A. , Tripathi Ashootosh
Published: July 2021

The antibiotic-resistant bacteria-associated infections are a major global healthcare threat. New classes of antimicrobial compounds are urgently needed as the frequency of infections caused by multidrug-resistant microbes continues to rise. Recent metagenomic data have demonstrated that there is still biosynthetic potential encoded in but transcriptionally silent in cultivatable bacterial genomes. However, the culture conditions required to identify and express silent biosynthetic gene clusters that yield natural products with antimicrobial activity are largely unknown. Here, we describe a new antibiotic discovery scheme, dubbed the modified crowded plate technique (mCPT), that utilizes complex microbial interactions to elicit antimicrobial production from otherwise silent biosynthetic gene clusters. Using the mCPT as part of the antibiotic crowdsourcing educational program Tiny EarthTM, we isolated over 1400 antibiotic-producing microbes, including 62 showing activity against multidrug-resistant pathogens. The natural product extracts generated from six microbial isolates showed potent activity against vancomycin-intermediate resistant Staphylococcus aureus. We utilized a targeted approach that coupled mass spectrometry data with bioactivity, yielding a new macrolactone class of metabolite, desertomycin H. In this study, we successfully demonstrate a concept that significantly increased our ability to quickly and efficiently identify microbes capable of the silent antibiotic production.
Clad Metals: Fabrication, Properties, and Applications
Authors: Cho Young-Rae
Published: July 2021

Studying clad metals has been an active field of research in the last few decades [...]
Experimental Investigation on Tensile Properties and Yield Strength Modeling of T5 Heat-Treated Counter Pressure Cast A356 Aluminum Alloys
Authors: Kim Sang-Won , Lee Seok-Jae , Kim Dae-Up , Kim Min-Su
Published: July 2021

In the present study, experimental investigations on microstructures and tensile properties of an counter-pressure cast (CPC) A356 aluminum alloy under different T5 heat treatment conditions were conducted in the temperature range of 160–200 ∘C for 1–48 h. As the T5 heat treatment time increased, both tensile and yield strength of the CPC A356 alloy either continuously increased at 160 ∘C until 48 h of heat treatment time or increased until the maximum strength values were achieved and then decreased, showing peak aging behavior at 180 and 200 ∘C. Changes in microstructural aspects, such as size and aspect ratio, of the eutectic Si, Mg and Si distribution in the α-Al grain and the stability of intermetallic compounds were found to be negligible during the T5 heat treatments employed in the present study. From high resolution-transmission electron microscope (HR-TEM) analysis, nanosized needle-like β″ precipitates were identified in the specimens, showing a significant increase in strength after the T5 heat treatment. Based on the measured tensile properties and observed microstructure changes, a yield strength model was proposed to predict yield strengths of CPC A356 alloys at arbitrary T5 heat treatment conditions. The calculation results of the model showed good agreement with the experimental data obtained in the present study. From the model calculations, the optimal T5 heat treatment time or temperature conditions were suggested.
Ultrasonic Metal Welding of Multilayered Copper Foils to Nickel-Plated Copper Sheet in Lithium-Ion Battery Cell
Authors: Shin Seungmin , Nam Sangwoo , Yu Jiyoung , Park Jiyong , Kim Dongcheol
Published: July 2021

The battery performance of electric vehicles depends on the density and capacity of the battery; thus, the battery cells must be assembled in as many layers as possible. Electric vehicle batteries are typically composed of several cells which form modules connected by busbars, with dozens of modules manufactured as battery packs. The ultrasonic metal welding (UMW) technology is applied to such multilayered foil welding. This study analyzed UMW to ensure the weldability of multilayered Cu foils and a Ni-plated Cu strip in lithium-ion battery cells through various approaches. In UMW, the effect of the alignment on weld production and quality were examined through the energy and mechanical performance of the weld by conducting comparative experiments on the alignment of the horn and anvil. Additionally, the effects of UMW process parameters, such as the welding pressure, amplitude, and welding time, were statistically analyzed. The weldability evaluation and characteristic analysis were performed based on these variables. Furthermore, the cross-sectional shapes and microstructure behavior of the Ni layers were analyzed based on the weld quality.
Design of a Hybrid Inertial and Magnetophoretic Microfluidic Device for CTCs Separation from Blood
Authors: Nasiri Rohollah , Shamloo Amir , Akbari Javad
Published: July 2021

Circulating tumor cells (CTCs) isolation from a blood sample plays an important role in cancer diagnosis and treatment. Microfluidics offers a great potential for cancer cell separation from the blood. Among the microfluidic-based methods for CTC separation, the inertial method as a passive method and magnetic method as an active method are two efficient well-established methods. Here, we investigated the combination of these two methods to separate CTCs from a blood sample in a single chip. Firstly, numerical simulations were performed to analyze the fluid flow within the proposed channel, and the particle trajectories within the inertial cell separation unit were investigated to determine/predict the particle trajectories within the inertial channel in the presence of fluid dynamic forces. Then, the designed device was fabricated using the soft-lithography technique. Later, the CTCs were conjugated with magnetic nanoparticles and Ep-CAM antibodies to improve the magnetic susceptibility of the cells in the presence of a magnetic field by using neodymium permanent magnets of 0.51 T. A diluted blood sample containing nanoparticle-conjugated CTCs was injected into the device at different flow rates to analyze its performance. It was found that the flow rate of 1000 µL/min resulted in the highest recovery rate and purity of ~95% and ~93% for CTCs, respectively.
Modified Hexagonal Split Ring Resonator Based on an Epsilon-Negative Metamaterial for Triple-Band Satellite Communication
Authors: Afsar Salah Uddin , Faruque Mohammad Rashed Iqbal , Hossain Mohammad Jakir , Khandaker Mayeen Uddin , Osman Hamid , Alamri Sultan
Published: July 2021

A triple-band epsilon-negative (ENG) metamaterial based on a split ring resonator (SSR) with a modified hexagonal-shaped metal strip proposed in this study is a new combination of a single slit square resonator and a modified hexagonal-shaped metal strip. The desired unit cell FR-4 (lossy) that was selected as the substrate was 1.6 mm thick. Following the assessment of the unit cell, a high-frequency electromagnetic simulator like the computer simulation technology (CST) microwave studio was applied to assess the S-parameters. The proposed design exhibited resonance at 2.89, 9.42, and 15.16 GHz. The unit cell also demonstrated negative permittivity in the frequency ranges 2.912–3.728 GHz, 9.552–10.144 GHz, and 15.216–17.328 GHz, along with a negative refractive index. An effective medium ratio (EMR) of 11.53 is an indicator of the goodness of the metamaterial unit cell. It is deliberate at the lowermost resonance frequency of 2.89 GHz. Moreover, the simulated results that were validated using HFSS and equivalent circuit model indicated slight variations. The proposed design was finalised based on several parametric studies, including design optimisation, different unit cell sizes, various substrate materials, and different electromagnetic (EM) field propagations. The proposed triple band (S, X, and Ku bands) negative permittivity metamaterial unit cell can be utilised for various wireless applications, such as microwave communication, satellite communication, and long-distance radio communication.
SMILE Platform: An Innovative Microfluidic Approach for On-Chip Sample Manipulation and Analysis in Oral Cancer Diagnosis
Authors: Zoupanou Sofia , Volpe Annalisa , Primiceri Elisabetta , Gaudiuso Caterina , Ancona Antonio , Ferrara Francesco , Chiriacò Maria Serena
Published: July 2021

Oral cancer belongs to the group of head and neck cancers, and, despite its large diffusion, it suffers from low consideration in terms of prevention and early diagnosis. The main objective of the SMILE platform is the development of a low-cost device for oral cancer early screening with features of high sensitivity, specificity, and ease of use, with the aim of reaching a large audience of possible users and realizing real prevention of the disease. To achieve this goal, we realized two microfluidic devices exploiting low-cost materials and processes. They can be used in combination or alone to obtain on-chip sample preparation and/or detection of circulating tumor cells, selected as biomarkers of oral cancer. The realized devices are completely transparent with plug-and-play features, obtained thanks to a highly customized architecture which enables users to easily use them, with potential for a common use among physicians or dentists with minimal training.
Characterization of Demolished Concretes with Three Different Strengths for Recycling as Coarse Aggregate
Authors: Hoffmann Sampaio Carlos , Cazacliu Bogdan , Ambrós Weslei , Kronbauer Márcio , Tubino Rejane , Dal Molin Denise , Oliva Moncunill Josep , Miltzarek Gérson , Waskow Regis , dos Santos Viviane , Silva Luis
Published: July 2021

This paper presents a physical characterization for the recycling into new concretes of three comminuted concretes: C16/20 (“ordinary concrete”), C50/60 (“high strength concrete”), and C70/85 (“very high strength concrete”). The top size of the crushed concretes was 19.1 mm and the size range was 4.75 to 19.1 mm. The characterization was carried out with coarse aggregate liberation, to be prepared and concentrated in a gravity concentration process. The density distribution of the coarse aggregate, cement paste, and sand was carried out in different size ranges (4.75/19.1 mm; 4.75/8.0 mm; 8.0/12.5 mm; and 12.5/19.1 mm) for the three concretes studied. The form factor of the samples, as well as the porosity determination of particles in different density ranges, are presented. The obtained results indicate that the coarse aggregate liberation was more intensive for the low resistance concrete (C16/20), but a reasonable coarse aggregate recovery is possible for all concretes.
Kaolinite-to-Chlorite Conversion from Si,Al-Rich Fluid-Origin Veins/Fe-Rich Carboniferous Shale Interaction
Authors: Bourdelle Franck , Dubois Michel , Lloret Emily , Durand Cyril , Addad Ahmed , Bounoua Schéhérazade , Ventalon Sandra , Recourt Philippe
Published: July 2021

The kaolinite-to-chlorite conversion is one of the chloritization processes that occurs in low temperature diagenetic and hydrothermal systems. The mechanism of this mineralogical transformation is still under discussion, since direct transformation, conversion via berthierine as intermediate phase or direct formation of berthierine/chlorite mix, either by dissolution-crystallization or by solid state transformation (or a combination of both), are all hypotheses put forward. In this context, each description of a kaolinite-to-chlorite conversion occurrence becomes an opportunity to shed new light and to renew this debate. Studying Carboniferous shale–crosscut by large quartz-kaolinite veins–from the mining basin of the North of France, we report therefore an uncommon kaolinite-Fe-rich chlorite assemblage. This assemblage appears as a chlorite fringe 20 µm wide along the interfaces between the shale and the quartz-kaolinite veins. All petrographical, mineralogical and chemical data suggest that the Fe-chlorite results from the interaction between the shale, providing the Fe,Mg supply, and the Si,Al-rich veins, leading to the chloritization of the kaolinite at a small scale via at least one dissolution-recrystallisation step. High-resolution observations highlight that neoformed Fe-rich chlorite contains some 7Å isochemical layers, as relict of berthierine. Therefore, we advance that the conversion takes place either through the precipitation of berthierine following by a second step involving solid state berthierine-chlorite conversion, or through the direct precipitation of a chlorite-rich/berthierine-poor mix driven by the Fe/(Fe + Mg) ratio, at low temperature and in reducing conditions. The comparison of our data with the recent literature allows to prefer the second hypothesis.
Cyclin-Dependent Kinase 4 and 6 Inhibitors in Cell Cycle Dysregulation for Breast Cancer Treatment
Authors: Susanti Ni Made Pitri , Tjahjono Daryono Hadi
Published: July 2021

In cell development, the cell cycle is crucial, and the cycle progression’s main controllers are endogenous CDK inhibitors, cyclin-dependent kinases (CDKs), and cyclins. In response to the mitogenic signal, cyclin D is produced and retinoblastoma protein (Rb) is phosphorylated due to activated CDK4/CDK6. This causes various proteins required in the cell cycle progression to be generated. In addition, complexes of CDK1-cyclin A/B, CDK2-cyclin E/A, and CDK4/CDK6-cyclin D are required in each phase of this progression. Cell cycle dysregulation has the ability to lead to cancer. Based on its role in the cell cycle, CDK has become a natural target of anticancer therapy. Therefore, understanding the CDK structures and the complex formed with the drug, helps to foster the development of CDK inhibitors. This development starts from non-selective CDK inhibitors to selective CDK4/CDK6 inhibitors, and these have been applied in clinical cancer treatment. However, these inhibitors currently require further development for various hematologic malignancies and solid tumors, based on the results demonstrated. In drug development, the main strategy is primarily to prevent and asphyxiate drug resistance, thus a determination of specific biomarkers is required to increase the therapy’s effectiveness as well as patient selection suitability in order to avoid therapy failure. This review is expected to serve as a reference for early and advanced-stage researchers in designing new molecules or repurposing existing molecules as CDK4/CDK6 inhibitors to treat breast cancer.
Antioxidant and Antisteatotic Activities of Fucoidan Fractions from Marine and Terrestrial Sources
Authors: El Rashed Zeinab , Lupidi Giulio , Grasselli Elena , Canesi Laura , Khalifeh Hala , Demori Ilaria
Published: July 2021

Fucoidan is a fucose-rich sulfated polysaccharide typically found in the cell wall of marine algae but also recently isolated from terrestrial sources. Due to a variety of biological activities, including antioxidant properties, fucoidan exhibits an attractive therapeutic potential against a wide array of metabolic diseases associated with oxidative stress. We used FTIR, 1H NMR and 13C NMR spectroscopy to investigate the structural features of a fucoidan fraction extracted from the brown alga Cystoseira compressa (CYS). The antioxidant potential of CYS was measured by DPPH, ABTS and FRAP assays, which revealed a radical scavenging capacity that was confirmed in in vitro cellular models of hepatic and endothelial cells. The same antioxidant effects were observed for another fucoidan fraction previously identified in the terrestrial tree Eucalyptus globulus (EUC). Moreover, in hepatic cells, CYS and EUC exhibited a significant antisteatotic action, being able to reduce intracellular triglyceride content through the regulation of key genes of hepatic lipid metabolism. EUC exerted stronger antioxidant and antisteatotic effects as compared to CYS, suggesting that both marine and terrestrial sources should be considered for fucoidan extraction and therapeutic applications.
Bioactive Components, Volatile Profile and In Vitro Antioxidative Properties of Taxus baccata L. Red Arils
Authors: Tabaszewska Małgorzata , Antoniewska Agata , Rutkowska Jaroslawa , Skoczylas Łukasz , Słupski Jacek , Skoczeń-Słupska Radosława
Published: July 2021

This study aimed at assessing the composition of bioactive compounds, including ascorbic acid, carotenoids and polyphenols, the volatile compound profile and the antioxidant activity of red arils (RAs) of Taxus baccata L. grown in diverse locations in Poland. Among the carotenoids assayed in high quantities (3.3–5.42 μg/g), the lycopene content (2.55–4.1 μg/g) was remarkably higher than that in many cultivated fruits. Samples collected from three sites were distinguished by higher amounts of ascorbic acid (125 mg/100 g, on average) than those found in many cultivated berries. Phenylpropanoids quantitatively dominated among the four groups of phenolic compounds. Chromatographic separation enabled the detection of two phenylpropanoid acids: ferulic and p-coumaric. Irrespectively of the growth site, RAs contained substantial amounts of (-)-epicatechin (1080 μg/100 g, on average). A higher ability to scavenge DPPH● and ABTS●+ radicals was found in the hydrophilic fraction of RAs from two sites (Warsaw and Koszalin) compared with the other two sites. The volatile compound profile of RAs was dominated by alcohols, followed by ketones, esters and aldehydes. The presence of some volatiles was exclusively related to the specific growth site, which may be regarded as a valuable indicator. The combination of bioactive and volatile compounds and the fairly good antioxidant potential of RAs render them an attractive source for preparing functional foods.
Prediction of Molecular Properties Using Molecular Topographic Map
Authors: Yoshimori Atsushi
Published: July 2021

Prediction of molecular properties plays a critical role towards rational drug design. In this study, the Molecular Topographic Map (MTM) is proposed, which is a two-dimensional (2D) map that can be used to represent a molecule. An MTM is generated from the atomic features set of a molecule using generative topographic mapping and is then used as input data for analyzing structure-property/activity relationships. In the visualization and classification of 20 amino acids, differences of the amino acids can be visually confirmed from and revealed by hierarchical clustering with a similarity matrix of their MTMs. The prediction of molecular properties was performed on the basis of convolutional neural networks using MTMs as input data. The performance of the predictive models using MTM was found to be equal to or better than that using Morgan fingerprint or MACCS keys. Furthermore, data augmentation of MTMs using mixup has improved the prediction performance. Since molecules converted to MTMs can be treated like 2D images, they can be easily used with existing neural networks for image recognition and related technologies. MTM can be effectively utilized to predict molecular properties of small molecules to aid drug discovery research.
Chemical Derivatization and Characterization of Novel Antitrypanosomals for African Trypanosomiasis
Authors: Dofuor Aboagye Kwarteng , Ademolue Temitayo Samson , Amisigo Cynthia Mmalebna , Kyeremeh Kwaku , Gwira Theresa Manful
Published: July 2021

The search for novel antitrypanosomals and the investigation into their mode of action remain crucial due to the toxicity and resistance of commercially available antitrypanosomal drugs. In this study, two novel antitrypanosomals, tortodofuordioxamide (compound 2) and tortodofuorpyramide (compound 3), were chemically derived from the natural N-alkylamide tortozanthoxylamide (compound 1) through structural modification. The chemical structures of these compounds were confirmed through spectrometric and spectroscopic analysis, and their in vitro efficacy and possible mechanisms of action were, subsequently, investigated in Trypanosoma brucei (T. brucei), one of the causative species of African trypanosomiasis (AT). The novel compounds 2 and 3 displayed significant antitrypanosomal potencies in terms of half-maximal effective concentrations (EC50) and selectivity indices (SI) (compound 1, EC50 = 7.3 μM, SI = 29.5; compound 2, EC50 = 3.2 μM, SI = 91.3; compound 3, EC50 = 4.5 μM, SI = 69.9). Microscopic analysis indicated that at the EC50 values, the compounds resulted in the coiling and clumping of parasite subpopulations without significantly affecting the normal ratio of nuclei to kinetoplasts. In contrast to the animal antitrypanosomal drug diminazene, compounds 1, 2 and 3 exhibited antioxidant absorbance properties comparable to the standard antioxidant Trolox (Trolox, 0.11 A; diminazene, 0.50 A; compound 1, 0.10 A; compound 2, 0.09 A; compound 3, 0.11 A). The analysis of growth kinetics suggested that the compounds exhibited a relatively gradual but consistent growth inhibition of T. brucei at different concentrations. The results suggest that further pharmacological optimization of compounds 2 and 3 may facilitate their development into novel AT chemotherapy.
Natural Products and Skin Diseases
Authors: Majtan Juraj , Bucekova Marcela , Jesenak Milos
Published: July 2021

The skin is the largest multifunctional organ in the human body, serving as an excellent barrier against chemical and biological hazards [...]
Protein and Polysaccharide-Based Electroactive and Conductive Materials for Biomedical Applications
Authors: Hu Xiao , Ricci Samuel , Naranjo Sebastian , Hill Zachary , Gawason Peter
Published: July 2021

Electrically responsive biomaterials are an important and emerging technology in the fields of biomedical and material sciences. A great deal of research explores the integral role of electrical conduction in normal and diseased cell biology, and material scientists are focusing an even greater amount of attention on natural and hybrid materials as sources of biomaterials which can mimic the properties of cells. This review establishes a summary of those efforts for the latter group, detailing the current materials, theories, methods, and applications of electrically conductive biomaterials fabricated from protein polymers and polysaccharides. These materials can be used to improve human life through novel drug delivery, tissue regeneration, and biosensing technologies. The immediate goal of this review is to establish fabrication methods for protein and polysaccharide-based materials that are biocompatible and feature modular electrical properties. Ideally, these materials will be inexpensive to make with salable production strategies, in addition to being both renewable and biocompatible.
Towards a Bioactive Food Packaging: Poly(Lactic Acid) Surface Functionalized by Chitosan Coating Embedding Clove and Argan Oils
Authors: Stoleru Elena , Vasile Cornelia , Irimia Anamaria , Brebu Mihai
Published: July 2021

Here we introduce a new method aiming the immobilization of bioactive principles onto polymeric substrates, combining a surface activation and emulsion entrapment approach. Natural products with antimicrobial/antioxidant properties (essential oil from Syzygium aromaticum—clove and vegetal oil from Argania spinosa L—argan) were stabilized in emulsions with chitosan, a natural biodegradable polymer that has antimicrobial activity. The emulsions were laid on poly(lactic acid) (PLA), a synthetic biodegradable plastic from renewable resources, which was previously activated by plasma treatment. Bioactive materials were obtained, with low permeability for oxygen, high radical scavenging activity and strong inhibition of growth for Listeria monocytogenes, Salmonella Typhimurium and Escherichia coli bacteria. Clove oil was better dispersed in a more stable emulsion (no separation after six months) compared with argan oil. This leads to a compact and finely structured coating, with better overall properties. While both clove and argan oils are highly hydrophobic, the coatings showed increased hydrophilicity, especially for argan, due to preferential interactions with different functional groups in chitosan. The PLA films coated with oil-loaded chitosan showed promising results in retarding the food spoilage of meat, and especially cheese. Argan, and in particular, clove oil offered good UV protection, suitable for sterilization purposes. Therefore, using the emulsion stabilization of bioactive principles and immobilization onto plasma activated polymeric surfaces we obtained a bioactive material that combines the physical properties and the biodegradability of PLA with the antibacterial activity of chitosan and the antioxidant function of vegetal oils. This prevents microbial growth and food oxidation and could open new perspectives in the field of food packaging materials.
Corneal Healing and Recovery of Ocular Crystallinity with a Dichloromethane Extract of Sedum dendroideum D.C. in a Novel Murine Model of Ocular Pterygium
Authors: Torrescano-De Labra Luiselva , Jiménez-Ferrer Enrique , Camacho-Díaz Brenda Hildeliza , Vargas-Villa Gabriela , González-Cortazar Manases , Herrera-Ruiz Maribel , Ávila Reyes Sandra Victoria , Solorza-Feria Javier , Jiménez-Aparicio Antonio Ruperto
Published: July 2021

Pterygium is a corneal alteration that can cause visual impairment, which has been traditionally treated with the sap of Sedum dendroideum D.C. The pharmacological effect of a dichloromethane extract of S. dendroideum was demonstrated and implemented in a pterygium model on the healing process of corneal damage caused by phorbol esters. In mice of the ICR strain, a corneal lesion was caused by intravitreal injection of tetradecanoylphorbol acetate (TPA). The evolution of the corneal scarring process was monitored with vehicle, dexamethasone, and dichloromethane extract of S. dendroideum treatments by daily ophthalmic administration for fifteen days. The lesions were evaluated in situ with highlighted images of fluorescence of the lesions. Following treatment levels in eyeballs of IL-1α, TNF-α, and IL-10 cytokines were measured. The effective dose of TPA to produce a pterygium-like lesion was determined. The follow-up of the evolution of the scarring process allowed us to define that the treatment with S. dendroideum improved the experimental pterygium and had an immunomodulatory effect by decreasing TNF-α, IL-1α, and maintaining the level of IL-10 expression, without difference with respect to the healthy control. Traditional medical use of S. dendroideum sap to treat pterygium is fully justified by its compound composition.
Determination of Triterpenoids and Phenolic Acids from Sanguisorba officinalis L. by HPLC-ELSD and Its Application
Authors: Sun Jiahui , Gan Chunli , Huang Jing , Wang Zhenyue , Wu Chengcui , Jiang Shuang , Yang Xinrong , Peng Hesong , Wei Fanshu , Yang Chunjuan
Published: July 2021

A novel analytical method involving high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) was developed for simultaneous determination of 11 phenolic acids and 12 triterpenes in Sanguisorba officinalis L. Chromatographic separation was conducted with gradient elution mode by using a DiamonsilTM C18 column (250 mm × 4.6 mm, 5 μm) with the mobile phase of 0.1% acetic acid water (A) and methanol (B). The drift tube temperature of ELSD was set at 70 °C and the nitrogen cumulative flow rate was 1.6 L/min. The method was fully validated to be linear over a wide concentration range (R2 ≥ 0.9991). The precisions (RSD) were less than 3.0% and the recoveries were between 97.7% and 101.4% for all compounds. The results indicated that this method is accurate and effective for the determination of 23 functional components in Sanguisorba officinalis L. and could also be successfully applied to study the influence of processing method on those functional components in Sanguisorba officinalis L.
Preclinical Bioavailability, Tissue Distribution, and Protein Binding Studies of Erinacine A, a Bioactive Compound from Hericium erinaceus Mycelia Using Validated LC-MS/MS Method
Authors: Tsai Pei-Ching , Wu Yi-Kai , Hu Jun-Hao , Li I-Chen , Lin Ting-Wei , Chen Chin-Chu , Kuo Chia-Feng
Published: July 2021

Erinacine A, derived from the mycelia of Hericium erinaceus, has attracted much attention due to its neuroprotective properties. However, very few studies have been conducted on the bioavailability, tissue distribution, and protein binding of erinacine A. This study aimed to investigate the bioavailability, tissue distribution, and protein binding of erinacine A in Sprague-Dawley rats. After oral administration (po) and intravenous administration (iv) of 2.381 g/kg BW of the H. erinaceus mycelia extract (equivalent to 50 mg/kg BW of erinacine A) and 5 mg/kg BW of erinacine A, respectively, the absolute bioavailability of erinacine A was estimated as 24.39%. Erinacine A was detected in brain at 1 h after oral dosing and reached the peak at 8 h. Protein binding assay showed unbound erinacine A fractions in brain to blood ratio is close to unity, supporting passive diffusion as the dominating transport. Feces was the major route for the elimination of erinacine A. This study is the first to show that erinacine A can penetrate the blood-brain barrier of rats by the means of passive diffusion and thus support the development of H. erinaceus mycelia for the improvement of neurohealth.
Metabolic Engineering of Microbial Cell Factories for Biosynthesis of Flavonoids: A Review
Authors: Lou Hanghang , Hu Lifei , Lu Hongyun , Wei Tianyu , Chen Qihe
Published: July 2021

Flavonoids belong to a class of plant secondary metabolites that have a polyphenol structure. Flavonoids show extensive biological activity, such as antioxidative, anti-inflammatory, anti-mutagenic, anti-cancer, and antibacterial properties, so they are widely used in the food, pharmaceutical, and nutraceutical industries. However, traditional sources of flavonoids are no longer sufficient to meet current demands. In recent years, with the clarification of the biosynthetic pathway of flavonoids and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce flavonoids. This article mainly reviews the biosynthetic pathways of flavonoids and the development of microbial expression systems for the production of flavonoids in order to provide a useful reference for further research on synthetic metabolic engineering of flavonoids. Meanwhile, the application of co-culture systems in the biosynthesis of flavonoids is emphasized in this review.
Neuroprotective Potential of Limonene and Limonene Containing Natural Products
Authors: Eddin Lujain Bader , Jha Niraj Kumar , Meeran M. F. Nagoor , Kesari Kavindra Kumar , Beiram Rami , Ojha Shreesh
Published: July 2021

Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternative or complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.
Interstrain Variability of Human Vaginal Lactobacillus crispatus for Metabolism of Biogenic Amines and Antimicrobial Activity against Urogenital Pathogens
Authors: Puebla-Barragan Scarlett , Watson Emiley , van der Veer Charlotte , Chmiel John A. , Carr Charles , Burton Jeremy P. , Sumarah Mark , Kort Remco , Reid Gregor
Published: July 2021

Lactobacillus crispatus is the dominant species in the vagina of many women. With the potential for strains of this species to be used as a probiotic to help prevent and treat dysbiosis, we investigated isolates from vaginal swabs with Lactobacillus-dominated and a dysbiotic microbiota. A comparative genome analysis led to the identification of metabolic pathways for synthesis and degradation of three major biogenic amines in most strains. However, targeted metabolomic analysis of the production and degradation of biogenic amines showed that certain strains have either the ability to produce or to degrade these compounds. Notably, six strains produced cadaverine, one produced putrescine, and two produced tyramine. These biogenic amines are known to raise vaginal pH, cause malodour, and make the environment more favourable to vaginal pathogens. In vitro experiments confirmed that strains isolated from women with a dysbiotic vaginal microbiota have higher antimicrobial effects against the common urogenital pathogens Escherichia coli and Enterococcus faecium. The results indicate that not all L. crispatus vaginal strains appear suitable for probiotic application and the basis for selection should not be only the overall composition of the vaginal microbiota of the host from which they came, but specific biochemical and genetic traits.
Study of the Molecule Adsorption Process during the Molecular Doping
Authors: Pizzone Mattia , Grimaldi Maria Grazia , La Magna Antonino , Rahmani Neda , Scalese Silvia , Adam Jost , Puglisi Rosaria A.
Published: July 2021

Molecular Doping (MD) involves the deposition of molecules, containing the dopant atoms and dissolved in liquid solutions, over the surface of a semiconductor before the drive-in step. The control on the characteristics of the final doped samples resides on the in-depth study of the molecule behaviour once deposited. It is already known that the molecules form a self-assembled monolayer over the surface of the sample, but little is known about the role and behaviour of possible multiple layers that could be deposited on it after extended deposition times. In this work, we investigate the molecular surface coverage over time of diethyl-propyl phosphonate on silicon, by employing high-resolution morphological and electrical characterization, and examine the effects of the post-deposition surface treatments on it. We present these data together with density functional theory simulations of the molecules–substrate system and electrical measurements of the doped samples. The results allow us to recognise a difference in the bonding types involved in the formation of the molecular layers and how these influence the final doping profile of the samples. This will improve the control on the electrical properties of MD-based devices, allowing for a finer tuning of their performance.
Identification of Tomato Infecting Viruses That Co-Isolate with Nanovesicles Using a Combined Proteomics and Electron-Microscopic Approach
Authors: Mammadova Ramila , Fiume Immacolata , Bokka Ramesh , Kralj-Iglič Veronika , Božič Darja , Kisovec Matic , Podobnik Marjetka , Zavec Apolonija Bedina , Hočevar Matej , Gellén Gabriella , Schlosser Gitta , Pocsfalvi Gabriella
Published: July 2021

Plant-derived nanovesicles (NVs) have attracted interest due to their anti-inflammatory, anticancer and antioxidative properties and their efficient uptake by human intestinal epithelial cells. Previously we showed that tomato (Solanum lycopersicum L.) fruit is one of the interesting plant resources from which NVs can be obtained at a high yield. In the course of the isolation of NVs from different batches of tomatoes, using the established differential ultracentrifugation or size-exclusion chromatography methods, we occasionally observed the co-isolation of viral particles. Density gradient ultracentrifugation (gUC), using sucrose or iodixanol gradient materials, turned out to be efficient in the separation of NVs from the viral particles. We applied cryogenic transmission electron microscopy (cryo-TEM), scanning electron microscopy (SEM) for the morphological assessment and LC–MS/MS-based proteomics for the protein identification of the gradient fractions. Cryo-TEM showed that a low-density gUC fraction was enriched in membrane-enclosed NVs, while the high-density fractions were rich in rod-shaped objects. Mass spectrometry–based proteomic analysis identified capsid proteins of tomato brown rugose fruit virus, tomato mosaic virus and tomato mottle mosaic virus. In another batch of tomatoes, we isolated tomato spotted wilt virus, potato virus Y and southern tomato virus in the vesicle sample. Our results show the frequent co-isolation of plant viruses with NVs and the utility of the combination of cryo-TEM, SEM and proteomics in the detection of possible viral contamination.
Electronic and Magnetic Properties of Building Blocks of Mn and Fe Atomic Chains on Nb(110)
Authors: Lászlóffy András , Palotás Krisztián , Rózsa Levente , Szunyogh László
Published: July 2021

We present results for the electronic and magnetic structure of Mn and Fe clusters on Nb(110) surface, focusing on building blocks of atomic chains as possible realizations of topological superconductivity. The magnetic ground states of the atomic dimers and most of the monatomic chains are determined by the nearest-neighbor isotropic interaction. To gain physical insight, the dependence on the crystallographic direction as well as on the atomic coordination number is analyzed via an orbital decomposition of this isotropic interaction based on the spin-cluster expansion and the difference in the local density of states between ferromagnetic and antiferromagnetic configurations. A spin-spiral ground state is obtained for Fe chains along the [11¯0] direction as a consequence of the frustration of the isotropic interactions. Here, a flat spin-spiral dispersion relation is identified, which can stabilize spin spirals with various wave vectors together with the magnetic anisotropy. This may lead to the observation of spin spirals of different wave vectors and chiralities in longer chains instead of a unique ground state.
Endometriosis and Phytoestrogens: Friends or Foes? A Systematic Review
Authors: Bartiromo Ludovica , Schimberni Matteo , Villanacci Roberta , Ottolina Jessica , Dolci Carolina , Salmeri Noemi , Viganò Paola , Candiani Massimo
Published: July 2021

The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.
Acetylcholine and Royal Jelly Fatty Acid Combinations as Potential Dry Eye Treatment Components in Mice
Authors: Yamaga Masayuki , Imada Toshihiro , Tani Hiroko , Nakamura Shigeru , Yamaki Ayanori , Tsubota Kazuo
Published: July 2021

Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Our previous studies have shown that royal jelly (RJ) has restored the capacity for tear secretion by modulating muscarinic calcium signaling. RJ contains acetylcholine, which is a major cholinergic neurotransmitter, and a unique set of fatty acids with C 8 to 12 chains, which are expected to be associated with health benefits. The purpose of the present study was to investigate the active components involved in tear secretion capacity, focusing on acetylcholine and fatty acids in RJ. Using the stress-induced dry-eye model mice, it was confirmed that acetylcholine with three fatty acids (10-hydroxydecanoic acid, 8-hydroxyoctanoic acid, and (R)-3,10-dihydroxydecanoic acid) was essential for tear secretion. In ex vivo Ca2+ imaging, these three fatty acids suppressed the decrease in intracellular modulation of Ca2+ in the lacrimal gland by acetylcholine when treated with acetylcholinesterase, indicating that the specific type of RJ fatty acids contributed to the stability of acetylcholine. To our knowledge, this study is the first to confirm that a specific compound combination is important for the pharmacological activities of RJ. Our results elucidate the active molecules and efficacy mechanisms of RJ.