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1
BRATSLAVETS, Bogdan. "RESTORATION OF PARTS OF AGRICULTURAL MACHINES WITH ZINC-BASED GALVANIC COATINGS." Herald of Khmelnytskyi National University. Technical sciences 309, no. 3 (2022): 82–84. http://dx.doi.org/10.31891/2307-5732-2022-309-3-82-84.
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Galvanizing is most often used to protect against corrosion. In repair production zinc coverings are used for protection against corrosion of fastening details and restoration of landing surfaces of lightly loaded details. Electroplating is the process of applying metal to the surface of parts by crystallizing it from an aqueous solution of the corresponding salts (electrolyte) when a direct current passes through them. An electrical circuit is closed by an electrolyte between two conductors called electrodes. The electrode to which the conductor of the external circuit with a plus is attached is called the anode, and with a minus – the cathode. The repaired part, on which the metal is built up, serves as the cathode, and the anode – plates, copper, lead, zinc, cadmium and other metals. In electrolysis, soluble and insoluble anodes are used. In practice, soluble lead is most often used, and insoluble lead is used only for chromium plating. The preparation of the surface of the part before coating (machining, degreasing, digestion) is important for the quality of the coating. The paper identifies the advantages and disadvantages of the method of updating parts of agricultural machinery with galvinic coatings based on zinc. This makes it possible to analyze the results of experiments and evaluate the effectiveness of using this method of restoring parts. The article presents the technological process of restoration of parts by galvinic galvanizing using an activator and the results of experiments using graphs of the dependence of the rate of coating on the current density and the speed of the activator. Determine whether the use of an experimental activator will increase the speed and quality of coating on parts.
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Mostoni, Milana, Credico, D’Arienzo, and Scotti. "Zinc-Based Curing Activators: New Trends for Reducing Zinc Content in Rubber Vulcanization Process." Catalysts 9, no. 8 (2019): 664. http://dx.doi.org/10.3390/catal9080664.
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The efficiency of sulfur vulcanization reaction in rubber industry is generally improved thanks to the combined use of accelerators (as sulphenamides), activators (inorganic oxides), and co-activators (fatty acids). The interaction among these species is responsible for the formation of intermediate metal complexes, which are able to increase the reactivity of sulfur towards the polymer and to promote the chemical cross-links between the rubber chains. The high number of species and reactions that are involved contemporarily in the process hinders the complete understanding of its mechanism despite the long history of vulcanization. In this process, ZnO is considered to be the most efficient and major employed activator and zinc-based complexes that formed during the first steps of the reaction are recognized to play a main role in determining both the kinetic and the nature of the cross-linked products. However, the low affinity of ZnO towards the rubber entails its high consumption (3–5 parts per hundred, phr) to achieve a good distribution in the matrix, leading to a possible zinc leaching in the environment during the life cycle of rubber products (i.e., tires). Thanks to the recent recognition of ZnO ecotoxicity, especially towards the aquatic environment, these aspects gain a critical importance in view of the urgent need to reduce or possibly substitute the ZnO employed in rubber vulcanization. In this review, the reactivity of ZnO as curing activator and its role in the vulcanization mechanism are highlighted and deeply discussed. A complete overview of the recent strategies that have been proposed in the literature to improve the vulcanization efficiency by reducing the amount of zinc that is used in the process is also reported.
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Heideman, Geert, Jacques W. M. Noordermeer, Rabin N. Datta, and Ben van Baarle. "Zinc Loaded Clay as Activator in Sulfur Vulcanization: A New Route for Zinc Oxide Reduction in Rubber Compounds." Rubber Chemistry and Technology 77, no. 2 (2004): 336–55. http://dx.doi.org/10.5254/1.3547827.
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Abstract Concern about the release of eco-toxic zinc species from rubbers into the environment leads to an increasing interest in potential substitutes. Although alternative metal oxides and zinc compounds as activators for sulfur vulcanization have been studied thoroughly, at present no viable alternative has been found to eliminate ZnO completely from rubber compounds, without significantly jeopardizing processing as well as performance characteristics. In this paper, the application of a new activator for sulfur vulcanization will be discussed. This activator is developed based on the assumption that an increase in the availability of Zn2+-ions could lead to a considerable reduction of ZnO in rubber compounds. Montmorillonite clay was used as carrier material and loaded with Zn2+-ions via an ion-exchange process. Application in a wide range of natural and synthetic rubbers has been explored. Results clearly demonstrate that this Zn-Clay can substitute conventional ZnO, retaining the curing and physical properties of the rubber products but reducing the zinc concentration with a factor 10 to 20. Model Compound Vulcanization studies have been used to gain an insight into the mechanism of this activator. It can be concluded that systems with Zn2+-ions on a support represent a new and novel route to reduce the zinc level, and therefore to minimize its environmental impact significantly.
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Javadi, Seyyed Mohammad. "Applications of ZnO and MgO Nanoparticles in Reducing Zinc Pollution Level in Rubber Manufacturing Processes: A Review." Current Biochemical Engineering 6, no. 2 (2020): 103–7. http://dx.doi.org/10.2174/2212711906666200224105931.
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Background: Rubber vulcanization is a consolidated chemical process to enhance the mechanical properties of the polymeric material by sulfur crosslinking of the polymer chains, such as rubber. Vulcanization Activators are important rubber processing additives that activate sulfur cure and improve the efficiency of sulfur-based cure systems. The most common activator is zinc fatty acid ester that is often formed in-situ by the reaction of fatty acid with zinc oxide. Although zinc is one of the less harmful heavy metals, according to European Council Directive 2004/73/EC, the reduction of zinc level in the environment has become an important task because of its toxic effect on aquatic organisms. : The current study reviews the research achievements in the field of reducing the consumption of micronutrients of ZnO particles based on the use of nanoparticles instead of them in the polymer industry. Among the proposed methods, due to the less environmental effects of magnesium oxide, the use of MgO nanoparticles instead of zinc oxide has also achieved good results. Objective: The aim of this paper is considering suggested different methods on the reduction of using ZnO particles in related industries, the use of ZnO nanoparticles has had better results than its particles. In addition, due to the less environmental effects of magnesium oxide, magnesium oxide nanoparticles can be used instead of micronutrients of zinc oxide. Overall, the results of various investigations show that reducing the diameter of the zinc oxide particles reduces the amount required for curing the rubber and thus reduces its toxic effects. Also, the use of magnesium oxide nanoparticles instead of zinc oxide in different concentrations is investigated.
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Guo, Lijie, Lei Zhang, Yue Zhao, et al. "Study On Mechanical Properties Of Cemented Paste Backfill Using Fly-Ash-Based Cementitious Materials." Journal of Asian Concrete Federation 10, no. 1 (2024): 1–7. http://dx.doi.org/10.18702/acf.2023.10.1.1.
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In Mongolia, the Ulan lead-zinc mine is now struggling with high backfill operating costs and poor Cemented Paste Backfill (CPB) mechanical performance after curing. To solve this problem, BGRIMM Technology Group has investigated an activator that could mix with fly ash from Choibalsan Power Plant in Mongolia as a supplementary cementitious material for backfill. In this study, the mechanical performance of CPB samples prepared with various fly ash content and activator types were studied to provide a basis for the industrial application of fly ash-based supplementary cementitious materials. The research results indicate that partially replacing cement with fly ash reduces the uniaxial compressive strength (UCS) of CPB samples. Compared with the CPB sample prepared with pure cement, when the fly ash substitution rate is 10%, 20%, and 30%, the UCS reduced by 15.66%, 18.69%, and 32.83%, respectively. With the use of chemical activators, the UCS of CPB samples could be significantly improved. Among them, CPB samples prepared by the activator sodium sulfate+ sodium chloride+ TEA have achieved the highest UCS. Overall, this study shows that the synergistic effect of fly ash and chemical activators could effectively enhance the mechanical performance of CPB, which is beneficial for mine backfill cost reduction and could provide a basis for the further industrial application of fly ash-based cementitious materials in mine backfill.
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Setianto, Wahyu Bahari, Nasruddin Nasruddin, Astuti Astuti, et al. "The Influence of Palm Oil-Based Zinc Stearate Application on Vulcanized Rubber: Analyzing Hardness, Tensile Strength, and Elongation at Break for Hand Grip Formulation Development." Key Engineering Materials 1001 (December 18, 2024): 111–17. https://doi.org/10.4028/p-wc8yqp.
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Vulcanization of rubber compounds is a crucial step in the process of developing natural rubber end products. Selected components are then used to formulate a rubber compound, which is further treated to create vulcanized rubber. In this study, a palm oil-based zinc stearate compound (ZS) developed by the National Research and Innovation Agency (BRIN) was used as a replacement for ZnO and stearic acid, which were previously used as activator and co-activator in the process of vulcanization. The goal of this study was to create a compound made of rubber formulation for use in the hand grip. The zinc stearate applied in this study ranged from 4 to 6 phr. To examine the effect of applying zinc stearate to vulcanized rubber, three primary parameters - tensile strength, hardness, and elongation at break of the vulcanized rubber - were evaluated. The results of the tests revealed that adding zinc stearate at a loading rate of 4 phr gave the hardness value of 27 Shore A, the tensile strength of 19 MPa, and the elongation at break by 590%. With this mechanical characteristic, the formula was identified as the optimal choice for achieving a robust and deformation-resistant hand grip while ensuring user comfort.
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Figueroa, Eric E., and Jerod S. Denton. "Zinc pyrithione activates the volume-regulated anion channel through an antioxidant-sensitive mechanism." American Journal of Physiology-Cell Physiology 320, no. 6 (2021): C1088—C1098. http://dx.doi.org/10.1152/ajpcell.00070.2021.
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Leucine-rich repeat-containing 8 (LRRC8) volume-regulated anion channels (VRACs) play important physiological roles in diverse cell types and may represent therapeutic targets for various diseases. To date, however, the pharmacological tools for evaluating the druggability of VRACs have been limited to inhibitors, as no activators of the channel have been reported. We therefore performed a fluorescence-based high-throughput screening (HTS) of 1,184 Food and Drug Administration-approved drugs for compounds that increase VRAC activity. The most potent VRAC potentiator identified was zinc pyrithione (ZPT), which is used commercially as an antifouling agent and for treating dandruff and other skin disorders. In intracellular Yellow Fluorescent Protein YFP(F46L/H148Q/I152L)-quenching assays, ZPT potentiates the rate and extent of swelling-induced iodide influx dose dependently with a half-maximal effective concentration (EC50) of 5.7 µM. Whole cell voltage-clamp experiments revealed that coapplication of hypotonic solution and 30 µM ZPT to human embryonic kidney 293 or human colorectal carcinoma 116 cells increases the rate of swelling-induced VRAC activation by approximately 10-fold. ZPT potentiates swelling-induced VRAC currents after currents have reached a steady state and activates currents in the absence of cell swelling. Neither ZnCl2 nor free pyrithione activated VRAC; however, treating cells with a mixture of ZnCl2 and pyrithione led to robust channel activation. Finally, the effects of ZPT on VRAC were inhibited by reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and NAD(P)H oxidase inhibitor diphenyleneiodonium chloride, suggesting the mechanism of action involves ROS generation. The discovery of ZPT as a potentiator/activator of VRAC demonstrates the utility of HTS for identifying small-molecule modulators of VRAC and adds to a growing repertoire of pharmacological tool compounds for probing the molecular physiology and regulation of this important channel.
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Sunkara, Jhansi R., and Sathish M. Botsa. "Facile Synthesis of 1,8-dioxooctahydro Xanthenes by Reusable Zinc Sulfide based Ternary Nanocomposite via Hydrothermal Route." Current Catalysis 9, no. 1 (2020): 72–79. http://dx.doi.org/10.2174/2211544708666191112120505.
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Background: Metal oxide or metal oxide composite nanoparticles are attaining tremendous importance due to their catalytic activities for various organic transformations. Objective: To report the one-pot synthesis of xanthene derivatives prepared by ZnS-Fe2O3-Ag composite under solvent-free conditions. Method: To prepare nanocomposite by a facile and simple hydrothermal approach. Results: The prepared composite is smaller (17.56 nm) in size and can be easily separable, recycled and reused six times without any significant loss of catalytic activity with excellent yields. In short reaction time, great catalytic activity was perceived with no co-catalyst and any other activator. Conclusion: In conclusion, ZnS-Fe2O3-Ag composite provides a simple, economical, efficient and greener method for the synthesis of one-pot multicomponent reaction of aldehyde with 1,3-diketones under solvent free conditions for the synthesis of 1,8-dioxooctahydro xanthenes. In short reaction time, great catalytic activity was perceived with no co-catalyst and any other activator.
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Ajekwene, Kingsley Kema, Johnson Oseghale Oboh, Ugonna Kingsley Ugo, and Simon Ikechukwu Ichetaonye. "Preparation of Multifunctional Additive [MFA] from Castor Oil (CO) and Study of its Effects on the Physical Properties of Natural Rubber Vulcanizates." International Journal of Research in Advent Technology 11, no. 3 (2023): 1–10. http://dx.doi.org/10.32622/ijrat.111202311.
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This experiment focuses on the synthesis of Multifunctional Additives (MFA) from Castor seed oil (CO) and pure Oleic acid (OA) respectively. These multifunctional additives (CO-MFA and OA-MFA) were investigated as potential substitutes for process oil, activator, co-activator, and accelerator in the formulation of a natural rubber vulcanizate. During processing, the castor seed oil was characterized for acid value (AV), free fatty acid (FFA) and saponification value (SV) and subsequently reacted with 1, 6-hexane diamine to obtain a mixture of salts termed castor oil-based multifunctional additives (CO-MFA), similarly, a pure oleic acid was also reacted with 1, 6-hexane diamine to obtain a pure salt termed oleic acid-based multifunctional additive (OA-MFA). These compounds were investigated as substitutes for process oil/stearic acid, process oil/stearic acid/zinc oxide, process oil/MBT, and process oil/stearic acid/zinc oxide/MBT in the formulation and compounding of natural rubber vulcanizate. The pre-mastication of the rubber and subsequent mixing with additives was carried out in a Banbury Internal Mixer at a rotor speed of 50 rpm for 7 mins while the vulcanization was achieved on a compression molding machine at a temperature of 140oC for 15 mins. The various vulcanizates samples were evaluated for tensile properties, compression set, abrasion resistance, and hardness. The use of castor seed oil-based multifunctional additives (CO-MFA) as a substitute for process oil/stearic acid/zinc oxide/MBT gave the highest value of tensile strength (12.24 MPa) as against the conventional rubber compound (4.21 MPa).
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Xie, Zhigang, Wei Guan, Fangying Ji, Zhongrong Song, and Yanling Zhao. "Production of Biologically Activated Carbon from Orange Peel and Landfill Leachate Subsequent Treatment Technology." Journal of Chemistry 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/491912.
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In order to improve adsorption of macromolecular contaminants and promote the growth of microorganisms, active carbon for biological wastewater treatment or follow-up processing requires abundant mesopore and good biophile ability. In this experiment, biophile mesopore active carbon is produced in one-step activation with orange peel as raw material, and zinc chloride as activator, and the adsorption characteristics of orange peel active carbon is studied by static adsorption method. BET specific surface area and pore volume reached 1477 m2/g and 2.090 m3/g, respectively. The surface functional groups were examined by Fourier transform infrared spectroscopy (FT-IR). The surface of the as-prepared activated carbon contained hydroxyl group, carbonyl group, and methoxy group. The analysis based on X-ray diffraction spectrogram (XRD) and three-dimensional fluorescence spectrum indicated that the as-prepared activated carbon, with smaller microcrystalline diameter and microcrystalline thickness and enhanced reactivity, exhibited enhanced adsorption performance. This research has a deep influence in effectively controlling water pollution, improving area water quality, easing orange peel waste pollution, and promoting coordinated development among society, economy, and environment.
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Alam, Md Najib, Vineet Kumar, and Sang-Shin Park. "Advances in Rubber Compounds Using ZnO and MgO as Co-Cure Activators." Polymers 14, no. 23 (2022): 5289. http://dx.doi.org/10.3390/polym14235289.
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Zinc oxide performs as the best cure activator in sulfur-based vulcanization of rubber, but it is regarded as a highly toxic material for aquatic organisms. Hence, the toxic cure activator should be replaced by a non-toxic one. Still, there is no suitable alternative industrially. However, binary activators combining ZnO and another metal oxide such as MgO can largely reduce the level of ZnO with some improved benefits in the vulcanization of rubber as investigated in this research. Curing, mechanical, and thermal characteristics were investigated to find out the suitability of MgO in the vulcanization of rubber. Curing studies reveal that significant reductions in the optimum curing times are found by using MgO as a co-cure activator. Especially, the rate of vulcanization with conventional 5 phr (per hundred grams) ZnO can be enhanced by more than double, going from 0.3 Nm/min to 0.85 Nm/min by the use of a 3:2 ratio of MgO to ZnO cure activator system that should have high industrial importance. Mechanical and thermal properties investigations suggest that MgO as a co-cure activator used at 60% can provide 7.5% higher M100 (modulus at 100% strain) (0.58 MPa from 0.54 MPa), 20% higher tensile strength (23.7 MPa from 19.5 MPa), 15% higher elongation at break (1455% from 1270%), 68% higher fracture toughness (126 MJ/m3 from 75 MJ/m3), and comparable thermal stability than conventionally using 100 % ZnO. Especially, MgO as a co-cure activator could be very useful for improving the fracture toughness in rubber compounds compared to ZnO as a single-site curing activator. The significant improvements in the curing and mechanical properties suggest that MgO and ZnO undergo chemical interactions during vulcanization. Such rubber compounds can be useful in advanced tough and stretchable applications.
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Troconis de Rincón, Oladis, Andrés Torres-Acosta, Alberto Sagüés, and Miguel Martinez-Madrid. "Galvanic Anodes for Reinforced Concrete Structures: A Review." Corrosion 74, no. 6 (2018): 715–23. http://dx.doi.org/10.5006/2613.
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In recent years, the use of sacrificial anodes for cathodic protection in reinforced concrete structures has increased, reflecting ease of installation, low-maintenance requirements, as well as desirability in prestressed concrete structures where the naturally controlled protection potential decreases the risk of hydrogen embrittlement. Zinc-based alloys have been among the most evaluated galvanic materials for concrete structures, especially in the United States, in many applications: thermal spray, superficial metal/mesh with and without hydrogel adhesive, embedded in concrete (point anodes) with or without salt activator, etc. However, the protection capacity lifetime of zinc alloys as used has been questioned based both on laboratory and on field application studies. Aluminum alloys have also been evaluated, sometimes showing better results as anode materials than zinc alloys. However, both zinc and aluminum alloy anodes may experience limited applicability in concrete structures exposed only to atmospheric conditions, as opposed to those in immersed, tidal, and splash zone service. This paper presents a review of the research work in the literature to date for both laboratory and field evaluations, toward identifying technically relevant situations where the use of sacrificial anodes may or may not be a practical option for reinforcement protection in concrete structures.
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Petrova A. V., Sidorova A. V., Sergeeva I. A., and Petrova G. P. "Evaluation of the influence of chromium and zinc ions on the collagenolysis process in solutions by the method of dynamic light scattering." Optics and Spectroscopy 130, no. 6 (2022): 663. http://dx.doi.org/10.21883/eos.2022.06.54701.23-22.
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Using the method of dynamic light scattering, it was found that the rate of collagen cleavage under the influence of bacterial collagenase decreases by almost 4 times when protein molecules are doped with Cr3+ ions, and when the enzyme activator of Zn2+ ions is added, it increases by 1.3 times. Based on the experimental data, the reaction rate constants k1 were calculated. It was found that when collagen molecules are tanned with a chromium salt, it becomes more resistant to degradation in solutions containing zinc ions than in solutions with the addition of calcium ions, as we described in earlier works. Keywords: collagen type 1, bacterial collagenase, chromium chloride, zinc chloride, dynamic light scattering method, translational diffusion coefficient, hydrodynamic radius, reaction rate constant, collagenolysis, Clostridium histolyticum.
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Darmayanti, Lita, Suprihanto Notodarmojo, Enri Damanhuri, Grandprix T. M. Kadja, and Rino R Mukti. "Preparation of alkali-activated fly ash-based geopolymer and their application in the adsorption of copper (II) and zinc (II) ions." MATEC Web of Conferences 276 (2019): 06012. http://dx.doi.org/10.1051/matecconf/201927606012.
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Alkali activation of fly ash can a promising alternative of the system to improve adsorption capability of fly ash. In finding the best chemical composition of the activator solution, geopolymer has been synthesized using molar ratios of Na2O/SiO2 0.16, 0.3, and 0.5 (Gr1, Gr3, Gr5). The results indicated that the geopolymer synthesized with a ratio molar of Na2O/SiO2 0.3 (Gr3) improved the adsorption properties of fly ash substantially. Gr3 was characterized by BET, XRD, and FTIR. The batch experiment was conducted at the different duration and initial concentrations. The equilibrium sorption data were fitted for the Langmuir and Freundlich equations. The maximum sorption capacities calculated from Langmuir isotherm was 54 mg g-1 and 47 mg g-1 for Cu (II) and Zn (II) respectively. The kinetic data reveal that the pseudo-second order model was appropriate for a description of the kinetic performance.
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Xu, Wenlina. "Research progress of gene editing technology CRISPR/Cas9 system in animal gene editing." International Journal of Veterinary Science and Research 4, no. 1 (2018): 015–19. https://doi.org/10.17352/ijvsr.000030.
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Gene editing technology, from the beginning of RNA interference (RNAi) technology to efficient developed enzyme technology, has been widely used in recent years. These efficient enzyme technologies include zinc finger nuclease (ZFN) technology, transcriptional activation-like effector nuclease (TALENs) technology, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system (CRISPR/Cas9) technology. The CRISPR/Cas (Cas) system is a gene editing tool for DNA modification regulated by a short RNA and is a new type of genome editing tool that is faster, more efficient, and more accurate than the zinc finger nuclease and transcription activator-like effector nuclease. This article reviews the structure and function of the CRISPR/Cas system, and is aimed to outline the Cas9 design strategy, factors that affect the Cas9 gene editing efficiency, off-target detection and analysis methods, and especially the application in animal gene editing studies. Based on CRISPR/Cas9 gene editing has been successfully implemented in a variety of animals, and it is expected to become a new feasible way to establish animal models and study disease prevention in veterinary science and research.
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Motorina, Daria M., Yuliya A. Galimova, Nadezhda V. Battulina, and Evgeniya S. Omelina. "Systems for Targeted Silencing of Gene Expression and Their Application in Plants and Animals." International Journal of Molecular Sciences 25, no. 10 (2024): 5231. http://dx.doi.org/10.3390/ijms25105231.
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At present, there are a variety of different approaches to the targeted regulation of gene expression. However, most approaches are devoted to the activation of gene transcription, and the methods for gene silencing are much fewer in number. In this review, we describe the main systems used for the targeted suppression of gene expression (including RNA interference (RNAi), chimeric transcription factors, chimeric zinc finger proteins, transcription activator-like effectors (TALEs)-based repressors, optogenetic tools, and CRISPR/Cas-based repressors) and their application in eukaryotes—plants and animals. We consider the advantages and disadvantages of each approach, compare their effectiveness, and discuss the peculiarities of their usage in plant and animal organisms. This review will be useful for researchers in the field of gene transcription suppression and will allow them to choose the optimal method for suppressing the expression of the gene of interest depending on the research object.
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Borislav, N. Malinovic, Zoric Dusko, and Djuricic Tijana. "Corrosion coupon testing of commercial inhibitor in simulated cooling water." Technologica Acta 13, no. 1 (2020): 27–32. https://doi.org/10.5281/zenodo.4059952.
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In maintaining cooling systems, one of the biggest challenges is to control the corrosion process. Various corrosion inhibitors are often used for this purpose. Which type of corrosion inhibitor will be chosen depends on the material from which the plant has made. The main causes of corrosion in these systems are: pH, dissolved gas, ammonia, temperature and microbiology. In this paper it was studied the efficiency of two multicomponent commercial corrosion inhibitors based on phosphates and one of which containing zinc chloride. For the purposes of research, the pilot plant of open recirculation cooling system is constructed and made of stainless steel (EN 1.4301) and copper (EN 13601). Experiments were performed in a simulated cooling water witch recirculated for 3.5h. For the purpose of accelerating corrosion processes, it was added a corrosion activator (5% NaCl). It was monitored the corrosion rate of the mentioned materials in the cooling water with the corrosion activator, with and without inhibitor. Corrosion rate is determined by using corrosion coupons according standard ASTM D2688 and by analyzing physical-chemical parameters of cooling water. The results showed it was achieved higher protection efficiency for copper and stainless steel by using an inhibitor containing zinc chloride in addition to phosphate.
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Cahill, Catherine M., Sanjan S. Sarang, Rachit Bakshi, Ning Xia, Debomoy K. Lahiri, and Jack T. Rogers. "Neuroprotective Strategies and Cell-Based Biomarkers for Manganese-Induced Toxicity in Human Neuroblastoma (SH-SY5Y) Cells." Biomolecules 14, no. 6 (2024): 647. http://dx.doi.org/10.3390/biom14060647.
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Manganese (Mn) is an essential heavy metal in the human body, while excess Mn leads to neurotoxicity, as observed in this study, where 100 µM of Mn was administered to the human neuroblastoma (SH-SY5Y) cell model of dopaminergic neurons in neurodegenerative diseases. We quantitated pathway and gene changes in homeostatic cell-based adaptations to Mn exposure. Utilizing the Gene Expression Omnibus, we accessed the GSE70845 dataset as a microarray of SH-SY5Y cells published by Gandhi et al. (2018) and applied statistical significance cutoffs at p < 0.05. We report 74 pathway and 10 gene changes with statistical significance. ReactomeGSA analyses demonstrated upregulation of histones (5 out of 10 induced genes) and histone deacetylases as a neuroprotective response to remodel/mitigate Mn-induced DNA/chromatin damage. Neurodegenerative-associated pathway changes occurred. NF-κB signaled protective responses via Sirtuin-1 to reduce neuroinflammation. Critically, Mn activated three pathways implicating deficits in purine metabolism. Therefore, we validated that urate, a purine and antioxidant, mitigated Mn-losses of viability in SH-SY5Y cells. We discuss Mn as a hypoxia mimetic and trans-activator of HIF-1α, the central trans-activator of vascular hypoxic mitochondrial dysfunction. Mn induced a 3-fold increase in mRNA levels for antioxidant metallothionein-III, which was induced 100-fold by hypoxia mimetics deferoxamine and zinc.
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Wallis, Christopher P., Louis H. Scott, Aleksandra Filipovska, and Oliver Rackham. "Manipulating and elucidating mitochondrial gene expression with engineered proteins." Philosophical Transactions of the Royal Society B: Biological Sciences 375, no. 1790 (2019): 20190185. http://dx.doi.org/10.1098/rstb.2019.0185.
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Many conventional, modern genome engineering tools cannot be used to study mitochondrial genetics due to the unusual structure and physiology of the mitochondrial genome. Here, we review a number of newly developed, synthetic biology-based approaches for altering levels of mutant mammalian mitochondrial DNA and mitochondrial RNAs, including transcription activator-like effector nucleases, zinc finger nucleases and engineered RNA-binding proteins. These approaches allow researchers to manipulate and visualize mitochondrial processes and may provide future therapeutics. This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
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Männistö, Riina H., A. Marika Grahn, Dennis H. Bamford, and Jaana K. H. Bamford. "Transcription of Bacteriophage PM2 Involves Phage-Encoded Regulators of Heterologous Origin." Journal of Bacteriology 185, no. 11 (2003): 3278–87. http://dx.doi.org/10.1128/jb.185.11.3278-3287.2003.
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ABSTRACT Bacteriophage PM2 is the only described member of the Corticoviridae family. It is an icosahedral dsDNA virus with a membrane residing underneath the protein coat. PM2 infects some gram-negative Pseudoalteromonas spp. In the present study, we mapped the viral promoters and showed that the PM2 genome consists of three operons. Four new virus genes were assigned based on their function in transcription. Proteins P15 and P16 are shown to repress early transcription, and proteins P13 and P14 are shown to activate late transcription events. The early regulatory region, containing genes for proteins P15 and P16, as well as the newly identified early promoter region in PM2, has significant sequence similarity with the Pseudoalteromonas pAS28 plasmid. P14, the transcription activator for the structural genes, has a zinc finger motif homologous to archaeal and eukaryotic TFIIS-type regulatory factors.
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Xu, Tao, Yongchao Li, Joy D. Van Nostrand, Zhili He, and Jizhong Zhou. "Cas9-Based Tools for Targeted Genome Editing and Transcriptional Control." Applied and Environmental Microbiology 80, no. 5 (2014): 1544–52. http://dx.doi.org/10.1128/aem.03786-13.
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ABSTRACTDevelopment of tools for targeted genome editing and regulation of gene expression has significantly expanded our ability to elucidate the mechanisms of interesting biological phenomena and to engineer desirable biological systems. Recent rapid progress in the study of a clustered, regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein system in bacteria has facilitated the development of newly facile and programmable platforms for genome editing and transcriptional control in a sequence-specific manner. The core RNA-guided Cas9 endonuclease in the type II CRISPR system has been harnessed to realize gene mutation and DNA deletion and insertion, as well as transcriptional activation and repression, with multiplex targeting ability, just by customizing 20-nucleotide RNA components. Here we describe the molecular basis of the type II CRISPR/Cas system and summarize applications and factors affecting its utilization in model organisms. We also discuss the advantages and disadvantages of Cas9-based tools in comparison with widely used customizable tools, such as Zinc finger nucleases and transcription activator-like effector nucleases.
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Pu, Mengjie, Daqi Ye, Jinquan Wan, Bentuo Xu, Wei Sun, and Wei Li. "Zinc-based metal–organic framework nanofibers membrane ZIF-65/PAN as efficient peroxymonosulfate activator to degrade aqueous ciprofloxacin." Separation and Purification Technology 299 (October 2022): 121716. http://dx.doi.org/10.1016/j.seppur.2022.121716.
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Петрова, А. В., А. В. Сидорова, И. А. Сергеева та Г. П. Петрова. "Оценка влияния ионов хрома и цинка на процесс коллагенолиза в растворах методом динамического рассеяния света". Оптика и спектроскопия 130, № 6 (2022): 838. http://dx.doi.org/10.21883/os.2022.06.52624.23-22.
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Using the method of dynamic light scattering, it was found that the rate of collagen cleavage under the influence of bacterial collagenase decreases by almost 4 times when protein molecules are doped with Cr3+ ions, and when the enzyme activator of Zn2+ ions is added, it increases by 1.3 times. Based on the experimental data, the reaction rate constants k1 were calculated. It was found that when collagen molecules are tanned with a chromium salt, it becomes more resistant to degradation in solutions containing zinc ions than in solutions with the addition of calcium ions, as we described in earlier works.
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Sandalov, S. I., N. F. Ushmarin, N. A. Chernova, and N. I. Kol'tsov. "Investigating Zinc Methacrylate as An activator of the Peroxide vulcanisation of A Rubber Mix Based on Nitrile Butadiene Rubber." International Polymer Science and Technology 40, no. 11 (2013): T25—T27. http://dx.doi.org/10.1177/0307174x1304001110.
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Riggs, K. J., S. Saleque, K. K. Wong, et al. "Yin-yang 1 activates the c-myc promoter." Molecular and Cellular Biology 13, no. 12 (1993): 7487–95. http://dx.doi.org/10.1128/mcb.13.12.7487-7495.1993.
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Previous studies on the murine c-myc promoter demonstrated that a ubiquitously present protein, common factor 1 (CF1), bound at two sites located -260 and -390 bp from the P1 transcription start site. CF1 has been purified to near homogeneity and shown to be identical to the zinc finger protein Yin-yang 1 (YY1) as judged by similarity of molecular weight and other biochemical properties, immunological cross-reactivity, and the ability of recombinant YY1 to bind to CF1 sites. In cotransfection experiments, YY1 is a strong activator of transcription from c-myc promoter-based reporters. Furthermore, in murine erythroleukemia cells, overexpressed YY1 causes increased levels of c-myc mRNA initiated from both major transcription initiation sites of the endogenous c-myc gene.
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Riggs, K. J., S. Saleque, K. K. Wong, et al. "Yin-yang 1 activates the c-myc promoter." Molecular and Cellular Biology 13, no. 12 (1993): 7487–95. http://dx.doi.org/10.1128/mcb.13.12.7487.
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Previous studies on the murine c-myc promoter demonstrated that a ubiquitously present protein, common factor 1 (CF1), bound at two sites located -260 and -390 bp from the P1 transcription start site. CF1 has been purified to near homogeneity and shown to be identical to the zinc finger protein Yin-yang 1 (YY1) as judged by similarity of molecular weight and other biochemical properties, immunological cross-reactivity, and the ability of recombinant YY1 to bind to CF1 sites. In cotransfection experiments, YY1 is a strong activator of transcription from c-myc promoter-based reporters. Furthermore, in murine erythroleukemia cells, overexpressed YY1 causes increased levels of c-myc mRNA initiated from both major transcription initiation sites of the endogenous c-myc gene.
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Taghvaei-Ganjali, Saeed, Mercedeh Malekzadeh, Mona Farahani, Ali Abbasian, and Morteza khosravi. "Effect of surface-modified zinc oxide as cure activator on the properties of a rubber compound based on NR/SBR." Journal of Applied Polymer Science 122, no. 1 (2011): 249–56. http://dx.doi.org/10.1002/app.33919.
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Pang, Xie Guan, Tien Yew Eeu, Pau Ming Leong, Wan Nurulhuda Wan Shamsuri, and Rosli Hussin. "Structural and Luminescence Study of Rare Earth and Transition Metal Ions Doped Lead Zinc Borophosphate Glasses." Advanced Materials Research 895 (February 2014): 280–83. http://dx.doi.org/10.4028/www.scientific.net/amr.895.280.
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A series of glasses with composition of xPbO-(50-x)ZnO-yB2O3-(50-y)P2O5 with 0 x 50 mol% and 10 y 20 mol% were prepared by melt quenching technique, with 30 minutes pre-heating and 10 minutes for melting. The structural properties of prepared samples were studied using Fourier Transform-Infrared spectroscopy. The glasses were mainly based on PO2, BOP and BO3 unit. In order to obtain luminescence properties, another series of sample at composition 20PbO-30ZnO-10B2O3-40P2O5 doped with Fe2+, Ti2+, Y2+ and Nd2+ were prepared. These samples were investigated using Photoluminescence Spectroscopy with different excitation wavelength to compare results. Results showed that with the presence of rare earth and transition metal ions as activator in lead zinc borophosphate glass system give rise to luminescence of visible light.
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Xu, Xiao Yan, Guo Tong Qian, Jian Zhou, Yao Yao, and Xu Chen. "Wettability of Sn-Zn Lead-Free Solder on Aluminum Substrate." Advanced Materials Research 815 (October 2013): 48–54. http://dx.doi.org/10.4028/www.scientific.net/amr.815.48.
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The effects of flux components and compositions of solder alloys on the wettability of the Sn-Zn alloys on aluminum surface was investigated. The results show that the wettability of the Sn-9Zn solder on aluminum substrate improved with flux of double solvents composed of diethanolamine and triethanolamine, which is better than single solvent. When flux is composed of 3% zinc fluoborate as activator and 30% triethanolamine plus 67% diethanolamine as double solvents, the spreading area of the Sn-9Zn solder reaches to 75%. Trace addition (0.002%-0.005%) of Al results in significant improvement of the wettability of the Sn-9Zn based solder. However, additions of Bi or Sb are not beneficial to the wettability of the solder on aluminum substrate.
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Kenzhalievich, Kenzhaliyev Bagdaulet, Koizhanova Aigul Kairgeldyevna, Magomedov David Rasimovich, et al. "A Study on the efficiency of organic activator application to process refractory hard-to-beneficiate raw materials." Jurnal Pendidikan Teknologi Kejuruan 7, no. 3 (2024): 185–203. http://dx.doi.org/10.24036/jptk.v7i3.38323.
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Polymetallic ores with complex mineralogical compositions pose significant challenges in flotation beneficiation, often resulting in suboptimal separation and recovery of valuable minerals. This study aims to analyse the effectiveness of alkyl benzene sulfonic acid (ABSA) as a frothing activator in improving the flotation performance and mineral recovery of polymetallic ore. It presents the results of flotation beneficiation experiments for polymetallic ore of complex mineralogical composition. Experiments were conducted on polymetallic ore samples using ABSA as the frothing activator in the flotation process. The performance was evaluated based on recovery rates and separation efficiency, comparing the results with standard floating frothing agents. The findings showed the highest efficiency of ABSA application for samples of mixed-type ores in increasing the recovery of gold, copper, zinc and lead in the collective concentrates of flotation beneficiation. ABSA activator promotes additional cleaning of fragments containing valuable metals from oxide films and coatings and the transfer of valuable metals' microparticles due to the organics' adsorption properties and the formation of metal-carbon bonds. Another effect of using this reagent is there was an increase in concentrate mass yield while maintaining the quality parameters. A similar effect was observed for beneficiation of copper ore with complex composition - copper recovery in the main concentrate increased. Selective flotation with the development of gold concentrate from hard-to-beneficiate polymetallic ore also showed a significant increase in gold recovery with ABSA pretreatment.
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Konjevic, Gordana, and Sandra Stankovic. "Matrix metalloproteinases in the process of invasion and metastasis of breast cancer." Archive of Oncology 14, no. 3-4 (2006): 136–40. http://dx.doi.org/10.2298/aoo0604136k.
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Metastatic cascade in malignant tumors, including breast cancer, starts with localized invasion of the host tissue. This process, requiring that tumor cells separate from each other, includes loss of homotypic and heterotypic cell adhesion and cell-cell contact inhibition, acquisition of motility, exacerbated by "epithelial-to-mesenchymal transition", and production of proteolytic enzymes which degrade basal membrane and extracellular matrix. In this sense, aside from urokinase type plasminogen activator, increased expression and activity of matrix metalloproteinases (MMPs) is one of the earliest and most sustained events in tumor progression, playing a role in angiogenesis, invasion and metastasis. MMPs are a family of 23 zinc metalloproteinases, secreted as latent pro-enzymes, activated by proteolytic cleavage, and inhibited by the tissue inhibitors of metalloproteinases. The most commonly connected MMPs with the processes of metastasis are MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their ability to degrade collagen type IV, major component of vascular basement membrane. MMP-2 and MMP-9 are also required for the switch to the "angiogenic phenotype" during tumor progression and activation of dormant tumor cells. The association of the increase in serum MMP-2 and MMP-9 activity and clinical stage suggests the usefulness of these parameters as markers in the follow-up and prognosis of breast cancer patients. The concept of "stromal-directed therapy" of cancer, with MMP-inhibitors directed against MMPs as targets, is based on the observed MMP up-regulation in tumors.
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Canver, Matthew C., та Stuart H. Orkin. "Customizing the genome as therapy for the β-hemoglobinopathies". Blood 127, № 21 (2016): 2536–45. http://dx.doi.org/10.1182/blood-2016-01-678128.
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Abstract Despite nearly complete understanding of the genetics of the β-hemoglobinopathies for several decades, definitive treatment options have lagged behind. Recent developments in technologies for facile manipulation of the genome (zinc finger nucleases, transcription activator-like effector nucleases, or clustered regularly interspaced short palindromic repeats–based nucleases) raise prospects for their clinical application. The use of genome-editing technologies in autologous CD34+ hematopoietic stem and progenitor cells represents a promising therapeutic avenue for the β-globin disorders. Genetic correction strategies relying on the homology-directed repair pathway may repair genetic defects, whereas genetic disruption strategies relying on the nonhomologous end joining pathway may induce compensatory fetal hemoglobin expression. Harnessing the power of genome editing may usher in a second-generation form of gene therapy for the β-globin disorders.
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Phan, Hong Thi Lam, Kyoungmi Kim, Ho Lee, and Je Kyung Seong. "Progress in and Prospects of Genome Editing Tools for Human Disease Model Development and Therapeutic Applications." Genes 14, no. 2 (2023): 483. http://dx.doi.org/10.3390/genes14020483.
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Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas, are widely accepted because of their diversity and enormous potential for targeted genomic modifications in eukaryotes and other animals. Moreover, rapid advances in genome editing tools have accelerated the ability to produce various genetically modified animal models for studying human diseases. Given the advances in gene editing tools, these animal models are gradually evolving toward mimicking human diseases through the introduction of human pathogenic mutations in their genome rather than the conventional gene knockout. In the present review, we summarize the current progress in and discuss the prospects for developing mouse models of human diseases and their therapeutic applications based on advances in the study of programmable nucleases.
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Radkowski, Adam, Iwona Radkowska, Tadeusz Lemek, and Tomasz Jakubowski. "Effect of Zinc Ammonium Acetate on Characteristics of Timothy Canopy and Seed Yield." Ecological Chemistry and Engineering S 26, no. 4 (2019): 797–806. http://dx.doi.org/10.1515/eces-2019-0056.
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Abstract The purpose of the experiment was to assess the effect of application of zinc ammonium acetate (ZAA) on yielding, morphological features and on selected vegetation indices of timothy cv. ‘Owacja’ cultivated for seeds. Zinc ammonium acetate that has a biostimulatory effect was used foliar in the carried out experiment. The experiment was conducted in the years 2015-2017 at the experimental station in Prusy near Krakow, a part of the Experimental Station of the Institute of Crop Production of the University of Agriculture in Krakow. The field experiment was set up in a randomized block design, in four replications, and the area of experimental plots was 10 m2. Degraded Chernozem formed from loess (classified to the first class quality soil) was present on the experimental area. The experiment consisted in applying ZAA as spray at three doses: 0.214, 0.267 and 0.400 kg(ZnNH4(CH3CO2)3)/ha. Based on the obtained preliminary results, it was found that application of foliar activator in a higher dose (0.400 kg/ha) caused a significant (p ≤ 0.05) increase in seed yield, 1000-seed weight and in germination capacity in relation to the control. Improvement in morphological properties was also observed. Leaf greenness index (SPAD) was also determined. Its highest value was found in plants from the treatment where the highest dose of the zinc ammonium acetate was applied. Seeds obtained from plants treated with ZAA were riper (ripeness was measured with 1000-seed weight) and had higher germination capacity in relation to control treatments.
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Urbano, Smith, Weeks, and Chatterjee. "Gene-Specific Targeting of DNA Methylation in the Mammalian Genome." Cancers 11, no. 10 (2019): 1515. http://dx.doi.org/10.3390/cancers11101515.
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DNA methylation is the most widely-studied epigenetic modification, playing a critical role in the regulation of gene expression. Dysregulation of DNA methylation is implicated in the pathogenesis of numerous diseases. For example, aberrant DNA methylation in promoter regions of tumor-suppressor genes has been strongly associated with the development and progression of many different tumors. Accordingly, technologies designed to manipulate DNA methylation at specific genomic loci are very important, especially in the context of cancer therapy. Traditionally, epigenomic editing technologies have centered around zinc finger proteins (ZFP)- and transcription activator-like effector protein (TALE)-based targeting. More recently, however, the emergence of clustered regulatory interspaced short palindromic repeats (CRISPR)-deactivated Cas9 (dCas9)-based editing systems have shown to be a more specific and efficient method for the targeted manipulation of DNA methylation. Here, we describe the regulation of the DNA methylome, its significance in cancer and the current state of locus-specific editing technologies for altering DNA methylation.
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Wu, Yanling, Qinggao Hou, Fangzhou Li, et al. "Mitigating Co Metal Particle Agglomeration and Enhancing ORR Catalytic Activity through Nitrogen-Enriched Porous Carbon Derived from Biomass." Catalysts 13, no. 7 (2023): 1118. http://dx.doi.org/10.3390/catal13071118.
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Biomass-derived porous carbon has gained significant attention as a cost-effective and sustainable material in non-noble metal carbon-based electrocatalysts for the oxygen reduction reaction (ORR). However, during the preparation of transition metal catalysts based on biomass-derived porous carbon, the agglomeration of transition metal atoms often occurs, leading to a notable decline in catalytic activity. In this study, we present a straightforward synthetic approach for the preparation of nitrogen-enriched soybean-derived porous carbon (Co@SP-C-a) as an electrocatalyst for the ORR. To achieve this, we employed a two-step method. In the first step, a chemical activator (KCl) was utilized to enhance the porosity of the self-doped nitrogen biomass carbon material. In the second step, a constant pressure drop funnel technique was employed to uniformly disperse bimetal cobalt/zinc-based zeolitic imidazolium frameworks (ZIF-L and ZIF-67) containing different metal ions (Zn2+ and Co2+) into the activated biomass carbon material. Subsequent high-temperature calcination of the ZIF-L and ZIF-67@SP-C-a composite precursor yielded the Co@SP-C-a catalyst. The obtained catalyst exhibited remarkable ORR activity in an alkaline solution (Eonset = 0.89 V, E1/2 = 0.83 V, JL = −6.13 mA·cm−2) and exceptional long-term stability. This study presents an effective strategy to prevent the agglomeration of metal nanoparticles when integrating them with biomass-based carbon materials, thus leading to enhanced catalytic performance.
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Schreurs, Juliët, Claudia Sacchetto, Robin M. W. Colpaert, Libero Vitiello, Alessandra Rampazzo, and Martina Calore. "Recent Advances in CRISPR/Cas9-Based Genome Editing Tools for Cardiac Diseases." International Journal of Molecular Sciences 22, no. 20 (2021): 10985. http://dx.doi.org/10.3390/ijms222010985.
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In the past two decades, genome editing has proven its value as a powerful tool for modeling or even treating numerous diseases. After the development of protein-guided systems such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), which for the first time made DNA editing an actual possibility, the advent of RNA-guided techniques has brought about an epochal change. Based on a bacterial anti-phage system, the CRISPR/Cas9 approach has provided a flexible and adaptable DNA-editing system that has been able to overcome several limitations associated with earlier methods, rapidly becoming the most common tool for both disease modeling and therapeutic studies. More recently, two novel CRISPR/Cas9-derived tools, namely base editing and prime editing, have further widened the range and accuracy of achievable genomic modifications. This review aims to provide an overview of the most recent developments in the genome-editing field and their applications in biomedical research, with a particular focus on models for the study and treatment of cardiac diseases.
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Cheng, Yangfan, Sirui Zhang, and Huifang Shang. "Latest advances on new promising molecular-based therapeutic approaches for Huntington’s disease." Journal of Translational Internal Medicine 12, no. 2 (2024): 134–47. http://dx.doi.org/10.2478/jtim-2023-0142.
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Abstract Huntington’s disease (HD) is a devastating, autosomal-dominant inherited, neurodegenerative disorder characterized by progressive motor deficits, cognitive impairments, and neuropsychiatric symptoms. It is caused by excessive cytosine-adenine-guanine (CAG) trinucleotide repeats within the huntingtin gene (HTT). Presently, therapeutic interventions capable of altering the trajectory of HD are lacking, while medications for abnormal movement and psychiatric symptoms are limited. Numerous pre-clinical and clinical studies have been conducted and are currently underway to test the efficacy of therapeutic approaches targeting some of these mechanisms with varying degrees of success. In this review, we update the latest advances on new promising molecular-based therapeutic strategies for this disorder, including DNA-targeting techniques such as zinc-finger proteins, transcription activator-like effector nucleases, and CRISPR/Cas9; post-transcriptional huntingtin-lowering approaches such as RNAi, antisense oligonucleotides, and small-molecule splicing modulators; and novel methods to clear the mHTT protein, such as proteolysis-targeting chimeras. We mainly focus on the ongoing clinical trials and the latest pre-clinical studies to explore the progress of emerging potential HD therapeutics.
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Yano, Naohiro, and Alexey V. Fedulov. "Targeted DNA Demethylation: Vectors, Effectors and Perspectives." Biomedicines 11, no. 5 (2023): 1334. http://dx.doi.org/10.3390/biomedicines11051334.
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Aberrant DNA hypermethylation at regulatory cis-elements of particular genes is seen in a plethora of pathological conditions including cardiovascular, neurological, immunological, gastrointestinal and renal diseases, as well as in cancer, diabetes and others. Thus, approaches for experimental and therapeutic DNA demethylation have a great potential to demonstrate mechanistic importance, and even causality of epigenetic alterations, and may open novel avenues to epigenetic cures. However, existing methods based on DNA methyltransferase inhibitors that elicit genome-wide demethylation are not suitable for treatment of diseases with specific epimutations and provide a limited experimental value. Therefore, gene-specific epigenetic editing is a critical approach for epigenetic re-activation of silenced genes. Site-specific demethylation can be achieved by utilizing sequence-dependent DNA-binding molecules such as zinc finger protein array (ZFA), transcription activator-like effector (TALE) and clustered regularly interspaced short palindromic repeat-associated dead Cas9 (CRISPR/dCas9). Synthetic proteins, where these DNA-binding domains are fused with the DNA demethylases such as ten-eleven translocation (Tet) and thymine DNA glycosylase (TDG) enzymes, successfully induced or enhanced transcriptional responsiveness at targeted loci. However, a number of challenges, including the dependence on transgenesis for delivery of the fusion constructs, remain issues to be solved. In this review, we detail current and potential approaches to gene-specific DNA demethylation as a novel epigenetic editing-based therapeutic strategy.
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Beil, J., L. Fairbairn, P. Pelczar, and T. Buch. "Is BAC Transgenesis Obsolete? State of the Art in the Era of Designer Nucleases." Journal of Biomedicine and Biotechnology 2012 (2012): 1–5. http://dx.doi.org/10.1155/2012/308414.
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DNA constructs based on bacterial artificial chromosomes (BACs) are frequently used to generate transgenic animals as they reduce the influence of position effects and allow predictable expression patterns for genes whose regulatory sequences are not fully identified. Despite these advantages BAC transgenics suffer from drawbacks such as complicated vector construction, low efficiency of transgenesis, and some remaining expression variegation. The recent development of transcription activator-like effector nucleases (TALENs) and zinc finger nucleases (ZFNs) has resulted in new transgenic techniques which do not have the drawbacks associated with BAC transgenesis. Initial reports indicate that such designer nucleases (DNs) allow the targeted insertion of transgenes into endogenous loci by direct injection of the targeting vector and mRNA/DNA encoding the predesigned nucleases into oocytes. This results in the transgene being inserted at a specific locus in the mouse genome, thus circumventing the drawbacks associated with BAC transgenesis.
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Khamaganova, Tatyana N. "Preparation, luminescence, and application of LiMeBO3 borates, Me = Mg, Ca, Sr, Ba, Zn, Cd. Review." Kondensirovannye sredy i mezhfaznye granitsy = Condensed Matter and Interphases 25, no. 3 (2023): 311–32. http://dx.doi.org/10.17308/kcmf.2023.25/11256.
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The review summarises and analyses data on the preparation, structure, and spectral-luminescent properties of LiMeBO3-based borates, Me = bivalent metal. These polycrystalline borates are prepared traditionally by solid-phase reactions and self-propagating high-temperature synthesis and its modifications based on a combustion reaction. Frameworks of lithium borates with alkaline earth metals, zinc, and cadmium are formed from large metal polyhedra between which there are boron-oxygen triangles isolated from each other. Doping with rare-earth and heavy metal ions leads to the formation of solid solutions which normally have defective structures. Doped activator ions often become the main part of the luminescence centre in the phosphor. The luminescent properties of ions of rare-earth elements arise from the possibility of electronic transitions between states within the 4f-configuration. The paper discusses the most likely mechanisms of charge compensation during heterovalent substitution in LiMeBO3 borates (co-doping and formationof cation vacancies). It is shown that charge compensation during the combined introduction of ions of REEs and alkali metals into the structure has a positive effect on the emission yield. The review considers the results of thermoluminescent, upconversion, and photoluminescent properties and processes and phenomena that cause them. It also explains the mechanism of resonance energy transfer from the sensitiser to the activator using the example of Yb3+→Er3+. It discusses the possibility of using the considered borates as phosphors that emit green, blue, and red light in white LEDs and as effective materials for personnel neutron dosimetry and the dosimetry of weak ionising radiation
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Ortiz-Vitali, Jose L., and Radbod Darabi. "iPSCs as a Platform for Disease Modeling, Drug Screening, and Personalized Therapy in Muscular Dystrophies." Cells 8, no. 1 (2019): 20. http://dx.doi.org/10.3390/cells8010020.
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Induced pluripotent stem cells (iPSCs) are the foundation of modern stem cell-based regenerative medicine, especially in the case of degenerative disorders, such as muscular dystrophies (MDs). Since their introduction in 2006, many studies have used iPSCs for disease modeling and identification of involved mechanisms, drug screening, as well as gene correction studies. In the case of muscular dystrophies, these studies commenced in 2008 and continue to address important issues, such as defining the main pathologic mechanisms in different types of MDs, drug screening to improve skeletal/cardiac muscle cell survival and to slow down disease progression, and evaluation of the efficiency of different gene correction approaches, such as exon skipping, Transcription activator-like effector nucleases (TALENs), Zinc finger nucleases (ZFNs) and RNA-guided endonuclease Cas9 (CRISPR/Cas9). In the current short review, we have summarized chronological progress of these studies and their key findings along with a perspective on the future road to successful iPSC-based cell therapy for MDs and the potential hurdles in this field.
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Thanh, Nguyen Duc. "Application of genome editing tools in plants." Vietnam Journal of Biotechnology 19, no. 1 (2021): 15–40. http://dx.doi.org/10.15625/1811-4989/15464.
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Genome editing technology is the genome modification techniques, such as targeted mutagenesis or insert/delete/replacement at specific locations in the genome of living organisms. Genome editing is based on the creation of double sequence break (DSB) in a specific location and DNA repair via nonhomologous end joining (NHEJ) or homology direct repair (HDR). The development of sequence-specific nuclease (SSN) allows precise editing of the target gene. These SSNs include: meganuclease (MN), zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and CRISPR-associated nuclease (Cas) including CRISPR/Cas9 (from Streptococcus pyogenes) and CRISPR/Cpf1 (from Prevoltella and Francisella1). These are the genome editing tools used to create DSBs at specific locations of the genome. Recently, the base editing (BE) and prime editing (PE) tools have been reported. This review will cover the basics of these tools and their application in genome editing in plants, especially providing the most up-to-date information on their application in crop improvement.
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Kim, Daesik, Kevin Luk, Scot A. Wolfe, and Jin-Soo Kim. "Evaluating and Enhancing Target Specificity of Gene-Editing Nucleases and Deaminases." Annual Review of Biochemistry 88, no. 1 (2019): 191–220. http://dx.doi.org/10.1146/annurev-biochem-013118-111730.
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Programmable nucleases and deaminases, which include zinc-finger nucleases, transcription activator-like effector nucleases, CRISPR RNA-guided nucleases, and RNA-guided base editors, are now widely employed for the targeted modification of genomes in cells and organisms. These gene-editing tools hold tremendous promise for therapeutic applications. Importantly, these nucleases and deaminases may display off-target activity through the recognition of near-cognate DNA sequences to their target sites, resulting in collateral damage to the genome in the form of local mutagenesis or genomic rearrangements. For therapeutic genome-editing applications with these classes of programmable enzymes, it is essential to measure and limit genome-wide off-target activity. Herein, we discuss the key determinants of off-target activity for these systems. We describe various cell-based and cell-free methods for identifying genome-wide off-target sites and diverse strategies that have been developed for reducing the off-target activity of programmable gene-editing enzymes.
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Pang, Jiahui. "Research Progress in The Application of CRISPR Gene Editing Technology in Virus Detection and Treatment." Highlights in Science, Engineering and Technology 45 (April 18, 2023): 302–7. http://dx.doi.org/10.54097/hset.v45i.7446.
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Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene editing (GE) technique is the latest generation of GE technology, which can carry out targeted and precise modification of the genome. In this article, a comparison of the Zinc-Finger Nucleases (ZFNs) , CRISPR/Cas and Transcription Activator-Like Effector Nucleases (TALENs) is presented, which indicates that CRISPR/Cas has significant advantages. For example, synthesis and screening are simpler and faster, and multiple genes can be edited simultaneously. To keep abreast of the times, current progress in the application of CRISPR in virus detection as well as treatment will be introduced in this paper. Firstly, CRISPR and its characteristics will be briefly introduced. Then the current application of CRISPR about detecting and treating viruses will be reviewed. Finally, the paper summarizes the shortcomings of CRISPR and looks forward to its future development.This article attempts to give readers a brief introduction to the emerging technology based on CRISPR and highlights its potential applications in virus detection and treatment.
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Geel, T. M., M. H. J. Ruiters, R. H. Cool, et al. "The past and presence of gene targeting: from chemicals and DNA via proteins to RNA." Philosophical Transactions of the Royal Society B: Biological Sciences 373, no. 1748 (2018): 20170077. http://dx.doi.org/10.1098/rstb.2017.0077.
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The ability to target DNA specifically at any given position within the genome allows many intriguing possibilities and has inspired scientists for decades. Early gene-targeting efforts exploited chemicals or DNA oligonucleotides to interfere with the DNA at a given location in order to inactivate a gene or to correct mutations. We here describe an example towards correcting a genetic mutation underlying Pompe's disease using a nucleotide-fused nuclease (TFO-MunI). In addition to the promise of gene correction, scientists soon realized that genes could be inactivated or even re-activated without inducing potentially harmful DNA damage by targeting transcriptional modulators to a particular gene. However, it proved difficult to fuse protein effector domains to the first generation of programmable DNA-binding agents. The engineering of gene-targeting proteins (zinc finger proteins (ZFPs), transcription activator-like effectors (TALEs)) circumvented this problem. The disadvantage of protein-based gene targeting is that a fusion protein needs to be engineered for every locus. The recent introduction of CRISPR/Cas offers a flexible approach to target a (fusion) protein to the locus of interest using cheap designer RNA molecules. Many research groups now exploit this platform and the first human clinical trials have been initiated: CRISPR/Cas has kicked off a new era of gene targeting and is revolutionizing biomedical sciences. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.
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Baya, Georgina, Stephen Muhindi, Valentine Ngendahimana, and Jonathan Caguiat. "Potential Whole-Cell Biosensors for Detection of Metal Using MerR Family Proteins from Enterobacter sp. YSU and Stenotrophomonas maltophilia OR02." Micromachines 12, no. 2 (2021): 142. http://dx.doi.org/10.3390/mi12020142.
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Cell-based biosensors harness a cell’s ability to respond to the environment by repurposing its sensing mechanisms. MerR family proteins are activator/repressor switches that regulate the expression of bacterial metal resistance genes and have been used in metal biosensors. Upon metal binding, a conformational change switches gene expression from off to on. The genomes of the multimetal resistant bacterial strains, Stenotrophomonas maltophilia Oak Ridge strain 02 (S. maltophilia 02) and Enterobacter sp. YSU, were recently sequenced. Sequence analysis and gene cloning identified three mercury resistance operons and three MerR switches in these strains. Transposon mutagenesis and sequence analysis identified Enterobacter sp. YSU zinc and copper resistance operons, which appear to be regulated by the protein switches, ZntR and CueR, respectively. Sequence analysis and reverse transcriptase polymerase chain reaction (RT-PCR) showed that a CueR switch appears to activate a S. maltophilia 02 copper transport gene in the presence of CuSO4 and HAuCl4·3H2O. In previous studies, genetic engineering replaced metal resistance genes with the reporter genes for β-galactosidase, luciferase or the green fluorescence protein (GFP). These produce a color change of a reagent, produce light, or fluoresce in the presence of ultraviolet (UV) light, respectively. Coupling these discovered operons with reporter genes has the potential to create whole-cell biosensors for HgCl2, ZnCl2, CuSO4 and HAuCl4·3H2O.
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Psatha, Nikoletta, Kiriaki Paschoudi, Anastasia Papadopoulou, and Evangelia Yannaki. "In Vivo Hematopoietic Stem Cell Genome Editing: Perspectives and Limitations." Genes 13, no. 12 (2022): 2222. http://dx.doi.org/10.3390/genes13122222.
Full textAbstract:
The tremendous evolution of genome-editing tools in the last two decades has provided innovative and effective approaches for gene therapy of congenital and acquired diseases. Zinc-finger nucleases (ZFNs), transcription activator- like effector nucleases (TALENs) and CRISPR-Cas9 have been already applied by ex vivo hematopoietic stem cell (HSC) gene therapy in genetic diseases (i.e., Hemoglobinopathies, Fanconi anemia and hereditary Immunodeficiencies) as well as infectious diseases (i.e., HIV), and the recent development of CRISPR-Cas9-based systems using base and prime editors as well as epigenome editors has provided safer tools for gene therapy. The ex vivo approach for gene addition or editing of HSCs, however, is complex, invasive, technically challenging, costly and not free of toxicity. In vivo gene addition or editing promise to transform gene therapy from a highly sophisticated strategy to a “user-friendly’ approach to eventually become a broadly available, highly accessible and potentially affordable treatment modality. In the present review article, based on the lessons gained by more than 3 decades of ex vivo HSC gene therapy, we discuss the concept, the tools, the progress made and the challenges to clinical translation of in vivo HSC gene editing.
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Bondareva, Olga, Roman Tsaryk, Vesna Bojovic, Maria Odenthal-Schnittler, Arndt F. Siekmann, and Hans-J. Schnittler. "Identification of atheroprone shear stress responsive regulatory elements in endothelial cells." Cardiovascular Research 115, no. 10 (2019): 1487–99. http://dx.doi.org/10.1093/cvr/cvz027.
Full textAbstract:
Abstract Aims Oscillatory shear stress (OSS) is an atheroprone haemodynamic force that occurs in areas of vessel irregularities and is implicated in the pathogenesis of atherosclerosis. Changes in signalling and transcriptional programme in response to OSS have been vigorously studied; however, the underlying changes in the chromatin landscape controlling transcription remain to be elucidated. Here, we investigated the changes in the regulatory element (RE) landscape of endothelial cells under atheroprone OSS conditions in an in vitro model. Methods and results Analyses of H3K27ac chromatin immunoprecipitation-Seq enrichment and RNA-Seq in primary human umbilical vein endothelial cells 6 h after onset of OSS identified 2806 differential responsive REs and 33 differentially expressed genes compared with control cells kept under static conditions. Furthermore, gene ontology analyses of putative RE-associated genes uncovered enrichment of WNT/HIPPO pathway and cytoskeleton reorganization signatures. Transcription factor (TF) binding motif analysis within RE sequences identified over-representation of ETS, Zinc finger, and activator protein 1 TF families that regulate cell cycle, proliferation, and apoptosis, implicating them in the development of atherosclerosis. Importantly, we confirmed the activation of EGR1 as well as the YAP/TAZ complex early (6 h) after onset of OSS in both cultured human vein and artery endothelial cells and, by undertaking luciferase assays, functionally verified their role in RE activation in response to OSS. Conclusions Based on the identification and verification of specific responsive REs early upon OSS exposure, we propose an expanded mechanism of how OSS might contribute to the development of atherosclerosis.
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Yu, N., J. Yang, Y. Mishina, and W. V. Giannobile. "Genome Editing: A New Horizon for Oral and Craniofacial Research." Journal of Dental Research 98, no. 1 (2018): 36–45. http://dx.doi.org/10.1177/0022034518805978.
Full textAbstract:
Precise and efficient genetic manipulations have enabled researchers to understand gene functions in disease and development, providing a platform to search for molecular cures. Over the past decade, the unprecedented advancement of genome editing techniques has revolutionized the biological research fields. Early genome editing strategies involved many naturally occurring nucleases, including meganucleases, zinc finger nucleases, and transcription activator-like effector-based nucleases. More recently, the clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated nucleases (CRISPR/Cas) system has greatly enriched genetic manipulation methods in conducting research. Those nucleases generate double-strand breaks in the target gene sequences and then utilize DNA repair mechanisms to permit precise yet versatile genetic manipulations. The oral and craniofacial field harbors a plethora of diseases and developmental defects that require genetic models that can exploit these genome editing techniques. This review provides an overview of the genome editing techniques, particularly the CRISPR/Cas9 technique, for the oral and craniofacial research community. We also discuss the details about the emerging applications of genome editing in oral and craniofacial biology.