bluuebunny/crossref_metadata_2025 huggingface dataset:
Review and Demonstration of the Potential of Bitcoin Mining as a Productive Use of Energy (PUE) to Aid Equitable Investment in Solar Micro- and Mini-Grids Worldwide
Authors: Hallinan Kevin P. , Hao Lu , Mulford Rydge , Bower Lauren , Russell Kaitlin , Mitchell Austin , Schroeder Alan
Published: January 2023

Despite the climate commitments made by countries in the Paris Climate Agreement adopted in 2015 and reinforced during COP 21 and with notably less success during COP 22, world carbon emissions increased in both 2021 and 2022. It is increasingly unlikely that the world will achieve the targeted 50% carbon reduction by 2030, the reduction approximately needed for reducing global temperature rise since the beginning of the Industrial Revolution to less than 1.5 deg. C. At the same time, there remain nearly 2 billion people in the world who have no or highly unreliable access to power. In developed countries, access to both clean energy and energy efficiency investment in residences within low to moderate income communities has also lagged. This paper provides a review of the “Productive Use of Energy (PUE)”, which is a means to add value to solar energy mini- and micro-grids to ensure investment worthiness and add more value to the communities being served. In this context, it posits an opportunity to leverage Bitcoin mining as a common PUE strategy applicable to new solar installations. Several actual pilot cases are described to demonstrate this potential throughout the world and at multiple scales. These include: (i) existing micro-grids with significant stranded energy to generate income that could be used to reduce the cost per kWh for the community; (ii) new solar micro-grids optimized to meet community load and mining operations; (iii) dedicated solar-powered Bitcoin mining mini-grids developed solely to create a funding stream for self-investment by communities for their benefit; and (iv) a low-income residential solar-powered Bitcoin miner to reduce the energy cost burden for residents. Several of these scenarios show significant potential to aid investment worthiness.
The Preparation of a Carbonaceous Adsorbent via Batch Pyrolysis of Waste Hemp Shives
Authors: Staf Marek , Šrámek Vít , Pohořelý Michael
Published: January 2023

The study focuses on the two-stage process of the thermal treatment of waste hemp shives aimed at obtaining a carbonaceous adsorbent. In the first stage, pyrolysis was carried out in a retort apparatus, which, at temperatures in the range of 450–850 °C, provided approximately 22.6–29.9% of the solid residue, 31.6–34.0% of the condensate, and 38.5–43.4% of gas with respect to the charge. The organic part of the condensates showed the net calorific value of 30.8–31.3 MJ kg−1, which makes it well suited for energy purposes. In the separated pyrolysis gases, GC-TCD-FID determined only five compounds, namely carbon dioxide, carbon monoxide, hydrogen, methane, and ethane, which together accounted for 98.5–99.8% of the gas volume. The remainder was composed mainly of ethene, propane, and propene. The highest net calorific value (14.7–14.8 MJ m−3) was exhibited by the gas collected in the range of 450–650 °C, which can be advantageously used for energy purposes. Non-activated solid pyrolysis residues had relatively low specific surface areas (BET), with the highest value determined being 294 m2 g−1. Therefore, they were activated by steam in a separate apparatus in the temperature range of 740–900 °C. The activation apparatus operated with a batch reactor of similar design to the pyrolysis retort. The activation increased the specific surface area of the pyrolysis residues up to the maximum of 915 m2 g−1. This study discusses the significant trends in specific surface area and total pore volume caused by a combination of different pyrolysis and activation temperatures. Better results were generally obtained for residues pyrolyzed at lower temperatures and then activated at high temperatures. The structure of the activated products mostly contained pores with a diameter of < 6 nm. Their development was mainly facilitated by the activation temperature of 850 °C, resulting in the relative presence of these pores in the range of 57.9–59.1%. All activated products were also characterized by an increased proportion of 20–80 nm pores, which formed, however, approximately one-third in comparison with the pores < 6 nm. Last but not least, the study also discusses the effect of activation conditions on the process loss of the product.
Benchmarking of Energy Consumption in Higher Education Buildings in Saudi Arabia to Be Sustainable: Sulaiman Al-Rajhi University Case
Authors: Alfaoyzan Faouzan Abdulaziz , Almasri Radwan A.
Published: January 2023

Electricity is used in educational buildings, and there are now numerous attempts to reduce consumption, achieve sustainability, and protect the environment. This paper aims to study energy consumption, identify opportunities to rationalize energy consumption, and propose solutions at Sulaiman Al-Rajhi University in the Kingdom of Saudi Arabia in order for the university campus to become sustainable. The results showed that total annual electrical consumption totaled 13,859 MWh in 2021. The air conditioning system, other devices, and lighting have the percentage of consumption 79, 14, and 7% of the total, respectively. Electricity consumption intensity was approximately 145–155 kWh/m2, and the per capita intensity was approximately 12,987–16,351 kWh, in the period 2017–2021. The price of the electrical energy generated on the university campus ranged between 0.3 and 0.53 SR/kWh in 2021, while the electricity tariff from the grid for educational buildings was 0.18 SR/kWh. This means that the public grid was 50% cheaper than campus-generated electricity. At the price of energy generated by generators, the total simple payback time (SPBT) for the suggested energy conservation measures (ECMs) is 4.13 years, whereas the SPBT is 8.96 in the case of the consumption of the electricity supplied by the national grid. The environmental benefits of the proposed ECMs were also identified.
Design Procedure and Testing for the Electrification of a Maintenance Railway Vehicle
Authors: D’Amato Davide , Lorito Marco , Monopoli Vito Giuseppe , Consoletti Rinaldo , Maiellaro Giuseppe , Cupertino Francesco
Published: January 2023

In response to climate change, governments around the world have committed to reducing greenhouse gas emissions, which contribute to global warming, through the energy transition from fossil fuels to renewable energy sources and electrification of transportation. This article outlines the design procedure for the electrification of a railway vehicle used for maintenance services on the rail network. The proposed methodology consists of the design of both an all-electric propulsion system and storage system with the aim of zero emissions when the vehicle is operating in tunnels and to minimise noise during maintenance services in cities. After highlighting the characteristics of the railway vehicle under consideration, a simulation model of the propulsion and generation system was developed in order to calculate the energy consumption of the entire railway system. Finally, experimental tests carried out on the prototype proved the effectiveness of the design procedure adopted and the proposed mathematical model, showing a good matching with the simulated results.
Adaptive-Energy-Sharing-Based Energy Management Strategy of Hybrid Sources in Electric Vehicles
Authors: Sidharthan Vishnu P. , Kashyap Yashwant , Kosmopoulos Panagiotis
Published: January 2023

The energy utilization of the transportation industry is increasing tremendously. The battery is one of the primary energy sources for a green and clean mode of transportation, but variations in driving profiles (NYCC, Artemis Urban, WLTP class-1) and higher C-rates affect the battery performance and lifespan of battery electric vehicles (BEVs). Hence, as a singular power source, batteries have difficulty in tackling these issues in BEVs, highlighting the significance of hybrid-source electric vehicles (HSEVs). The supercapacitor (SC) and photovoltaic panels (PVs) are the auxiliary power sources coupled with the battery in the proposed hybrid electric three-wheeler (3W). However, energy management strategies (EMS) are critical to ensure optimal and safe power allocation in HSEVs. A novel adaptive Intelligent Hybrid Source Energy Management Strategy (IHSEMS) is proposed to perform energy management in hybrid sources. The IHSEMS optimizes the power sources using an absolute energy-sharing algorithm to meet the required motor power demand using the fuzzy logic controller. Techno-economic assessment wass conducted to analyze the effectiveness of the IHSEMS. Based on the comprehensive discussion, the proposed strategy reduces peak battery power by 50.20% compared to BEVs. It also reduces the battery capacity loss by 48.1%, 44%, and 24%, and reduces total operation cost by 60%, 43.9%, and 23.68% compared with standard BEVs, state machine control (SMC), and frequency decoupling strategy (FDS), respectively.
Enhanced Liquid Fuel Production from Pyrolysis of Plastic Waste Mixtures Using a Natural Mineral Catalyst
Authors: Abnisa Faisal
Published: January 2023

Since plastic wastes are commonly found and accumulate in numerous types and forms, the pyrolysis of plastic waste mixtures seems more feasible to be selected for large-scale production. However, the process typically produces less liquid than individual plastic pyrolysis. This study proposed a viable approach for catalytic pyrolysis by using natural mineral catalysts without modification. Bentonite was selected as a natural mineral catalyst while HZSM-5 was used for performance comparison. The process was evaluated in situ using a fixed-bed reactor at temperatures between 400 °C and 500 °C. The mixture of plastic waste composition was designed based on the non-recycled plastics data. The results showed that 42.55 wt% of liquid yield was obtained from thermal pyrolysis using Malaysia’s non-recycled plastics data. It was then found that using HZSM-5 and bentonite catalysts significantly boosted liquid products to about 56 and 60%, respectively. The presence of catalysts also positively minimized tar formation and eliminated wax formation in the liquid product. Furthermore, the catalytic process showed remarkable improvements in aromatics and alkane compounds in the liquid while only alkenes were found to be high when bentonite was used.
Gate Driver Circuit with All-Magnetic Isolation for Cascode-Connected SiC JFETs in a Three-Level T-Type Bridge-Leg
Authors: McNeill Neville , Vozikis Dimitrios , Peña-Alzola Rafael , Wang Shuren , Pollock Richard , Holliday Derrick , Williams Barry
Published: January 2023

This article presents a gate driver circuit with all-magnetic isolation for driving silicon carbide (SiC) power devices in a three-level T-type bridge-leg. Gate driver circuitry for SiC devices has to be tolerant of rapid common-mode voltage changes. With respect to the resultant potentially problematic common-mode current paths, an arrangement of transformers is proposed for supplying the power devices with drive signals and power for their local floating gate driver circuits. The high-frequency carrier phase-switching technique is used to reduce the number of transformers. Signal timing and other implementation issues are addressed when using this arrangement with the T-type converter. The circuit is demonstrated in a 540 V bridge-leg constructed around 650 V and 1200 V cascode-connected normally-on SiC junction field effect transistors (JFETs).
Rodlet Cells Provide First Line of Defense against Swimbladder Nematode and Intestinal Coccidian in Anguilla anguilla
Authors: Sayyaf Dezfuli Bahram , Castaldelli Giuseppe , Lorenzoni Massimo , Carosi Antonella , Ovcharenko Mykola , Bosi Giampaolo
Published: January 2023

A subpopulation of 97 European eels, Anguilla anguilla, was obtained from a local consortium of Lake Trasimeno. The fish were examined for parasites in the swimbladder (SB) and intestine; the SBs of 66 (68%) of the 97 eels contained 480 adult specimens of the nematode Anguillicoloides crassus (Kuwahara, Niimi and Itagaki, 1974) and the intensity of infection ranged from 1 to 18 adult worms per SB (7.27 ± 0.43, mean ± SE). In heavily infected SB, the wall was thicker; upon excision, black-brownish adult nematodes were noticed inside the lumen. The infected SBs showed a papillose aspect of the epithelium and frequent erosion, inflammation, hemorrhages, and dilation of blood vessels. In parasitized SBs, mast cells and macrophages were encountered in the mucosal layer; in several heavily infected SB, rodlet cells were the sole fish immune cells noticed in the epithelium and in close contact with the A. crassus. With reference to the eel intestinal epithelium, in fifteen eels, two developmental stages of coccidian were close to clusters of rodlet cells, the coccidian induced erosion of the epithelium. The results of a panel of 12 antibodies in the European eel infected tissues will be presented.
A Class of Fractional Stochastic Differential Equations with a Soft Wall
Authors: Kubilius Kęstutis , Medžiūnas Aidas
Published: January 2023

In this paper we are interested in fractional stochactic differential equations (SDEs) with a soft wall. What do we mean by such a type of equation? It has been established that SDE with reflection can be imagined as equations having a hard wall. Now, by introducing repulsion instead of reflection, one obtains an SDE with a soft wall. In contrast to the SDE with reflection, where the process cannot pass the hard wall, the soft wall is repulsive but not impenetrable. As the process crosses the soft wall boundary, it experiences the force of a chosen magnitude in the opposite direction. When the process is far from the wall, the force acts weakly. We find conditions under which SDE with a soft wall has a unique solution and construct an implicit Euler approximation with a rate of convergence for this equation. Using the example of the fractional Vasicek process with soft walls, we illustrate the dependence of the behaviour of the solution on the repulsion force.
Maximize Eco-Economic Benefits with Minimum Land Resources Input: Evaluation and Evolution of Land Use Eco-Efficiency of Agglomerations in Middle Reaches of Yangtze River, China
Authors: Zhang Jie , Wang Yajing , Li Jiangfeng
Published: January 2023

Increasing land-use eco-efficiency can alleviate human-land conflict in urban areas as well as improve regional urbanization quality to achieve sustainable development. As the central urban agglomeration in China, the Middle Reaches of Yangtze River (MRYR) has experienced rapid urbanization and huge land-use change during 2000 to 2020, which poses great threats to its ecological environment. This study adopted the Super-Slack-Based Data Envelopment Analysis (Super SBM-DEA) model to evaluate the eco-efficiency of land use in MRYR. The result shows that the average eco-efficiency value of land use is above 0.77 for each year, indicating that the general efficiency is at a middle level. The trend of the evolution of the eco-efficiency can be summarized as a “U-shape” style curve. The variance between the four urban agglomerations of the MRYR changed over time. Not all capital cities or cities with higher GDP per capita obtain higher eco-efficiency in this study. Policy intervention, population and land use, technique, and environmental pollution are influencing factors of land-use eco-efficiency. Based on slacks analysis, this study proposed the optimization of the land-use structure to improve eco-efficiency from four aspects of land-use structure, investment and labor, ecosystem services value (ESV) and environment pollution, and industry structure.
Assessment of Regional Health Resource Carrying Capacity and Security in Public Health Emergencies Based on the COVID-19 Outbreak
Authors: Huang Xiaoran , Yu Demiao
Published: January 2023

The Omicron variant of COVID-19, which emerged at the end of 2021, has caused a new wave of infections around the world and is causing a new wave of the crisis due to the extreme variability of the pathogen. In response to public health emergencies such as SARS and COVID-19, the first task is to identify the vulnerabilities of regional health systems and perform a comprehensive assessment of the region’s resilience. In this paper, we take the carrying capacity of medical resources as the focus; evaluate the medical, human, and financial resources of various regions; and construct an epidemic safety index based on the actual situation or future trend of the epidemic outbreak to evaluate and predict the risk level of each region in response to the epidemic. The study firstly evaluates the epidemic safety index for each province and city in China and 150 countries around the world, using the first wave of the COVID-19 epidemic in 2020 and the Omicron variant virus in 2022 as the background, respectively, and justifies the index through the actual performance in terms of epidemic prevention and control, based on which the epidemic safety index for 150 countries in the next year is predicted. The conclusions show that Europe, the Americas, and parts of Asia will face a significant risk of epidemic shocks in the coming period and that countries need to formulate policies in response to the actual situation of the epidemic.
Interaction of Aggregated Cationic Porphyrins with Human Serum Albumin
Authors: Samperi Mario , Vittorio Serena , De Luca Laura , Romeo Andrea , Monsù Scolaro Luigi
Published: January 2023

The interaction of an equilibrium mixture of monomeric and aggregated cationic trans-5,15-bis(N-methylpyridinium-4-yl)-10,15-bis-diphenylporphine (t-H2Pagg) chloride salt with human serum albumin (HSA) has been investigated through UV/Vis absorption, fluorescence emission, circular dichroism and resonant light scattering techniques. The spectroscopic evidence reveals that both the monomeric t-H2Pagg and its aggregates bind instantaneously to HSA, leading to the formation of a tight adduct in which the porphyrin is encapsulated within the protein scaffold (S430) and to clusters of aggregated porphyrins in electrostatic interaction with the charged biomolecules. These latter species eventually interconvert into the final S430 species following pseudo-first-order kinetics. Molecular docking simulations have been performed to get some insights into the nature of the final adduct. Analogously to hemin bound to HSA, the obtained model supports favorable interactions of the porphyrin in the same 1B subdomain of the protein. Hydrophobic and van der Waals energy terms are the main contributions to the calculated ΔGbind value of −117.24 kcal/mol.
Inhibition Effect of Adipogenesis and Lipogenesis via Activation of AMPK in Preadipocytes Treated with Canavalia gladiata Extract
Authors: Hong Ji Woo , Park Ha Young , Kim Han A. , Hwang Yun Seon , Lee Eun Jae , Kim Jin Woo
Published: January 2023

The aim of this study was to investigate the effect of Canavalia gladiata extract (CGE) on the regulation of AMP-activated protein kinase (AMPK) in 3T3-L1 preadipocytes and evaluate the adipogenesis and lipogenesis mechanisms. In 3T3-L1 preadipocytes, lipid accumulation and differentiation were suppressed by 1.1, 1.3, and 1.4 times under the CGE treatment at 0.25, 0.5, and 1.0 mg/mL, respectively. The expression of the main genes involved in the inhibition of adipogenesis was evaluated at the mRNA level via a transcription-polymerase chain reaction. The extract at 1.0 mg/mL increased the mRNA expressions of AMPK and carnitine palmitoyl transferase-1 (CPT-1) by 1.9 and 1.2 times, respectively, while it decreased the expression of sterol regulatory element binding proteins-1c (SREBP-1c), peroxisome proliferator activated receptor-γ (PPAR-γ), CCAAT enhancer binding protein-α (C/EBP-α), and fatty acid synthase (FAS) by 1.1, 1.2, 1.8, and 1.5 times, respectively, indicating inhibition of the adipogenesis and lipogenesis potential of CGE. Gallic acid (4.02 mg/g) was identified as the main component of the CGE via LC-MS/MS and HPLC analysis. The results of this study suggested that CGE can be utilized as an anti-obesity food additive or medication by activating the AMPK-induced regulation and suppressing adipogenesis transcription factors.
Regulatory miPEP Open Reading Frames Contained in the Primary Transcripts of microRNAs
Authors: Erokhina Tatiana N. , Ryazantsev Dmitriy Y. , Zavriev Sergey K. , Morozov Sergey Y.
Published: January 2023

This review aims to consider retrospectively the available data on the coding properties of pri-microRNAs and the regulatory functions of their open reading frames (ORFs) and the encoded peptides (miPEPs). Studies identifying miPEPs and analyzing the fine molecular mechanisms of their functional activities are reviewed together with a brief description of the methods to identify pri-miRNA ORFs and the encoded protein products. Generally, miPEPs have been identified in many plant species of several families and in a few animal species. Importantly, molecular mechanisms of the miPEP action are often quite different between flowering plants and metazoan species. Requirement for the additional studies in these directions is highlighted by alternative findings concerning negative or positive regulation of pri-miRNA/miRNA expression by miPEPs in plants and animals. Additionally, the question of how miPEPs are distributed in non-flowering plant taxa is very important for understanding the evolutionary origin of such micropeptides. Evidently, further extensive studies are needed to explore the functions of miPEPs and the corresponding ORFs and to understand the full set of their roles in eukaryotic organisms. Thus, we address the most recent integrative views of different genomic, physiological, and molecular aspects concerning the expression of miPEPs and their possible fine functions.
Mexican Colorectal Cancer Research Consortium (MEX-CCRC): Etiology, Diagnosis/Prognosis, and Innovative Therapies
Authors: Andrade-Meza Antonio , Arias-Romero Luis E. , Armas-López Leonel , Ávila-Moreno Federico , Chirino Yolanda I. , Delgado-Buenrostro Norma L. , García-Castillo Verónica , Gutiérrez-Cirlos Emma B. , Juárez-Avelar Imelda , Leon-Cabrera Sonia , Mendoza-Rodríguez Mónica G. , Olguín Jonadab E. , Perez-Lopez Araceli , Pérez-Plasencia Carlos , Reyes José L. , Sánchez-Pérez Yesennia , Terrazas Luis I. , Vaca-Paniagua Felipe , Villamar-Cruz Olga , Rodríguez-Sosa Miriam
Published: January 2023

In 2013, recognizing that Colorectal Cancer (CRC) is the second leading cause of death by cancer worldwide and that it was a neglected disease increasing rapidly in Mexico, the community of researchers at the Biomedicine Research Unit of the Facultad de Estudios Superiores Iztacala from the Universidad Nacional Autónoma de México (UNAM) established an intramural consortium that involves a multidisciplinary group of researchers, technicians, and postgraduate students to contribute to the understanding of this pathology in Mexico. This article is about the work developed by the Mexican Colorectal Cancer Research Consortium (MEX-CCRC): how the Consortium was created, its members, and its short- and long-term goals. Moreover, it is a narrative of the accomplishments of this project. Finally, we reflect on possible strategies against CRC in Mexico and contrast all the data presented with another international strategy to prevent and treat CRC. We believe that the Consortium’s characteristics must be maintained to initiate a national strategy, and the reported data could be useful to establish future collaborations with other countries in Latin America and the world.
The Role of Arginine-Vasopressin in Stroke and the Potential Use of Arginine-Vasopressin Type 1 Receptor Antagonists in Stroke Therapy: A Narrative Review
Authors: Chojnowski Karol , Opiełka Mikołaj , Gozdalski Jacek , Radziwon Jakub , Dańczyszyn Aleksandra , Aitken Andrew Vieira , Biancardi Vinicia Campana , Winklewski Paweł Jan
Published: January 2023

Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences.
Biliary Metabolome Profiling for Evaluation of Liver Metabolism and Biliary Tract Function Related to Organ Preservation Method and Degree of Ischemia in a Porcine Model
Authors: Łuczykowski Kamil , Warmuzińska Natalia , Kollmann Dagmar , Selzner Markus , Bojko Barbara
Published: January 2023

The development of surgical techniques, immunosuppressive strategies and new organ preservation methods have meant that transplant centers have to face the problem of an insufficient number of organs for transplantation concerning the constantly growing demand. Therefore, using organs from expanded criteria donors and developing new analytical solutions to find parameters or compounds that would allow a more efficient assessment of organ quality before transplantation are options for meeting this challenge. This study proposed bile metabolomic analysis to evaluate liver metabolism and biliary tract function depending on the organ preservation method and degree of warm ischemia time. The analyses were performed on solid-phase microextraction-prepared bile samples from porcine model donors with mild (heart beating donor [HBD]) and moderate warm ischemia (donation after circulatory death [DCD]) grafts subjected to static cold storage (SCS) or normothermic ex vivo liver perfusion (NEVLP) before transplantation. Bile produced in the SCS-preserved livers was characterized by increased levels of metabolites such as chenodeoxycholic acid, arachidonic acid and 5S-hydroxyeicosatetraeonic acid, as well as saturated and monounsaturated lysophosphatidylcholines (LPC). Such changes may be associated with differences in the bile acid synthesis pathways and organ inflammation. Moreover, it has been shown that NEVLP reduced the negative effect of ischemia on organ function. A linear relationship was observed between levels of lipids from the LPC group and the time of organ ischemia. This study identified metabolites worth considering as potential markers of changes occurring in preserved grafts.
4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing
Authors: Tsitrina Alexandra A. , Halimani Noreen , Andreichenko Irina N. , Sabirov Marat , Nesterchuk Mikhail , Dashenkova Nataliya O. , Romanov Roman , Bulgakova Elena V. , Mikaelyan Arsen , Kotelevtsev Yuri
Published: January 2023

4-methylumbelliferone (4MU) is a well-known hyaluronic acid synthesis inhibitor and an approved drug for the treatment of cholestasis. In animal models, 4MU decreases inflammation, reduces fibrosis, and lowers body weight, serum cholesterol, and insulin resistance. It also inhibits tumor progression and metastasis. The broad spectrum of effects suggests multiple and yet unknown targets of 4MU. Aiming at 4MU target deconvolution, we have analyzed publicly available data bases, including: 1. Small molecule library Bio Assay screening (PubChemBioAssay); 2. GO pathway databases screening; 3. Protein Atlas Database. We also performed comparative liver transcriptome analysis of mice on normal diet and mice fed with 4MU for two weeks. Potential targets of 4MU public data base analysis fall into two big groups, enzymes and transcription factors (TFs), including 13 members of the nuclear receptor superfamily regulating lipid and carbohydrate metabolism. Transcriptome analysis revealed changes in the expression of genes involved in bile acid metabolism, gluconeogenesis, and immune response. It was found that 4MU feeding decreased the accumulation of the glycogen granules in the liver. Thus, 4MU has multiple targets and can regulate cell metabolism by modulating signaling via nuclear receptors.
Emerging Role of Protein O-GlcNAcylation in Liver Metabolism: Implications for Diabetes and NAFLD
Authors: Xie Ziyan , Xie Ting , Liu Jieying , Zhang Qian , Xiao Xinhua
Published: January 2023

O-linked b-N-acetyl-glucosaminylation (O-GlcNAcylation) is one of the most common post-translational modifications of proteins, and is established by modifying the serine or threonine residues of nuclear, cytoplasmic, and mitochondrial proteins. O-GlcNAc signaling is considered a critical nutrient sensor, and affects numerous proteins involved in cellular metabolic processes. O-GlcNAcylation modulates protein functions in different patterns, including protein stabilization, enzymatic activity, transcriptional activity, and protein interactions. Disrupted O-GlcNAcylation is associated with an abnormal metabolic state, and may result in metabolic disorders. As the liver is the center of nutrient metabolism, this review provides a brief description of the features of the O-GlcNAc signaling pathway, and summarizes the regulatory functions and underlying molecular mechanisms of O-GlcNAcylation in liver metabolism. Finally, this review highlights the role of O-GlcNAcylation in liver-associated diseases, such as diabetes and nonalcoholic fatty liver disease (NAFLD). We hope this review not only benefits the understanding of O-GlcNAc biology, but also provides new insights for treatments against liver-associated metabolic disorders.
Ca2+-Triggered Coelenterazine-Binding Protein Renilla: Expected and Unexpected Features
Authors: Kudryavtsev Alexander N. , Krasitskaya Vasilisa V. , Efremov Maxim K. , Zangeeva Sayana V. , Rogova Anastasia V. , Tomilin Felix N. , Frank Ludmila A.
Published: January 2023

Ca2+-triggered coelenterazine-binding protein (CBP) is a natural form of the luciferase substrate involved in the Renilla bioluminescence reaction. It is a stable complex of coelenterazine and apoprotein that, unlike coelenterazine, is soluble and stable in an aquatic environment and yields a significantly higher bioluminescent signal. This makes CBP a convenient substrate for luciferase-based in vitro assay. In search of a similar substrate form for the luciferase NanoLuc, a furimazine-apoCBP complex was prepared and verified against furimazine, coelenterazine, and CBP. Furimazine-apoCBP is relatively stable in solution and in a frozen or lyophilized state, but as distinct from CBP, its bioluminescence reaction with NanoLuc is independent of Ca2+. NanoLuc turned out to utilize all the four substrates under consideration. The pairs of CBP-NanoLuc and coelenterazine-NanoLuc generate bioluminescence with close efficiency. As for furimazine-apoCBP-NanoLuc pair, the efficiency with which it generates bioluminescence is almost twice lower than that of the furimazine-NanoLuc. The integral signal of the CBP-NanoLuc pair is only 22% lower than that of furimazine-NanoLuc. Thus, along with furimazine as the most effective NanoLuc substrate, CBP can also be recommended as a substrate for in vitro analytical application in view of its water solubility, stability, and Ca2+-triggering “character”.
Liaisons dangereuses: Intrinsic Disorder in Cellular Proteins Recruited to Viral Infection-Related Biocondensates
Authors: Bianchi Greta , Brocca Stefania , Longhi Sonia , Uversky Vladimir N.
Published: January 2023

Liquid–liquid phase separation (LLPS) is responsible for the formation of so-called membrane-less organelles (MLOs) that are essential for the spatio-temporal organization of the cell. Intrinsically disordered proteins (IDPs) or regions (IDRs), either alone or in conjunction with nucleic acids, are involved in the formation of these intracellular condensates. Notably, viruses exploit LLPS at their own benefit to form viral replication compartments. Beyond giving rise to biomolecular condensates, viral proteins are also known to partition into cellular MLOs, thus raising the question as to whether these cellular phase-separating proteins are drivers of LLPS or behave as clients/regulators. Here, we focus on a set of eukaryotic proteins that are either sequestered in viral factories or colocalize with viral proteins within cellular MLOs, with the primary goal of gathering organized, predicted, and experimental information on these proteins, which constitute promising targets for innovative antiviral strategies. Using various computational approaches, we thoroughly investigated their disorder content and inherent propensity to undergo LLPS, along with their biological functions and interactivity networks. Results show that these proteins are on average, though to varying degrees, enriched in disorder, with their propensity for phase separation being correlated, as expected, with their disorder content. A trend, which awaits further validation, tends to emerge whereby the most disordered proteins serve as drivers, while more ordered cellular proteins tend instead to be clients of viral factories. In light of their high disorder content and their annotated LLPS behavior, most proteins in our data set are drivers or co-drivers of molecular condensation, foreshadowing a key role of these cellular proteins in the scaffolding of viral infection-related MLOs.
A Simplified and Efficient Method for Production of Manganese Ferrite Magnetic Nanoparticles and Their Application in DNA Isolation
Authors: Gerzsenyi Tímea B. , Ilosvai Ágnes M. , Szilágyi Gergely , Szőri Milán , Váradi Csaba , Viskolcz Béla , Vanyorek László , Szőri-Dorogházi Emma
Published: January 2023

A simplified, fast, and effective production method has been developed for the synthesis of manganese ferrite (MnFe2O4) magnetic nanoparticles (MNPs). In addition to the wide applicability of MnFe2O4 MNPs, this work also reports their application in DNA isolation for the first time. An ultrasonic-cavitation-assisted combustion method was applied in the synthesis of MnFe2O4 MNPs at different furnace temperatures (573 K, 623 K, 673 K, and 773 K) to optimize the particles’ properties. It was shown that MnFe2O4 nanoparticles synthesized at 573 K consist of a spinel phase only with adequate size and zeta potential distributions and superparamagnetic properties. It was also demonstrated that superparamagnetic manganese ferrite nanoparticles bind DNA in buffer with a high NaCl concentration (2.5 M), and the DNA desorbs from the MNPs by decreasing the NaCl concentration of the elution buffer. This resulted in a DNA yield comparable to that of commercial DNA extraction products. Both the DNA concentration measurements and electrophoresis confirmed that a high amount of isolated bacterial plasmid DNA (pDNA) with adequate purity can be extracted with MnFe2O4 (573 K) nanoparticles by applying the DNA extraction method proposed in this article.
Trimeric Architecture Ensures the Stability and Biological Activity of the Calf Purine Nucleoside Phosphorylase: In Silico and In Vitro Studies of Monomeric and Trimeric Forms of the Enzyme
Authors: Dyzma Alicja , Wielgus-Kutrowska Beata , Girstun Agnieszka , Matošević Zoe Jelić , Staroń Krzysztof , Bertoša Branimir , Trylska Joanna , Bzowska Agnieszka
Published: January 2023

Mammalian purine nucleoside phosphorylase (PNP) is biologically active as a homotrimer, in which each monomer catalyzes a reaction independently of the others. To answer the question of why the native PNP forms a trimeric structure, we constructed, in silico and in vitro, the monomeric form of the enzyme. Molecular dynamics simulations showed different geometries of the active site in the non-mutated trimeric and monomeric PNP forms, which suggested that the active site in the isolated monomer could be non-functional. To confirm this hypothesis, six amino acids located at the interface of the subunits were selected and mutated to alanines to disrupt the trimer and obtain a monomer (6Ala PNP). The effects of these mutations on the enzyme structure, stability, conformational dynamics, and activity were examined. The solution experiments confirmed that the 6Ala PNP mutant occurs mainly as a monomer, with a secondary structure almost identical to the wild type, WT PNP, and importantly, it shows no enzymatic activity. Simulations confirmed that, although the secondary structure of the 6Ala monomer is similar to the WT PNP, the positions of the amino acids building the 6Ala PNP active site significantly differ. These data suggest that a trimeric structure is necessary to stabilize the geometry of the active site of this enzyme.
The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma
Authors: Loch Florian N. , Kamphues Carsten , Beyer Katharina , Schineis Christian , Rayya Wael , Lauscher Johannes C. , Horst David , Dragomir Mihnea P. , Schallenberg Simon
Published: January 2023

Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression and its prognostic relevance in cancer cells of PDAC. Therefore, tumor cells from peripheral and central tissue microarray (TMA) spots from histologically confirmed PDAC of 68 patients after tumor resection were investigated in terms of expressions of TIM3, IDO, B7H4, LAG3, VISTA, and PD-L1 using immunohistochemistry. The presence of the respective ICs was compared to overall survival (OS). The presence of VISTA and PD-L1 significantly correlates with shorter OS (median OS: 22 months vs. 7 months and 22 months vs. 11 months, respectively, p < 0.05). For the presence of TIM3, IDO, B7H4, and LAG3, no difference in OS was observed (p > 0.05). The analysis of OS of combined subgroups for VISTA and PD-L1 (VISTA and PD-L1 neg., VISTA pos. and PD-L1 neg., VISTA neg. and PD-L1 pos., and VISTA and PD-L1 pos.) yielded overall statistical significance difference (p = 0.02). These results suggest that the presence of VISTA and PD-L1 is of prognostic relevance and potentially qualifies them as targets for ICT.
Evaluation of CRISPR/Cas9 Constructs in Wheat Cell Suspension Cultures
Authors: Michalski Krzysztof , Ziąbska Paulina , Sowa Sławomir , Zimny Janusz , Linkiewicz Anna M.
Published: January 2023

Despite intensive optimization efforts, developing an efficient sequence-specific CRISPR/Cas-mediated genome editing method remains a challenge, especially in polyploid cereal species such as wheat. Validating the efficacy of nuclease constructs prior to using them in planta is, thus, a major step of every editing experiment. Several construct evaluation strategies were proposed, with PEG-mediated plasmid transfection of seedling-derived protoplasts becoming the most popular. However, the usefulness of this approach is affected by associated construct copy number bias and chromatin relaxation, both influencing the outcome. Therefore, to achieve a reliable evaluation of CRISPR/Cas9 constructs, we proposed a system based on an Agrobacterium-mediated transformation of established wheat cell suspension cultures. This system was used for the evaluation of a CRISPR/Cas9 construct designed to target the ABA 8′-hydroxylase 1 gene. The efficiency of editing was verified by cost-effective means of Sanger sequencing and bioinformatic analysis. We discuss advantages and potential future developments of this method in contrast to other in vitro approaches.
Meta-Analysis and Multivariate GWAS Analyses in 80,950 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits
Authors: Udosen Brenda , Soremekun Opeyemi , Kamiza Abram , Machipisa Tafadzwa , Cheickna Cisse , Omotuyi Olaposi , Soliman Mahmoud , Wélé Mamadou , Nashiru Oyekanmi , Chikowore Tinashe , Fatumo Segun
Published: January 2023

High blood pressure (HBP) has been implicated as a major risk factor for cardiovascular diseases in several populations, including individuals of African ancestry. Despite the elevated burden of HBP-induced cardiovascular diseases in Africa and other populations of African descent, limited genetic studies have been carried out to explore the genetic mechanism driving this phenomenon. We performed genome-wide association univariate and multivariate analyses of both systolic (SBP) and diastolic blood pressure (DBP) traits in 80,950 individuals of African ancestry. We used summary statistics data from six independent cohorts, including the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). FUMA was used to annotate, prioritize, visualize, and interpret our findings to gain a better understanding of the molecular mechanism(s) underlying the genetics of BP traits. Finally, we undertook a Bayesian fine-mapping analysis to identify potential causal variants. Our meta-analysis identified 10 independent variants associated with SBP and 9 with DBP traits. Whilst our multivariate GWAS method identified 21 independent signals, 18 of these SNPs have been previously identified. SBP was linked to gene sets involved in biological processes such as synapse assembly and cell–cell adhesion via plasma membrane adhesion. Of the 19 independent SNPs identified in the BP meta-analysis, only 11 variants had posterior probability (PP) of > 50%, including one novel variant: rs562545 (MOBP, PP = 77%). To facilitate further research and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits, large-scale genomic datasets are needed. Our findings highlight the importance of including ancestrally diverse populations in large GWASs and the need for diversity in genetic research.
Impact of the TRPV2 Inhibitor on Advanced Heart Failure in Patients with Muscular Dystrophy: Exploratory Study of Biomarkers Related to the Efficacy of Tranilast
Authors: Takahashi Chisato , Oishi Mariko , Iwata Yuko , Maekawa Keiko , Matsumura Tsuyoshi
Published: January 2023

Cardiomyopathy is the leading cause of death in patients with muscular dystrophy (MD). Tranilast, a widely used anti-allergic drug, has displayed inhibitory activity against the transient receptor potential cation channel subfamily V member 2 and improved cardiac function in MD patients. To identify urinary biomarkers that assess improved cardiac function after tranilast administration, we performed a urinary metabolomic study focused on oxidative fatty acids. Accompanying the clinical trial of tranilast, urine specimens were collected over 24 weeks from MD patients with advanced heart failure. Urinary levels of tetranor-PGDM (tetranor-prostaglandin D metabolite), a metabolite of prostaglandin D2, significantly decreased 12 weeks after tranilast administration and were correlated with BNP. These results suggest that prostaglandin-mediated inflammation, which increases with the pathological progression of heart failure in MD patients, was attenuated. Urinary prostaglandin E3 (PGE3) levels significantly increased 4 weeks after tranilast administration. There were positive correlations between the urinary levels of PGE3 and 8-hydroxy-2′-deoxyguanosine, an oxidative stress marker. High PGE3 levels may have a protective effect against cardiomyopathy in MD patients with high oxidative stress. Although further validation studies are necessary, urinary tetranor-PGDM and PGE3 levels may help the current understanding of the extent of advanced heart failure in patients with MD after tranilast administration.
Molecular Characterization, Expression, and Regulatory Signal Pathway Analysis of Inflammasome Component Apoptosis-Associated Speck-like Protein Containing a CARD Domain (ASC) in Large Yellow Croaker (Larimichthys crocea)
Authors: Tang Xin , Liu Xiande , Wang Zhiyong , Chen Meiling , Zhang Dongling
Published: January 2023

ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)) is the only adaptor involved in the formation of multiple types of inflammasomes. Accumulating evidence demonstrates that ASC plays a critical role in the protection of the host against pathogen infection. In this study, we identified an ASC gene in the large yellow croaker (Larimichthys crocea), namely LcASC, and then investigated the expression characteristics and related signal pathways. On one hand, LcASC has several conserved protein modules, i.e., an N-terminal PYD region, a C-terminal CARD region, and twelve α-helix structures. On the other hand, it has a high variable linker between PYD and CARD domains. Moreover, LcASC has varying degrees of expression in different tissues, among which the highest expression is observed in the spleen followed by the gills and skin. It also shows induced expressions in the head kidney, liver, and spleen following immune stimulation, especially Vibrio Parahaemolyticus infection. Further subcellular localization analysis showed that LcASC formed a clear aggregated speck in the cytoplasm close to the nucleus. In addition, we found 46 DEGs in a comparative transcriptome analysis between the LcASC overexpression group and the control vector group. Notedly, the up-regulated gene Fos and down-regulated gene DOK3 in LcASC overexpressed cells play important roles in the immune system. How ASC contacts these two genes needs to be clarified in upcoming studies. These findings collectively provide new insights into finfish ASC and its potential regulatory signaling pathway as well.
Lysosomes as a Target of Anticancer Therapy
Authors: Trybus Wojciech , Trybus Ewa , Król Teodora
Published: January 2023

Lysosomes are organelles containing acidic hydrolases that are responsible for lysosomal degradation and the maintenance of cellular homeostasis. They play an important role in autophagy, as well as in various cell death pathways, such as lysosomal and apoptotic death. Various agents, including drugs, can induce lysosomal membrane permeability, resulting in the translocation of acidic hydrolases into the cytoplasm, which promotes lysosomal-mediated death. This type of death may be of great importance in anti-cancer therapy, as both cancer cells with disturbed pathways leading to apoptosis and drug-resistant cells can undergo it. Important compounds that damage the lysosomal membrane include lysosomotropic compounds, antihistamines, immunosuppressants, DNA-damaging drugs, chemotherapeutics, photosensitizers and various plant compounds. An interesting approach in the treatment of cancer and the search for ways to overcome the chemoresistance of cancer cells may also be combining lysosomotropic compounds with targeted modulators of autophagy to induce cell death. These compounds may be an alternative in oncological treatment, and lysosomes may become a promising therapeutic target for many diseases, including cancer. Understanding the functional relationships between autophagy and apoptosis and the possibilities of their regulation, both in relation to normal and cancer cells, can be used to develop new and more effective anticancer therapies.