bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Hydrogen-Containing Fuels and Environmentally Friendly Lubricating Coolant on Nitrogen Steels’ Wear Resistance for Spark Ignition Engine Pistons and Rings Kit Gasket Set
Authors: Balitskii Alexander , Kolesnikov Valerii , Abramek Karol F. , Balitskii Olexiy , Eliasz Jacek , Marya Havrylyuk , Ivaskevych Lyubomir , Kolesnikova Ielyzaveta
Published: November 2021

In this study, modern nitrogen steels used for the manufacture of rings for Honda engines (70CC, 90CC, CRF70F, XL70, XR70, C70, CT70, ATC70, CL70) as well as other transport tribotechnical units was investigated. Due to the present ecological situation in the world, new environmentally friendly lubricating fluids for nitrogen steels’ tribotechnical units and surface treatments have been proposed. The results of tribotechnical tests are presented in the form of diagrams, graphs and step polynomials obtained by mathematically describing the changes in wear intensity when the load changes for different lubricating fluids. Friction pairs were compared with ShellHF-E 46 (synthetic lubricating fluid), ShellHF-R (biological origin) and lubricating and cooling liquids with 1%, 3% and 5% vegetable oil concentrations. In tribocoupling it was found that hydrogen diffuses into the metal because the tribodestruction of lubricating coolants plays an active role in the destruction of friction surfaces.
Waste-to-Energy: An Opportunity to Increase Renewable Energy Share and Reduce Ecological Footprint in Small Island Developing States (SIDS)
Authors: Mata-Lima Herlander , Silva Deborah Wollmann , Nardi Deborah Cristina , Klering Samanta Andrize , de Oliveira Thays Car Feliciano , Morgado-Dias Fernando
Published: November 2021

Small Island Developing States (SIDSs) are faced with challenges such as reducing the share of fossil energy and waste landfilling. This work summarizes the main aspects of 53 SIDSs that constrain economic development, energy sources, and waste management strategies. An integrative bibliographical review is conducted to synthesize the state-of-the-art of waste-to-energy (WtE) strategies and compare the technologies in light of their suitability to SIDS. The findings show that considering the large amount of waste produced annually, WtE technologies are of the utmost importance to reduce ecological footprints (EFs) and greenhouse gas (GHG) emissions, and to increase the share of renewable energy with the installation of incineration plants with energy recovery to replace fossil fuel power plants. Although WtE is recommended for all SIDSs, the Atlantic, Indian Ocean, Mediterranean, and South China Sea (AIMS) countries exhibit higher population density (1509 inhab/km2) and a high share of fossil fuel in their electricity mix, so that there is greater urgency to replace landfilling practices with WtE. The estimation of potential power generation capacity (MWh) from annual municipal solid waste (MSW) in each SIDS as well as the reduced land area required demonstrate the feasibility of WtE technologies. Only 3% of the landfill area is necessary for buildings and landscaping associated with a WtE plant able to treat 1 million tons of MSW, considering a 30 year lifespan. Furthermore, incineration with energy recovery benefits from high penetration worldwide and affordable cost among thermochemical processes.
Towards Climate Neutrality in Poland by 2050: Assessment of Policy Implications in the Farm Sector
Authors: Wąs Adam , Krupin Vitaliy , Kobus Paweł , Witajewski-Baltvilks Jan , Jeszke Robert , Szczepański Krystian
Published: November 2021

Climate neutrality achievement in the European Union assumes the necessity of efforts and transformations in most economic sectors of its member-states. The farm sector in Poland, being the second largest contributor to the country’s greenhouse gas (GHG) emissions and in the top fifth of farm sectors in the EU-27 countries, needs to undergo structural and technological transformations to contribute to the climate action goals. The article assesses the potential impacts of Poland’s climate neutrality achievement path on the domestic farm sector in terms of its structure, output, income, and prices of agricultural products. The approach is based on complex economic modelling combining computable general equilibrium (CGE) and optimisation modelling, with the farm sector model consisting of farm, structural, and market modules. While the modelling results cover three GHG emission-reduction scenarios up to 2050, to understand the transformation impact within varying policy approaches, the study for each scenario of farm sector development also outlines three policy options: carbon pricing, forced emission limit, and carbon subsidies. Results in all scenarios and policy options indicate a strong foreseeable impact on agricultural output and prices (mainly livestock production), shifts in the production structure toward crops, as well as changes in farm income along the analysed timeframe.
The Electrodynamic Mechanism of Collisionless Multicomponent Plasma Expansion in Vacuum Discharges: From Estimates to Kinetic Theory
Authors: Kozhevnikov Vasily , Kozyrev Andrey , Kokovin Aleksandr , Semeniuk Natalia
Published: November 2021

This paper is devoted to the study of collisionless multicomponent plasma expansion in vacuum discharges. Based on the fundamental principles of physical kinetics formulated for vacuum discharge plasma, an answer is given to the following question: What is the main mechanism of cathode plasma transport from cathode to anode, which ensures non-thermal metallic positive ion movement? Theoretical modeling is provided based on the Vlasov–Poisson system of equations for a current flow in a planar vacuum discharge gap. It was shown that the non-thermal plasma expansion is of a purely electrodynamic nature, caused by the formation of a “potential hump” in the interelectrode space and its subsequent movement under certain conditions consistent with plasma electrodynamic transportation. The presented results reveal two cases of the described phenomenon: (1) the dynamics of single-component cathode plasma and (2) multicomponent plasma (consisting of multiple charged ions) expansion.
Assessing Hybrid Solar-Wind Potential for Industrial Decarbonization Strategies: Global Shift to Green Development
Authors: Rashid Khan Haroon ur , Awan Usama , Zaman Khalid , Nassani Abdelmohsen A. , Haffar Mohamed , Abro Muhammad Moinuddin Qazi
Published: November 2021

The global energy mix is shifting from fossil fuels to combinations of multiple energy storage and generation types. Hybrid energy system advancements provide opportunities for developing and deploying innovative green technology solutions that can further reduce emissions and achieve net-zero emissions by 2050. This study examined the impact of an increasing share of wind and solar electricity production on reducing carbon intensity by controlling coal and lignite domestic consumption and the production of refined oil products in a world aggregated data panel. Data covering the last three decades were used for the analysis by the ARDL bounds testing approach. The results showed that an increasing share of wind and solar electricity production would be helpful to decrease carbon intensity in the short and long term. On the other hand, a 1% increase in coal and domestic lignite consumption increased carbon intensity by 0.343% in the short run and 0.174% in the long run. The production of refined oil products decreases carbon intensity by 0.510% in the short run and 0.700% in the long run. However, refining oil products is associated with positive and negative environmental externalities. The positive aspect depends upon the removal of harmful pollutants and the production of cleaner-burning fuels, while the negative part is related to the operational side of refineries and processing plants that may release contaminants into the atmosphere, affecting global air and water quality. Hence, it is crucial to improve processing and refining capacity to produce better-refined oil products by using renewable fuels in energy production. It is proposed that these are the most cost-effective pathways to achieve industrial decarbonization.
Fast Optimization of Injector Selection for Waterflood, CO2-EOR and Storage Using an Innovative Machine Learning Framework
Authors: Selveindran Anand , Zargar Zeinab , Razavi Seyed Mahdi , Thakur Ganesh
Published: November 2021

Optimal injector selection is a key oilfield development endeavor that can be computationally costly. Methods proposed in the literature to reduce the number of function evaluations are often designed for pattern level analysis and do not scale easily to full field analysis. These methods are rarely applied to both water and miscible gas floods with carbon storage objectives; reservoir management decision making under geological uncertainty is also relatively underexplored. In this work, several innovations are proposed to efficiently determine the optimal injector location under geological uncertainty. A geomodel ensemble is prepared in order to capture the range of geological uncertainty. In these models, the reservoir is divided into multiple well regions that are delineated through spatial clustering. Streamline simulation results are used to train a meta-learner proxy. A posterior sampling algorithm evaluates injector locations across multiple geological realizations. The proposed methodology was applied to a producing field in Asia. The proxy predicted optimal injector locations for water and CO2 EOR and storage floods within several seconds (94–98% R2 scores). Blind tests with geomodels not used in training yielded accuracies greater than 90% (R2 scores). Posterior sampling selected optimal injection locations within minutes compared to hours using numerical simulation. This methodology enabled the rapid evaluation of injector well location for a variety of flood projects. This will aid reservoir managers to rapidly make field development decisions for field scale injection and storage projects under geological uncertainty.
Impact of Chilling Rate on the Evolution of Volatile and Non-Volatile Compounds in Raw Lamb Meat during Refrigeration
Authors: Xiang Can , Li Shaobo , Liu Huan , Liang Ce , Fang Fei , Zhang Dequan , Wang Zhenyu
Published: November 2021

The aim of this study was to investigate the effect of chilling rate (1.44, 22.2, and 32.4 °C/h) on the evolution of volatile and non-volatile compounds in raw lamb meat during refrigeration (1, 24, 72, and 120 h). Through orthogonal projection to latent structure-discriminant analysis, the calculation of odor activity values (OAV > 1) and taste activity values (TAV > 1) analysis, 1-octen-3-ol, (E, E)-2,4-decadienal, nonanal, hexanal, nona-3,5-dien-2-one, 2,3-octanedione, hexanoic acid, 1-nonen-4-ol, aspartate (Asp), Glutamic Acid (Glu), 5′-GMP, 5′-IMP, and 5′-AMP were regarded as differential flavor or taste compounds for raw meat undergone different chilling rates. With a rapid chilling rate at 24 h after slaughter, the contribution of 1-octen-3-ol decreased, but (E, E)-2,4-decadienal increased. Moreover, at 24 h post-mortem, the equivalent umami concentration of Asp, Glu, 5′-GMP, 5′-IMP and 5′-AMP in raw meat were significantly lower at a chilling rate of 1.44 °C/h than 32.4 °C/h (p < 0.05). Conclusively, under the rapid chilling rate, more fatty odor and umami compounds accumulated in 24 h aged meat.
An Investigation on a Coptic Embroidered Panel from the 13th Century “Crucifixion with the Twelve Apostles” (Benaki Museum, Athens)
Authors: de Chaves Lila
Published: November 2021

The “Crucifixion with the twelve Apostles”, a unique Coptic embroidered panel, was on display at the Benaki Museum (Athens, Greece). The representation of the “Crucifixion” with Christ in the center and six Apostles on either side, standing next to each other in frontal poses, is quite a rare one. This rare iconographic image of the twelve Apostles could be linked to the Ascension or the Pentecost. This unique representation of the Crucifixion with the twelve Apostles, which also involves the Ascension, is a one-of-a-kind compositional formula representing Christ’s Death as a triumph over Death, emphasizing, along with the other factors, its non-Chalcedonic origin. Moreover, the interpretation of an inscription, written in at least three languages embroidered in black silk thread, is a matter which confuses the issue even more. In the present study, we will attempt a comprehensive investigation, a detailed description, and interpretation of this rare iconography, based on written and iconographic evidence traced in the history of art heritage objects.
An Ancient Science to Improve Today’s Clinical Practice: Oral Surgery Meets Human Anatomy
Authors: Pistilli Roberto , Bonifazi Lorenzo , Barausse Carlo , Ruggeri Alessandra , Covelli Michele , Karaban Maryia , Felice Pietro
Published: November 2021

Human body dissection was a ubiquitous practice in the past, to better understand anatomy and to develop medicine. Today, its role could still be important to answer everyday clinical queries and help surgeons. The example of the possible lack of anesthesia during symphysis surgeries can emphasize the usefulness of dissection. The mandibular symphysis usually receives innervation from inferior alveolar nerve terminations, but, in some rare cases, a particular anastomosis involves the lingual nerve and the nerve to the mylohyoid. The anatomical knowledge resulting from body dissections could help oral surgeons to understand the reason why the patient could feel pain during the surgery, and ensure performance of the right lingual nerve block to obtain complete anesthesia. This clinical situation shows the educational role of an ancient, yet still valid, practice, human dissection, and the importance of anatomical studies to improve surgical skills, to provide better treatment for the patient.
Do Migrant and Native Robbers Target Different Places?
Authors: Long Dongping , Liu Lin
Published: November 2021

The spatial pattern of crime has been a central theme of criminological research. Recently, the spatial variation in the crime location choice of offenders by different population groups has been gaining more attention. This study addresses the issue of whether the spatial distribution of migrant robbers’ crime location choices is different from those of native robbers. Further, what factors contribute to such differences? Using a kernel density estimation and the discrete spatial choice modeling, we combine the offender data, POI data, and mobile phone data to explain the crime location choice of the street robbers who committed offenses and were arrested from 2012 to 2016 in ZG City, China. The results demonstrate that the crime location choices between migrant robbers and native robbers have obvious spatial differences. Migrant robbers tend to choose the labor-intensive industrial cluster, while native robbers prefer the old urban areas and urban villages. Wholesale markets, sports stadiums, transportation hubs, and subway stations only affect migrant robbers’ crime location choices, but not native robbers’. These results may be attributable to the different spatial awareness between migrant robbers and native robbers. The implications of the findings for criminological theory and crime prevention are discussed.
Fertility Sparing Treatments in Endometrial Cancer Patients: The Potential Role of the New Molecular Classification
Authors: Cavaliere Anna Franca , Perelli Federica , Zaami Simona , D’Indinosante Marco , Turrini Irene , Giusti Marco , Gullo Giuseppe , Vizzielli Giuseppe , Mattei Alberto , Scambia Giovanni , Vidiri Annalisa , Signore Fabrizio
Published: November 2021

Endometrial cancer is the most frequent gynecological malignancy, and, although epidemiologically it mainly affects advanced age women, it can also affect young patients who want children and who have not yet completed their procreative project. Fertility sparing treatments are the subject of many studies and research in continuous evolution, and represent a light of hope for young cancer patients who find themselves having to face an oncological path before fulfilling their desire for motherhood. The advances in molecular biology and the more precise clinical and prognostic classification of endometrial cancer based on the 2013 The Cancer Genome Atlas classification allow for the selection of patients who can be submitted to fertility sparing treatments with increasing oncological safety. It would also be possible to predict the response to hormonal treatment by investigating the state of the genes of the mismatch repair.
Effect of Cold Atmospheric Plasma on Epigenetic Changes, DNA Damage, and Possibilities for Its Use in Synergistic Cancer Therapy
Authors: Braný Dušan , Dvorská Dana , Strnádel Ján , Matáková Tatiana , Halašová Erika , Škovierová Henrieta
Published: November 2021

Cold atmospheric plasma has great potential for use in modern medicine. It has been used in the clinical treatment of skin diseases and chronic wounds, and in laboratory settings it has shown effects on selective decrease in tumour-cell viability, reduced tumour mass in animal models and stem-cell proliferation. Many researchers are currently focusing on its application to internal structures and the use of plasma-activated liquids in tolerated and effective human treatment. There has also been analysis of plasma’s beneficial synergy with standard pharmaceuticals to enhance their effect. Cold atmospheric plasma triggers various responses in tumour cells, and this can result in epigenetic changes in both DNA methylation levels and histone modification. The expression and activity of non-coding RNAs with their many important cell regulatory functions can also be altered by cold atmospheric plasma action. Finally, there is ongoing debate whether plasma-produced radicals can directly affect DNA damage in the nucleus or only initiate apoptosis or other forms of cell death. This article therefore summarises accepted knowledge of cold atmospheric plasma’s influence on epigenetic changes, the expression and activity of non-coding RNAs, and DNA damage and its effect in synergistic treatment with routinely used pharmaceuticals.
Therapeutic Effects of Inhibitor of ompA Expression against Carbapenem-Resistant Acinetobacter baumannii Strains
Authors: Na Seok-Hyeon , Jeon Hyejin , Oh Man-Hwan , Kim Yoo-Jeong , Chu Mingi , Lee Ill-Young , Lee Je-Chul
Published: November 2021

The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the ompA promoter activity of A. baumannii, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the ompA expression and biofilm formation in A. baumannii ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging A. baumannii strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with A. baumannii ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections.
Sirtuins and Autophagy in Age-Associated Neurodegenerative Diseases: Lessons from the C. elegans Model
Authors: Naseer Anam , Mir Snober Shabnam , Takacs-Vellai Krisztina , Nazir Aamir
Published: November 2021

Age-associated neurodegenerative diseases are known to have “impaired protein clearance” as one of the key features causing their onset and progression. Hence, homeostasis is the key to maintaining balance throughout the cellular system as an organism ages. Any imbalance in the protein clearance machinery is responsible for accumulation of unwanted proteins, leading to pathological consequences—manifesting in neurodegeneration and associated debilitating outcomes. Multiple processes are involved in regulating this phenomenon; however, failure to regulate the autophagic machinery is a critical process that hampers the protein clearing pathway, leading to neurodegeneration. Another important and widely known component that plays a role in modulating neurodegeneration is a class of proteins called sirtuins. These are class III histone deacetylases (HDACs) that are known to regulate various vital processes such as longevity, genomic stability, transcription and DNA repair. These enzymes are also known to modulate neurodegeneration in an autophagy-dependent manner. Considering its genetic relevance and ease of studying disease-related endpoints in neurodegeneration, the model system Caenorhabditis elegans has been successfully employed in deciphering various functional outcomes related to critical protein molecules, cell death pathways and their association with ageing. This review summarizes the vital role of sirtuins and autophagy in ageing and neurodegeneration, in particular highlighting the knowledge obtained using the C. elegans model system.
JI017, a Complex Herbal Medication, Induces Apoptosis via the Nox4–PERK–CHOP Axis in Ovarian Cancer Cells
Authors: Kim Taewoo , Ko Seong-Gyu
Published: November 2021

Many anti-cancer drugs, including paclitaxel and etoposide, have originated and been developed from natural products, and traditional herbal medicines have fewer adverse effects and lesser toxicity than anti-tumor reagents. Therefore, we developed a novel complex herbal medicine, JI017, which mediates endoplasmic reticulum (ER) stress and apoptosis through the Nox4–PERK–CHOP signaling pathway in ovarian cancer cells. JI017 treatment increases the expression of GRP78, ATF4, and CHOP and the phosphorylation of PERK and eIF2α via the upregulation of Nox4. Furthermore, it increases the release of intracellular reactive oxygen species (ROS), the production of intracellular Ca2+, and the activation of exosomal GRP78 and cell lysate GRP78. Combination treatment using the sarco/endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (TG) and JI017 reportedly induces increased ER stress and cell death in comparison to the control; however, knockdown experiments of PERK and CHOP indicated suppressed apoptosis and ER stress in JI017-treated ovarian cancer cells. Furthermore, targeting Nox4 using specific siRNA and pharmacological ROS inhibitors, including N-acetylcystein and diphenylene iodonium, blocked apoptosis and ER stress in JI017-treated ovarian cancer cells. In the radioresistant ovarian cancer model, when compared to JI017 alone, JI017 co-treatment with radiation induced greater cell death and resulted in overcoming radioresistance by inhibiting epithelial–mesenchymal-transition-related phenomena such as the reduction of E-cadherin and the increase of N-cadherin, vimentin, Slug, and Snail. These findings suggest that JI017 is a powerful anti-cancer drug for ovarian cancer treatment and that its combination treatment with radiation may be a novel therapeutic strategy for radioresistant ovarian cancer.
Thermoresponsive Molecular Brushes with a Rigid-Chain Aromatic Polyester Backbone and Poly-2-alkyl-2-oxazoline Side Chains
Authors: Tarabukina Elena , Fatullaev Emil , Krasova Anna , Sokolova Maria , Kurlykin Mikhail , Neelov Igor , Tenkovtsev Andrey , Filippov Alexander
Published: November 2021

A new polycondensation aromatic rigid-chain polyester macroinitiator was synthesized and used to graft linear poly-2-ethyl-2-oxazoline as well as poly-2-isopropyl-2-oxazoline by cationic polymerization. The prepared copolymers and the macroinitiator were characterized by NMR, GPC, AFM, turbidimetry, static, and dynamic light scattering. The molar masses of the polyester main chain and the grafted copolymers with poly-2-ethyl-2-oxazoline and poly-2-isopropyl-2-oxazoline side chains were 26,500, 208,000, and 67,900, respectively. The molar masses of the side chains of poly-2-ethyl-2-oxazoline and poly-2-isopropyl-2-oxazoline and their grafting densities were 7400 and 3400 and 0.53 and 0.27, respectively. In chloroform, the copolymers conformation can be considered as a cylinder wormlike chain, the diameter of which depends on the side chain length. In water at low temperatures, the macromolecules of the poly-2-ethyl-2-oxazoline copolymer assume a wormlike conformation because their backbones are well shielded by side chains, whereas the copolymer with short side chains and low grafting density strongly aggregates, which was visualized by AFM. The phase separation temperatures of the copolymers were lower than those of linear analogs of the side chains and decreased with the concentration for both samples. The LCST were estimated to be around 45 °C for the poly-2-ethyl-2-oxazoline graft copolymer, and below 20 °C for the poly-2-isopropyl-2-oxazoline graft copolymer.
MemDis: Predicting Disordered Regions in Transmembrane Proteins
Authors: Dobson Laszlo , Tusnády Gábor E.
Published: November 2021

Transmembrane proteins (TMPs) play important roles in cells, ranging from transport processes and cell adhesion to communication. Many of these functions are mediated by intrinsically disordered regions (IDRs), flexible protein segments without a well-defined structure. Although a variety of prediction methods are available for predicting IDRs, their accuracy is very limited on TMPs due to their special physico-chemical properties. We prepared a dataset containing membrane proteins exclusively, using X-ray crystallography data. MemDis is a novel prediction method, utilizing convolutional neural network and long short-term memory networks for predicting disordered regions in TMPs. In addition to attributes commonly used in IDR predictors, we defined several TMP specific features to enhance the accuracy of our method further. MemDis achieved the highest prediction accuracy on TMP-specific dataset among other popular IDR prediction methods.
The Two-Way Interaction between the Molecules That Cause Vaginal Malodour and Lactobacilli: An Opportunity for Probiotics
Authors: Puebla-Barragan Scarlett , Akouris Polycronis Paul , Al Kait F. , Carr Charles , Lamb Britney , Sumarah Mark , van der Veer Charlotte , Kort Remco , Burton Jeremy , Reid Gregor
Published: November 2021

Vaginal malodour is a sign of dysbiosis. The biogenic amines (BAs) cadaverine, putrescine and tyramine are known to be causative compounds. Recent reports suggest these compounds produced by pathogens might have a role beyond causing malodour; namely inhibiting the growth of lactobacilli bacteria that are crucial in the maintenance of vaginal homeostasis. The aim of this study was to identify whether certain lactobacilli strains could reduce BAs and to evaluate how Lactobacillus species were affected by these compounds. Using LC–MS and HPLC-UV, five Lactobacillus crispatus strains were identified as being capable of significantly reducing BAs from the media under in vitro conditions. Through 16S rRNA gene sequencing of vaginal swabs exposed to Bas, cadaverine was found to reduce the relative abundance of lactobacilli. When L. crispatus was exposed to media supplemented with BAs with an HCl adjusted lower pH, its growth was enhanced, demonstrating the relevance of the maintenance of an acidic vaginal environment. If strains are to be developed for probiotic application to alleviate bacterial vaginosis and other conditions affecting large numbers of women worldwide, their ability to adapt to Bas and regulate pH should be part of the experimentation.
Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer’s Disease
Authors: Maity Sabyasachi , Farrell Kayla , Navabpour Shaghayegh , Narayanan Sareesh Naduvil , Jarome Timothy J.
Published: November 2021

Epigenetic mechanisms, which include DNA methylation, a variety of post-translational modifications of histone proteins (acetylation, phosphorylation, methylation, ubiquitination, sumoylation, serotonylation, dopaminylation), chromatin remodeling enzymes, and long non-coding RNAs, are robust regulators of activity-dependent changes in gene transcription. In the brain, many of these epigenetic modifications have been widely implicated in synaptic plasticity and memory formation. Dysregulation of epigenetic mechanisms has been reported in the aged brain and is associated with or contributes to memory decline across the lifespan. Furthermore, alterations in the epigenome have been reported in neurodegenerative disorders, including Alzheimer’s disease. Here, we review the diverse types of epigenetic modifications and their role in activity- and learning-dependent synaptic plasticity. We then discuss how these mechanisms become dysregulated across the lifespan and contribute to memory loss with age and in Alzheimer’s disease. Collectively, the evidence reviewed here strongly supports a role for diverse epigenetic mechanisms in memory formation, aging, and neurodegeneration in the brain.
The Post-Storage Performance of RBCs from Beta-Thalassemia Trait Donors Is Related to Their Storability Profile
Authors: Anastasiadi Alkmini T. , Paronis Efthymios C. , Arvaniti Vasiliki-Zoi , Velentzas Athanasios D. , Apostolidou Anastasia C. , Balafas Evangelos G. , Dzieciatkowska Monika , Kostomitsopoulos Nikolaos G. , Stamoulis Konstantinos , Papassideri Issidora S. , D’Alessandro Angelo , Kriebardis Anastasios G. , Antonelou Marianna H. , Tzounakas Vassilis L.
Published: November 2021

Blood donors with beta-thalassemia traits (βThal+) have proven to be good “storers”, since their stored RBCs are resistant to lysis and resilient against oxidative/proteotoxic stress. To examine the performance of these RBCs post-storage, stored βThal+ and control RBCs were reconstituted in plasma donated from transfusion-dependent beta-thalassemic patients and healthy controls, and incubated for 24 h at body temperature. Several physiological parameters, including hemolysis, were evaluated. Moreover, labeled fresh/stored RBCs from the two groups were transfused in mice to assess 24 h recovery. All hemolysis metrics were better in the group of heterozygotes and distinguished them against controls in the plasma environment. The reconstituted βThal+ samples also presented higher proteasome activity and fewer procoagulant extracellular vesicles. Transfusion to mice demonstrated that βThal+ RBCs present a marginal trend for higher recovery, regardless of the recipient’s immune background and the RBC storage age. According to correlation analysis, several of these advantageous post-storage characteristics are related to storage phenotypes, like the cytoskeleton composition, low cellular fragility, and enhanced membrane proteostasis that characterize stored βThal+ RBCs. Overall, it seems that the intrinsic physiology of βThal+ RBCs benefits them in conditions mimicking a recipient environment, and in the circulation of animal models; findings that warrant validation in clinical trials.
In-Depth Sequence Analysis of Bread Wheat VRN1 Genes
Authors: Strejčková Beáta , Milec Zbyněk , Holušová Kateřina , Cápal Petr , Vojtková Tereza , Čegan Radim , Šafář Jan
Published: November 2021

The VERNALIZATION1 (VRN1) gene encodes a MADS-box transcription factor and plays an important role in the cold-induced transition from the vegetative to reproductive stage. Allelic variability of VRN1 homoeologs has been associated with large differences in flowering time. The aim of this study was to investigate the genetic variability of VRN1 homoeologs (VRN-A1, VRN-B1 and VRN-D1). We performed an in-depth sequence analysis of VRN1 homoeologs in a panel of 105 winter and spring varieties of hexaploid wheat. We describe the novel allele Vrn-B1f with an 836 bp insertion within intron 1 and show its specific expression pattern associated with reduced heading time. We further provide the complete sequence of the Vrn-A1b allele, revealing a 177 bp insertion in intron 1, which is transcribed into an alternative splice variant. Copy number variation (CNV) analysis of VRN1 homoeologs showed that VRN-B1 and VRN-D1 are present in only one copy. The copy number of recessive vrn-A1 ranged from one to four, while that of dominant Vrn-A1 was one or two. Different numbers of Vrn-A1a copies in the spring cultivars Branisovicka IX/49 and Bastion did not significantly affect heading time. We also report on the deletion of secondary structures (G-quadruplex) in promoter sequences of cultivars with more vrn-A1 copies.
Early Adventitial Activation and Proliferation in a Mouse Model of Arteriovenous Stenosis: Opportunities for Intervention
Authors: Chan Jenq-Shyong , Wang Yang , Cornea Virgilius , Roy-Chaudhury Prabir , Campos Begoña
Published: November 2021

Background: Arteriovenous fistula (AVF) stenosis remains an important cause of AVF maturation failure, for which there are currently no effective therapies. We examined the pattern and phenotype of cellular proliferation at different timepoints in a mouse model characterized by a peri-anastomotic AVF stenosis. Methods: Standard immunohistochemical analyses for cellular proliferation and macrophage infiltration were performed at 2, 7 and 14 d on our validated mouse model of AVF stenosis to study the temporal profile, geographical location and cellular phenotype of proliferating and infiltrating cells in this model. Results: Adventitial proliferation and macrophage infiltration (into the adventitia) began at 2 d, peaked at 7 d and then declined over time. Surprisingly, there was minimal macrophage infiltration or proliferation in the neointimal region at either 7 or 14 d, although endothelial cell proliferation increased rapidly between 2 d and 7 d, and peaked at 14 d. Conclusions: Early and rapid macrophage infiltration and cellular proliferation within the adventitia could play an important role in the downstream pathways of both neointimal hyperplasia and inward or outward remodelling.
Metal Sulfide Semiconductor Nanomaterials and Polymer Microgels for Biomedical Applications
Authors: Paca Athandwe M. , Ajibade Peter A.
Published: November 2021

The development of nanomaterials with therapeutic and/or diagnostic properties has been an active area of research in biomedical sciences over the past decade. Nanomaterials have been identified as significant medical tools with potential therapeutic and diagnostic capabilities that are practically impossible to accomplish using larger molecules or bulk materials. Fabrication of nanomaterials is the most effective platform to engineer therapeutic agents and delivery systems for the treatment of cancer. This is mostly due to the high selectivity of nanomaterials for cancerous cells, which is attributable to the porous morphology of tumour cells which allows nanomaterials to accumulate more in tumour cells more than in normal cells. Nanomaterials can be used as potential drug delivery systems since they exist in similar scale as proteins. The unique properties of nanomaterials have drawn a lot of interest from researchers in search of new chemotherapeutic treatment for cancer. Metal sulfide nanomaterials have emerged as the most used frameworks in the past decade, but they tend to aggregate because of their high surface energy which triggers the thermodynamically favoured interaction. Stabilizing agents such as polymer and microgels have been utilized to inhibit the particles from any aggregations. In this review, we explore the development of metal sulfide polymer/microgel nanocomposites as therapeutic agents against cancerous cells.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)
Authors: Palicelli Andrea , Croci Stefania , Bisagni Alessandra , Zanetti Eleonora , De Biase Dario , Melli Beatrice , Sanguedolce Francesca , Ragazzi Moira , Zanelli Magda , Chaux Alcides , Cañete-Portillo Sofia , Bonasoni Maria Paola , Soriano Alessandra , Ascani Stefano , Zizzo Maurizio , Castro Ruiz Carolina , De Leo Antonio , Giordano Guido , Landriscina Matteo , Carrieri Giuseppe , Cormio Luigi , Berney Daniel M. , Gandhi Jatin , Santandrea Giacomo , Bonacini Martina
Published: November 2021

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapy-resistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ T-cells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and RB deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223).
Small Reduced Graphene Oxides for Highly Efficient Oxygen Reduction Catalysts
Authors: Bak Su-Jeong , Kim Sun-I , Lim Su-yeong , Kim Taehyo , Kwon Se-Hun , Lee Duck Hyun
Published: November 2021

We demonstrated highly efficient oxygen reduction catalysts composed of uniform Pt nanoparticles on small, reduced graphene oxides (srGO). The reduced graphene oxide (rGO) size was controlled by applying ultrasonication, and the resultant srGO enabled the morphological control of the Pt nanoparticles. The prepared catalysts provided efficient surface reactions and exhibited large surface areas and high metal dispersions. The resulting Pt/srGO samples exhibited excellent oxygen reduction performance and high stability over 1000 cycles of accelerated durability tests, especially the sample treated with 2 h of sonication. Detailed investigations of the structural and electrochemical properties of the resulting catalysts suggested that both the chemical functionality and electrical conductivity of these samples greatly influence their enhanced oxygen reduction efficiency.
Ammonium Formate-Pd/C as a New Reducing System for 1,2,4-Oxadiazoles. Synthesis of Guanidine Derivatives and Reductive Rearrangement to Quinazolin-4-Ones with Potential Anti-Diabetic Activity
Authors: Marzullo Paola , Vasto Sonya , Buscemi Silvestre , Pace Andrea , Nuzzo Domenico , Palumbo Piccionello Antonio
Published: November 2021

1,2,4-Oxadiazole is a heterocycle with wide reactivity and many useful applications. The reactive O-N bond is usually reduced using molecular hydrogen to obtain amidine derivatives. NH4CO2H-Pd/C is here demonstrated as a new system for the O-N reduction, allowing us to obtain differently substituted acylamidine, acylguanidine and diacylguanidine derivatives. The proposed system is also effective for the achievement of a reductive rearrangement of 5-(2′-aminophenyl)-1,2,4-oxadiazoles into 1-alkylquinazolin-4(1H)-ones. The alkaloid glycosine was also obtained with this method. The obtained compounds were preliminarily tested for their biological activity in terms of their cytotoxicity, induced oxidative stress, α-glucosidase and DPP4 inhibition, showing potential application as anti-diabetics.
Tumor-Progressive Mechanisms Mediating miRNA–Protein Interaction
Authors: Konishi Hiroaki , Sato Hiroki , Takahashi Kenji , Fujiya Mikihiro
Published: November 2021

MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA–protein systems in cancer progression and its future applications in cancer treatment.
Alzheimer’s Disease and Type 2 Diabetes Mellitus: The Use of MCT Oil and a Ketogenic Diet
Authors: Takeishi Junpei , Tatewaki Yasuko , Nakase Taizen , Takano Yumi , Tomita Naoki , Yamamoto Shuzo , Mutoh Tatsushi , Taki Yasuyuki
Published: November 2021

Recently, type 2 diabetes mellitus (T2DM) has been reported to be strongly associated with Alzheimer’s disease (AD). This is partly due to insulin resistance in the brain. Insulin signaling and the number of insulin receptors may decline in the brain of T2DM patients, resulting in impaired synaptic formation, neuronal plasticity, and mitochondrial metabolism. In AD patients, hypometabolism of glucose in the brain is observed before the onset of symptoms. Amyloid-β accumulation, a main pathology of AD, also relates to impaired insulin action and glucose metabolism, although ketone metabolism is not affected. Therefore, the shift from glucose metabolism to ketone metabolism may be a reasonable pathway for neuronal protection. To promote ketone metabolism, medium-chain triglyceride (MCT) oil and a ketogenic diet could be introduced as an alternative source of energy in the brain of AD patients.
Comparative Efficiency of Native Insect Pollinators in Reproductive Performance of Medicago sativa L. in Pakistan
Authors: Rauf Abdur , Saeed Shafqat , Ali Mudssar , Nadeem Tahir Muhammad Hammad
Published: November 2021

Lucerne (Medicago sativa L.) is a cross-pollinated crop and requires entomophilous pollination for tripping of flowers and subsequent pod and seed set. To discover the best pollinators for lucerne seed production, a two-year field trial was carried out at the research farm of MNS University of Agriculture, Multan, Pakistan. Abundance and diversity of insect pollinators along with the foraging behavior were recorded in terms of tripping efficiency, stay time, visitation rate and pollen harvest. The single-visit efficiency of abundant insect pollinators was also evaluated in terms of number of seeds and seed weight per raceme along with germination percentage. Ten most abundant floral visitors (five solitary bee species, three honeybee species and two syrphid fly species) were tested for their pollination efficiency. Honeybees were most abundant in both the years followed by the solitary bees and syrphid flies. Single-visit efficacy in terms of number of pods per raceme, number of seeds per raceme, 1000 seed weight and germination percentage revealed Megachile cephalotes as the most efficient insect pollinator followed by Megachile hera and Amegilla sp. Future studies should investigate the biology and ecology of these bee species with special emphasis on their nesting behavior and seasonality.
Three-Device (3D) Technique for Liver Parenchyma Dissection in Robotic Liver Surgery
Authors: Perrakis Aristotelis , Rahimli Mirhasan , Gumbs Andrew , Negrini Victor , Andric Mihailo , Stockheim Jessica , Wex Cora , Lorenz Eric , Arend Joerg , Franz Mareike , Croner Roland
Published: November 2021

Background: The implementation of robotics in liver surgery offers several advantages compared to conventional open and laparoscopic techniques. One major advantage is the enhanced degree of freedom at the tip of the robotic tools compared to laparoscopic instruments. This enables excellent vessel control during inflow and outflow dissection of the liver. Parenchymal transection remains the most challenging part during robotic liver resection because currently available robotic instruments for parenchymal transection have several limitations and there is no standardized technique as of yet. We established a new strategy and share our experience. Methods: We present a novel technique for the transection of liver parenchyma during robotic surgery, using three devices (3D) simultaneously: monopolar scissors and bipolar Maryland forceps of the robot and laparoscopic-guided waterjet. We collected the perioperative data of twenty-eight patients who underwent this procedure for minor and major liver resections between February 2019 and December 2020 from the Magdeburg Registry of minimally invasive liver surgery (MD-MILS). Results: Twenty-eight patients underwent robotic-assisted 3D parenchyma dissection within the investigation period. Twelve cases of major and sixteen cases of minor hepatectomy for malignant and non-malignant cases were performed. Operative time for major liver resections (≥ 3 liver segments) was 381.7 (SD 80.6) min vs. 252.0 (70.4) min for minor resections (p < 0.01). Intraoperative measured blood loss was 495.8 (SD 508.8) ml for major and 256.3 (170.2) ml for minor liver resections (p = 0.090). The mean postoperative stay was 13.3 (SD 11.1) days for all cases. Liver surgery-related morbidity was 10.7%, no mortalities occurred. We achieved an R0 resection in all malignant cases. Conclusions: The 3D technique for parenchyma dissection in robotic liver surgery is a safe and feasible procedure. This novel method offers an advanced locally controlled preparation of intrahepatic vessels and bile ducts. The combination of precise extrahepatic vessel handling with the 3D technique of parenchyma dissection is a fundamental step forward to the standardization of robotic liver surgery for teaching purposing and the wider adoption of robotic hepatectomy into routine patient care.