bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and Swarm Algorithms for Optimizing the Control of Building HVAC Systems Using Real Data: A Comparative Study
Authors: Garces-Jimenez Alberto , Gomez-Pulido Jose-Manuel , Gallego-Salvador Nuria , Garcia-Tejedor Alvaro-Jose
Published: September 2021

Buildings consume a considerable amount of electrical energy, the Heating, Ventilation, and Air Conditioning (HVAC) system being the most demanding. Saving energy and maintaining comfort still challenge scientists as they conflict. The control of HVAC systems can be improved by modeling their behavior, which is nonlinear, complex, and dynamic and works in uncertain contexts. Scientific literature shows that Soft Computing techniques require fewer computing resources but at the expense of some controlled accuracy loss. Metaheuristics-search-based algorithms show positive results, although further research will be necessary to resolve new challenging multi-objective optimization problems. This article compares the performance of selected genetic and swarm-intelligence-based algorithms with the aim of discerning their capabilities in the field of smart buildings. MOGA, NSGA-II/III, OMOPSO, SMPSO, and Random Search, as benchmarking, are compared in hypervolume, generational distance, ε-indicator, and execution time. Real data from the Building Management System of Teatro Real de Madrid have been used to train a data model used for the multiple objective calculations. The novelty brought by the analysis of the different proposed dynamic optimization algorithms in the transient time of an HVAC system also includes the addition, to the conventional optimization objectives of comfort and energy efficiency, of the coefficient of performance, and of the rate of change in ambient temperature, aiming to extend the equipment lifecycle and minimize the overshooting effect when passing to the steady state. The optimization works impressively well in energy savings, although the results must be balanced with other real considerations, such as realistic constraints on chillers’ operational capacity. The intuitive visualization of the performance of the two families of algorithms in a real multi-HVAC system increases the novelty of this proposal.
Application Multi-Fuzzy Soft Sets in Hypermodules
Authors: Kazancı Osman , Hoskova-Mayerova Sarka , Davvaz Bijan
Published: September 2021

The goal of this paper is to introduce a novel soft hyperstructure called multi-fuzzy soft hyperstructure. We investigate the notion of multi-fuzzy soft hypermodules and some of their structural properties are discussed. We discuss the behavior image and inverse image of a multi-fuzzy soft set under the multi-fuzzy soft function. According to Zadeh’s extension principle, we prove that the image and inverse image of a multi-fuzzy soft hypermodules are further multi-fuzzy soft hypermodule.
Asymptotic Analysis for Systems with Deferred Abandonment
Authors: Sasanuma Katsunobu
Published: September 2021

This short paper concerns the analysis of the M/M/k queueing system with customer abandonment. In this system, service managers provide a finite buffer space, which is a waiting area that prevents customers from abandoning the system. Abandonment of the system can occur from reneging (exiting from the queue while waiting), and/or balking (leaving the system without waiting). We derive an analytical expression to represent the impact of the buffer space capacity on the delay probability and the abandonment probability for a system with deferred abandonment. The result indicates the provision of the buffer space in a large system could only increase the delay probability while the abandonment probability remains unchanged. Despite the benevolent intentions of service managers, providing a buffer space may exacerbate the performance of larger systems.
RSK1 vs. RSK2 Inhibitory Activity of the Marine β-Carboline Alkaloid Manzamine A: A Biochemical, Cervical Cancer Protein Expression, and Computational Study
Authors: Mayer Alejandro M. S. , Hall Mary L. , Lach Joseph , Clifford Jonathan , Chandrasena Kevin , Canton Caitlin , Kontoyianni Maria , Choo Yeun-Mun , Karan Dev , Hamann Mark T.
Published: September 2021

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia, and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, SIX1, and vacuolar ATPases. We hypothesized that additional, yet undiscovered molecular targets might be associated with Manzamine A’s (MZA) reported pharmacological properties. We report here, for the first time, that MZA selectively inhibited a 90 kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases, while in vitro RSK kinase assays demonstrated a 10-fold selectivity in the potency of MZA against RSK1 versus RSK2. The effect of MZA on inhibiting cellular RSK1 and RSK2 protein expression was validated in SiHa and CaSki human cervical carcinoma cell lines. MZA’s differential binding and selectivity toward the two isoforms was also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2–MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes, including growth, survival, and proliferation. Consequently, our findings have led us to hypothesize that MZA and the currently known manzamine-type alkaloids isolated from several sponge genera may have novel pharmacological properties with unique molecular targets, and MZA provides a new tool for chemical-biology studies involving RSK1.
Intracardiac Migration of the Ureteral Double-J Stent during Percutaneous Nephrolithotomy
Authors: Chang Chun-Kai , Wu Yi-Hsuan , Shih Ming-Chen Paul , Geng Jiun-Hung
Published: September 2021

The complications of percutaneous nephrolithotomy (PNL) include hemorrhage, damage to adjuvant organs, and other medical issues, although intracardiac migration of ureteral double-J stent has never been found during PNL and delaying the diagnosis might cause mortality. We report the case of a 60-year-old male who was admitted to receive one-stage PNL for right renal stones. During operation, an unexpected atrial fibrillation with a drop in blood pressure was suddenly encountered and the chest X-ray subsequently showed that the ureteral double-J had penetrated deep into the heart. Emergent endovascular intervention was performed to remove the stent and the patient was uneventfully discharged 2 days later.
Counterclockwise Drilling with Different Tapered Drills Condenses the Implant Bed—An Optical Coherence Tomography In Vitro Study
Authors: Delgado-Ruiz Rafael , Mahdian Mina , Benezha Ilyasse , Romanos Georgios
Published: September 2021

Background and Objectives: To evaluate the condensation and the microarchitecture of implant bed walls of sites prepared with counterclockwise drilling with tapered implant drills using optical coherence tomography. Materials and Methods: Four drill designs with different wall and tip angles were used. Polyurethane laminas resembling type IV bone microarchitecture were superimposed and clamped with a vice to simulate the coronal, middle, and apical aspects of the implant site. Twenty implant beds were prepared at 1200 rpm in clockwise (control) and counterclockwise (test) directions (N = 160). Optical coherence tomography (OCT) was used to evaluate the condensation and microarchitecture characteristics of the implant bed walls. The relative condensation was calculated using the Image J software Bone application. The microarchitecture was evaluated in reconstructed 3D volumes in XY, XZ, and YZ sections. Statistical analysis was performed using one-way ANOVA. Dunnet test was applied to determine differences between groups. Significance was set as p < 0.05. Results: Counterclockwise drilling (Test) condensed and changed the microarchitecture of the apical regions for all the implant beds in all of the groups when compared to clockwise drilling (control). The apical region of test groups showed the highest relative bone condensation (p = 0.026) when compared to controls. Conclusions: The direction of rotation (counterclockwise drilling) and not the design of tapered drills (tip and wall angles) is responsible for the condensation at the apical area observed in polyurethane blocks. The OCT method can be used for the evaluation of changes in density and microstructure of polyurethane blocks.
Knee-High Devices Are Gold in Closing the Foot Ulcer Gap: A Review of Offloading Treatments to Heal Diabetic Foot Ulcers
Authors: Lazzarini Peter A. , Jarl Gustav
Published: September 2021

Diabetic foot ulcers (DFU) are a leading cause of the global disease burden. Most DFUs are caused, and prolonged, by high plantar tissue stress under the insensate foot of a person with peripheral neuropathy. Multiple different offloading treatments have been used to try to reduce high plantar tissue stress and heal DFUs, including bedrest, casting, offloading devices, footwear, and surgical procedures. The best offloading treatments are those that balance the benefits of maximizing reductions in high plantar tissue stress, whilst reducing the risks of poor satisfaction, high costs and potential adverse events outcomes. This review aimed to summarize the best available evidence on the effects of offloading treatments to heal people with DFUs, plus review their use in clinical practice, the common barriers and solutions to using these treatments, and discuss promising emerging solutions that may improve offloading treatments in future. Findings demonstrate that knee-high offloading devices, non-removable or removable knee-high devices worn for all weight-bearing activities, are the gold standard offloading treatments to heal most patients with DFU, as they are much more effective, and typically safer, quicker, and cheaper to use compared with other offloading treatments. The effectiveness of offloading treatments also seems to increase when increased offloading mechanical features are incorporated within treatments, including customized insoles, rocker-bottom soles, controlled ankle motion, and higher cast walls. However, in clinical practice these gold standard knee-high offloading devices have low rates of prescription by clinicians and low rates of acceptance or adherence by patients. The common barriers resulting in this low use seem to surround historical misperceptions that are mostly dispelled by contemporary evidence. Further, research is now urgently required to close the implementation gap between the high-quality of supporting evidence and the low use of knee-high devices in clinical practice to reduce the high global disease burden of DFU in future.
Negotiating Gestational Diabetes Mellitus in India: A National Approach
Authors: Thanawala Uday , Divakar Hema , Jain Rajesh , Agarwal Mukesh M.
Published: September 2021

The worldwide epidemic of diabetes mellitus and hyperglycemia in pregnancy (HIP) presents many challenges, some of which are country-specific. To address these specific problems, parochial resolutions are essential. In India, the government, by working in tandem with (a) national groups such as the Diabetes in Pregnancy Study Group of India, and (b) global organizations such as the International Diabetes Federation, has empowered the medical and paramedical staff throughout the country to manage HIP. Additionally, despite their academic university backgrounds, Indian health planners have provided practical guidelines for caregivers at the ground level, who look up to these experts for guidance. This multipronged process has helped to negotiate some of the multiple problems that are indigenous and exclusive to India. This review traces the Indian journey to manage and prevent HIP with simple, constructive, and pragmatic solutions.
Kiwifruit Metabolomics—An Investigation of within Orchard Metabolite Variability of Two Cultivars of Actinidia chinensis
Authors: Rowan Daryl , Boldingh Helen , Cordiner Sarah , Cooney Janine , Hedderley Duncan , Hewitt Katrin , Jensen Dwayne , Pereira Trisha , Trower Tania , McGhie Tony
Published: September 2021

Plant metabolomics within field-based food production systems is challenging owing to environmental variability and the complex architecture and metabolic growth cycles of plants. Kiwifruit cultivars of Actinidia chinensis are vigorous perennial vines grown as clones in highly structured orchard environments, intensively managed to maximize fruit yield and quality. To understand the metabolic responses of vines to orchard management practices, we needed to better understand the various sources of metabolic variability encountered in the orchard. Triplicate composite leaf, internode and fruit (mature and immature) samples were collected from each of six Actinidia chinensis var. deliciosa ‘Hayward’ and A. chinensis var. chinensis ‘Zesy002’ kiwifruit vines at three times during the growing season and measured by LC-MS. In general, there was more variation in metabolite concentrations within vines than between vines, with ‘Hayward’ showing a greater percentage of within-vine variability than ‘Zesy002’ (c. 90 vs. 70% respectively). In specific tissues, the sampler, infection by Pseudomonas syringae var. actinidiae and the rootstock also influenced metabolite variability. A similar pattern of metabolic variability was observed from quantitative analysis of specific carbohydrates and phytohormones. High within-vine metabolic variability indicates that it is more important to obtain sufficient replicate samples than to sample from multiple vines. These data provide an objective basis for optimizing metabolite sampling strategies within kiwifruit orchards.
Serum Metabolite Profile Associated with Sex-Dependent Visceral Adiposity Index and Low Bone Mineral Density in a Mexican Population
Authors: Palacios-González Berenice , León-Reyes Guadalupe , Rivera-Paredez Berenice , Ibarra-González Isabel , Vela-Amieva Marcela , Flores Yvonne N. , Canizales-Quinteros Samuel , Salmerón Jorge , Velázquez-Cruz Rafael
Published: September 2021

Recent evidence shows that obesity correlates negatively with bone mass. However, traditional anthropometric measures such as body mass index could not discriminate visceral adipose tissue from subcutaneous adipose tissue. The visceral adiposity index (VAI) is a reliable sex-specified indicator of visceral adipose distribution and function. Thus, we aimed to identify metabolomic profiles associated with VAI and low bone mineral density (BMD). A total of 602 individuals from the Health Workers Cohort Study were included. Forty serum metabolites were measured using the targeted metabolomics approach, and multivariate regression models were used to test associations of metabolomic profiles with anthropometric, clinical, and biochemical parameters. The analysis showed a serum amino acid signature composed of glycine, leucine, arginine, valine, and acylcarnitines associated with high VAI and low BMD. In addition, we found a sex-dependent VAI in pathways related to primary bile acid biosynthesis, branched-chain amino acids, and the biosynthesis of pantothenate and coenzyme A (CoA). In conclusion, a metabolic profile differs by VAI and BMD status, and these changes are gender-dependent.
RNA-Seq Provides New Insights into the Gene Expression Changes in Azoarcus olearius BH72 under Nitrogen-Deficient and Replete Conditions beyond the Nitrogen Fixation Process
Authors: Solaiyappan Mani Shanmugam , Reinhold-Hurek Barbara
Published: September 2021

Azoarcus olearius BH72 is an endophyte capable of biological nitrogen fixation (BNF) and of supplying nitrogen to its host plant. Our previous microarray approach provided insights into the transcriptome of strain BH72 under N2-fixation in comparison to ammonium-grown conditions, which already indicated the induction of genes not related to the BNF process. Due to the known limitations of the technique, we might have missed additional differentially expressed genes (DEGs). Thus, we used directional RNA-Seq to better comprehend the transcriptional landscape under these growth conditions. RNA-Seq detected almost 24% of the annotated genes to be regulated, twice the amount identified by microarray. In addition to confirming entire regulated operons containing known DEGs, the new approach detected the induction of genes involved in carbon metabolism and flagellar and twitching motility. This may support N2-fixation by increasing energy production and by finding suitable microaerobic niches. On the other hand, energy expenditures were reduced by suppressing translation and vitamin biosynthesis. Nonetheless, strain BH72 does not appear to be content with N2-fixation but is primed for alternative economic N-sources, such as nitrate, urea or amino acids; a strong gene induction of machineries for their uptake and assimilation was detected. RNA-Seq has thus provided a better understanding of a lifestyle under limiting nitrogen sources by elucidating hitherto unknown regulated processes.
Uptake of Dimethylsulfoniopropionate (DMSP) by Natural Microbial Communities of the Great Barrier Reef (GBR), Australia
Authors: Fernandez Eva , Ostrowski Martin , Siboni Nachshon , Seymour Justin R. , Petrou Katherina
Published: September 2021

Dimethylsulfoniopropionate (DMSP) is a key organic sulfur compound that is produced by many phytoplankton and macrophytes and is ubiquitous in marine environments. Following its release into the water column, DMSP is primarily metabolised by heterotrophic bacterioplankton, but recent evidence indicates that non-DMSP producing phytoplankton can also assimilate DMSP from the surrounding environment. In this study, we examined the uptake of DMSP by communities of bacteria and phytoplankton within the waters of the Great Barrier Reef (GBR), Australia. We incubated natural GBR seawater with DMSP and quantified the uptake of DMSP by different fractions of the microbial community (>8 µm, 3–8 µm, <3 µm). We also evaluated how microbial community composition and the abundances of DMSP degrading genes are influenced by elevated dissolved DMSP levels. Our results showed uptake and accumulation of DMSP in all size fractions of the microbial community, with the largest fraction (>8 µm) forming the dominant sink, increasing in particulate DMSP by 44–115% upon DMSP enrichment. Longer-term incubations showed however, that DMSP retention was short lived (<24 h) and microbial responses to DMSP enrichment differed depending on the community carbon and sulfur demand. The response of the microbial communities from inside the reef indicated a preference towards cleaving DMSP into the climatically active aerosol dimethyl sulfide (DMS), whereas communities from the outer reef were sulfur and carbon limited, resulting in more DMSP being utilised by the cells. Our results show that DMSP uptake is shared across members of the microbial community, highlighting larger phytoplankton taxa as potentially relevant DMSP reservoirs and provide new information on sulfur cycling as a function of community metabolism in deeper, oligotrophic GBR waters.
RTG Signaling Sustains Mitochondrial Respiratory Capacity in HOG1-Dependent Osmoadaptation
Authors: Guaragnella Nicoletta , Agrimi Gennaro , Scarcia Pasquale , Suriano Clelia , Pisano Isabella , Bobba Antonella , Mazzoni Cristina , Palmieri Luigi , Giannattasio Sergio
Published: September 2021

Mitochondrial RTG-dependent retrograde signaling, whose regulators have been characterized in Saccharomyces cerevisiae, plays a recognized role under various environmental stresses. Of special significance, the activity of the transcriptional complex Rtg1/3 has been shown to be modulated by Hog1, the master regulator of the high osmolarity glycerol pathway, in response to osmotic stress. The present work focuses on the role of RTG signaling in salt-induced osmotic stress and its interaction with HOG1. Wild-type and mutant cells, lacking HOG1 and/or RTG genes, are compared with respect to cell growth features, retrograde signaling activation and mitochondrial function in the presence and in the absence of high osmostress. We show that RTG2, the main upstream regulator of the RTG pathway, contributes to osmoadaptation in an HOG1-dependent manner and that, with RTG3, it is notably involved in a late phase of growth. Our data demonstrate that impairment of RTG signaling causes a decrease in mitochondrial respiratory capacity exclusively under osmostress. Overall, these results suggest that HOG1 and the RTG pathway may interact sequentially in the stress signaling cascade and that the RTG pathway may play a role in inter-organellar metabolic communication for osmoadaptation.
Herpes Simplex Virus Re-Activation in Patients with SARS-CoV-2 Pneumonia: A Prospective, Observational Study
Authors: Franceschini Erica , Cozzi-Lepri Alessandro , Santoro Antonella , Bacca Erica , Lancellotti Guido , Menozzi Marianna , Gennari William , Meschiari Marianna , Bedini Andrea , Orlando Gabriella , Puzzolante Cinzia , Digaetano Margherita , Milic Jovana , Codeluppi Mauro , Pecorari Monica , Carli Federica , Cuomo Gianluca , Alfano Gaetano , Corradi Luca , Tonelli Roberto , De Maria Nicola , Busani Stefano , Biagioni Emanuela , Coloretti Irene , Guaraldi Giovanni , Sarti Mario , Luppi Mario , Clini Enrico , Girardis Massimo , Gyssens Inge , Mussini Cristina
Published: September 2021

Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care units were published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week. Methods: we conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena. Results: of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs. 49.0%, p = 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs. 22.4%, p = 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with the use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR = 5.13, 95% CI:1.36–19.32, p = 0.016). The effect size was larger when restricting to participants who were treated with high doses of steroids while there was no evidence to support an association with the use of tocilizumab Conclusions: our study shows a high incidence of HSV-1 re-activation both virologically and clinically in patients with SARS-CoV-2 severe pneumonia, especially in those treated with steroids.
High Diversity of Leptospira Species Infecting Bats Captured in the Urabá Region (Antioquia-Colombia)
Authors: Monroy Fernando P. , Solari Sergio , Lopez Juan Álvaro , Agudelo-Flórez Piedad , Peláez Sánchez Ronald Guillermo
Published: September 2021

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the genus Leptospira. This zoonotic disease affects humans, domestic animals and wild animals. Colombia is considered an endemic country for leptospirosis; Antioquia is the second department in Colombia, with the highest number of reported leptospirosis cases. Currently, many studies report bats as reservoirs of Leptospira spp. but the prevalence in these mammals is unknown. The goal of this study was to better understand the role of bats as reservoir hosts of Leptospira species and to evaluate the genetic diversity of circulating Leptospira species in Antioquia-Colombia. We captured 206 bats in the municipalities of Chigorodó (43 bats), Carepa (43 bats), Apartadó (39 bats), Turbo (40 bats), and Necoclí (41 bats) in the Urabá region (Antioquia-Colombia). Twenty bats tested positive for Leptospira spp. infection (20/206—9.70%) and the species of infected bats were Carollia perspicillata, Dermanura rava, Glossophaga soricina, Molossus molossus, Artibeus planirostris, and Uroderma convexum. These species have different feeding strategies such as frugivorous, insectivores, and nectarivores. The infecting Leptospira species identified were Leptospira borgpetersenii (3/20–15%), Leptospira alexanderi (2/20–10%), Leptospira noguchii (6/20–30%), Leptospira interrogans (3/20–15%), and Leptospira kirschneri (6/20–30%). Our results showed the importance of bats in the epidemiology, ecology, and evolution of Leptospira in this host-pathogen association. This is the first step in deciphering the role played by bats in the epidemiology of human leptospirosis in the endemic region of Urabá (Antioquia-Colombia).
OXA-900, a Novel OXA Sub-Family Carbapenemase Identified in Citrobacter freundii, Evades Detection by Commercial Molecular Diagnostics Tests
Authors: Frenk Sammy , Rakovitsky Nadya , Kon Hadas , Rov Reut , Abramov Shirin , Lurie-Weinberger Mor Nadia , Schwartz David , Pinco Erica , Lellouche Jonathan , Carmeli Yehuda
Published: September 2021

Using whole-genome sequencing and cloning of the target gene, we identified blaOXA-900 carbapenemase, a novel blaOXA belonging to a distant and distinct sub-family of blaOXA-48-like. The plasmid-mediated gene was identified in a C. freundii isolate with elevated carbapenem MICs that evaded detection by commercial DNA-based methods. The novel gene, an OXA-48 family carbapenem-hydrolyzing class D β-lactamase, OXA-900, likely originates from marine environmental Shewanella. Since this plasmid-mediated gene has entered a member of the Enterobacterales and evades detection by commonly used tests, it may gain wide dissemination among Enterobacterales.
The Many Faces of Enterococcus spp.—Commensal, Probiotic and Opportunistic Pathogen
Authors: Krawczyk Beata , Wityk Paweł , Gałęcka Mirosława , Michalik Michał
Published: September 2021

Enterococcus spp. are Gram-positive, facultative, anaerobic cocci, which are found in the intestinal flora and, less frequently, in the vagina or mouth. Enterococcus faecalis and Enterococcus faecium are the most common species found in humans. As commensals, enterococci colonize the digestive system and participate in the modulation of the immune system in humans and animals. For many years reference enterococcal strains have been used as probiotic food additives or have been recommended as supplements for the treatment of intestinal dysbiosis and other conditions. The use of Enterococcus strains as probiotics has recently become controversial due to the ease of acquiring different virulence factors and resistance to various classes of antibiotics. Enterococci are also seen as opportunistic pathogens. This problem is especially relevant in hospital environments, where enterococcal outbreaks often occur. Their ability to translocate from the gastro-intestinal tract to various tissues and organs as well as their virulence and antibiotic resistance are risk factors that hinder eradication. Due to numerous reports on the plasticity of the enterococcal genome and the acquisition of pathogenic microbial features, we ask ourselves, how far is this commensal genus from acquiring pathogenicity? This paper discusses both the beneficial properties of these microorganisms and the risk factors related to their evolution towards pathogenicity.
Role of Gln79 in Feedback Inhibition of the Yeast γ-Glutamyl Kinase by Proline
Authors: Nishimura Akira , Takasaki Yurie , Isogai Shota , Toyokawa Yoichi , Tanahashi Ryoya , Takagi Hiroshi
Published: September 2021

Awamori, the traditional distilled alcoholic beverage of Okinawa, Japan, is brewed with the yeast Saccharomyces cerevisiae. During the distillation process after the fermentation, enormous quantities of distillation residues containing yeast cells must be disposed of, and this has recently been recognized as a major problem both environmentally and economically. Proline, a multifunctional amino acid, has the highest water retention capacity among amino acids. Therefore, distillation residues with large amounts of proline could be useful in cosmetics. Here, we isolated a yeast mutant with high levels of intracellular proline and found a missense mutation (Gln79His) on the PRO1 gene encoding the γ-glutamyl kinase Pro1, a limiting enzyme in proline biosynthesis. The amino acid change of Gln79 to His in Pro1 resulted in desensitization to the proline-mediated feedback inhibition of GK activity, leading to the accumulation of proline in cells. Biochemical and in silico analyses showed that the amino acid residue at position 79 is involved in the stabilization of the proline binding pocket in Pro1 via a hydrogen-bonding network, which plays an important role in feedback inhibition. Our current study, therefore, proposed a possible mechanism underlying the feedback inhibition of γ-glutamyl kinase activity. This mechanism can be applied to construct proline-accumulating yeast strains to effectively utilize distillation residues.
Harnessing the Anti-Nociceptive Potential of NK2 and NK3 Ligands in the Design of New Multifunctional μ/δ-Opioid Agonist–Neurokinin Antagonist Peptidomimetics
Authors: Gadais Charlène , Piekielna-Ciesielska Justyna , De Neve Jolien , Martin Charlotte , Janecka Anna , Ballet Steven
Published: September 2021

Opioid agonists are well-established analgesics, widely prescribed for acute but also chronic pain. However, their efficiency comes with the price of drastically impacting side effects that are inherently linked to their prolonged use. To answer these liabilities, designed multiple ligands (DMLs) offer a promising strategy by co-targeting opioid and non-opioid signaling pathways involved in nociception. Despite being intimately linked to the Substance P (SP)/neurokinin 1 (NK1) system, which is broadly examined for pain treatment, the neurokinin receptors NK2 and NK3 have so far been neglected in such DMLs. Herein, a series of newly designed opioid agonist-NK2 or -NK3 antagonists is reported. A selection of reported peptidic, pseudo-peptidic, and non-peptide neurokinin NK2 and NK3 ligands were covalently linked to the peptidic μ-opioid selective pharmacophore Dmt-DALDA (H-Dmt-d-Arg-Phe-Lys-NH2) and the dual μ/δ opioid agonist H-Dmt-d-Arg-Aba-βAla-NH2 (KGOP01). Opioid binding assays unequivocally demonstrated that only hybrids SBL-OPNK-5, SBL-OPNK-7 and SBL-OPNK-9, bearing the KGOP01 scaffold, conserved nanomolar range μ-opioid receptor (MOR) affinity, and slightly reduced affinity for the δ-opioid receptor (DOR). Moreover, NK binding experiments proved that compounds SBL-OPNK-5, SBL-OPNK-7, and SBL-OPNK-9 exhibited (sub)nanomolar binding affinity for NK2 and NK3, opening promising opportunities for the design of next-generation opioid hybrids.
Computational Identification of Dithymoquinone as a Potential Inhibitor of Myostatin and Regulator of Muscle Mass
Authors: Ahmad Syed Sayeed , Ahmad Khurshid , Lee Eun Ju , Shaikh Sibhghatulla , Choi Inho
Published: September 2021

The skeletal muscle (SM) is the largest organ in the body and has tremendous regenerative power due to its myogenic stem cell population. Myostatin (MSTN), a protein produced by SM, is released into the bloodstream and is responsible for age-related reduced muscle fiber development. The objective of this study was to identify the natural compounds that inhibit MSTN with therapeutic potential for the management of age-related disorders, specifically muscle atrophy and sarcopenia. Sequential screening of 2000 natural compounds was performed, and dithymoquinone (DTQ) was found to inhibit MSTN with a binding free energy of −7.40 kcal/mol. Furthermore, the docking results showed that DTQ reduced the binding interaction between MSTN and its receptor, activin receptor type-2B (ActR2B). The global energy of MSTN-ActR2B was found to be reduced from −47.75 to −40.45 by DTQ. The stability of the DTQ–MSTN complex was subjected to a molecular dynamics analysis for up to 100 ns to check the stability of the complex using RMSD, RMSF, Rg, SASA, and H-bond number. The complex was found to be stable after 10 ns to the end of the simulation. These results suggest that DTQ blocks MSTN signaling through ActR2B and that it has potential use as a muscle growth-promoting agent during the aging process.
Metabolomic Profiling of Fresh Goji (Lycium barbarum L.) Berries from Two Cultivars Grown in Central Italy: A Multi-Methodological Approach
Authors: Spano Mattia , Maccelli Alessandro , Di Matteo Giacomo , Ingallina Cinzia , Biava Mariangela , Crestoni Maria Elisa , Bardaud Jean-Xavier , Giusti Anna Maria , Mariano Alessia , Scotto D’Abusco Anna , Sobolev Anatoly P. , Lasalvia Alba , Fornarini Simonetta , Mannina Luisa
Published: September 2021

The metabolite profile of fresh Goji berries from two cultivars, namely Big Lifeberry (BL) and Sweet Lifeberry (SL), grown in the Lazio region (Central Italy) and harvested at two different periods, August and October, corresponding at the beginning and the end of the maturation, was characterized by means of nuclear magnetic resonance (NMR) and electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR MS) methodologies. Several classes of compounds such as sugars, amino acids, organic acids, fatty acids, polyphenols, and terpenes were identified and quantified in hydroalcoholic and organic Bligh-Dyer extracts. Sweet Lifeberry extracts were characterized by a higher content of sucrose with respect to the Big Lifeberry ones and high levels of amino acids (glycine, betaine, proline) were observed in SL berries harvested in October. Spectrophotometric analysis of chlorophylls and total carotenoids was also carried out, showing a decrease of carotenoids during the time. These results can be useful not only to valorize local products but also to suggest the best harvesting period to obtain a product with a chemical composition suitable for specific industrial use. Finally, preliminary studies regarding both the chemical characterization of Goji leaves generally considered a waste product, and the biological activity of Big Lifeberry berries extracts was also investigated. Goji leaves showed a chemical profile rich in healthy compounds (polyphenols, flavonoids, etc.) confirming their promising use in the supplements/nutraceutical/cosmetic field. MG63 cells treated with Big Lifeberry berries extracts showed a decrease of iNOS, COX-2, IL-6, and IL-8 expression indicating their significant biological activity.
Anti-Inflammatory CeO2 Nanoparticles Prevented Cytotoxicity Due to Exogenous Nitric Oxide Donors via Induction Rather Than Inhibition of Superoxide/Nitric Oxide in HUVE Cells
Authors: Akhtar Mohd Javed , Ahamed Maqusood , Alhadlaq Hisham
Published: September 2021

The mechanism behind the cytoprotective potential of cerium oxide nanoparticles (CeO2 NPs) against cytotoxic nitric oxide (NO) donors and H2O2 is still not clear. Synthesized and characterized CeO2 NPs significantly ameliorated the lipopolysaccharide (LPS)-induced cytokines IL-1β and TNF-α. The main goal of this study was to determine the capacities of NPs regarding signaling effects that could have occurred due to reactive oxygen species (ROS) and/or NO, since NP-induced ROS/NO did not lead to toxicity in HUVE cells. Concentrations that induced 50% cell death (i.e., IC50s) of two NO donors (DETA-NO; 1250 ± 110 µM and sodium nitroprusside (SNP); 950 ± 89 µM) along with the IC50 of H2O2 (120 ± 7 µM) were utilized to evaluate cytoprotective potential and its underlying mechanism. We determined total ROS (as a collective marker of hydrogen peroxide, superoxide radical (O2•−), hydroxyl radical, etc.) by DCFH-DA and used a O2•− specific probe DHE to decipher prominent ROS. The findings revealed that signaling effects mediated mainly by O2•− and/or NO are responsible for the amelioration of toxicity by CeO2 NPs at 100 µg/mL. The unaltered effect on mitochondrial membrane potential (MMP) due to NP exposure and, again, CeO2 NPs-mediated recovery in the loss of MMP due to exogenous NO donors and H2O2 suggested that NP-mediated O2•− production might be extra-mitochondrial. Data on activated glutathione reductase (GR) and unaffected glutathione peroxidase (GPx) activities partially explain the mechanism behind the NP-induced gain in GSH and persistent cytoplasmic ROS. The promoted antioxidant capacity due to non-cytotoxic ROS and/or NO production, rather than inhibition, by CeO2 NP treatment may allow cells to develop the capacity to tolerate exogenously induced toxicity.
Factors Affecting Synthetic Dye Adsorption; Desorption Studies: A Review of Results from the Last Five Years (2017–2021)
Authors: Rápó Eszter , Tonk Szende
Published: September 2021

The primary, most obvious parameter indicating water quality is the color of the water. Not only can it be aesthetically disturbing, but it can also be an indicator of contamination. Clean, high-quality water is a valuable, essential asset. Of the available technologies for removing dyes, adsorption is the most used method due to its ease of use, cost-effectiveness, and high efficiency. The adsorption process is influenced by several parameters, which are the basis of all laboratories researching the optimum conditions. The main objective of this review is to provide up-to-date information on the most studied influencing factors. The effects of initial dye concentration, pH, adsorbent dosage, particle size and temperature are illustrated through examples from the last five years (2017–2021) of research. Moreover, general trends are drawn based on these findings. The removal time ranged from 5 min to 36 h (E = 100% was achieved within 5–60 min). In addition, nearly 80% efficiency can be achieved with just 0.05 g of adsorbent. It is important to reduce adsorbent particle size (with Φ decrease E = 8–99%). Among the dyes analyzed in this paper, Methylene Blue, Congo Red, Malachite Green, Crystal Violet were the most frequently studied. Our conclusions are based on previously published literature.
Artemisia anomala Herba Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice and the Production of Pro-Inflammatory Mediators in Tumor Necrosis Factor Alpha-/Interferon Gamma-Induced HaCaT Cells
Authors: Yang Ju-Hye , Kim Kwang-Youn , Kim Young-Woo , Park Kwang-Il
Published: September 2021

Artemisia anomala S. Moore is a perennial herbaceous plant classified as Asteraceae of the genus Artemisia. Many species of Artemisia have been used as medicinal materials. Artemisia anomala S. Moore has been widely used in China to treat inflammatory diseases. However, the mechanism of its action on the keratinocyte inflammatory response is poorly understood. Here, we investigated the anti-inflammatory reaction of Artemisia anomala S. Moore ethanol extract (EAA) using human keratinocyte (HaCaT) cells, which involved investigating the nuclear factor kappa B (NF-κB), signal transducer, and activator of transcription-1 (STAT-1), as well as mitogen-activated protein kinase (MAPK) signaling pathways and atopic dermatitis-like skin lesions in mice. We elucidated the anti-inflammatory effects of EAA on tumor necrosis factor-α/interferon-γ (TNF-α/IFN-γ)-treated human keratinocyte cells and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like mice. The levels of chemokines and cytokines (IL-8, IL-6, TARC, and RANTES) were determined by an enzyme-linked immunosorbent assay. The NF-κB, STAT-1, and MAPK signaling pathways in HaCaT cells were analyzed by western blotting. Thickening of the mice dorsal and ear skin was measured and inflammatory cell infiltration was observed by hematoxylin and eosin staining. Results showed that EAA suppressed IL-8, IL-6, TARC, and RANTES production. EAA inhibited nuclear translocation of NFκB and STAT-1, as well as reduced the levels of phosphorylated ERK MAPKs. EAA improved AD-like skin lesions in DNCB-treated mice. These findings suggest that EAA possesses stronger anti-inflammatory properties and can be useful as a functional food or candidate agent for AD.
A Rapid HPLC-UV Protocol Coupled to Chemometric Analysis for the Determination of the Major Phenolic Constituents and Tocopherol Content in Almonds and the Discrimination of the Geographical Origin
Authors: Kalogiouri Natasa P. , Mitsikaris Petros D. , Klaoudatos Dimitris , Papadopoulos Athanasios N. , Samanidou Victoria F.
Published: September 2021

Reversed phase-high-pressure liquid chromatographic methodologies equipped with UV detector (RP-HPLC-UV) were developed for the determination of phenolic compounds and tocopherols in almonds. Nineteen samples of Texas almonds originating from USA and Greece were analyzed and 7 phenolic acids, 7 flavonoids, and tocopherols (−α, −β + γ) were determined. The analytical methodologies were validated and presented excellent linearity (r2 > 0.99), high recoveries over the range between 83.1 (syringic acid) to 95.5% (ferulic acid) for within-day assay (n = 6), and between 90.2 (diosmin) to 103.4% (rosmarinic acid) for between-day assay (n = 3 × 3), for phenolic compounds, and between 95.1 and 100.4% for within-day assay (n = 6), and between 93.2–96.2% for between-day assay (n = 3 × 3) for tocopherols. The analytes were further quantified, and the results were analyzed by principal component analysis (PCA), and agglomerative hierarchical clustering (AHC) to investigate potential differences between the bioactive content of almonds and the geographical origin. A decision tree (DT) was developed for the prediction of the geographical origin of almonds proposing a characteristic marker with a concentration threshold, proving to be a promising and reliable tool for the guarantee of the authenticity of the almonds.
Application of Three Ecological Assessment Tools in Examining Chromatographic Methods for the Green Analysis of a Mixture of Dopamine, Serotonin, Glutamate and GABA: A Comparative Study
Authors: Almalki Atiah H. , Naguib Ibrahim A. , Alshehri Fahad S. , Alghamdi Badrah S. , Alsaab Hashem O. , Althobaiti Yusuf S. , Alshehri Sameer , Abdallah Fatma F.
Published: September 2021

The assessment of greenness of analytical protocols is of great importance now to preserve the environment. Some studies have analyzed either only the neurotransmitters, dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA), together or with other neurotransmitters and biomarkers. However, these methods have not been investigated for their greenness and were not compared with each other to find the optimum one. Therefore, this study aims to compare seven published chromatographic methods that analyzed the four neurotransmitters and their mixtures using the National Environmental Method Index, Analytical Eco-Scale Assessment (ESA), and Green Analytical Procedure Index (GAPI). As these methods cover both qualitative and quantitative aspects, they offer better transparency. Overall, GAPI showed maximum greenness throughout the analysis. Method 6 was proven to be the method of choice for analyzing the mixture, owing to its greenness, according to NEMI, ESA, and GAPI. Additionally, method 6 has a wide scope of application (13 components can be analyzed), high sensitivity (low LOQ values), and fast analysis (low retention times, especially for glutamate and GABA).
Evaluation of Different Interstimulus Rinse Protocols on Smoke Attribute Perception in Wildfire-Affected Wines
Authors: Fryer Jenna A. , Collins Thomas S. , Tomasino Elizabeth
Published: September 2021

Wildfires produce smoke that can carry organic compounds to a vineyard, which are then absorbed by the grape berry and result in wines with elevated levels of smoke-related phenols. These phenols have been found to have a large impact on the flavor of wines, being the cause of a smokey flavor with a lasting ashy aftertaste. When evaluating the sensory profile of these wines, there is an observed problem due to the lasting nature of these undesirable attributes and potential flavor carryover between samples. Through the use of standard and temporal attribute check-all-that-apply, this research desires to better understand the impact of smoke on the sensorial profiles of wines with various levels of smoke phenols (high, moderate, and low). Additionally, through the employment of different interstimulus protocols, the effectiveness of rinses on diminishing the smoke flavor in wines and optimal time separation were investigated. It was determined that a 1 g/L pectin rinse in between samples with a 120 s separation is optimal to ensure the removal of smoke attribute perception. This work also indicated the need to look deeper at the effects of the in-mouth hydrolysis of glyconjugate phenols that impact overall smoke flavor.
Effect of Sorbent Additives to Copper-Contaminated Soils on Seed Germination and Early Growth of Grass Seedlings
Authors: Możdżeń Katarzyna , Barabasz-Krasny Beata , Kviatková Tatiana , Zandi Peiman , Turisová Ingrid
Published: September 2021

Heavy metal and metalloid-contaminated soil is a serious barrier to colonization for many plant species. The problem of the elimination of toxic waste accumulated in technogenous soils in many highly transformed regions is extremely important. Hence, another attempt was made to analyze the effect of the addition of sorbents (BCH—biochar, B—bentonite, ChM—chicken manure, OS—organo-zeolitic substrate) to contaminated copper soil on the germination and early growth of Eurasian common grass species (Agrostis capillaris, A. stolonifera, Festuca rubra and Poa pratensis), which could potentially be used in recultivation. This experiment was based on the laboratory sandwich method. Standard germination indexes, morphometry and biomass analysis were used. The percentage of germinating seeds was lower in each of the soil variants and sorbents used compared to the control. Dry mass was positively stimulated by all sorbents. The response to the addition of sorbents, expressed as the electrolyte leakage of seedlings, was different depending on the species and type of sorbent. Among all sorbents, the most positive effects on germination and growth were observed in the case of OS. Overall, the response to the addition of sorbents was different in the studied species, depending on their stage of development.
Antimicrobial, Antioxidant and Antiproliferative Secondary Metabolites from Inonotus nidus-pici
Authors: Garádi Zsófia , Dékány Miklós , Móricz Ágnes M. , Gaál Anikó , Papp Viktor , Béni Szabolcs , Ványolós Attila
Published: September 2021

Inonotus nidus-pici is a sterile conk which produces macrofungus, a neglected Central-Eastern European relative of the prized Inonotus obliquus, also known as chaga. Investigation of the methanol extract of the poroid fungus I. nidus-pici resulted in the isolation of citropremide (1), 3,4-dihydroxybenzalacetone (2) , lanosterol (3), ergost-6,8,22-trien-3β-ol (4), and ergosterol peroxide (5). The structures of fungal compounds were determined on the basis of one- and two-dimensional NMR and MS spectroscopic analysis. Compounds 1–2 and 4–5 were evaluated for their antioxidant and antimicrobial properties against several bacterial and fungal strains. 3,4-dihydroxybenzalacetone (2) and ergost-6,8,22-trien-3β-ol (4) demonstrated moderate antimicrobial activity, while the former possessed notable antioxidant activity in DPPH assay. The antiproliferative examinations performed on three human cancer (MES-SA, MES-SA/Dx5, A431) cell lines demonstrated that compounds 4 and 5 have notable cytotoxic activity with IC values in micromolar range. The current study represents the first report on the chemical profile of I. nidus-pici, providing a comprehensive study on the isolation and structure determination of bioactive secondary metabolites of this macrofungus.