What is metabolic pathways
1. Definition of metabolic pathways
Metabolic pathways are a series of chemical reactions catalyzed by enzymes within organisms, gradually converting substrates into compounds or energy required by the organism. Simply put, it is a routine enzymatic reaction sequence from A to X (A → B → C →... X). Taking the glucose metabolism pathway as an example, after glucose enters the cell, it first undergoes glycolysis under the action of a series of enzymes, converting into pyruvate. Pyruvate then further enters the mitochondria, participating in the citric acid cycle, and is ultimately oxidized completely, releasing energy to power various cellular activities. In this process, each step of the reaction is catalyzed by specific enzymes, ensuring that the reactions proceed efficiently and orderly. These metabolic pathways not only participate in the use and storage of substances but can also trigger other metabolic pathways, forming complex metabolic networks to maintain normal physiological functions of the organism.
2. Characteristics of metabolic pathways
Forming a Complex Metabolic Network: Metabolic pathways generate numerous branches from intermediates, thus forming a complex metabolic network. For example, within cells, the metabolic pathways of carbohydrates, lipids, and proteins are interconnected. The metabolic products of one substance may serve as substrates for another pathway, intertwining the entire metabolic process into a vast and intricate network structure.
The pathways of forward and reverse reactions differ: the pathways of forward reaction (A→X) and reverse reaction (X→A) are often distinct. This characteristic prevents metabolic processes from reaching a simple equilibrium state. For example, in gluconeogenesis and glycolysis, although the substrates and products are largely the same, there are differences in the enzymes involved and specific reaction steps, ensuring that metabolic processes can be flexibly regulated according to cellular needs.
Metabolic regulation exists: Various metabolic regulatory mechanisms occur in some intermediate processes of metabolic pathways. This regulation ensures that metabolic pathways proceed at the appropriate time and under suitable conditions, maintaining the stability of the cellular environment. Common regulatory methods include feedback regulation, where metabolites modulate the activity of certain key enzymes in the metabolic pathway, thereby controlling the rate and direction of metabolism.
3. Metabolic pathways and metabolic maps
Metabolic maps are tools that represent metabolic pathways in the form of line patterns. They present complex metabolic pathways in an intuitive graphical manner, clearly illustrating the relationships between various metabolic reactions and the direction of material and energy flow. Metabolic maps are closely related to metabolic pathways; they serve as visual representations of these pathways. Through metabolic maps, researchers can gain a more comprehensive and in-depth understanding of metabolic pathways. In the study of metabolic pathways, metabolic maps play a crucial role. They help researchers quickly grasp the overall framework of metabolic processes, analyze the connections between different metabolic pathways, and identify potential regulatory nodes. At the same time, metabolic maps provide important references for metabolic engineering and drug development, aiding in the design of rational experimental protocols and the exploration of new therapeutic targets.
A portion of the human metabolic chart
Classification and process of metabolic pathway
1. Carbohydrate metabolic pathway
As the main energy source of living organisms, the metabolic process of carbohydrates is complex and critical. First, in the absorption stage, the carbohydrates in food are decomposed into monosaccharides such as glucose and fructose by the digestive system, and then absorbed by the epithelial cells of the small intestine into the blood circulation and transported to all kinds of cells in the whole body.
After entering the cell, glucose undergoes glycolysis. Under the action of a series of enzymes, glucose is gradually converted into pyruvate, while producing small amounts of ATP and NADH. This process takes place in the cytoplasm without oxygen participation, which is an important way for cells to obtain energy under anaerobic or hypoxic conditions.
If there is sufficient oxygen, pyruvate enters the mitochondria and participates in the citric acid cycle. Inside the mitochondria, pyruvate is completely oxidized and broken down into carbon dioxide and water, releasing a large amount of energy to produce more ATP. The citric acid cycle is a common pathway for carbohydrate, lipid, and protein metabolism, closely linking material metabolism with energy metabolism.
However, when sugar metabolism becomes abnormal, it can trigger various diseases. For example, diabetes is a common metabolic disorder, primarily divided into Type 1 and Type 2. Type 1 diabetes often results from the autoimmune system destroying pancreatic β cells, leading to insufficient insulin secretion; Type 2 diabetes is associated with insulin resistance and relatively inadequate insulin production. Long-term hyperglycemia in diabetic patients, which remains above normal levels, can damage various organs in the body and lead to multiple complications.
Carbohydrate metabolic pathway
2. Lipid metabolism pathway
The metabolism of lipids begins with absorption and transport. Lipids in food are broken down into small molecules such as fatty acids and glycerol monoglycerides by digestive enzymes in the small intestine. These then bind with bile salts to form mixed micelles, which pass through the intestinal mucosal epithelial cells and enter the cells. Inside the cells, these small molecules recombine to form triglycerides and bind with apoproteins to form lipoproteins, which enter the bloodstream via the lymphatic system.
Lipoproteins transport lipids in the blood, delivering them to various tissues throughout the body. The metabolism of fatty acids primarily involves two processes: synthesis and oxidation. Fatty acid synthesis occurs in the cytoplasm, where acetyl-CoA serves as the starting material, and fatty acids are gradually synthesized under the action of multiple enzymes. On the other hand, fatty acid oxidation takes place in mitochondria, where fatty acids are progressively oxidized and broken down into acetyl-CoA, which then enters the citric acid cycle to release energy.
Dysregulation of lipid metabolism can have severe impacts on health. Hyperlipidemia is a common disorder characterized by excessively high levels of lipids in the blood, particularly triglycerides and cholesterol. Long-term hyperlipidemia leads to fat deposition on the walls of blood vessels, forming atherosclerotic plaques that narrow and block arteries, increasing the risk of cardiovascular diseases such as coronary heart disease and myocardial infarction. Additionally, abnormal lipid metabolism may also cause obesity and fatty liver disease, posing significant threats to human health.
Lipid metabolism signaling pathway
3. Protein metabolic pathways
The metabolism of proteins involves two crucial processes: synthesis and degradation. Protein synthesis is a complex and precise process that begins in the cell nucleus, where genetic information from DNA is passed to mRNA through transcription. The mRNA then enters the cytoplasm and binds to ribosomes. On the ribosome, tRNAs carry specific amino acids, which are linked in sequence according to the codons on the mRNA, forming polypeptide chains with specific amino acid sequences. These polypeptide chains undergo folding, modification, and other processing steps, ultimately resulting in proteins with biological activity.
Protein degradation involves the breakdown of proteins into amino acids by enzymes such as proteases within cells. Some of these amino acids can be reused by the cell to synthesize new proteins; others are further broken down through amino acid metabolism pathways. Different amino acids have distinct metabolic pathways, but most first undergo deamination to form ammonia and the corresponding α-keto acid. Ammonia is synthesized into urea in the liver via the ornithine cycle and excreted from the body; α-keto acids can enter the tricarboxylic acid cycle for oxidation for energy or participate in the synthesis of sugars and fats.
Proteins play a variety of crucial roles in living organisms. As enzymes, they catalyze various biochemical reactions within the body, accelerating the reaction process; as hormones, they participate in regulating metabolism and growth development within the organism; as antibodies, they engage in immune responses to defend against pathogen invasion; as structural proteins, they maintain the shape and function of cells and tissues; as carrier proteins, they facilitate the transport of substances both inside and outside the cell. These functions make proteins an indispensable material foundation for life activities.
4. Examples of Major Pathways
| Pathway | Type | Function | Location |
|---|---|---|---|
| Glycolysis | Catabolic | Converts glucose to pyruvate, generating ATP | Cytosol |
| Citric Acid Cycle | Catabolic | Oxidizes acetyl-CoA to produce ATP, NADH, FADH₂ | Mitochondria |
| Fatty Acid Synthesis | Anabolic | Builds lipids from acetyl-CoA | Cytosol/ER |
Key elements in metabolic pathways
1. The role of enzymes in metabolic pathways
Enzymes, as biological catalysts, play an irreplaceable and crucial role in metabolic pathways. First, enzymes can significantly accelerate the rate of chemical reactions. In normal chemical conditions, many metabolic reactions proceed extremely slowly or almost not at all. However, with the participation of enzymes, reaction rates can be greatly increased, enabling efficient metabolism. For example, during glycolysis, hexokinase specifically catalyzes the phosphorylation of glucose to form glucose-6-phosphate. Without the catalysis of hexokinase, this reaction would be extremely slow and unable to meet the cells energy needs.
Secondly, enzymes exhibit highly specific catalytic functions. An enzyme typically catalyzes only one or a class of specific chemical reactions, ensuring the precision and orderliness of metabolic pathways. For example, urease specifically catalyzes the hydrolysis of urea into ammonia and carbon dioxide, without affecting other substances. It is this specificity of enzymes that allows numerous complex metabolic reactions to proceed in an orderly manner, preventing interference between different metabolic pathways. This ensures that the metabolism of organisms operates stably and efficiently, maintaining normal life activities.
2. Metabolic intermediates and substrates and products
In metabolic pathways, substrates are the reactants at the beginning of metabolic reactions. For example, in glycolysis, glucose is the substrate, which undergoes reactions step by step under the action of various enzymes. Metabolic intermediates are compounds that exist between substrates and products in metabolic pathways. In glycolysis, glucose-6-phosphate and fructose-6-phosphate are both metabolic intermediates. They serve as transitional substances in the reaction process, acting as products from one step and substrates for the next, driving the metabolic pathway forward continuously.
The product is the substance ultimately formed by metabolic reactions. Taking glycolysis as an example, the final product is pyruvate. These substances transform into each other within metabolic pathways, where substrates undergo a series of reactions to form intermediate metabolites, which eventually become products. Products may also, under specific conditions, revert to substrates through reverse reactions or other metabolic pathways, participating in other metabolic processes. This interconversion relationship forms a dynamic, cyclical network of metabolic pathways, maintaining the balance of matter and energy within cells, ensuring normal physiological functions and the continuous metabolism of organisms.
3. Energy conversion and recycling
Metabolic processes involve various energy conversion methods, among which the synthesis and breakdown of ATP are particularly crucial. During cellular respiration, such as glycolysis and the citric acid cycle, substances like sugars and lipids are gradually oxidized and broken down, releasing energy in two forms: some is dissipated as heat, while the rest is used to synthesize ATP. ATP serves as the "currency" of energy within cells. When cells require energy for various life activities, such as muscle contraction or substance transport, ATP breaks down into ADP and phosphate, simultaneously releasing stored energy for cellular use.
In addition to energy conversion, the recycling mechanism of metabolic products is also crucial. For example, in the citric acid cycle, oxaloacetate binds with acetyl-CoA at the beginning of the reaction and, after a series of reactions, regenerates as oxaloacetate to continue participating in the next cycle. This recycling mechanism ensures that limited substances are fully utilized during metabolism, improving the efficiency of material and energy use, reducing resource waste, and maintaining normal life activities under relatively stable supply of materials and energy. It guarantees the continuous and efficient operation of metabolic pathways.
Factors affecting metabolic pathways
1. The influence of genetic factors
Genes play a fundamental role in metabolic pathways. Through the transmission of genetic information, genes determine the types and quantities of enzymes. Specific sequences of genes encode the information for synthesizing different enzymes, and various combinations of genes guide the synthesis of different types of enzymes, thus determining which metabolic pathways can occur within cells. At the same time, the level of gene expression also controls the amount of enzyme synthesized. If a gene is actively expressed, the corresponding enzyme will be produced in larger quantities, potentially accelerating the reaction rate of the metabolic pathway it participates in; conversely, if gene expression is suppressed, the amount of enzyme produced decreases, leading to a slower metabolic pathway rate.
Many genetic diseases are associated with metabolic pathway abnormalities caused by gene defects. For example, phenylketonuria is a common hereditary metabolic disorder. Due to gene mutations, patients lack the key enzyme ——-phenylalanine hydroxylase in their liver, which is responsible for converting phenylalanine to tyrosine. This prevents phenylalanine from being metabolized properly, leading to its accumulation in the body and causing damage to the nervous system, affecting the patients intellectual development and overall health. It is evident that genetic factors have a profound impact on metabolic pathways, directly relating to the normal physiological functions and health status of organisms.
2. The role of environmental factors
Environmental conditions significantly impact metabolic pathways, with temperature, light, and pH being particularly critical. The effect of temperature on enzyme activity follows a typical bell curve. Within a certain range, as the temperature increases, enzyme activity enhances, and the metabolic reaction rate accelerates; however, when the temperature is too high, the spatial structure of enzymes can be disrupted, leading to deactivation and inhibition of metabolic processes. For example, in high-temperature environments, the activity of enzymes involved in photosynthesis decreases in some plants, reducing the rate of photosynthesis and affecting plant growth and development.
Light is also a crucial factor affecting metabolism, especially for plants. Plants convert light energy into chemical energy through photosynthesis. The intensity, quality, and duration of light all influence the activity and metabolic pathways of enzymes related to photosynthesis. Under low-light conditions, the activity of enzymes involved in photosynthesis decreases, leading to reduced production of photosynthetic products, which in turn affects the material and energy metabolism within the plant.
The pH value also affects enzyme activity. Different enzymes have their optimal pH values; deviations from these values can lead to reduced enzyme activity. For example, pepsin has an optimal pH range of about 1.5 to 2.5, and it is highly active in acidic environments, effectively catalyzing protein breakdown. If the pH changes, the activity of pepsin will be inhibited, affecting the digestion and metabolism of proteins. These examples illustrate that environmental factors influence enzyme activity, playing a crucial role in metabolic pathways and physiological functions.
3. Nutrition and hormonal factors
Food nutrients and hormones play an indispensable role in regulating metabolic pathways. Nutrients serve as the material foundation for these pathways, with different nutrients participating in various metabolic processes. For example, carbohydrates are the primary raw materials for carbohydrate metabolism, fats serve as substrates for lipid metabolism, and proteins provide the material basis for amino acid metabolism. When nutrient intake is insufficient or imbalanced, the corresponding metabolic pathways will be affected.
Hormones, as signaling molecules in the body, finely regulate metabolic pathways. Take insulin regulation of glucose metabolism as an example. Insulin is a hormone secreted by pancreatic β cells. When blood glucose levels rise, insulin secretion increases, promoting cell uptake and utilization of glucose, accelerating glucose synthesis into glycogen, and inhibiting gluconeogenesis, thereby lowering blood glucose levels. Conversely, when blood glucose levels drop, insulin secretion decreases, while glucagon and other hormones increase, promoting glycogen breakdown and gluconeogenesis, leading to elevated blood glucose levels. This hormonal regulatory mechanism ensures stable blood glucose levels and maintains the normal operation of glucose metabolism pathways. Additionally, various hormones such as thyroid hormones and adrenaline regulate fat metabolism, protein metabolism, and other pathways, collectively maintaining metabolic balance in organisms.
Regulation mechanism of metabolic pathway
1. Enzyme activity regulation
The regulation of enzyme activity is a critical method for controlling the speed and direction of metabolic pathways. The substrate concentration significantly affects enzyme activity; within a certain range, as the substrate concentration increases, the chances of enzyme-substrate binding rise, accelerating the enzymatic reaction rate. However, once the substrate concentration reaches a certain level, enzyme molecules become saturated with substrates, and the reaction rate no longer increases with further substrate concentration. For example, during the action of some digestive enzymes, when there is an adequate supply of substrates in food, the digestion process proceeds efficiently.
Product concentration also affects enzyme activity. In many metabolic pathways, the accumulation of products to a certain extent can inhibit enzyme activity, which is a negative feedback regulation mechanism. For example, in glycolysis, when reaction products accumulate excessively, they can inhibit the activity of some key enzymes involved in this pathway, slowing down the reaction rate to prevent overproduction of products. Additionally, allosteric effects are another important way to regulate enzyme activity. When small molecule effectors bind to the allosteric center of an enzyme, they cause conformational changes in the enzyme molecule, thereby affecting its activity and allowing metabolic pathways to adjust according to cellular needs.
2. Gene expression regulation
Gene expression regulation is the mechanism that alters the activity of metabolic pathways at their root, primarily involving the control of gene transcription and translation. At the transcriptional level, cells decide whether to initiate gene transcription based on their needs by binding transcription factors to the promoter regions of genes. When cells need to increase the synthesis of a specific enzyme, the corresponding transcription factor is activated and binds to the gene promoter, facilitating the binding of RNA polymerase to the gene and initiating the transcription process, leading to the production of more mRNA.
In terms of translation, the stability of mRNA and the efficiency of ribosome binding to mRNA can both affect protein synthesis. For example, certain mRNAs contain specific regulatory sequences that can interact with proteins or small RNA molecules within cells, influencing the degradation rate of mRNA and thus controlling protein synthesis. By finely regulating gene expression, cells can flexibly adjust the amount of enzymes involved in metabolic pathways according to metabolic needs, thereby altering the activity of these pathways and ensuring efficient and orderly metabolic processes.
3. Metabolite concentration and hormone regulation
The feedback regulation of enzyme activity in response to metabolite concentrations is a crucial principle for maintaining metabolic balance. When the concentration of metabolites increases, it inhibits the activity of certain key enzymes in the metabolic pathway through negative feedback mechanisms, slowing down the metabolic rate; conversely, when the concentration of metabolites decreases, the inhibition on enzymes is relieved, and the metabolic pathway accelerates. For example, in the cholesterol synthesis pathway, if the intracellular cholesterol concentration is too high, it will inhibit the activity of key enzymes involved in cholesterol synthesis, reducing cholesterol production.
Hormones regulate metabolic pathways by influencing enzyme activity or gene expression. As signaling molecules, hormones bind to receptors on the cell surface or within cells, triggering a series of signal transduction pathways. For example, when insulin binds to receptors on the cell surface, it activates intracellular signaling molecules. On one hand, this promotes the transport of glucose by glucose transporter proteins to the cell membrane, increasing glucose uptake by the cell; on the other hand, it enhances the synthesis of enzymes involved in carbohydrate metabolism through gene expression regulation, thereby boosting the activity of carbohydrate metabolism pathways. Thyroid hormones, on the other hand, regulate metabolic pathways by influencing gene transcription, specifically by regulating the synthesis of enzymes involved in fat and protein metabolism.
The significance and method of metabolic pathway analysis
1. The significance of metabolic pathway analysis
Metabolic pathway analysis holds significant importance in the field of life sciences. First, it aids in a deeper understanding of metabolic processes. By deciphering metabolic pathways, researchers can clearly understand how organisms convert nutrients into energy and materials for building their structures, as well as how these processes are regulated under different physiological conditions. For example, studies on the metabolic pathways of plant photosynthesis have revealed how plants use light energy to convert carbon dioxide and water into organic compounds, providing the material and energy foundation for life on Earth.
Secondly, metabolic pathway analysis provides strong support for identifying potential drug targets. Many diseases are closely related to abnormalities in metabolic pathways. By analyzing these pathways, key metabolic links and associated enzymes that cause diseases can be identified. These targets can be used to develop targeted drugs. For example, in cancer research, the abnormal activation of certain metabolic pathways in cancer cells has been discovered. Drugs targeting key enzymes in these abnormal pathways have brought new hope for cancer treatment.
In addition, metabolic pathway analysis plays a crucial role in promoting the development of biotechnology. In the field of biotechnology, by modifying and optimizing metabolic pathways, efficient production targets can be achieved. For example, using genetic engineering to regulate microbial metabolic pathways enables them to produce large amounts of important substances such as biofuels and pharmaceutical intermediates, driving progress in sustainable development and the biotechnology industry. In summary, metabolic pathway analysis holds irreplaceable value in both life science research and practical applications.
2. Common analytical methods
In metabolic pathway analysis, various commonly used methods exist. Isotope labeling is one of the important techniques. The principle involves using radioactive or stable isotopes to label specific atoms or molecules. After introducing these labeled substances into a biological system, their distribution and changes in metabolites are tracked to infer metabolic pathways. For example, by labeling glucose with radioactive carbon-14, the exact metabolic fate of glucose within cells can be clearly understood through detecting the location and concentration of carbon-14 in metabolites. This method helps determine the specific processes of glycolysis, the citric acid cycle, and other metabolic pathways. It is often used to study intermediate steps and reaction mechanisms in material metabolism.
Gene knockout or overexpression are also commonly used analytical methods. Gene knockout involves using gene editing technology to disable a specific gene, while gene overexpression is achieved through genetic engineering techniques to express a particular gene excessively. By observing changes in the phenotype and metabolic products of organisms after gene knockout or overexpression, one can infer the role of the enzyme encoded by that gene in the metabolic pathway. For example, if the expression of a gene involved in fatty acid synthesis is significantly reduced after its knockout, it indicates that this gene is crucial to the fatty acid synthesis pathway. This method is often used to determine the relationship between genes and metabolic pathways, as well as to explore new metabolic regulatory mechanisms. These methods provide effective tools for in-depth research on metabolic pathways.
Metabolomics and metabolic pathways
1. Overview of metabolomics
Metabolomics is the discipline that involves qualitative and quantitative analysis of all small molecule metabolites in a specific physiological state of an organism or cell. It focuses on endogenous small molecules with a relative molecular mass less than 1000, such as carbohydrates, lipids, and amino acids. These small molecule metabolites are the ultimate products of interactions between gene expression, enzyme activity, and environmental factors. Changes in their types and quantities can reflect the physiological and pathological states of an organism.
In deciphering the complexity of biological systems, metabolomics plays a unique role. A biological system is a highly complex and dynamically changing network involving numerous genes, proteins, and metabolic pathways. Metabolomics can integrate information from these levels to present the metabolic characteristics of the biological system as a whole. By analyzing changes in metabolites, researchers can gain deep insights into the interrelationships among various metabolic pathways within organisms and how they respond to internal and external stimuli, providing new perspectives for a comprehensive understanding of life processes.
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2. Application of metabolomics in various fields
Metabolomics demonstrates tremendous application potential across multiple fields. In the medical field, metabolomics can be used for disease diagnosis and treatment monitoring. For instance, in cancer research, analyzing patient blood or tissue samples through metabolomics can uncover characteristic metabolic markers associated with cancer onset and progression. These markers not only aid in early cancer diagnosis but also provide a basis for personalized treatment plans. Additionally, during drug development, metabolomics can evaluate the efficacy and toxicity of drugs, accelerating the process of new drug discovery.
In the agricultural sector, metabolomics helps enhance crop yield and quality. Researchers analyze the metabolomes of crops under different growth conditions to understand how environmental factors affect metabolic pathways, thereby optimizing planting strategies. For example, metabolomics studies have revealed that certain specific metabolites are associated with crop stress resistance. By regulating the synthesis pathways of these metabolites, it is possible to develop crop varieties with stronger disease and pest resistance and better adaptation to harsh environments. Additionally, metabolomics can be used for evaluating the quality of agricultural products, ensuring consumers receive nutrient-rich, safe, and reliable food.
In the field of environmental science, metabolomics can be used to assess the impact of pollution on organisms. By analyzing changes in metabolites within organisms, it is possible to rapidly and accurately monitor exposure to environmental pollutants and their ecological toxicity. For example, studying the metabolic changes in aquatic organisms when exposed to heavy metal pollution helps reveal the mechanisms of pollutant action, providing scientific evidence for environmental protection and ecological restoration.
References
- Wallen ZD, Demirkan A, Twa G, Cohen G, Dean MN, Standaert DG, Sampson TR, Payami H. Metagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanisms. Nat Commun. 2022 Nov 15;13(1):6958. DOI: 10.1038/s41467-022-34667-x. PMID: 36376318; PMCID: PMC9663292.
- Schuster, S., Fell, D. & Dandekar, T. A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nat Biotechnol 18, 326–332 (2000). https://doi.org/10.1038/73786
- Chandel NS. Basics of Metabolic Reactions. Cold Spring Harb Perspect Biol. 2021 Aug 2;13(8):a040527. doi: 10.1101/cshperspect.a040527. PMID: 34341010; PMCID: PMC8327831.
- Paley S, Billington R, Herson J, Krummenacker M, Karp PD. Pathway Tools Visualization of Organism-Scale Metabolic Networks. Metabolites. 2021 Jan 22;11(2):64. doi: 10.3390/metabo11020064. PMID: 33499002; PMCID: PMC7911265.
- Fountain, J.C., Koh, J., Yang, L. et al. Proteome analysis of Aspergillus flavus isolate-specific responses to oxidative stress in relationship to aflatoxin production capability. Sci Rep 8, 3430 (2018). https://doi.org/10.1038/s41598-018-21653-x
- Naserkheil, M.; Manzari, Z.; Dang, C.G.; Lee, S.S.; Park, M.N. Exploring and Identifying Candidate Genes and Genomic Regions Related to Economically Important Traits in Hanwoo Cattle. Curr. Issues Mol. Biol. 2022, 44, 6075-6092. https://doi.org/10.3390/cimb44120414
