The study was undertaken on both normoglycemic and alloxan (90 mg/kg) induced diabetic Sprague Dawley rats weighing 150–250 g. At the completion of the treatment phase , rats were anesthetized and mounted on the modified Langendorff's apparatus. IRI was produced by myocardial no-flow global ischemia. Developed tension (DT) and heart rate (HR) were recorded both before and after ischemia. The perfusate was collected to estimate the leakage of cardiac biomarkers (Creatine Kinase-MB: CK-MB and Lactate dehydrogenase: LDH). Hearts were removed from the setup and utilized to prepare heart tissue homogenate (HTH) and histological slides. The endogenous antioxidants, superoxide dismutase (SOD) and catalase (CAT), in addition to oxidative thiobarbituric acid substances (TBS), were estimated in HTH.  The hemodynamic parameters, including percentage recovery in HR and DT, were found significantly higher in animals pretreated with garlic and MET in diabetic rats (DR). Both SOD and CAT enzyme activities increased significantly while TBS levels were reduced in the HTH of animals treated with garlic and MET. The cardiac markers CK-MB and LDH levels also increased in HTH with a corresponding decrease in the perfusate. The histopathological changes in the heart and pancreas demonstrated noticeable protection of the tissues due to pretreatment with garlic and MET. Taken together, these findings advocate that reactive oxygen species derived from hyperglycemia execute an important function in myocardial global IRI; the therapy of garlic homogenate was found to be effective in alleviating these toxic effects.  The combined therapy of MET and garlic provided synergistic cardioprotection, implying that garlic seems to possess promise in lowering toxic parameters by protecting diabetic induced myocardial injury. It is among the leading causes of cardiovascular disease, contributing to 80% of all diabetic deaths. Polyuria, polydipsia, weight gain, polyphagia, and impaired eyesight are all indications of hyperglycemia. Cardiovascular disease (CD) mortality is 2–4 times greater in diabetic individuals than in nondiabetic individuals. DM has been linked to the deterioration of heart function. In diabetic patients, many pathogenic mechanisms can cause myocyte injury and dysfunction . Type 1 es of DM –9.Allium sativum), a member of the Alliaceae family, is said to have come from Central Asia. It is used as traditional medicine, as flavoring agent, and as a functional food all over the world to boost physical and cognitive health. Garlic's therapeutic properties in the treatment of various human illnesses and medical problems have been acknowledged for years. Numerous epidemiologic investigations have found that eating habits comprising garlic as a spice are linked to a lower risk of human diseases [Dietary factors have a significant impact on the progression of certain diseases in human, like CD . Garlic diseases . Garlic diseases . Garlic diseases  worldwiddiseases . Garlic diseases .ß-cells from further insulin release induced by hyperglycemia.Metformin (MET), a biguanide antihyperglycemic drug, is commonly used to treat type 2 DM. It has favorable outcomes for type 2 DM, like weight loss and improved lipid profile/endothelial function because of its antihyperglycemic impact. As a result, MET is given to people who are IR before they develop hyperglycemia . MET sloSince garlic has antioxidant properties and MET is a cell-protective drug, a synergistic effect of the two may be possible in preventing cardiac muscle damage. Therefore, the intent of this study was to appraise the potential of oral dietary supplementation of garlic in the presence of MET for the prevention of alloxan-induced diabetic rats (DR) using an ischemia-reperfusion experimental model.The experimental protocol was approved by the institution's Animal Ethics Committee. Male Sprague Dawley (SD) rats in a weight range of 150–250 g were kept at standard conditions and unlimited access to food and drink. The animals were kept in an animal house under standard conditions, as directed by the Committee for Control and Supervision of Experiments on Animals (CPCSEA). The experimental protocol was approved by the Institutional Ethical Committee (KCP/IAEC-27/2119). These experiments were conducted in isolated tissues from a perfused heart and were backed up by biochemical and histological data.Allium sativum, Liliaceae family) were obtained from single source of garlic field throughout the research study to keep uniformity of its contents. They were peeled, sliced, and ground into paste and a stock solution of 0/1 g/ml [Garlic bulbs  and MET was determined in diabetic and nondiabetic rats. The male SD rats were divided into eight groups consisting of six animals each. Animals in groups I to IV were nondiabetic. Group I was kept as normal control with vehicle treatment for 30 days by oral gavage. Groups II and III were given GH   and MET For the isolated perfused heart, a modified Langendorff's setup was created and used for research. With minor adjustments, animal models of myocardial ischemia and reperfusion were created using the techniques previously described . The ratAt the end of the initial 15 minutes of perfusion for equilibrium, tracings were recorded for another 15 minutes before subjecting the heart to 15 minutes of global no-flow ischemia. After that, the regular flow rate (5 ml/min) was restored, and perfusion was continued for another 30 minutes. The level of cardioprotection owing to preventive therapy was examined by measuring the developed tension (DT) and heart rate (HR). A thermoregulated chamber kept the heart at 37°C throughout the experiment to avoid hypothermia-induced cardioprotection . None ofHemodynamic parameters such as HR and DT were recorded both before and after ischemia and percentage recoveries were calculated. The perfusate (perfusing fluid) was collected after ischemia to estimate the CK-MB and LDH activities in the perfusate to determine the extent of damage to the myocardium due to ischemia. HTH was prepared by a method described by Elastner, 1976 , to estip˂0.05 significance level considered.One-way analysis of variance (ANOVA) was used to determine statistical significance, followed by Dunnett comparison tests using the GraphPad Prism 8.0 computer software kit. The findings were presented as mean ± standard error of mean (SEM), with a P < 0.001) increase in the body weight of all animals was observed. Similarly, a significantly (P < 0.01) elevated blood sugar level was found in animals of all groups at the end of eight weeks of a high-fat diet that was further augmented significantly (P < 0.05) 72 hours after administration of alloxan. None of the animals in any group died or were given insulin doses to control blood sugar levels.P < 0.01) fall of CK-MB activity was noticed in the perfusate with a concurrent increase in heart tissue homogenate (HTH) in the groups of rats that were given GH when related to the normal control group. The average reading of a group of animals that received combined therapy of GH (30 days) and MET (10 days) showed a significant (P < 0.05) elevation of CK-MB activity in HTH in comparison with MET alone and normal control groups. Alloxan-induced diabetic rats exhibited significantly (P < 0.01) low CK-MB activity in HTH with greater leakage of the enzyme in the perfusate. Administration of GH and MET demonstrated the best incline of CK-MB activity in HTH with a decline in enzyme leakage in the perfusate when compared to all other diabetic groups.As indicated in P < 0.01) high in GH, MET, and GH + MET groups with normal control (P < 0.05) better outcomes when related to MET alone. The leakage of LDH enzymes in the perfusate was significantly (P 0.001) elevated in diabetic animals than in normal control animals. However, prior treatment with GH/MET either individually or together produced a significant (P < 0.01) improvement in LDH activity in HTH when compared to diabetic animals. Furthermore, when compared with the MET alone group, the release of LDH enzymes in the perfusate was significantly (P 0.05) lower in animals given GH and MET.The activities of LDH enzymes in HTH were significantly ( control . The comP < 0.001) increase in SOD and CAT activities when compared to the normal control group. Further, when animals received both GH and MET, they showed significantly higher CAT activity compared to the MET alone group. A significant (P < 0.01) depletion of antioxidant activity was noticed in the diabetic control group compared to the normal control. However, administration of GH alone or along with MET significantly increased the SOD and CAT activities in comparison with diabetic control. Among all treated groups in diabetic animals, the combination of GH and MET showed a greater increase in antioxidant activity (Thirty days of GH treatment before the experiment caused a significant (activity .The proportion of thiobarbituric acid substances (TBS) produced during the decomposition of lipid hydroperoxides was used to measure lipid peroxidation. P < 0.001) increased in animals that were given GH for 0 days when compared to normal control animals (P < 0.05) increased recoveries in both hemodynamic parameters were recorded when compared to the MET alone group. Alloxan-induced diabetic animals showed poor recovery in both DT and HR. GH or MET administration either alone or together produced significant (P < 0.001) increased postischemic recovery in both parameters when compared to diabetic control.The percentage recovery in postischemic DT and HR was significantly  with the biguanide derivative, metformin (MET), defends the myocardium from ischemia-reperfusion injury (IRI) in alloxan-induced diabetic rats. The results also indicate that prophylactic treatment with MET and GH has a synergistic cardioprotective effect as well as a beneficial effect on the pancreas in alloxan diabetic animals. Furthermore, the current data shows that the cardioprotective efficacy of GH at 250 is due to free radical scavenging. Based on functional recovery and LDH released from the heart during reperfusion, data showed that long-term treatment with GH, alone or in combination with MET, before induction of ischemia significantly protects the DH and myocardial function during ischemia-reperfusion.ß cells (pancreatic ß-cell dysfunction). Animal models must replicate the phenotypic and mimic the disease's developmental phase to be similar to humans. Thus, the T2DM model was established by feeding a high-fat diet to induce insulin resistance, followed by an alloxan injection. At the end of 8 weeks of high-fat diet, rats in the diabetic group became obese and only those that developed a blood glucose level of more than 300 mg/dl after alloxan administration were taken up for the study. Alloxan produces cytotoxic ROS, which is involved in the genesis of pancreatic ß-cell dysfunction, ischemic heart disease, and lack of endogenous antioxidant defenses [Type 2 diabetes mellitus (T2DM) is a complicated disease marked by a decrease in insulin function that will follow a decreased release of insulin from defenses . An artidefenses . The IRIdefenses . Myocarddefenses . It shouEpidemiologic research indicates a contrary relationship concerning garlic consumption and the evolution of CD. Garlic products have been acclaimed worldwide as remedies for the avoidance and control of DM, hypertension, thrombosis, hyperlipidemia, and atherosclerosis . When coLipid peroxidation is believed to be a critical mechanism of injury that happens during myocardium reperfusion after an ischemia period. Elevated levels of LP in IRI could be credited with lipid buildup in the heart and irretrievable impairment of myocardial membranes. Thiobarbituric acid reactive substance concentration in plasma is an indicator of OS and lipid peroxidation. Elevated TBS levels are linked to an augmented threat of CD. Due to the difficulty of directly measuring liberated ROS due to their instability, TBS, a stable lipid peroxidation end-product, is normally utilized as a marker of ROS creation. Allicin, a molecule existing in garlic, has increased antioxidant activity , and theAllium sativum) is instigated by the presence of allicin and volatile substances, which are produced by the act of alliinase on allin. When fresh garlic is mashed or chopped, allin  is hydrolyzed by alliinase. The corresponding derivatives of allicin , ammonia, and pyruvic acid are formed in the presence of water [γ-L-glutamyl-S-alkyl-L-cysteine, 1-propenyl allyl thiosulfonate, and adenosine, all of which have antioxidant and cardioprotective properties, as well as supporting part in the treatment of diabetic myocardial dysfunction.Because of the presence of thiosulfonate and S-alkyl-substituted cysteine sulfoxide derivatives, garlic possesses a variety of biological roles. The odor of fresh raw garlic  and the absence of these biomarkers in HTH reveal substantial diabetic myocardial damage .ß cells as well as cardioprotective potential.Abnormalities in free fatty acid (FFA) metabolism are a major contributor to aberrant cardiac function, and they can cause glucose oxidation impairment, which can lead to diabetic cardiomyopathy. These deviations are symbolized by an increase in circulating FFAs due to increased adipose tissue lipolysis, in addition to high tissue FFAs due to hydrolysis of augmented myocardial triglyceride stores, which is a crucial risk factor for the initiation and advancement of atherosclerosis and one of the major risk factors in diabetic myocardium in rats. Garlic has antiatherogenic and lipid-lowering properties due to organosulphur compounds that may inactivate the thiol group (-SH) comprising enzymes like 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-Co-A) reductase and fatty acid synthase . Earlierß cells (70%) with basophilic granules, while the periphery is composed of alpha cells with eosinophilic granules (25%) in the combination treatment, which aids in protecting the ß cells from further damage in DR. This study's findings are consistent with another study that found MET to play an imperative role in heart and pancreatic cells [Since MET has a peripheral action in type 2 DM, it will reduce hyperglycemia while also assisting GH in lowering hyperinsulinemia levels to normal levels. In type 2 DR, hyperinsulinemia is caused by IR, which stimulates sympathetic activity, causing an increase in Na + reabsorption in the kidneys and an increase in blood pressure, resulting in endothelial dysfunction. When compared to normal rats, our findings from histopathology studies show that the center of islet cells is composed of ic cells . MET notic cells , 43. Furß-cell viability in alloxan-induced diabetic rats.In this study, the prophylactic administration of garlic homogenate with the antidiabetic and cardioprotective synthetic drug metformin helped protect the isolated diabetic heart during ischemic reperfusion injury. Moreover, garlic homogenate in combinational therapy decreases pancreatic oxidative radical increase and promotes the antioxidant defense system, correcting hyperinsulinemia and


Despite meticulous surgical care and systemic antibiotics, open fracture wounds have high rates of infection leading to increased morbidity. To reduce infection rates, orthopaedic surgeons may administer local antibiotics using various carriers that may be ineffective due to poor antibiotic release from carriers, subsequent surgery to remove nondegradable carriers, and mismatch between release kinetics and material degradation. Biofilms form rapidly as bacteria that are within the wound multiply quickly and transform from the antibiotic-susceptible planktonic phenotype to the antibiotic-tolerant biofilm phenotype. This tolerance to antibiotics can occur within hours. Currently, local antibiotics are placed in the wounds using a carrier such as polymethylmethacrylate beads; however, this occurs after surgical debridement that can be hours to even a day after initial injury allowing bacteria enough time to form a biofilm that makes the antibiotic containing polymethylmethacrylate beads less effective. In contrast, emerging practices in elective surgical procedures, such as spine fusion, place antibiotic powder (e.g. vancomycin) in the wound at the time of closure. This has been shown to be extremely effective, presumably because of the very small-time period between potential contamination and local antibiotic application. There is evidence that suggests that the ineffectiveness of local antibiotic use in open fractures is primarily due to the delay in application of local antibiotics from the time of injury and propose a concept of topical antibiotic powder application in the prehospital or emergency department setting. The current mainstays for preventing infection in open fractures are thorough debridement of the wound and use of systemic antibiotics. Despite this, many wounds still become infected. To decrease infection rates in open fracture wounds, local antibiotics have been used in surgery as an adjunct to systemic antibiotics.,5 Unlike systemic antibiotics, high concentrations of antibiotic are capable with use of local depots, which are believed to be more effective. Despite the theoretical advantages and studies that demonstrated effectiveness in preclinical models, there is little clinical evidence that local antibiotics improve outcomes of open fractures. Most antibiotic carriers used clinically have poor release kinetics of antibiotics and introduce foreign bodies to the wound. These factors may play a role, but they are likely not the primary reason why local antibiotic delivery appears to be relatively ineffective in open fractures.Open fracture wounds are exposed to contaminated environments which makes them at high risk of infection–9 This will be explained with the backdrop of the biofilm theory, which describes how bacteria divide and grow in number until they have reached a certain population density and change from the antibiotic-susceptible planktonic phenotype to the antibiotic-tolerant biofilm phenotype.,11 This can occur in as little as a few hours. To effectively take advantage of local antibiotic therapy, the application of local antibiotics must be uncoupled from surgery, which often is not performed until hours or up to a day after injury and contamination of the wound. The use of topical antibiotic powders in the prehospital or emergency department setting will allow high levels of antibiotics at the wound site while not allowing the bacteria to form a biofilm and become recalcitrant to antibiotic therapy.We propose that the most likely explanation is the timing from injury to application of local antibiotics. Preclinical evidence, elective orthopaedic procedures, and specific clinical studies on open fractures have shown a reduction in infection rates when antibiotics are applied early. This suggests that infection mitigation has more to do with antibiotics reaching the bacteria quickly than the delivery method or type of antibiotic chosen.2 These bacteria secrete extracellular polymeric substances that form a matrix of protein, polysaccharide, and extracellular DNA, which provides a barrier and protects them from being phagocytosed by host immune cells. Some of the cells, particularly the ones deep within the sessile community, reduce their metabolism and replication which makes them tolerant to antibiotic therapy. It has been shown that it can take 1000-fold more antibiotic to eradicate persister cells within a biofilm. The exact timing of biofilm formation and maturation depends on many factors such as the amount of initial colonization, environment, and bacteria species and strain. With that said, it has been shown that development of a biofilm occurs as early as 5 hours after inoculation, with maturation of this biofilm by 10 hours. After the systemic or local antibiotic therapy is finished, the persisting bacteria become metabolically active and replicate. This is believed to be one of the major reasons behind the high infection rates in open fracture wounds.Specific to open fracture wounds, the biofilm theory explains why the current approach for preventing infection is often unsuccessful. Bacteria enter the wound in a planktonic, antibiotic-susceptible phenotype, attach to the surface of tissue, divide and grow in numbers until they reach a certain population density, and shift into an antibiotic-tolerant biofilm phenotype.3 The primary methods for infection mitigation and prevention in the treatment of open fracture wounds are antibiotic administration, debridement, irrigation, and wound closure. Intravenous antibiotics is the current practice for open fracture prophylaxis. However blood flow is often compromised in these wounds, which affects the ability for systemic antibiotics to reach the injury site in high enough concentrations. Furthermore, increasing the dose of antibiotics to adequately eradicate bacteria puts the patient at risk for toxicity to nontarget organs . Local antibiotic therapies have provided a way to overcome poor perfusion issues in open fractures, but unfortunately infection still persists.,21 We believe this is due to high concentrations of antibiotic not reaching the wound site quickly enough through the currently used local antibiotic delivery methods, which is generally polymethylmethacrylate (PMMA) beads. Overall, clinical evidence for the early administration of antibiotics reducing infections has not been consistent , the vancomycin powder eradicated the infection within the wound and the levels of antibiotic within the blood were extremely low. However, if the local therapy was delayed until 24 hours, the vancomycin powder did not reduce the amount of bacteria within the wound. This is likely due to the increased concentration of bacteria in the wound and biofilm formation. Although the concept of applying an antibiotic powder directly into the wound appears foreign or unconventional, it has been done previously. In World War II, American soldiers were given first-aid kits containing sulfa powder and were instructed to sprinkle the powder on open wounds. However, these sulfonamide drugs were replaced when the introduction of penicillin proved to be a more potent antibiotic therapy, and the method of applying antibiotic powder topically was left behind. More than 75 years later, locally applied antibiotic powder has potential to reemerge as an adjunct treatment for open-fracture wounds. Additionally, vancomycin appears to be one of the safest drugs when it comes to host cell toxicity and does not impair bone healing in a gap defect rodent model.The application of antibiotics directly into the wound site circumvents many of the delayed application issues posed by PMMA beads and other local antibiotic delivery methods, while retaining benefit of high local drug concentrations. The direct application of vancomycin powder has been primarily studied and supported in the elective spinal surgery setting.ion Fig. .[38] Thi6 “Placement Of antibiotic powder in Wounds During the Emergency Room” (POWDER) (NCT# 03765567), will be assessing patient-centered outcomes of emergency department application of the vancomycin powder in wounds with exposed bone fragments amenable to powder application without injection into the wound site; the POWDER study will directly test the concept we presented herein. The results of these studies could have clinical implications for a new antibiotic application method in the treatment of open fracture wounds.Clinical trials using the vancomycin powder are underway that may provide higher levels of evidence related to our proposed use. The Major Extremity Trauma Research Consortium's Vancomycin Study (NCT# 02227446) and the University of Tennessee's Local Application of Vancomycin Powder in Grade I-IIIA Open Fractures (NCT# 02400112) are analyzing the postoperative rates of infection after the vancomycin powder is placed at the time of surgical closure. We will study this concept in a multicenter clinical trial,7The morbidity burden of open fractures, especially of long bones, is high, and strongly influenced by the presence of infection. Strategies to mitigate infection risk, such as parenteral antibiotics or early surgery, are unsatisfactory as evidenced by continued high infection rates. Timing of the intervention may be crucial, as bacteria quickly set up antibiotic, surgery, and immune-resistant biofilms. An early intervention that exposes pathogenic bacteria to high concentrations of antibiotic prior to biofilm development may confer significant advantage over current approaches. Topical administration of antibiotic may in the future be shown to confer benefit. As a time-sensitive therapy it is within the scope of emergency physician practice and could easily and quickly be applied at the bedside soon after arrival in the emergency department. If studies support such use , administration of antibiotic in the prehospital setting is a logical extension and may improve efficacy if transport times are prolonged. In military medicine and other austere environments, early application of topical antibiotics may prove significant as the technical skill needed to apply the antibiotic is likely modest, thus allowing far-forward medics and other first responders to provide the therapy.8,24 The ideal method for localized antibiotic delivery is described as one that can be applied quickly, prevents infection, does not require subsequent surgery for removal, does not cause system toxicity, and provides high concentrations of antibiotic to the wound site.,46 Local antibiotic delivery methods such as PMMA cement, collagen gauze, chitosan sponge, and calcium sulfate cannot be applied until surgery, which does not allow for timely administration. A topical antibiotic powder, such as vancomycin, can be applied in high concentrations in the prehospital or emergency department setting and without the need for a delivery vehicle suggesting it could be a better treatment for open fractures. Vancomycin powder appears safe and effective on elective surgeries, and its low cost will not be a financial burden to hospitals. Although the results of the ongoing clinical studies are needed for a change in clinical practice to occur, this is one of the few new concepts which can be rapidly implemented in the emergency department or prehospital environment that may improve outcomes of open fractures.Open fracture wounds are inherently difficult to manage due to immediate bacterial contamination upon injury.


The aim of this article is to predict the compressive strength of environmentally friendly concrete modified with eggshell powder. For this purpose, an optimized artificial neural network, combined with a novel metaheuristic shuffled frog leaping optimization algorithm, was employed and compared with a well-known genetic algorithm and multiple linear regression. The presented results confirm that the highest compressive strength (46 MPa on average) can be achieved for mix designs containing 7 to 9% of eggshell powder. This means that the strength increased by 55% when compared to conventional Portland cement-based concrete. The comparative results also show that the proposed artificial neural network, combined with the novel metaheuristic shuffled frog leaping optimization algorithm, offers satisfactory results of compressive strength predictions for concrete modified using eggshell powder concrete. Moreover, it has a higher accuracy than the genetic algorithm and the multiple linear regression. This finding makes the present method useful for construction practice because it enables a concrete mix with a specific compressive strength to be developed based on industrial waste that is locally available. During the past decade, many countries have focused on various aspects of cleaner production, including the partial reduction of cement when producing concrete ,2,3. TheReusing industrial and agricultural waste as an alternative building material significantly improves sustainability in the building sector ,16. NeveEggshell (ES) is an environmentally friendly biowaste material that can be utilized for cost-effective construction. Since 1999, ES has been widely employed for its calcium for calcium phosphate synthesis applications ,23. The 3) in the ES was extracted, which in turn accelerated the hydration in the FA concrete. Incorporating CaCO3 in HVFA concrete causes carbo-aluminates to be formed, which result from the interaction of the carbonate ion from the Calcium-chloro (CC)with the aluminate hydrate from the Portland cement hydration  range, and maxX and minX are its maximum and minimum values, respectively.In statistics, any statistical relationship, whether causal or not, between two random variables is called a correlation or dependency. In the broadest sense, a correlation refers to the degree to which a pair of parameters are linearly associated. A correlation matrix is a table that provides the correlation coefficients among the various input variables. Since the statistical behavior of the output parameter (compressive strength) should be evaluated, a distribution plot was constructed, as shown in HN denotes the number of neurons in the hidden layers, IN is the number of input variables, and TRN is the number of training samples in the database.A trial-and-error method is often used to obtain the most efficient ANN model architecture that best reflects the characteristics of the experimental test data. In the present study, the hidden layers’ neurons are determined according to Equation (2) :(2)NH≤miAAE), coefficient of determination (2R), variance account factor (VAF), and MSE, which are expressed in Equations (3)–(6), were employed to assess the efficiency of the various topologies:Considering that we have four input variables, the mentioned Equation computed less than nine neurons for the hidden layers. Therefore, several networks with different topologies, with a maximum of two hidden layers and 9 neurons at each hidden layer, were trained and examined in this study. We utilized the hyperbolic tangent transfer function and the Levenberg–Marquardt training algorithm for all the networks. Moreover, the statistical indices, including the average absolute error —as shown in In total, 12 different network topologies were examined. It was found that the network with a topology that consists of 4–4–3–1-layer architecture obtained the lowest values of errors for The SFLA optimization algorithm was used to provide the least prediction error for the trained structure and to optimize the ANN’s weights and biases. The properties of the SFLA algorithm’s parameters are given in y is a dependent variable; x1, x2, …, are independent variables, and a1, a2, … are coefficients of the Equation.To validate the proposed hybrid SFLA-ANN model used in this study, a multiple linear regression (MLR) model and a genetic algorithm combined with an ANN (GA-ANN) were also developed. In an MLR model, two or more independent variables significantly affect the dependent variable, as shown in the following Equation:The following Equation shows the most suitable coefficients for the MLR model for estimating the overall deflection of the studied specimens.A genetic algorithm combined with an ANN (GA-ANN) was implemented for the second evaluation. Its characteristics are summarized in VAF and average of the hybrid SFLA-ANN model were closest to unity, indicating its robust predictive capability.When analyzing the histogram, it can be seen that the distribution of the SFLA-ANN hybrid model is less dispersed than in the case of the GA-ANN and MLR models. In addition, the COV and STDEV values, which were determined for the SFLA-ANN model, are equal to 0.077 and 0.079, respectively . The lowThe highest slump (12.5 cm) was recorded for the mix design containing 14 and 15% of eggshell powder, while the average slump for the specimens containing 4 to 15% of eggshell powder was 10.5 cm.The highest compressive strength was achieved for the mix containing 7 to 9% of eggshell powder (an average of 46 MPa at the age of 28 days); this result is 55% higher than that of the control specimen. However, the lowest compressive strength among the eggshell powder modified concretes was achieved by the mix designs containing 1 and 15% of eggshell powder-34.4 and 30.9 MPa, respectively. Such results are in compliance with those of Yerramala , who conVarious statistical metrics were deployed to compare the actual compressive strength of eggshell powder modified concrete with the corresponding values predicted by the diverse information models. The results confirmed that the proposed SFLA-ANN model attained the most reliable and robust results for determining the compressive strength of eggshell powder modified concrete.The obtained histogram of the test-to-prediction ratios indicated that the SFL-ANN model is better fitted and less dispersed than the other models. Such a result indicates that the proposed information model can achieve a more accurate, safer, and more reliable estimation of the compressive strength of eggshell powder modified concrete.It is recommended to compare the life cycle of eggshell powder modified concrete against OPC-based concrete. The boundary of the cradle-to-gate system should be extended to include the mechanical and durability properties of mix designs. By using this approach, not only is the impact of material manufacturing accounted for, but the impacts of service life are also incorporated in the life cycle assessment criteria.This study examined the mechanical properties of concrete modified with eggshell powder. By following existing literature and by performing an electron microscopy test, the chemical and physical properties of eggshell powder were examined. Subsequently, in order to find the optimum percentage of eggshell powder in concrete, 16 different mix designs containing various percentages of eggshell powder were prepared, and their compressive strengths were tested at different ages. The eggshell powder substituted the cement by 0.01% to a maximum of 15%. Finally, using the experimental test database thus generated, an optimized artificial neural network (ANN) combined with the shuffled frog-leaping algorithm (SFLA-ANN) was developed to estimate the compressive strength of the mix designs. The most important findings of the conducted research include:


Mass concrete is usually poured in layers. To ensure the interlayer bonding quality of concrete, the lower layer should be kept in a plastic state before the upper layer is added. Ultimately, it will lead to the prediction of concrete setting time as a critical task in concrete pouring. In this experiment, the setting time of concrete in laboratory and field environments was investigated. The equivalent age of concrete at the initial setting was also analyzed based on the maturity theory. Meanwhile, factors affecting the setting time in the field environment were studied by means of multiple stepwise regression analysis. Besides, the interlayer splitting tensile strength of concrete subjected to different temperatures and wind speeds was determined. The results of laboratory tests show that both setting time and interlayer splitting tensile strength of concrete decrease significantly with the increase of air temperature and wind speed. In addition, the equivalent age of concrete at initial setting remains the same when subjected to different temperatures, while it decreases obviously with the increase of wind speed. In the field environment, the equivalent age of concrete at initial setting is greatly different, which is related to the variability of relative humidity and wind speed. The average air temperature and maximum wind speed are the main factors affecting the initial setting time of concrete. Furthermore, a prediction model is established based on the stepwise regression analysis results, which can predict the actual setting state in real-time, and hence controlling the interlayer bonding quality of dam concrete. The Wudongde and Baihetan Hydropower Stations in China’s Jinsha River Basin are classified as 300-m-level ultra-high concrete double-curved arch dams. These dams are currently the world’s largest, most complex hydropower projects under construction and face the most technical difficulties . These kMany methods have been used to obtain the setting time of concrete, such as penetration resistance, ultrasonic wave, electricity, maturity, the heat of hydration, and nuclear magnetic resonance. Penetration resistance is the standard test method for setting time. However, the traditional penetration resistance test requires wet screening of concrete, and the coarse aggregates after wet screening cannot be reused. That is, the penetration resistance test consumes a lot of manpower and material resources, which affects the construction progress.The electrical methods can be further subdivided into resistivity, conductivity, and electromotive force methods. Li  and XiaoThe change of ultrasonic wave velocity reflects the hardening process of concrete. A setting time calculation method based on ultrasonic wave velocity can be established and compared with the setting time obtained by penetration resistance method. For cement paste without gas or of low air content, the initial setting time corresponds to the time when the P-wave velocity begins to increase . The samBased on the factors that affect concrete setting time, some researchers have provided prediction equations of concrete setting time by using mathematical techniques to train existing data. Ahmadi et al.  proposedMoreover, the influence of ambient temperature on setting time of concrete by using maturity method was first proposed by Pinto et al. . MeanwhiIn summary, maturity theory and multiple stepwise regression analysis are more convenient to predict concrete setting time. However, some shortcomings still exist. For instance, the maturity method only considers the effect of temperature on setting time, but ignores the influences of relative humidity and wind speed. In the case of multiple stepwise regression analysis method, previous studies did not consider the maximum value of environmental factors, which may affect the accuracy of the prediction model.Therefore, in order to accurately perceive setting state of concrete, the setting time of low-heat cement concrete under different temperatures  and wind speeds  was studied based on maturity theory. In addition, on the basis of considering the maximum temperature, relative humidity and wind speed, the setting time of concrete in the field environment was analyzed by multiple stepwise regression analysis method. Meanwhile, the interlayer splitting tensile strengths of concrete subjected to different temperatures  and wind speeds  were tested. The interlayer bonding quality was controlled according to the relationship between the layer state and interlayer splitting tensile strength of concrete.3, respectively. Artificial sand, with the fineness modulus of 2.76 and apparent density of 2780 kg/m3 was used as fine aggregate. Further, retarded type II superplasticizer (water-reducing rate was about 19%) and concrete high-efficiency air-entraining agent (air content is about 4.3%), which meet Chinese National Standards GB8076-2008 [The mix proportions of dam concrete are given in 076-2008 , were al076-2008  by usingPenetration resistance tests of mortar were used accordingly with the China standard DL/T 5150-2017. The mortar was wet screened out of the concrete with a 5 mm sieve. Then pour mortar into cylindrical molds (ø100 mm × 150 mm). After vibrating and compacting, the samples were put into environmental simulation chambers a with prIt should be noted that there is no difference between ASTM C403  and ChinThis study comprehensively considers the actual environmental characteristics of the Wudongde dam project. Set the temperature to 0, 22, 26 and 40 °C according to the average temperature in different seasons. Set the wind speed to 5 m/s and 13 m/s according to the monthly average lower and higher wind speed.According to the air temperatures  and wind speeds , specimens were classified into six groups: T10W0, T22W0, T26W0, T40W0, T22W5 and T22W13.2, and the height of each storehouse was 3 m. The thickness of each layer of concrete was about 500 mm. After the concrete was poured, it needed to go through a paving and vibrating process, which lasted about 4 to 8 h. A small weather station in the field was used to collect the air temperature, relative humidity, wind speed, and rainfall information. The intelligent sprayers were installed around it to control the temperature and humidity of the storehouse, as shown in Four-graded concrete was used in this project and lower gradation was adopted in some reinforcement areas. To achieve high accuracy, the setting time of four-graded concrete in the field environment was tested. The pouring area of each storehouse of the dam was kept up to 1100 mConcrete penetration resistance test was conducted on the storehouse surface. In the first stage, the four-graded concrete was wet screened, and then put into mortar barrels, as shown in The setting time of 9 storehouses of concrete was measured, and the initial temperature of concrete was controlled at about 8.9 °C (as shown in Table 6 presented later). It is noteworthy that the environmental temperature, humidity, and wind speed on the storehouse surface are not constant and change in real time, which are greatly different with those in the laboratory. According to the values of maximum air temperature, average temperature, maximum humidity, average humidity, maximum wind speed, and average wind speed before initial setting, a prediction model of initial setting time of concrete in the filed environment was established by means of stepwise regression analysis.Concrete was prepared according to 3. During the test, place specimens in the center of the lower plate of pressure testing machine. Then, a spacer between the upper and lower plates and specimens are placed. Afterwards, the specimens are split along the layer with a loading rate of 0.04 MPa/s~0.06 MPa/s  and wind speeds , specimens were classified into five groups: C0, T22W0, T26W0, T22W5, and T22W13. Among them, group C0 refers to the concrete without layers, and the rest groups were poured in layers.In general, increasing the air temperature or wind speed can significantly accelerate the hardening process of mortar and shorten the setting time. It means that, both air temperature and wind speed are key factors affecting the setting time of mortar.From the perspective of cement hydration, Freiesleben and Pedersen et al.  showed tTake the natural logarithm on both sides of Equation (1) results in Equation (3):According to Pinto et al. , the timSimilarly, the initial setting time at any constant temperature can be calculated through the equivalent age, as shown in Equation (6):According to the values in Replacing the average value of equivalent age in Based on the relationship between interval time and setting time, the layer state of concrete can be divided into three types: hot joint, warm joint, and cold joint, respectively. When the interval time between layers is less than the initial setting time, the layer is defined as the hot joint; the layer with the interlayer interval exceeding the initial setting time but without final setting is defined as the warm joint; the layer with the interlayer interval exceeding the final setting time is defined as the cold joint.3 respectively, when the mortar was subjected to 13 m/s and 40 °C for 6 h [It should be noted that an abnormal phenomenon was observed in the experiment, as shown in  for 6 h . In otheThe interlayer bonding quality will decrease seriously in the harsh construction environment. To ensure the interlayer splitting tensile strength above 80% of bulk concrete, it is necessary to control the layer state at the hot joint stage . Secondly, it is necessary to monitor the water content of the lower concrete to ensure that the concrete has enough water for hydration reaction.The equivalent age of concrete at initial setting under the storehouse surface environment was calculated based on Equation (2). The results are shown in The equivalent ages of concrete at the initial setting are different from that under constant temperatures. It is mainly attributed to the variability of relative humidity and wind speed under the storehouse surface environment, which affects both water evaporation and cement hydration process significantly. A previous research indicated that high wind speed can accelerate the dewatering rate of concrete. If the surface water content of concrete is less than total water requirement, the false setting will occur .Due to the different equivalent ages of initial setting of concrete in field environment, maturity theory could not be applied to the complex storehouse surface environment. Therefore, from the data processing level, the functional relationship between the setting time of concrete and the environmental factors on the storehouse surface is established. It is assumed that the maximum temperature, average temperature, maximum relative humidity, average relative humidity, maximum wind speed, and average wind speed are the factors affecting the setting time of concrete before the initial setting. Taking the above six factors as independent variables and initial setting time as the dependent variable, the Statistical Product and Service Solutions (SPSS) software was used for stepwise regression analysis of the data series see . SPSS isT-test results proved that the associated probability of the regression coefficients of the maximum temperature, maximum relative humidity, average relative humidity and average wind speed before the initial setting of concrete was more significant than 0.05 , which had been eliminated from the linear model. Therefore, the prediction model of the initial setting time of concrete under the storehouse surface environment could be expressed according to Equation (9):In the field environment, the hydration process of concrete is mainly related to the ambient temperature and wind speed. On the one hand, the change of air temperature affects the hydration reaction rate of cementitious materials. On the other hand, higher temperature and wind speed accelerate the water evaporation rate of concrete, thus shortening the setting time of concrete.By substituting the environmental parameters into Equation (9), the predicted values of setting time in the field environment can be obtained. Therefore, the setting time of concrete can be predicted according to the field environmental parametersThe methods mentioned in this study can be applied to the prediction of setting state of mass concrete in complex environments. However, the data used in the article is obtained from a specific environment, so the prediction model has certain limitations. In the future, more general models should be studied to predict the setting time of concrete in various environments.(1)Under the conditions of non-wind and constant humidity, the corresponding equivalent age of concrete in the initial setting in different temperature fields is the same. However, the equivalent age of concrete at the initial setting is different in the field environment which is related to humidity and wind speed.(2)In the field environment, the concrete setting state is influenced by the average air temperature and maximum wind speed before concrete initial setting. The prediction model established via stepwise regression analysis can accurately perceive the actual setting state of concrete.(3)The setting state of concrete and interlayer splitting tensile strength are significantly influenced by temperature. When pouring concrete at the construction site, the quality of interlayer bonding can be controlled based on the relationship between the concrete setting state and the splitting tensile strength.To study the influence of environmental factors on the setting time of low-heat cement concrete, the penetration resistance tests in laboratory and field environment are carried out in this paper. The following conclusions are drawn:


The basic properties of the fresh self-compacting concrete were evaluated and the lateral formwork pressure exerted by the freshly mixed self-compacting concrete was measured and analyzed. An original test setup was developed for the determination of the lateral pressure on the square column formwork with pressure measurements carried out using six strain gauge pressure transducers, which was adequate for heavyweight concrete mixture testing. Self-compacting concrete mixtures containing a magnetite aggregate or blends of serpentine and magnetite aggregates with a slump flow of at least 550 mm were developed. The lateral pressure on the formwork was directly proportional to the density of the self-compacting heavyweight concrete mixes. The maximum values of the lateral pressure recorded in the test at a casting speed of 1.5 m/h did not exceed 27 kPa and 55% of hydrostatic pressure. Concrete mixtures with basalt, magnetite, and magnetite/serpentine blended aggregates were found to develop sufficient shear strength for proper stability during casting.High-fluidity and self-compacting concrete (SCC) mixes were developed using special aggregates for radiation-shielding concrete. The special aggregates comprised heavyweight and hydrous aggregates , which were selected to provide an enhanced attenuation of gamma and neutron radiation, respectively. For the mixed concrete design with a bulk density of up to 3570 kg/m A substitution normal-weight aggregate (granite) with a heavyweight aggregate (magnetite) resulted in an initial slump increase, but only had a small impact on the compressive and tensile strengths of the concrete. The design equations of the ACI 349 and International Federation for Structural Concrete (fib) provisions were found useful for predicting the mechanical properties of heavyweight magnetite concrete, except for the modulus of elasticity and the splitting tensile strength [The performance of radiation-shielding concrete structures that are designed for nuclear power plants is highly influenced by the concrete mix design. Depending on the type of radiation and its energy spectrum, special mineral aggregates are used, such as a high-density aggregate or a hydrogen-bearing aggregate, to enhance the shielding capacity against gamma radiation and neutron radiation, respectively ,2. The uThe shielding structure performance may also be affected by inhomogeneities in the concrete placed in the formwork. Voids and flaws in the mix compaction, facilitated by a dense mesh of reinforcing bars and inadequate control of rheological properties, may result in local radiation surges ,5. Furth3. The lateral pressure was found to be in the range of 50 to 90% of the hydrostatic pressure for placement rates between 2.7 and 6.4 m/h. The study revealed the general adequacy of the ten examined models for predicting the lateral pressure, pointing out the need for consideration of the structural behavior of concrete at rest.The presented arguments justify seeking methods to master the fresh mix control of concrete that is designed for radiation-shielding structures. Why not aim to use self-compacting concrete (SCC) technology in such a case? A known drawback of SCC technology is the increased formwork pressure that is expected to increase while increasing the density of the concrete; such an effect becomes worse for heavyweight concrete. As is known from the ACI guide , the lat2 and the tensile strength of the ties is 90 to 160 kN. Adjusting the placement rate is completely sufficient for the laying and compacting of normal weight mixes. It has been shown that when concreting walls with ordinary self-compacting concrete at a rate of 2 to 2.5 m/h when it is already at a height of 2 m, the formwork pressure can even take values over 90 kN/m2 with braces at 180 kN [Apart from the density of concrete and the placement rate, the lateral pressure of an SCC mix on the formwork depends on several factors ,14,15, it 180 kN .3 was developed using a barite aggregate. The obtained slump was 630 mm, the V funnel flow time was 4 s, and the blocking ratio was 0.75. No segregation or visual flaws were observed in columns cast with this mix. Heavyweight concrete mixtures with a high slump of ≥150 mm were developed in [2·h. There is no data available for authors on the formwork pressure of heavyweight self-compacting concrete.In the literature, there is very little data on heavyweight self-compacting concrete. In , a self-The objective of the current investigation was to develop a design for highly flowable and self-compacting concrete mixes using high-density aggregates and hydrous aggregates, which were selected in order to enhance the shielding capacity against gamma and neutron radiation, respectively. This research also aimed to evaluate the lateral formwork pressure exerted by freshly mixed self-compacting radiation-shielding concrete. The range of the investigation was related to materials that might be useful for the construction of the first Polish nuclear power plant.The selection of materials for radiation-shielding concrete, especially aggregates, was based on their elemental composition. Elements with a high atomic number provide effective shielding for γ radiation. The attenuation of neutron radiation is enhanced for elements with a low atomic number; therefore, hydrous aggregates containing a large amount of chemically bound water are very effective . HydrousThe properties of both types of cement are presented in w/c) was a constant 0.48, except for one mix, which had a w/c = 0.60 (but with w/ceff = 0.48). The aggregate fractions and their amounts were selected to ensure that the mineral grains were properly packed with the minimum amount of natural sand. The principal target properties of the SCC mixes were a slump flow of 600 ± 50 mm and the highest feasible mix density (for gamma attenuation) or the highest feasible content of hydrogen in the aggregates (for neutron attenuation). For such a consistency, a lower initial lateral pressure and faster rates of pressure drop with time could be expected [The variable parameters of the self-compacting concrete mix are given in expected . For theThe serpentine aggregate was characterized by high water absorption . Therefo3 planetary pan forced mixer. The following properties of the mixtures were determined:The mix consistency using the slump method BS EN 12350-2  or the sThe air content and the mix density according to BS EN 12350-7  and BS EThe resistance to segregation of the mixture according to BS EN 12350-11 ;The rheological properties using a BT2 rheometer  .The concrete mixes were prepared in a 30 dmg and the plastic viscosity h; however, they are presented in conventional units, not physical units. Using measurement constants, one may represent the values of the yield stress and the plastic viscosity in physical units, but the measurement constants have not yet been determined for the BT2 rheometer. The general principles for measuring parameters with the BT2 rheometer are presented and discussed in detail in [For the measurement, the BT2 rheometer was placed in the middle of the container filled with the concrete mixture and then one full revolution was made. The tests adopted a constant measurement time (full rotation) of 15 ± 2 s. During this rotation, the torque and angular velocity were measured with two probes. On this basis, the rheological parameters of the mixture were calculated according to the Bingham model, namely, the yield stress etail in . Three mFor the determination of the lateral pressure on the formwork, the mixture was placed in the square column formwork 20 min after mixing. The formwork was filled up to a height of 1 m at a rate of 1.5 m/h. After reaching this height, further concrete placement was simulated by placing 25 kg weights (up to eight pieces) at appropriate time intervals. The load was transferred by means of a 20 cm × 20 cm mold insert, which was placed on the surface of the mixture. One weight represented the load of a concrete mix layer that was 20 ± 5 cm thick, depending on the mix density. Thus, in order to obtain a load corresponding to the concreting speed of 1.5 m/h, weights were laid about every 8 min. This method corresponded to the method of laying the mixture in the formwork in subsequent layers. However, it should be remembered that this method of loading does not take into account the influence of the adhesion of the mixture to the formwork. Thus, the resulting pressure on the formwork may be greater than in reality.The pressure measurement was carried out using six strain gauge pressure transducers located on two opposite formwork walls. Such a strain gauge sensor method has previously been used to measure the formwork pressure . The senCompanion tests were performed to establish the hardened concrete properties. The compressive strength was tested on 150 mm cube specimens after 28 days of standard moist curing according to BS EN 12390-3 . The dep3. For blends of magnetite and serpentine aggregates, the bound water content in the aggregates was up to 4% of the concrete mass, which is important for gamma and neutron radiation shielding [The properties of the fresh self-compacting concrete made of CEM I and CEM III/A cement are presented in hielding . The airhielding . The effThe results of the measurements of the lateral pressure exerted on the formwork by the SCC mixtures are given in w/c ratio. It was higher than the strength of the reference concrete with basalt aggregates. The observed differences in the concrete density for the top and the bottom parts of the column were small, not higher than 1.5%. Therefore, no indication of significant mix segregation was found.The results of the companion tests of the hardened concrete properties are presented in The influence of serpentine aggregate and blended magnetite and serpentine aggregate on the workability of fresh concrete and hardened concrete properties are illustrated in T500 may not be adequate for the assessment of plastic viscosity . The inadequacy of the slump flow test to evaluate the viscosity of the SCC mixtures with a slump flow of 550–600 mm is discussed, e.g., in [As mentioned in e.g., in .The maximum lateral pressure of the self-compacting concrete mixtures with a similar slump flow  on the formwork of the column with a cross-section of 0.20 m × 0.20 m was directly proportional to their density . At the For all the tested mixtures, with the exception of the mixture with serpentine S3B2m, the maximum lateral pressure was recorded for the mixture column height of 2.4 m with the sensor at the 0.75 m level. This pressure did not exceed 27 kPa and was about 50–55% of the hydrostatic pressure. At this point, the formwork pressure at the level of the lower sensors was 2–3 times smaller and showed a tendency to decrease despite the increased load. This means that at the concreting speed of 1.5 m/h, the level of the highest pressure on the formwork was about 1.5 m below the level of the concreting; at greater depths, the pressure on the formwork did not increase and even decreased despite the progress of the concreting. When the concrete mix was left at rest in the formworks, it developed shear strength, which increased with time. The presence of high-density aggregates and large aggregate grains in the self-compacting mixtures (grain size up to 16 mm), as well as in a small volume of paste, favored the faster build-up of a consolidated internal structure and developed a shear strength that was capable of carrying vertical loads. The decrease in pressure was the result of the development of shear strength due to the disappearance of the superplasticizer effect and the progressing process of cement hydration. It should be kept in mind that if the casting rate is increased, the specified concrete height is achieved in a shorter time. The time of resting of the mixture is also reduced, and thus, its shear strength is lower ,41. TherIn the case of the mixture with the serpentine aggregate, namely, S3B2m, the pressure distribution on the formwork was different from the others. In this case, the pressure at the levels of all the sensors was quite similar. After the end of casting in the formwork, the S3B2m mixture did not obtain the ability to carry as much of a load as the other mixtures: the pressure at the bottom of the formwork was higher than for the other mixtures, despite having the lowest mix density. On the basis of this investigation, such an effect cannot be explained.Relating the results obtained to previous studies, it can be stated that no systematic test results on the formwork pressure of SCC designed for radiation-shielding have been published . It is uw/c = 0.3 and 0.4 were used. The slump flows of these mixtures were in the range of 600 to 750 mm and the casting rate was 1.0 m/h. The maximum pressure on the formwork obtained after the end of casting at a height of 1 m was in the range of 9 to 14 kPa, and at a height of 2.4 m, the maximum pressure was in the range from 12 to 23 kPa. A comparison of the results of the current investigation and those from [In the investigation reported in , the latose from  revealedose from .Referring to the current state of the knowledge ,47,48,49In , signifiA greater depth of water penetration in the direction parallel to concreting than in the perpendicular direction was found. An explanation of this effect could be a vertically directed capillary pore system resulting from bleeding and the orientation of the interfacial transition zone relative to the casting direction. However, this issue requires further clarification. The water penetration resistance of the concrete made of CEM III/A cement in the direction perpendicular to concreting was higher than that of concrete made of CEM I cement. This was expected due to the densification of the hydrated paste and the interfacial transition zone, which is associated with long-term hydration of this cement type. In the parallel direction, the beneficial effect of using CEM III/A cement cannot be seen. Increasing the amount of serpentine aggregate in CEM I concrete led to a significant increase in water penetration; in the case of S1B4d concrete, complete water penetration through the specimen in both directions after exposure to water pressure was observed. Interestingly, quite low water penetration was revealed in the concrete with CEM III/A and serpentine aggregate. The observed differences in the compressive strength of the concrete in cut specimens were relevant to the different rates of hardening associated with the types of cement used.Poor concrete properties with serpentine aggregate were reported in , indicatw/c ratio of 0.48 when using dry serpentine aggregate. In order to obtain the required consistency in such a case, it was necessary to significantly increase the amount of water added to the mixture (V1B2d4). However, this induced a marked reduction in the compressive strength of the concrete. A more efficient way to obtain an S2–S4 mixture consistency was revealed: the use of a presaturated serpentine aggregate . It should be noted, however, that even then, the mixtures sometimes displayed a rapid workability loss . Furthermore, the process of aggregate saturation is a technological impediment. The use of serpentine aggregate saturated with water did not adversely affect the compressive strength, which is an important observation. By removing the fraction below 2 mm from serpentine aggregate and replacing this fraction with quartz sand, it was feasible to obtain a stable S4 consistency of the concrete mixture  for 60 min without the need for presaturating the aggregate. It should be noted that a partial reduction in the serpentine fraction below 2 mm (V1B2d2) did not bring any significant improvement in the mixture’s workability.Despite a high superplasticizer content, it was impossible to obtain an S4 consistency at a It should be noted that the use of the magnetite aggregate allowed for good workability of the mixtures  to attain the consistency class S4. The amount of superplasticizer needed to obtain the slump of 20 cm was the same for mixtures with magnetite (V1B1) as for the control mixture (V1B0); these mixtures also did not differ significantly in terms of the workability loss.3 and mixtures with a chemically bound water content of 3–7% with self-compacting characteristics related to a slump flow from 55 to 65 cm were obtained using crushed magnetite and serpentine aggregates. A stable consistency was obtained for the magnetite aggregate, while the presence of serpentine aggregate resulted in a loss of slump flow by 10 cm. Both the yield stress and plastic viscosity of the self-compacting mixtures were increased with the use of magnetite and serpentine aggregates. The mixes exhibited resistance to the segregation of the SR2 class.Heavyweight concrete mixes with a density of up to 3570 kg/m3.An original test setup was developed for the determination of lateral pressure on the square column formwork with pressure measurements carried out using six strain gauge pressure transducers located on two opposite formwork walls. The setup was found to be adequate for heavyweight concrete mixtures when testing up to the density of 3570 kg/mSimilar to conventional concrete, at the same casting rate and mix consistency, the maximum lateral pressure was directly proportional to the density of the self-compacting radiation-shielding concrete mixes. The maximum values of the lateral pressure recorded in the test at a casting speed of 1.5 m/h did not exceed 27 kPa and 55% of the hydrostatic pressure. Concrete mixtures with basalt, magnetite, and magnetite/serpentine blended aggregates were able to develop shear strength after casting for proper stability during concreting.At the casting speed of 1.5 m/h, the maximum pressure was registered 1.5 m below the concreting level. The pressure on the formwork was changed or even decreased at deeper levels, despite the progress of concreting. The mixture with the serpentine aggregate showed a lower load-carrying capacity, where in this case, despite the lowest density, the highest pressure on the formwork was observed at the level of the bottom sensor.The dependencies determined for normal concrete that allow for the prediction of pressure on the formwork can also be used for radiation-shielding concrete after taking into consideration their different densities.No flowable concrete mixes with a dry serpentine aggregate were obtained. For a presaturated serpentine aggregate with water in the amount corresponding to its water absorption, concrete mixtures with an S3–S4 consistency could be obtained while avoiding a significant reduction in the strength of the concrete. For proper workability control, it is more beneficial to replace the 0–2 mm fraction of the serpentine aggregate with ordinary quartz sand.It is possible to obtain concrete mixtures with magnetite aggregate with an S4 consistency S4 that is stable over time and mixtures with serpentine and magnetite aggregates blended in various proportions with an S3–S4 consistency. For a higher dose of superplasticizer, an increased loss of workability was observed, which was more pronounced for CEM III/A cement than for CEM I cement.The following conclusions can be drawn from the performed investigation:


To perform non-compartmental pharmacokinetic analysis, the Pharmacokinetic program (PK Solver) was used. The method’s greenness was analyzed using two tools: the Analytical GREEnness calculator and the RGB additive color model. Taking papaya with MET improved the rate of absorption substantially (time for reaching maximum concentration (Tmax) significantly decreased by 75% while maximum plasma concentration (Cmax) increased by 7.33%). The extent of absorption reduced by 22.90%. Furthermore, the amount of medication distributed increased  and the clearance rate rose by roughly 13.50%. The results of the greenness assessment indicated that the method is environmentally friendly. Taking papaya with MET changed the pharmacokinetics of the drug dramatically. Hence, this combination will be particularly effective in maintaining quick blood glucose control.Foods with medical value have been proven to be beneficial, and they are extensively employed since they integrate two essential elements: food and medication. Accordingly, diabetic patients can benefit from papaya because the fruit is low in sugar and high in antioxidants. An RP-HPLC method was designed for studying the pharmacokinetics of metformin (MET) when concurrently administered with papaya extract. A mobile phase of 0.5 mM of KH Type 2 diabetes mellitus (T2DM) is a type of metabolic disorder that includes chronic hyperglycemia resulting from insulin insensitivity on appropriate tissues ,2. The tCarica papaya that is a member of family Caricaceae, which is characterized by its edible, pleasant fruit that provides good nutritional value in addition to being easily digestible. It has been reported that papaya leaves can help with asthma, worming, and dysentery symptoms [In the same vein, medicinal plants are progressively gaining global acceptability for their use as bioactive agents in pharmaceuticals. Some of the secondary consequences of diabetes, such as kidney damage, fatty liver, and oxidative stress, have been improved by new hypoglycemic medicines derived from plants ,6. Amongsymptoms . In addisymptoms ,9,10. A symptoms ,12. Moresymptoms .The co-administration of herbal medicines with common antidiabetic drugs, like metformin (MET), on the other hand, has the potential to alter their pharmacokinetic and pharmacodynamic properties; hence, it was critical to look into herb–drug interactions. This study looked into the pharmacokinetics of MET and papaya extract when they are simultaneously administered.Following a thorough study of the literature, several methods for analyzing MET alone in various samples  were reported, including HPLC ,17,18,19Green chemistry principles have recently attracted scientists’ interest to reduce human health and environmental risks. Various criteria are currently utilized to evaluate the environmental impact of various analytical methodologies, however, multi-criteria decision analysis (MCDA) allows for a rating of available analytical methods based on many evaluation criteria at the same time. The Analytical GREEnness (AGREE)  calculatIn this study, our aim was to see if the pharmacokinetics of an oral hypoglycemic drug, MET, when given to rats as an animal model, are affected by taking papaya extract at the same time. After a few basic sample pretreatment steps, the samples were ready to be used and the proposed pharmacokinetic investigation was completed using a low-impact RP-HPLC method. In addition, method validation was carried out in accordance with Food and Drug Administration (FDA)  guidelinVarious aspects were investigated during method optimization so as to separate MET completely from the plasma matrix in a short time. Due to the high polarity of MET, it is difficult to keep it in the stationary phase. Hence, increasing its retention period was a challenge during the optimization step. Different stationary phases  were tested. Unfortunately, there was no discernible difference in the separation effectiveness of these stationary phases.18   column was then used to continue the optimization process. The previously published mobile-phase solvent mixture of acetonitrile , and varying pH levels of the aqueous phase (from 3.8 to 7), were used to evaluate a number of mobile phase mixtures with varying flow rates (from 0.5 to 2 mL/min). All studies found that the plasma matrix impeded the detection of the early MET peak. All of these tests were subsequently performed again, but this time with methanol as an organic modifier, which is more environmentally friendly than acetonitrile. Unfortunately, this resulted in an unclear plasma matrix and MET signals. Water was then changed by 10 mM of KH2PO4 solution. The retention period of MET was greatly increased when water was used as the aqueous phase, however, extremely little retention was found when 10 mM of KH2PO4 solution was used. After that, lower concentrations of KH2PO4 solution  were attempted with various methanol ratios. The plasma matrix and MET were completely separated based on the use of a mixture of 0.5 mM of KH2PO4 solution and methanol . Furthermore, the flow rate of the mobile phase was adjusted at different values (from 0.5 to 2 mL/min), where complete separation within an acceptable time occurred when using 1.7 mL/min. Scanning was done at various wavelengths , with 235 nm providing the best sensitivity with the least amount of noise.The ZORBAX Eclipse Plus CAn internal standard is particularly valuable for improving the precision, accuracy, and resilience of a bio-analytical method throughout development. Additionally, it is vital to take variability in sample preparation and analysis into consideration, as well as to adjust for analyte loss during sample preparation. It was difficult to choose an internal standard that had the same chromatographic behavior as the analyte while also being completely separated from the analyte and plasma peaks. Additionally, it should have chemical and physical properties that are comparable to the target analyte in order to be extracted with the same method. There were tests on internal standards such as atenolol, metoclopramide, olanzapine, ibuprofen, and guaiphenesin (GUF). GUF was the best internal standard in terms of chromatographic performance in relation to the plasma matrix and MET separated peaks. Finally, within 7.5 min, a complete plasma matrix, MET, and GUF separation was accomplished and the resulted retention times were: 2.4, 4.9, and 6.3 min, respectively . In addiTo ensure the bio-analytical approach established was valid, US Food and Drug Administration (FDA)  guidelinThe calibration standards and QC samples were prepared and used to validate the proposed method by diluting the previously prepared working solutions of MET and GUF with the mobile phase mixture to prepare their corresponding working solutions.r), was assessed using a least-squares regression line. The regression equation that was generated was found to be:A is the ratio of peak area and C is MET concentration in µg mL−1, and r is the correlation coefficient.The calibration line was plotted at nine concentrations , and linearity, as measured by the correlation coefficient (−1.The low limit of quantitation (LOQ) was calculated for sensitivity, and it was the concentration of analyte that produced a repeatable response that was a minimum five times as the blank. The LOQ calculated was 0.5 µg mLQuality control samples were analyzed five times each, and accuracy was calculated by comparing the averaged measurements to the nominal values and was expressed in % relative error (RE) ((measured concentration − true concentration/true concentration) × 100). The permissible limit was ±15% of the genuine concentration. The computed %RE ranged from −6.82 to 0.99%, according to the values in The chromatograms of blank rat plasma, plasma spiked with target analyte and IS, and plasma samples taken from rats given MET and papaya extract (two hours after administration) and spiked with the prescribed amount of the internal standard were compared to assess specificity. As displayed in The quality of the extraction process was calculated by comparing the peak area ratios of the analyte in rat plasma at QC concentrations to those in the mobile phase at corresponding concentrations. The stability of MET in rat plasma was studied for a short period of time (one day) at room temperature (bench top stability), three freeze thaw cycles, and auto-sampler stability (processed sample stability) over a 24 h period. If the medication’s plasma stability results were within 15% of the current concentrations, the medication was pronounced stable. The final results were 108.30% ± 7.38, 95.03% ± 8.04, and 97.15% ± 4.35. After drug administration without papaya extract (group II) or with it (group III), plasma concentrations of the administered drug were considered using the formerly calculated regression equation and then a mean plasma concentration versus time graph was designed, max = 15 min in group III compared to one hour in group II). As Tmax is important for estimating the rate of absorption, onset of action, and to evaluate the efficacy of single-dose drugs used in acute conditions, one can conclude that the combination of MET and papaya extract will be an effective and fast hypoglycemic remedy. Additionally, the amount of drug absorbed increased by 7.33% in the group of rats that received both the drug and the plant extract. This may be attributed to the fact that papaya extract contains saponin, which acts as a surface active agent that increases the solubility of MET blood plasma, resulting in an improved absorption rate and extent of the studied drug. Regarding MET’s half-life (t1/2), volume of distribution (Vd), and clearance (Cl), they increased by 11.86, 27.16, and 13.51%, respectively, in group III relative to group II. All the results of the pharmacokinetic study are shown in Looking at Green analytical chemistry aims to make analytical techniques less harmful to the environment and more human friendly. The use of greenness assessment standards necessitates the use of certain tools. Several methods used for GAC measures have been created thus far, with the Analytical GREEnness calculator (AGREE)  being onFor further assessment of the greenness of this method, another greenness metric tool, the RGB additive color model , was useThis tool also features a quantitative parameter that combines all three scales by applying different weights to them, which are defined subjectively by the user (W). This is called “Method Brilliance” (MB). It refers to a method’s genuine capabilities and expresses its “perfection or flawlessness.”Based on the RGB results in For powdering of the plant seeds: Jet mill machinery .For extract evaporation: A rotary evaporator .Rongtai micropipettes with adaptable volume (100–1000 L) and (0.1–100 L) .A VM vortex blender 250 .80–2C Low-speed Electric Centrifuge , (4000 rpm) and (12 tube × 20 mL).Dionex Ultimate 3000 UHPLC that has a quaternary solvent transfer pump, diode array detection system, and automatic sampler (Germany). Chromeleon software was used.A digital balance was also used .2PO4 solution and methanol , adjusting the flow rate constant at 1.7 mL/min, and scanning at 235 nm. A C18 column  (ZORBAX Eclipse Plus)  was used as a stationary phase and the temperature of the column was set unchanged at 25 °C. A total of 30 µL of each sample was injected and GUF was chosen as the internal standard with a run duration of 7.5 min.Separation was performed using a developing system: 0.5 mM of KH18  , ZORBAX Eclipse Plus C18  , XBridge C8  , and ZORBAX Eclipse Plus C8  .For method optimization different columns were tested including: XBridge CMetformin  Co., Giza, Egypt) and Guaiphenesin .Methanol (HPLC grade)  and KH2PO4 and ethanol .Deionized water .Stock solutions of metformin and guaiphenesin (IS) (1 mg/mL) were prepared in methanol. Their working solutions (0.1 mg/mL) were made by diluting the previously produced stock solutions with the mixture of the optimum mobile phase to make 10 mL solutions. Solutions were then reserved at −20 °C until the study was performed.Eighteen adult rats, female Wistar albinos, obtained from the Animal House of Nahda University in Beni-Suef (NUB), Egypt, and weighing 200 ± 50 g, were used in this study. The rats were kept in an air-conditioned (25 ± 1 °C), pathogen-controlled animal room in the Nahda University Animal House for two weeks for adaptation and to investigate differences in pharmacokinetic characteristics between the treatment and control groups before being subjected to the experiments. The rats had freely available forage and water from the tap. The experimental animals were handled according to guidelines set forth by the Nahda University Animal House and accepted by the Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University in Beni-Suef (NUB).A kilo of plant seeds was bought on the open market . Dr. Ahmed M. Sayed, Department of Pharmacognosy, NUB, evaluated and identified the acquired seeds, followed by finely powdering the seeds using small jet mill machinery from the laboratory. To yield 60 g of rough extract, the extract was macerated without stirring with 1 to 1.5 L of 70% ethanol over a period of 3 days. For biological investigation, the extract was saved at −4 °C.−1) and placed into a series of test tubes previously containing 0.5 mL of blank rat plasma. From the previously produced working solution (100 µg mL−1), 250 µL of GUF (IS) was added to each sample, and the volume was subsequently corrected to 2 mL with methanol. One minute’s worth of vortex mixing was followed by 10 min of centrifugation at 4000 rpm to remove the plasma protein. Supernatants were transferred to different novel tubes and dried completely by evaporation for each sample. MET samples with a contaminant concentration of 0.5–30 µg mL−1 with 50 µg mL−1 of IS were prepared by reconstituting the deposit resulted from separate drying of each sample with the mobile phase mixture in 0.5 mL. Three injections of 30 µL of each were made into the HPLC apparatus, and the chromatographic conditions were then tracked. The peak area ratio (peak area of MET/peak area of IS) was calculated for each sample and then used to derive the regression equation after building a calibration curve. To further validate the suggested approach, three quality control samples  were prepared and analyzed using the optimum separation conditions.Variable amounts of MET (2.5–150 µL) were taken from its working standard solution  was kept as a normal control group and received only saline solution. A total of 300 mg/kg of MET solution in saline was given to the second group (II) ([according to a previously published study ), and 30−1) was then added to each sample, and methanol was then used to adjust the volume to 2 mL. One minute of mixing the materials was followed by a ten-minute centrifugation process. Each sample’s supernatant was accurately transferred to a clean test tube, where it was thoroughly evaporated until the tube was nearly empty. The remainder of each sample was reconstituted with 0.5 mL of solvent mixture of the mobile phase. To estimate administered drug concentrations, the created method’s instructions were followed, and then substitution in the regression equation was completed. The method developed by Fares et al.  was modiIt was possible to plot the graph representing the estimated mean plasma concentration in the independently collected plasma samples from groups II and III, MET (300 mg/kg) and MET + papaya extract (300 mg/kg + 500 mg/kg), respectively, at various times versus the corresponding collection time. A study was then performed on non-compartmental pharmacokinetic parameters in Microsoft Excel , using tFor studying the effects of the concurrent administration of papaya extract on MET pharmacokinetics, a unique ecological RP-HPLC approach was developed and refined. MET solubility and bioavailability are both enhanced by papaya saponin content, which acts as an emulsifying agent. The use of papaya extract in conjunction with MET may be an advantageous treatment for effective and fast diabetes control during acute conditions since MET reaches its plasma peak concentration within 15 min, compared to 1 h for MET alone. Concurrent administration of papaya extract with MET may reduce the risk of long-term MET problems. Furthermore, the proposed RP-HPLC method prioritizes being sensitive as well as a green method with minimal risk to the environment, as evidenced by the findings of the greenness assessment. Furthermore, the sample preparation necessitates a simple protein precipitation procedure, hence a short analysis time.