bluuebunny/crossref_metadata_2025 huggingface dataset:
The Constitutionality of Providing Public Funds for U.S. Houses of Worship during the Coronavirus
Authors: Chopko Mark
Published: January 2021

U.S. constitutional jurisprudence precludes the direct government funding of religious activity. At the same time, the jurisprudence surrounding the U.S. First Amendment Religion Clauses has evolved to support the general inclusion of religious entities in programs through which a government advances some overarching public interest, such as health care or social services, but does not involve the Government in advancing religion per se. Moreover, the most recent U.S. Supreme Court cases hold that it is a violation of the First Amendment to exclude a religious actor, solely because it is religious, from a general public program and funding on equal terms with secular actors. Pandemic relief from the federal government has been made available to houses of worship (churches, mosques, synagogues, etc.) to mitigate the economic impact of government lockdown orders and public health restrictions on assembly, by offsetting loss of revenue and avoiding the suspension or termination of employees. The extension of such relief sits precisely at the crossroads of debated legal questions about whether such assistance is aid to religion—prohibited—or neutral disaster relief on equal terms with other community-serving entities—permitted. This article concludes that the inclusion of houses of worship is constitutional, given the trend and direction of U.S. law, although the matter will continue to be debated as the effects of the pandemic recede.
Resistance Training in Hypoxia as a New Therapeutic Modality for Sarcopenia—A Narrative Review
Authors: Jung Won-Sang , Kim Sung-Woo , Kim Jeong-Weon , Park Hun-Young
Published: January 2021

Hypoxic training is believed to be generally useful for improving exercise performance in various athletes. Nowadays, exercise intervention in hypoxia is recognized as a new therapeutic modality for health promotion and disease prevention or treatment based on the lower mortality and prevalence of people living in high-altitude environments than those living in low-altitude environments. Recently, resistance training in hypoxia (RTH), a new therapeutic modality combining hypoxia and resistance exercise, has been attempted to improve muscle hypertrophy and muscle function. RTH is known to induce greater muscle size, lean mass, increased muscle strength and endurance, bodily function, and angiogenesis of skeletal muscles than traditional resistance exercise. Therefore, we examined previous studies to understand the clinical and physiological aspects of sarcopenia and RTH for muscular function and hypertrophy. However, few investigations have examined the combined effects of hypoxic stress and resistance exercise, and as such, it is difficult to make recommendations for implementing universal RTH programs for sarcopenia based on current understanding. It should also be acknowledged that a number of mechanisms proposed to facilitate the augmented response to RTH remain poorly understood, particularly the role of metabolic, hormonal, and intracellular signaling pathways. Further RTH intervention studies considering various exercise parameters (e.g., load, recovery time between sets, hypoxic dose, and intervention period) are strongly recommended to reinforce knowledge about the adaptational processes and the effects of this type of resistance training for sarcopenia in older people.
Tetraedron minimum, First Reported Member of Hydrodictyaceae to Accumulate Secondary Carotenoids
Authors: Doppler Philipp , Kornpointner Christoph , Halbwirth Heidi , Remias Daniel , Spadiut Oliver
Published: January 2021

We isolated a novel strain of the microalga Tetraedron minimum in Iceland from a terrestrial habitat. During long-term cultivation, a dish culture turned orange, indicating the presence of secondary pigments. Thus, we characterized T. minimum for growth and possible carotenoid production in different inorganic media. In a lab-scale photobioreactor, we confirmed that nitrogen starvation in combination with salt stress triggered a secondary carotenoid accumulation. The development of the pigment composition and the antioxidant capacity of the extracts was analyzed throughout the cultivations. The final secondary carotenoid composition was, on average, 61.1% astaxanthin and 38.9% adonixanthin. Moreover, the cells accumulated approx. 83.1% unsaturated fatty acids. This work presents the first report of the formation of secondary carotenoids within the family Hydrodictyaceae (Sphaeropleales, Chlorophyta).
Experimental and Numerical Investigation on the Perforation Resistance of Double-Layered Metal Shield under High-Velocity Impact of Armor-Piercing Projectiles
Authors: Scazzosi Riccardo , Giglio Marco , Manes Andrea
Published: January 2021

In the case of protection of transportation systems, the optimization of the shield is of practical interest to reduce the weight of such components and thus increase the payload or reduce the fuel consumption. As far as metal shields are concerned, some investigations based on numerical simulations showed that a multi-layered configuration made of layers of different metals could be a promising solution to reduce the weight of the shield. However, only a few experimental studies on this subject are available. The aim of this study is therefore to discuss whether or not a monolithic shield can be substituted by a double-layered configuration manufactured from two different metals and if such a configuration can guarantee the same perforation resistance at a lower weight. In order to answer this question, the performance of a ballistic shield constituted of a layer of high-strength steel and a layer of an aluminum alloy impacted by an armor piercing projectile was investigated in experimental tests. Furthermore, an axisymmetric finite element model was developed. The effect of the strain rate hardening parameter C and the thermal softening parameter m of the Johnson–Cook constitutive model was investigated. The numerical model was used to understand the perforation process and the energy dissipation mechanism inside the target. It was found that if the high-strength steel plate is used as a front layer, the specific ballistic energy increases by 54% with respect to the monolithic high-strength steel plate. On the other hand, the specific ballistic energy decreases if the aluminum plate is used as the front layer.
Alkali Activation of Metallurgical Slags: Reactivity, Chemical Behavior, and Environmental Assessment
Authors: Lancellotti Isabella , Piccolo Federica , Traven Katja , Češnovar Mark , Ducman Vilma , Leonelli Cristina
Published: January 2021

Alkali-activated materials (AAMs) represent a promising alternative to conventional building materials and ceramics. Being produced in large amounts as aluminosilicate-rich secondary products, such as slags, they can be utilized for the formulation of AAMs. Slags are partially crystalline metallurgical residues produced during the high temperature separation of metallic and non-metallic materials in the steelmaking processes. In the present study, the electric arc furnace carbon or stainless steel slag (EAF) and secondary metallurgical slag such as ladle furnace basic slag (LS) were used as precursors in an alkali-activation process. EAF slag, with its amorphous fraction of about 56%, presented higher contents of soluble Si and Al species with respect to ladle slag R (35%). However, both are suitable to produce AAM. The leaching behavior shows that all the release values are below the regulation limit. All the bivalent ions (Ba, Cd, Cu, Ni, Pb, and Zn) are well immobilized in a geopolymeric matrix, while amphoteric elements, such as As and Cr, show a slight increase of release with respect to the corresponding slag in alkaline and aqueous environments. In particular, for Sb and As of AAM, release still remains below the regulation limits, while Mo presents an increase of leaching values that slightly exceeds the limit for landfill non-dangerous waste.
Use of Quorum Sensing Inhibition Strategies to Control Microfouling
Authors: Muras Andrea , Parga Ana , Mayer Celia , Otero Ana
Published: January 2021

Interfering with the quorum sensing bacterial communication systems has been proposed as a promising strategy to control bacterial biofilm formation, a key process in biofouling development. Appropriate in vitro biofilm-forming bacteria models are needed to establish screening methods for innovative anti-biofilm and anti-microfouling compounds. Four marine strains, two Pseudoalteromonas spp. and two Vibrio spp., were selected and studied with regard to their biofilm-forming capacity and sensitivity to quorum sensing (QS) inhibitors. Biofilm experiments were performed using two biofilm cultivation and quantification methods: the xCELLigence® system, which allows online monitoring of biofilm formation, and the active attachment model, which allows refreshment of the culture medium to obtain a strong biofilm that can be quantified with standard staining methods. Although all selected strains produced acyl-homoserine-lactone (AHL) QS signals, only the P. flavipulchra biofilm, measured with both quantification systems, was significantly reduced with the addition of the AHL-lactonase Aii20J without a significant effect on planktonic growth. Two-species biofilms containing P. flavipulchra were also affected by the addition of Aii20J, indicating an influence on the target bacterial strain as well as an indirect effect on the co-cultured bacterium. The use of xCELLigence® is proposed as a time-saving method to quantify biofilm formation and search for eco-friendly anti-microfouling compounds based on quorum sensing inhibition (QSI) strategies. The results obtained from these two in vitro biofilm formation methods revealed important differences in the response of biosensor bacteria to culture medium and conditions, indicating that several strains should be used simultaneously for screening purposes and the cultivation conditions should be carefully optimized for each specific purpose.
Susceptibility Testing Is Key for the Success of Cefiderocol Treatment: A Retrospective Cohort Study
Authors: Bleibtreu Alexandre , Dortet Laurent , Bonnin Remy , Wyplosz Benjamin , Sacleux Sophie-Caroline , Mihaila Liliana , Dupont Hervé , Junot Helga , Bunel Vincent , Grall Nathalie , Razazi Keyvan , Duran Clara , Tattevin Pierre , Dinh Aurélien ,   on behalf of the Cefiderocol French Study Group
Published: January 2021

Cefiderocol is a novel siderophore cephalosporin, which has proven in vitro activity against carbapenem-resistant (CR) Gram-negative pathogens and stability towards all carbapenemases. The aim of this study was to describe the first cases of prescriptions and the efficacy of cefiderocol for compassionate use in the 2 months following its access in France. We performed a national retrospective study of all patients who received at least one dose of cefiderocol from 2 November 2018 to 5 November 2019. We collected clinical characteristics and outcome through a standard questionnaire. Bacterial isolates from 12 patients were centralized and analyzed in the French National Reference Center for Antimicrobial Resistance, and sequenced using Illumina technology. Finally, 13 patients from 7 French university hospitals were included in the study. The main type of infection treated by cefiderocol was respiratory tract infections (RTI, n = 10). The targeted bacteria were Pseudomonas aeruginosa (n = 12), including carbapenemase-producing P. aeruginosa (n = 9), Acinetobacter baumannii (n = 2), Klebsiella pneumoniae (n = 1), and Enterobacter hormaechei (n = 1). Overall, of the 12 patients whose samples were analyzed, 5 P. aeruginosa strains were not susceptible to cefiderocol (4 categorized as resistant and 1 as intermediate) according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. If considering susceptible strains, the cure rate was 6/7, while being 0/5 among not-susceptible strains. This study underlines the necessity to test strains in adequate conditions.
Gypsum Precipitation under Saline Conditions: Thermodynamics, Kinetics, Morphology, and Size Distribution
Authors: Reiss Amit G. , Gavrieli Ittai , Rosenberg Yoav O. , Reznik Itay J. , Luttge Andreas , Emmanuel Simon , Ganor Jiwchar
Published: January 2021

Gypsum (CaSO4·2H2O) is the most common sulfate mineral on Earth and is also found on Mars. It is an evaporitic mineral that predominantly precipitates from brines. In addition to its precipitation in natural environments, gypsum also forms an undesired scale in many industrial processes that utilize or produce brines. Thus, better insights into gypsum formation can contribute to the understanding of natural processes, as well as improving industrial practices. Subsequently, the thermodynamics, nucleation and crystal growth mechanisms and kinetics, and how these factors shape the morphology of gypsum have been widely studied. Over the last decade, the precipitation of gypsum under saline and hypersaline conditions has been the focus of several studies. However, to date, most of the thermodynamic data are derived from experiments with artificial solutions that have limited background electrolytes and have Ca2+/SO42− ratios that are similar to the 1:1 ratio in the mineral. Moreover, direct observations of the nucleation and growth processes of gypsum are still derived from experimental settings that can be described as having low ionic strength. Thus, the mechanisms of gypsum precipitation under conditions from which the mineral precipitates in many natural environments and industrial processes are still less well known. The present review focuses on the precipitation of gypsum from a range of aspects. Special attention is given to brines. The effects of ionic strength, brine composition, and temperature on the thermodynamic settings are broadly discussed. The mechanisms and rates of gypsum nucleation and growth, and the effect the thermodynamic properties of the brine have on these processes is demonstrated by recent microscopic and macroscopic observations. The morphology and size distribution of gypsum crystals precipitation is examined in the light of the precipitation processes that shape these properties. Finally, the present review highlights discrepancies between microscopic and macroscopic observations, and studies carried out under low and high ionic strengths. The special challenges posed by experiments with brines are also discussed. Thus, while this review covers contemporary literature, it also outlines further research that is required in order to improve our understanding of gypsum precipitation in natural environments and industrial settings.
Tentative Peptide‒Lipid Bilayer Models Elucidating Molecular Behaviors and Interactions Driving Passive Cellular Uptake of Collagen-Derived Small Peptides
Authors: Wongrattanakamon Pathomwat , Yooin Wipawadee , Sirithunyalug Busaban , Nimmanpipug Piyarat , Jiranusornkul Supat
Published: January 2021

Collagen contains hydroxyproline (Hyp), which is a unique amino acid. Three collagen-derived small peptides (Gly-Pro-Hyp, Pro-Hyp, and Gly-Hyp) interacting across a lipid bilayer (POPC model membrane) for cellular uptakes of these collagen-derived small peptides were studied using accelerated molecular dynamics simulation. The ligands were investigated for their binding modes, hydrogen bonds in each coordinate frame, and mean square displacement (MSD) in the Z direction. The lipid bilayers were evaluated for mass and electron density profiles of the lipid molecules, surface area of the head groups, and root mean square deviation (RMSD). The simulation results show that hydrogen bonding between the small collagen peptides and plasma membrane plays a significant role in their internalization. The translocation of the small collagen peptides across the cell membranes was shown. Pro-Hyp laterally condensed the membrane, resulting in an increase in the bilayer thickness and rigidity. Perception regarding molecular behaviors of collagen-derived peptides within the cell membrane, including their interactions, provides the novel design of specific bioactive collagen peptides for their applications.
In Silico Study of Polyunsaturated Fatty Acids as Potential SARS-CoV-2 Spike Protein Closed Conformation Stabilizers: Epidemiological and Computational Approaches
Authors: Vivar-Sierra Alonso , Araiza-Macías María José , Hernández-Contreras José Patricio , Vergara-Castañeda Arely , Ramírez-Vélez Gabriela , Pinto-Almazán Rodolfo , Salazar Juan Rodrigo , Loza-Mejía Marco A.
Published: January 2021

SARS-CoV-2 infects host cells by interacting its spike protein with surface angiotensin-converting enzyme 2 (ACE2) receptors, expressed in lung and other cell types. Although several risk factors could explain why some countries have lower incidence and fatality rates than others, environmental factors such as diet should be considered. It has been described that countries with high polyunsaturated fatty acid (PUFA) intake have a lower number of COVID-19 victims and a higher rate of recovery from the disease. Moreover, it was found that linoleic acid, an omega-6 PUFA, could stabilize the spike protein in a closed conformation, blocking its interaction with ACE2. These facts prompted us to perform in silico simulations to determine if other PUFA could also stabilize the closed conformation of spike protein and potentially lead to a reduction in SARS-CoV-2 infection. We found that: (a) countries whose source of omega-3 is from marine origin have lower fatality rates; and (b) like linoleic acid, omega-3 PUFA could also bind to the closed conformation of spike protein and therefore, could help reduce COVID-19 complications by reducing viral entrance to cells, in addition to their known anti-inflammatory effects.
Bottle Aging and Storage of Wines: A Review
Authors: Echave Javier , Barral Marta , Fraga-Corral Maria , Prieto Miguel A. , Simal-Gandara Jesus
Published: January 2021

Wine is perhaps the most ancient and popular alcoholic beverage worldwide. Winemaking practices involve careful vineyard management alongside controlled alcoholic fermentation and potential aging of the wine in barrels. Afterwards, the wine is placed in bottles and stored or distributed in retail. Yet, it is considered that wine achieves its optimum properties after a certain storage time in the bottle. The main outcome of bottle storage is a decrease of astringency and bitterness, improvement of aroma and a lighter and more stable color. This is due to a series of complex chemical changes of its components revolving around the minimized and controlled passage of oxygen into the bottle. For this matter, antioxidants like sulfur oxide are added to avoid excessive oxidation and consequent degradation of the wine. In the same sense, bottles must be closed with appropriate stoppers and stored in adequate, stable conditions, as the wine may develop unappealing color, aromas and flavors otherwise. In this review, features of bottle aging, relevance of stoppers, involved chemical reactions and storage conditions affecting wine quality will be addressed.
Clinical Efficacy of Brown Seaweeds Ascophyllum nodosum and Fucus vesiculosus in the Prevention or Delay Progression of the Metabolic Syndrome: A Review of Clinical Trials
Authors: Keleszade Enver , Patterson Michael , Trangmar Steven , Guinan Kieran J. , Costabile Adele
Published: January 2021

Metabolic syndrome (MetS) is a global public health problem affecting nearly 25.9% of the world population characterised by a cluster of disorders dominated by abdominal obesity, high blood pressure, high fasting plasma glucose, hypertriacylglycerolaemia and low HDL-cholesterol. In recent years, marine organisms, especially seaweeds, have been highlighted as potential natural sources of bioactive compounds and useful metabolites, with many biological and physiological activities to be used in functional foods or in human nutraceuticals for the management of MetS and related disorders. Of the three groups of seaweeds, brown seaweeds are known to contain more bioactive components than either red and green seaweeds. Among the different brown seaweed species, Ascophyllum nodosum and Fucus vesiculosus have the highest antioxidant values and highest total phenolic content. However, the evidence base relies mainly on cell line and small animal models, with few studies to date involving humans. This review intends to provide an overview of the potential of brown seaweed extracts Ascophyllum nodosum and Fucus vesiculosus for the management and prevention of MetS and related conditions, based on the available evidence obtained from clinical trials.
Acid-Activated Motion Switching of DB24C8 between Two Discrete Platinum(II) Metallacycles
Authors: Hu Yi-Xiong , Wu Gui-Yuan , Wang Xu-Qing , Yin Guang-Qiang , Zhang Chang-Wei , Li Xiaopeng , Xu Lin , Yang Hai-Bo
Published: January 2021

The precise operation of molecular motion for constructing complicated mechanically interlocked molecules has received considerable attention and is still an energetic field of supramolecular chemistry. Herein, we reported the construction of two tris[2]pseudorotaxanes metallacycles with acid–base controllable molecular motion through self-sorting strategy and host–guest interaction. Firstly, two hexagonal Pt(II) metallacycles M1 and M2 decorated with different host–guest recognition sites have been constructed via coordination-driven self-assembly strategy. The binding of metallacycles M1 and M2 with dibenzo-24-crown-8 (DB24C8) to form tris[2]pseudorotaxanes complexes TPRM1 and TPRM2 have been investigated. Furthermore, by taking advantage of the strong binding affinity between the protonated metallacycle M2 and DB24C8, the addition of trifluoroacetic acid (TFA) as a stimulus successfully induces an acid-activated motion switching of DB24C8 between the discrete metallacycles M1 and M2. This research not only affords a highly efficient way to construct stimuli-responsive smart supramolecular systems but also offers prospects for precisely control multicomponent cooperative motion.
Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models
Authors: Hundsberger Harald , Stierschneider Anna , Sarne Victoria , Ripper Doris , Schimon Jasmin , Weitzenböck Hans Peter , Schild Dominik , Jacobi Nico , Eger Andreas , Atzler Josef , Klein Christian T. , Wiesner Christoph
Published: January 2021

Quercetin, a dietary flavonoid found in fruits and vegetables, has been described as a substance with many anti-cancer properties in a variety of preclinical investigations. In the present study, we demonstrate that 2D and 3D melanoma models exhibit not only different sensitivities to quercetin, but also opposite, cancer-promoting effects when metastatic melanoma spheroids are treated with quercetin. Higher concentrations of quercetin reduce melanoma growth in three tested cell lines, whereas low concentrations induce the opposite effect in metastatic melanoma spheroids but not in the non-metastatic cell line. High (>12.5 µM) or low (<6.3 µM) quercetin concentrations decrease or enhance cell viability, spheroid size, and cell proliferation, respectively. Additionally, melanoma cells cultivated in 2D already show significant caspase 3 activity at very low concentrations (>0.4 µM), whereas in 3D spheroids apoptotic cells, caspase 3 activity can only be detected in concentrations ≥12.5 µM. Further, we show that the tumor promoting or repressing effect in the 3D metastatic melanoma spheroids are likely to be elicited by a precisely controlled regulation of Nrf2/ARE-mediated cytoprotective genes, as well as ERK and NF-κB phosphorylation. According to the results obtained here, further studies are needed to better characterize the mechanisms of action underlying the pro- and anti-carcinogenic effects of quercetin on human melanomas.
Computational Design of Macrocyclic Binders of S100B(ββ): Novel Peptide Theranostics
Authors: Kannan Srinivasaraghavan , Aronica Pietro G. A. , Nguyen Thanh Binh , Li Jianguo , Verma Chandra S.
Published: January 2021

S100B(ββ) proteins are a family of multifunctional proteins that are present in several tissues and regulate a wide variety of cellular processes. Their altered expression levels have been associated with several human diseases, such as cancer, inflammatory disorders and neurodegenerative conditions, and hence are of interest as a therapeutic target and a biomarker. Small molecule inhibitors of S100B(ββ) have achieved limited success. Guided by the wealth of available experimental structures of S100B(ββ) in complex with diverse peptides from various protein interacting partners, we combine comparative structural analysis and molecular dynamics simulations to design a series of peptides and their analogues (stapled) as S100B(ββ) binders. The stapled peptides were subject to in silico mutagenesis experiments, resulting in optimized analogues that are predicted to bind to S100B(ββ) with high affinity, and were also modified with imaging agents to serve as diagnostic tools. These stapled peptides can serve as theranostics, which can be used to not only diagnose the levels of S100B(ββ) but also to disrupt the interactions of S100B(ββ) with partner proteins which drive disease progression, thus serving as novel therapeutics.
Natural Herbal Estrogen-Mimetics (Phytoestrogens) Promote the Differentiation of Fallopian Tube Epithelium into Multi-Ciliated Cells via Estrogen Receptor Beta
Authors: Zhu Maobi , Takeda Sen , Iwano Tomohiko
Published: January 2021

Phytoestrogens are herbal polyphenolic compounds that exert various estrogen-like effects in animals and can be taken in easily from a foodstuff in daily life. The fallopian tube lumen, where transportation of the oocyte occurs, is lined with secretory cells and multi-ciliated epithelial cells. Recently, we showed that estrogen induces multi-ciliogenesis in the porcine fallopian tube epithelial cells (FTECs) through the activation of the estrogen receptor beta (ERβ) pathway and simultaneous inhibition of the Notch pathway. Thus, ingested phytoestrogens may induce FTEC ciliogenesis and thereby affect the fecundity. To address this issue, we added isoflavones (genistein, daidzein, or glycitin) and coumestan (coumestrol) to primary culture FTECs under air–liquid interface conditions and assessed the effects of each compound. All phytoestrogens except glycitin induced multi-ciliated cell differentiation, which followed Notch signal downregulation. On the contrary, the differentiation of secretory cells decreased slightly. Furthermore, genistein and daidzein had a slight effect on the proportion of proliferating cells exhibited by Ki67 expression. Ciliated-cell differentiation is inhibited by the ERβ antagonist, PHTPP. Thus, this study suggests that phytoestrogens can improve the fallopian tube epithelial sheet homeostasis by facilitating the genesis of multi-ciliated cells and this effect depends on the ERβ-mediated pathway.
Mesoporous Carbon Fibers with Tunable Mesoporosity for Electrode Materials in Energy Devices
Authors: Huang Ting-Wei , Nagayama Mayumi , Matsuda Junko , Sasaki Kazunari , Hayashi Akari
Published: January 2021

To improve the properties of mesoporous carbon (MC), used as a catalyst support within electrodes, MC fibers (MCFs) were successfully synthesized by combining organic–organic self-assembly and electrospinning deposition and optimizing heat treatment conditions. The pore structure was controlled by varying the experimental conditions. Among MCFs, MCF-A, which was made in the most acidic condition, resulted in the largest pore diameter (4–5 nm), and the porous structure and carbonization degree were further optimized by adjusting heat treatment conditions. Then, since the fiber structure is expected to have an advantage when MCFs are applied to devices, MCF-A layers were prepared by spray printing. For the resistance to compression, MCF-A layers showed higher resistance (5.5% change in thickness) than the bulk MC layer (12.8% change in thickness). The through-plane resistance was lower when the fiber structure remained more within the thin layer, for example, +8 mΩ for 450 rpm milled MCF-A and +12 mΩ for 800 rpm milled MCF-A against the gas diffusion layer (GDL) 25BC carbon paper without a carbon layer coating. The additional advantages of MCF-A compared with bulk MC demonstrate that MCF-A has the potential to be used as a catalyst support within electrodes in energy devices.
Potential of Naturally Derived Alkaloids as Multi-Targeted Therapeutic Agents for Neurodegenerative Diseases
Authors: Kong Yew Rong , Tay Kai Ching , Su Yi Xiang , Wong Choon Kwang , Tan Wen Nee , Khaw Kooi Yeong
Published: January 2021

Alkaloids are a class of secondary metabolites that can be derived from plants, fungi and marine sponges. They are widely known as a continuous source of medicine for the management of chronic disease including cancer, diabetes and neurodegenerative diseases. For example, galanthamine and huperzine A are alkaloid derivatives currently being used for the symptomatic management of neurodegenerative disease. The etiology of neurodegenerative diseases is polygenic and multifactorial including but not limited to inflammation, oxidative stress and protein aggregation. Therefore, natural-product-based alkaloids with polypharmacology modulation properties are potentially useful for further drug development or, to a lesser extent, as nutraceuticals to manage neurodegeneration. This review aims to discuss and summarise recent developments in relation to naturally derived alkaloids for neurodegenerative diseases.
Resting Energy Expenditure in the Elderly: Systematic Review and Comparison of Equations in an Experimental Population
Authors: Ocagli Honoria , Lanera Corrado , Azzolina Danila , Piras Gianluca , Soltanmohammadi Rozita , Gallipoli Silvia , Gafare Claudia Elena , Cavion Monica , Roccon Daniele , Vedovelli Luca , Lorenzoni Giulia , Gregori Dario
Published: January 2021

Elderly patients are at risk of malnutrition and need an appropriate assessment of energy requirements. Predictive equations are widely used to estimate resting energy expenditure (REE). In the study, we conducted a systematic review of REE predictive equations in the elderly population and compared them in an experimental population. Studies involving subjects older than 65 years of age that evaluated the performance of a predictive equation vs. a gold standard were included. The retrieved equations were then tested on a sample of 88 elderly subjects enrolled in an Italian nursing home to evaluate the agreement among the estimated REEs. The agreement was assessed using the intraclass correlation coefficient (ICC). A web application, equationer, was developed to calculate all the estimated REEs according to the available variables. The review identified 68 studies (210 different equations). The agreement among the equations in our sample was higher for equations with fewer parameters, especially those that included body weight, ICC = 0.75 (95% CI = 0.69–0.81). There is great heterogeneity among REE estimates. Such differences should be considered and evaluated when estimates are applied to particularly fragile populations since the results have the potential to impact the patient’s overall clinical outcome.
Magnesium in Aging, Health and Diseases
Authors: Barbagallo Mario , Veronese Nicola , Dominguez Ligia J.
Published: January 2021

Several changes of magnesium (Mg) metabolism have been reported with aging, including diminished Mg intake, impaired intestinal Mg absorption and renal Mg wasting. Mild Mg deficits are generally asymptomatic and clinical signs are usually non-specific or absent. Asthenia, sleep disorders, hyperemotionality, and cognitive disorders are common in the elderly with mild Mg deficit, and may be often confused with age-related symptoms. Chronic Mg deficits increase the production of free radicals which have been implicated in the development of several chronic age-related disorders. Numerous human diseases have been associated with Mg deficits, including cardiovascular diseases, hypertension and stroke, cardio-metabolic syndrome and type 2 diabetes mellitus, airways constrictive syndromes and asthma, depression, stress-related conditions and psychiatric disorders, Alzheimer’s disease (AD) and other dementia syndromes, muscular diseases (muscle pain, chronic fatigue, and fibromyalgia), bone fragility, and cancer. Dietary Mg and/or Mg consumed in drinking water (generally more bioavailable than Mg contained in food) or in alternative Mg supplements should be taken into consideration in the correction of Mg deficits. Maintaining an optimal Mg balance all through life may help in the prevention of oxidative stress and chronic conditions associated with aging. This needs to be demonstrated by future studies.
Phytonutrient and Nutraceutical Action against COVID-19: Current Review of Characteristics and Benefits
Authors: Pastor Nitida , Collado Maria Carmen , Manzoni Paolo
Published: January 2021

The trend toward using phytonutrients and/or nutraceuticals (P/Ns) with the aim of impacting immune health has increased in recent years. The main reason is that properties of P/Ns are associated with possible immunomodulating effects in the prevention and complementary treatment of viral diseases, including COVID-19 and other respiratory infections. In the present review, we assess the scientific plausibility of specific P/Ns for this purpose of preventative and therapeutic interventions against COVID-19, with an emphasis on safety, validity, and evidence of efficacy against other viruses. Five potential candidates have been identified after reviewing available studies (in silico, in vitro, and in vivo) in which certain flavonoids have demonstrated a potential for use as adjuvant therapeutic agents against viral infections, including COVID-19. As these are often better tolerated than pharmacological treatments, their use could be more widely considered if additional detailed studies can validate the existing evidence.
Stratification of Volunteers According to Flavanone Metabolite Excretion and Phase II Metabolism Profile after Single Doses of ‘Pera’ Orange and ‘Moro’ Blood Orange Juices
Authors: Nishioka Alessandra , Tobaruela Eric de Castro , Fraga Layanne Nascimento , Tomás-Barberán Francisco A. , Lajolo Franco Maria , Hassimotto Neuza Mariko Aymoto
Published: January 2021

Large interindividual variations in the biological response to citrus flavanones have been observed, and this could be associated with high variations in their bioavailability. The aim of this study was to identify the main determinants underlying interindividual differences in citrus flavanone metabolism and excretion. In a randomized cross-over study, non-obese and obese volunteers, aged 19–40 years, ingested single doses of Pera and Moro orange juices, and urine was collected for 24 h. A large difference in the recovery of the urinary flavanone phase II metabolites was observed, with hesperetin-sulfate and hesperetin-sulfo-O-glucuronide being the major metabolites. Subjects were stratified according to their total excretion of flavanone metabolites as high, medium, and low excretors, but the expected correlation with the microbiome was not observed at the genus level. A second stratification was proposed according to phase II flavanone metabolism, whereby participants were divided into two excretion groups: Profiles A and B. Profile B individuals showed greater biotransformation of hesperetin-sulfate to hesperetin-sulfo-O-glucuronide, as well as transformation of flavanone-monoglucuronide to the respective diglucuronides, suggestive of an influence of polymorphisms on UDP-glucuronosyltransferase. In conclusion, this study proposes a new stratification of volunteers based on their metabolic profiles. Gut microbiota composition and polymorphisms of phase II enzymes may be related to the interindividual variability of metabolism.
Characterization and Applications of Colloidal Systems as Versatile Drug Delivery Carriers for Parenteral Formulations
Authors: Kolluru Lakshmi , Atre Prachi , Rizvi Syed
Published: January 2021

Preparing a suitable formulation for parenteral administration is already a difficult task; this, coupled with poor water-soluble new chemical entity (NCE), complicates this situation even further. There are several methodologies available to enhance water solubility, but this alone does not entail successful formulation. Making a micro/nano emulsion with a suitable surfactant not only increases the drug solubility but also the cell membrane permeability. Thus, not only biopharmaceutic classification system (BCS)-II (low solubility compounds) but also BCS-III (low permeability) and BCS-IV drugs (low solubility and low permeability) can be further exploited. Those drug candidates otherwise will not move further in NCE evaluation or clinical trials. This succinct review article delves into various aspects of biphasic micro/nano emulsion systems for parenteral drug delivery including the structure of the biphasic colloidal systems, characterization parameters, stability issues, regulatory considerations, and applications in life sciences.
Comparative Study of Several Fe Deficiency Responses in the Arabidopsis thaliana Ethylene Insensitive Mutants ein2-1 and ein2-5
Authors: Angulo Macarena , García María José , Alcántara Esteban , Pérez-Vicente Rafael , Romera Francisco Javier
Published: January 2021

Iron (Fe) is an essential micronutrient for plants since it participates in essential processes such as photosynthesis, respiration and nitrogen assimilation. Fe is an abundant element in most soils, but its availability for plants is low, especially in calcareous soils. Fe deficiency causes Fe chlorosis, which can affect the productivity of the affected crops. Plants favor Fe acquisition by developing morphological and physiological responses in their roots. Ethylene (ET) and nitric oxide (NO) have been involved in the induction of Fe deficiency responses in dicot (Strategy I) plants, such as Arabidopsis. In this work, we have conducted a comparative study on the development of subapical root hairs, of the expression of the main Fe acquisition genes FRO2 and IRT1, and of the master transcription factor FIT, in two Arabidopsis thaliana ET insensitive mutants, ein2-1 and ein2-5, affected in EIN2, a critical component of the ET transduction pathway. The results obtained show that both mutants do not induce subapical root hairs either under Fe deficiency or upon treatments with the ET precursor 1-aminocyclopropane-1-carboxylate (ACC) and the NO donor S-nitrosoglutathione (GSNO). By contrast, both of them upregulate the Fe acquisition genes FRO2 and IRT1 (and FIT) under Fe deficiency. However, the upregulation was different when the mutants were exposed to ET [ACC and cobalt (Co), an ET synthesis inhibitor] and GSNO treatments. All these results clearly support the participation of ET and NO, through EIN2, in the regulation of subapical root hairs and Fe acquisition genes. The results will be discussed, taking into account the role of both ET and NO in the regulation of Fe deficiency responses.
Physiological Conditions and dsRNA Application Approaches for Exogenously induced RNA Interference in Arabidopsis thaliana
Authors: Kiselev Konstantin V. , Suprun Andrey R. , Aleynova Olga A. , Ogneva Zlata V. , Dubrovina Alexandra S.
Published: January 2021

Recent studies have revealed that foliar application of double-stranded RNAs (dsRNAs) or small-interfering RNAs (siRNAs) encoding specific genes of plant pathogens triggered RNA interference (RNAi)-mediated silencing of the gene targets. However, a limited number of reports documented silencing of plant endogenes or transgenes after direct foliar RNA application. This study analyzed the importance of physiological conditions (plant age, time of day, soil moisture, high salinity, heat, and cold stresses) and different dsRNA application means (brush spreading, spraying, infiltration, inoculation, needle injection, and pipetting) for suppression of neomycin phosphotransferase II (NPTII) transgene in Arabidopsis thaliana, as transgenes are more prone to silencing. We observed a higher NPTII suppression when dsRNA was applied at late day period, being most efficient at night, which revealed a diurnal variation in dsRNA treatment efficacy. Exogenous NPTII-dsRNA considerably reduced NPTII expression in 4-week-old plants and only limited it in 2- and 6-week-old plants. In addition, a more discernible NPTII downregulation was detected under low soil moisture conditions. Treatment of adaxial and abaxial leaf surfaces by brushes, spraying, and pipetting showed a higher NPTII suppression, while infiltration and inoculation were less efficient. Thus, appropriate plant age, late time of day, low soil moisture, and optimal dsRNA application modes are important for exogenously induced gene silencing.
Plantago media L.—Explored and Potential Applications of an Underutilized Plant
Authors: Fierascu Radu Claudiu , Fierascu Irina , Ortan Alina , Paunescu Alina
Published: January 2021

The search of valuable natural compounds should be directed towards alternative vegetal resources, and to the re-discovery of underutilized plants. Belonging to the Plantaginaceae family, the hoary plantain (Plantago media L.) represents one of the lesser studied species from the Plantago genus. The literature study revealed the under-utilization of the hoary plantain, a surprising aspect, considering its widespread. If the composition of Plantago media L. is rather well established, its applications are not nearly studied as for other Plantago species. The goal of the present paper is to summarize the findings regarding the applications of P. media, and, having as starting point the applications of related species, to propose new emerging areas of research, such as the biomedical applications validation through in vivo assays, and the evaluation of its potential towards industrial applications (i.e., development of food or personal care products), pisciculture or zootechny, phytoremediation and other environmental protection applications, or in the nanotechnology area (materials phytosynthesis). The present work constitutes not only a brief presentation of this plant’s present and potential applications, but also an invitation to research groups world-wide to explore the available vegetal resources.
Photoprotective Activity of Buddleja cordata Cell Culture Methanolic Extract on UVB-irradiated 3T3-Swiss Albino Fibroblasts
Authors: Gómez-Hernández Milton Abraham , Flores-Merino Miriam V. , Sánchez-Flores Jesús Enrique , Burrola-Aguilar Cristina , Zepeda-Gómez Carmen , Nieto-Trujillo Aurelio , Estrada-Zúñiga María Elena
Published: January 2021

The research on compounds exhibiting photoprotection against ultraviolet radiation (UVR) is a matter of increasing interest. The methanolic extract of a cell culture of Buddleja cordata has potential photoprotective effects as these cells produce phenolic secondary metabolites (SMs). These metabolites are attributed with biological activities capable of counteracting the harmful effects caused by UVR on skin. In the present work, the methanolic extract (310–2500 µg/mL) of B. cordata cell culture showed a photoprotective effect on UVB-irradiated 3T3-Swiss albino fibroblasts with a significant increase in cell viability. The greatest photoprotective effect (75%) of the extract was observed at 2500 µg/mL, which was statistically comparable with that of 250 µg/mL verbascoside, used as positive control. In addition, concentrations of the extract higher than 2500 µg/mL resulted in decreased cell viability (≤83%) after 24 h of exposure. Phytochemical analysis of the extract allowed us to determine that it was characterized by high concentrations of total phenol and total phenolic acid contents (138 ± 4.7 mg gallic acid equivalents and 44.01 ± 1.33 mg verbascoside equivalents per gram of extract, respectively) as well as absorption of UV light (first and second bands peaking at 294 and 330 nm, respectively). Some phenylethanoid glycosides were identified from the extract.
Rice RBH1 Encoding A Pectate Lyase is Critical for Apical Panicle Development
Authors: He Dong , Liang Rui , Long Tuan , Yang Ying , Wu Changyin
Published: January 2021

Panicle morphology is one of the main determinants of the rice yield. Panicle abortion, a typical panicle morphological defect results in yield reduction due to defective spikelet development. To further elucidate the molecular mechanism of panicle abortion in rice, a rice panicle bald head 1 (rbh1) mutant with transfer DNA (T-DNA) insertion showing severely aborted apical spikelets during panicle development was identified and characterized. The rbh1-1 mutant showed obviously altered cell morphology and structure in the degenerated spikelet. Molecular genetic studies revealed that RBH1 encodes a pectate lyase protein. Pectate lyase-specific activity of Rice panicle Bald Head 1 (RBH1) protein assay using polygalacturonic acid (PGA) as substrates illustrated that the enzyme retained a significant capacity to degrade PGA. In addition, immunohistochemical analysis showed that the degradation of pectin is inhibited in the rbh1-1 mutant. Further analysis revealed that a significant increase in reactive oxygen species (ROS) level was found in degenerated rbh1-1 spikelets. Taken together, our findings suggest that RBH1 is required for the formation of panicle and for preventing panicle abortion.
Combination of Self-Healing Butyl Rubber and Natural Rubber Composites for Improving the Stability
Authors: Chumnum Kunakorn , Kalkornsurapranee Ekwipoo , Johns Jobish , Sengloyluan Karnda , Nakaramontri Yeampon
Published: January 2021

The self-healing composites were prepared from the combination of bromobutyl rubber (BIIR) and natural rubber (NR) blends filled with carbon nanotubes (CNT) and carbon black (CB). To reach the optimized self-healing propagation, the BIIR was modified with ionic liquid (IL) and butylimidazole (IM), and blended with NR using the ratios of 70:30 and 80:20 BIIR:NR. Physical and chemical modifications were confirmed from the mixing torque and attenuated total reflection-fourier transform infrared spectroscopy (ATR-FTIR). It was found that the BIIR/NR-CNTCB with IL and IM effectively improved the cure properties with enhanced tensile properties relative to pure BIIR/NR blends. For the healed composites, BIIR/NR-CNTCB-IM exhibited superior mechanical and electrical properties due to the existing ionic linkages in rubber matrix. For the abrasion resistances, puncture stress and electrical recyclability were examined to know the possibility of inner liner applications and Taber abrasion with dynamic mechanical properties were elucidated for tire tread applications. Based on the obtained Tg and Tan δ values, the composites are proposed for tire applications in the future with a simplified preparation procedure.
The “Right” History: Religion, Race, and Nostalgic Stories of Christian America
Authors: Braunstein Ruth
Published: January 2021

A wide range of right-wing movements are bound together by their adherence to a nostalgic vision of the United States as a “Christian nation,” yet there are meaningful differences in the specific narratives promoted by these groups that are not fully understood. This article identifies two ideal-typical versions of this narrative: the white Christian nation and the colorblind Judeo-Christian nation. The two narratives share a common declension structure, but differ in their framing of how religion and race intersect as markers of American belonging and power. Although participants in right-wing movements often slide back and forth between the two narratives in practice, distinguishing between them analytically enables us to better understand how the two renderings of American history carry different meanings and perform different kinds of political work for participants in these movements. Theoretically, the analysis extends the insights of a “complex religion” approach to sites beyond organized religion, while also demonstrating how scholarship on Christian nationalism and on right-wing movements’ use of national history could each be enhanced by greater attention to the other.