The modern development of nanotechnology requires the discovery of simple approaches that ensure the controlled formation of functional nanostructures with a predetermined morphology. One of the simplest approaches is the self-assembly of nanostructures. The widespread implementation of self-assembly is limited by the complexity of controlled processes in a large volume where, due to the temperature, ion concentration, and other thermodynamics factors, local changes in diffusion-limited processes may occur, leading to unexpected nanostructure growth. The easiest ways to control the diffusion-limited processes are spatial limitation and localized growth of nanostructures in a porous matrix. In this paper, we propose to apply the method of controlled self-assembly of gold nanostructures in a limited pore volume of a silicon oxide matrix with submicron pore sizes. A detailed study of achieved gold nanostructures’ morphology, microstructure, and surface composition at different formation stages is carried out to understand the peculiarities of realized nanostructures. Based on the obtained results, a mechanism for the growth of gold nanostructures in a limited volume, which can be used for the controlled formation of nanostructures with a predetermined geometry and composition, has been proposed. The results observed in the present study can be useful for the design of plasmonic-active surfaces for surface-enhanced Raman spectroscopy-based detection of ultra-low concentration of different chemical or biological analytes, where the size of the localized gold nanostructures is comparable with the spot area of the focused laser beam. In the recent years, the usage of gold, silver, and copper nanostructures for surface-enhanced Raman spectroscopy (SERS) has aroused a lot of interest ,5,6,7,8 The coupled plasmon resonance deserves special attention, as it appears in the gap between nanostructures and leads to the appearance of so-called “hot spots”—areas with a high intensity of local electric fields ,10,11. DThe using of stabilizers can be avoided by the controlled aggregation of nanostructures on the solid substrates. Mettela et al. have proposed a promising approach to the formation of silver nanostructures with repetitive dendritic-like morphology, which allows the realization of Raman signal with high amplification . HoweverA simple method based on the application of a porous matrix for the controlled and localized formation of complex shape plasmonic metal nanostructures has been proposed in our previous publications ,24,25. IConsidering the fact that silver and copper nanostructures have low long-term chemical stability against oxidation at ambient atmospheric conditions, especially in water-based solutions, the implementation of gold nanostructures is more realistic. In our previous work, we have already demonstrated the possibility of obtaining gold nanostructures by means of template synthesis . It is i2/Si matrix, we used the swift heavy ions-track technology ) with selected crystallite orientation along the plane (111) was observed for longer than 15 s growth time. The calculation of the lattice parameter in the observed samples was carried out using the Nelson–Taylor extrapolation function as presented in Equation (4): a are determined by linear extrapolation of the function to the argument zero value (θ = 90°). The value and error of the parameter k = 0.9 is the dimensionless coefficient of the particle shape (Scherer constant), λ = 1.54 Å is the X-ray wavelength, β is the half-width, half-height reflex (FWHM) and θ is the diffraction angle (Bragg angle). The calculation results of crystallographic parameters of observed gold nanostructures localized in the porous SiO2/Si matrix are given in The average crystallite size can be calculated by the Scherer Equation (5):dpristine, dexp are interplanar distances of the reference sample and the experimentally obtained data. The dependence of the stresses in deposited gold on deposition time is presented in The results presented in Gold deposition time causes an increase in the stresses and deformations in the crystal structure of the gold precipitant. This effect can take place due to the crystallite formation processes, which leads to a change in the dislocation density of the structures, which is shown in 7/2 and 4f5/2 core levels binding energy values correspond to the presence of different chemical states of gold and can be direct evidence of the presence of different gold oxidation states: Au(0), Au(I), and Au(III) [The results on the obtained surface composition studies by high-resolution XPS are presented in  Au(III) ,23. The  Au(III) ,23. The 2/Si pore filling. From the analysis of the chemical reaction Equations (1)−(3), it is obvious that three chemical scenarios can take place during the gold deposition: electrochemical reduction of gold on silicon (1), oxidation of silicon (2), and etching of SiO2 in fluorine acid (3). The schematic illustration of the pore filling process is demonstrated in XPS data shown in 2 pores along the edges, providing access to the silicon surface for the “generation” of new electrons. Thus, there is a diffusion-limited process, and it becomes clear why the structures expand (increase) mainly along the edges of the pores  ions to Au(0)) [3Si intermetallic alloys at near room temperature have been reported in the 1970s by Bhattacharya et al. [2 layers between the pores and the release of the silicon surface, so that gold(III) ions can fully be reduced to the metallic state, as evidenced by XPS spectra without additional contribution of another gold oxidation state have been observed  ions on silicon. In the first stage up to 5 s, the number of electrons pulled out from the silicon surface is in equilibrium with the amount of gold(III) ions, and therefore all ions can be reduced up to a metallic gold(0) state, as was observed in o Au(0)) ,30. Howeo Au(0)) . The fora et al. . To deteobserved f,g.Nevertheless, it should be noted that the XPS spectra indicate the absence of the formation of any gold bonds with the components of the initial solution from which the gold nanostructures were obtained. The analysis of the surface states of observed gold nanostructures grown at different deposition times make it possible to demonstrate the possibility of producing gold nanostructures with a positively charged surface due to the presence of silicide (Au-Si) in the structure. As mentioned in , metal s−4 M–10−8 M). The gold precipitates obtained after a deposition time of 180 s were selected, because they approach the necessary size of the laser spot of about 1 µm. Depending on the measured spot, the intensity of the Raman signal varies, so we used a scanning laser beam, where the area of 25 × 25 µm2 is continuously scanned during the Raman scattering measurement. We found that for concentrations of 10−4 M to 10−7 M the similar Raman spectrum is obtained, as presented in The potential of the realized gold nanostructures as a SERS-active substrate is tested on model analyte, MBT solutions, with different concentrations  and Au(III) gold states in XPS spectra. It is assumed that this fact is caused by an incomplete reduction of gold ions to a metallic state, due to diffusion-limited processes occurring in the pores of the SiO2/Si matrix. It should be noted that these SERS-active substrates were tested by being in a usual atmosphere for 1 year, while maintaining their SERS-activity. Thus, the proposed structures are stable at ambient atmospheric conditions for at least a year. Such functional surfaces are well-suited for the SERS-based detection of molecules. Additionally, observed surfaces with different oxidized states of gold have perspectives as promising catalysts.The localized gold nanostructures were obtained by galvanic replacement in the pores of the SiO


In coronary artery disease (CAD) the adipocytokine content in the heart fat depot is altered, but it has not been established whether these changes are associated with the degree of atherosclerotic damage to the coronary artery (CA). Were examined 84 patients with CAD, and according to the degree of atherosclerotic state based on the SYNTAX Score scale, were divided: 39 moderate (≤22 points), 20 severe (23–31 points) and 25 extremely severe (≥32 points). Biopsies of subcutaneous (SAT), epicardial (EAT) and perivascular adipose tissue (PVAT) were obtained during elective coronary artery bypass grafting (CABG). The expression of adipocytokine was determined using real-time PCR. The concentration of the studied adipocytokines in adipocyte culture medium was measured by ELISA. Statistical analysis was performed using logistic regression analysis. In the adipocytes of the cardiac depot of patients with CAD, an increase in the expression and secretion of leptin and IL-6 and a decrease in adiponectin, with a maximum manifestation in severe and extremely severe CA lesions, was observed. EAT adipocytes were characterized by minimal expression of the adiponectin gene maximal gene expression leptin and IL-6 compared to SAT and PVAT adipocytes. Coronary artery disease (CAD) remains the leading cause of death in industrialized countries. Previous studies have shown a close relationship between CAD and obesity, but the mechanisms mediating this relationship are complex and not entirely understood . Of partin vitro of transforming growth factor (TGF)-β by endothelial cells, plasminogen activator inhibitor (PAI-1), and platelet P-selectin, which may also contribute to atherothrombosis [Of particular interest is the relationship between CAD and adiponectin, the levels of which are significantly reduced in obese people. It is known that adiponectin has antidiabetic and antiatherogenic properties, and its low plasma level is associated with multivessel CA disease in men with CAD . Leptin rombosis .It is not known whether there is an obvious associated between the progression of CAD and changes in the expression of adipocytokine genes in various heart fat depots. Notably, the results of this type of work can theoretically justify the development of new therapeutic targets.ADIPOQ, LEP and IL-6 expression by EAT, perivascular adipose tissue (PVAT), and subcutaneous (SAT) adipocytes, depending on the degree of coronary lesions in CAD.To identify the features of This retrospective study was carried out according to the Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovascular Diseases. The research protocol was approved by the local ethics committee of the Research Institute for Complex Issues of Cardiovascular Diseases. Patients were recruited according to inclusion and exclusion criteria in 2017–2020 in accordance with the guidelines of good clinical practice and the principles of the World Medical Association’s Declaration of Helsinki , amended in 2000, as well as the "Rules of Clinical Practice in the Russian Federation" approved by the Order of the Ministry of Health of the Russian Federation (266/19.06.2003). All patients gave written voluntary informed consent prior to participation. A total of 84 CAD patients aged 64.6  years were examined. As a comparison group, 35 patients without CAD were included in the study according to the coronary angiographic study (CAG)  or the equivalent of a stem lesion, proximal lesion of all three vessels (>70%) or other lesions involving the proximal anterior descending artery.In patients with severe stable angina pectoris refractory to drug therapy, surgery was indicated for one- or two-vessel lesions without significant proximal stenosis of the anterior descending artery in the presence of a significant volume of viable myocardiumThree-vessel lesion, complete functional revascularization at SYNTAX ≤22Three-vessel lesion, incomplete functional revascularization with SYNTAX >22Stenosis of the left trunk of the coronary artery Stenosis of the left trunk of the coronary artery Technically complex calcified lesion of the left trunk of the coronary arteryLesion of the orifice of the trunk of the left coronary artery and the circumflex artery, non-extended, multiple lesionStenosis of the left trunk of the coronary artery and two- or three-vessel lesion, SYNTAX ≤32Stenosis of the left trunk of the coronary artery and two- or three-vessel lesion, SYNTAX ≤32High risk of bleeding due to concomitant pathology , which excluded the use of two-component antiplatelet therapy during the time frame corresponding to clinical guidelinesHistory of postinfarction cardiosclerosis with left ventricular aneurysm requiring resectionInclusion criteria for persons with heart defects included the following: availability of indications for surgical correction of valvular pathology, age up to 75 years, and consent provided for research.The study did not include patients that were >75 years with a history of type 1 and type 2 DM and/or myocardial infarction (MI) that was identified during examination during hospitalization, as well as a clinically significant concomitant pathology . The examined individuals with CAD and heart defects received standard antianginal and antiplatelet therapy.http://www.syntaxscore.com/): low , intermediate , and high .All patients underwent echocardiography  as described by Judkins  on a twoADIPOQ from biopsy samples (3–5 g of fat) obtained during surgery. The EAT samples were obtained from fat depots localized mainly around the right heart, while the SAT samples were from the lower angle of the mediastinal wound, and the PVAT samples were obtained from the mammacoronary vascular bundle in the anterior mediastinum, the ascending aorta. The resulting biopsies were placed in a Hanks balanced saline solution  with the addition of penicillin (100 units/l), streptomycin (100 mg/ml), gentamicin (50 μg/ml) and delivered to the laboratory. The adipocyte isolation from adipose tissue was carried out under sterile conditions in a Class II laminar cabinet  according to the procedure described previously [We determined the expression of the eviously .® Plus Universal Mini Kit  according to the manufacturer’s protocol with some modifications as described previously [™ XR+ System . Extracted RNA was stored at –70°C.Total RNA was isolated from the adipocytes using the commercial RNeasyeviously . The quaSingle-stranded cDNA was synthesized using the High-Capacity cDNA Reverse Transcription Kit  on a VeritiTM 96-Well Thermal Cycler (Applied Biosystems). Reverse transcription was performed using the program suggested by the kit’s manufacturer. The quantity and quality of synthesized cDNA were assessed using a NanoDrop 2000 Spectrophotometer. Samples were stored at –20°C.ADIPOQ), leptin (LEP) and IL6 genes was evaluated by quantitative real-time polymerase chain reaction (qPCR) using TaqManTM Gene Expression Assays  on a ViiA 7 Real-Time PCR System (Applied Biosystems). Each 20-μL reaction mix contained 10 μL of TaqManTM Gene Expression Master Mix (Applied Biosystems), 1 μL of TaqManTM Gene Expression Assay (Applied Biosystems), and 9 μL of cDNA template (100 ng of cDNA + nuclease-free water) and was amplified under the following thermal cycling conditions: 2 min at 50°C, 10 min at 95°C, and 40 cycles of 15 sec at 95°C and 1 min at 60°C. As a negative control, we used 20 μL of reaction mix with no cDNA template. For each sample, a negative control, and three technical replicates were prepared. The results were normalized using reference genes HPRT1, GAPDH, and B2M. Test gene expression was calculated using the Pfaffl method and expressed on a logarithmic (log10) scale as a multiple change relative to the control samples.Expression of the adiponectin  in the culture medium was evaluated by enzyme-linked immunosorbent assay test systems , according to the manufacturers’ instructions.www.statsoft.com, Tulsa, OK, USA). Nonparametric criteria were used to evaluate and analyze the data obtained. Comparison of two independent groups was carried out using the nonparametric Mann-Whitney test. Differences between the three groups were compared using one-way analysis of variance (ANOVA) for continuous variables. Categorical variables are expressed as percentages and were compared using chi-squared test or Fisher’s exact test. A P-value of <0.05 was considered statistically significant. A critical level of significance in testing statistical hypotheses was taken to be <0.05. Predictors of CAD progression were determined using one-dimensional polynomial logistic regression analysis and Area Under the Curve (AUC) definitions. The group with the absence of damage (Group 0) was used as a reference in the subsequent multivariate analysis for the phased inclusion of variables that were significant following the one-dimensional analysis. The results are presented as median, upper and lower quartiles .Statistical analysis was performed using GraphPad Prism 6  and Statistica software, version 9.1  vs. 2.41  in the EAT, and 3.11  vs. 3.62  in the PVAT. In contrast, the level of LEP increased in CAD patients and was higher in the EAT  and the PVAT . Similar results were observed for the expression of IL-6 in the EAT and PVAT of CAD patients which increased to 0.080  vs. 0.058  and 0.058  vs. 0.030 , respectively.In CAD patients, in vitro. The adiponectin concentration in the adipocyte culture medium in the EAT of CAD patients was lower than in individuals without CAD , and the same trend was observed for the PVAT medium . The concentration of leptin in the culture medium of adipocytes was 7.67  ng/ml and 6.96  ng/ml for EAT and PVAT, respectively, in patients with CAD. This exceeded the level of individuals without CAD . The concentration of IL-6 in the culture medium of adipocytes of cardiac localization of patients with CAD was higher than in individuals without CAD: 30.77  pg/ml vs. 22.26  pg/ml for EAT and 16.92  pg/ml vs. 12.49  pg/ml for PVAT. In the SAT of patients with CAD the expression and concentration of adipocytokines tended to decrease for adiponectin and increase for leptin relative to the comparison group (p>0.05).The impaired gene expression was accompanied by a change in the concentration of adipocytokines in the adipocyte culture medium The expression of adipocytokine genes and their concentrations in adipocytes of the adipose tissue localized in the heart depended on the degree of atherosclerotic lesion of the coronary lesion .ADIPOQ expression was maximal in Group 1 in all studied fat depot types compared to Groups 2 and 3. With an increase in the degree of CA lesion, ADIPOQ expression decreased. It should be noted that in the EAT the ADIPOQ expression was lower than in the PVAT at all stages of atherosclerotic lesion of the coronary channel .The ADIPOQ expression was 2.73  in Group 1, 2.25  in Group 2, and 2.20  in Group 3, which was higher than in the EAT, but lower than in the PVAT.In SAT the With an increase in the degree of lesion of the coronary lesion, gene expression and adiponectin concentration in the SAT decreased. In Group 1 the adiponectin mRNA level and its concentration in the SAT exceeded the same indicator in the EAT by 1.3 times in Groups 2 and 3 by 1.5 and 2 times, and its concentration—by 1.2 and 1.3 times, respectively.ADIPOQ, LEP expression was lower in Group 1. With an increase in the degree of atherosclerosis, LEP expression increased. In the EAT, a maximum expression of LEP was detected in Group 2: an increase of 2.2 times compared with Group 1, and 1.9 times compared with Group 3. In the PVAT, a high expression of LEP was observed in Group 3 individuals: an increase of 1.4 times relative to Group 1. Moreover, in Group 2 in adipocytes of the EAT, LEP expression exceeded 2 times its expression in the PVAT.In contrast to IL-6 in fat depots of the heart increased with an increase in the degree of coronary lesion. Thus, the concentration of IL-6 mRNA in adipocytes of the EAT in Group 2 and 3 patients exceeded that of individuals in Group 1 by 2.4 and 2.5 times, respectively, and that in adipocytes of the PVAT, by 2.1 and 1.9 times. In addition, the expression of IL-6 in adipocytes of the EAT was 1.5 times higher than in the PVAT in Group 3.The expression of Along with expression, the concentration of adipocytokines also depended on the degree of damage to the coronary lesion .The highest adiponectin concentration in the culture medium of adipocytes of cardiac fat depots was in Group 1 patients compared to Groups 2 and 3: EAT  and PVAT . As atherosclerosis progressed, the concentration of adiponectin in the pericardial VAT decreased and was minimal in Group 3.Comparative analysis of the groups showed that Group 2 was characterized by high gene expression, and an elevated level of leptin in the adipocyte culture both in the EAT and PVAT . The concentration of leptin in the culture medium of the EAT exceeded that of the PVAT in Groups 1 and 3 by 1.4 and 1.1 times, respectively.LEP in the SAT was 0.30  in Group 1, 0.77  in Group 2, and 0.33  in Group 3, which was significantly lower than in the EAT. The expression of LEP in the PVAT was higher than that in the SAT in Groups 1 and 3 .In the SAT, the expression and concentration of leptin was lower than in adipocytes localized in fatty deposits of the heart. Thus, the expression of The concentration of leptin in the SAT was 4.31  ng/ml, 7.57  ng/ml, and 4.33  ng/ml in Groups 1, 2 and 3, respectively. The concentration of leptin in the PVAT in Group 1 was reduced relative to the SAT and increased in Groups 2 and 3 by 1.1 and 1.6 times, respectively.The concentration of IL-6 in the culture medium of adipocytes of the EAT and PVAT in Group 1 decreased by 1.8 and 2 times, respectively, compared with Group 2 and 1.9 times, respectively, compared with Group 3. The concentration of IL-6 in the culture medium of adipocytes of the EAT exceeded that of the PVAT .IL-6 in heart fat depots compared to the SAT increased by 2–2.5 times in the EAT and by 1.6–1.7 times in the PVAT in Groups 2 and 3.It should be noted that the increase in gene expression and IL-6 concentration was maximal in adipocytes localized around the heart, as compared with the SAT. Expression of ADIPOQ in the EAT  and the PVAT , a decrease in the left ventricular ejection fraction (LV EF) , and an increase in IL-6 expression in the EAT  and the PVAT . Additionally, the risk of developing atherosclerosis was lower in women compared with men   .Thus, in CAD, the gene expression and adiponectin concentration decreased, and the expression and concentration leptin and IL-6 in fat depots increased, with maximum deviations in the pericardial adipocytes. In Group 1 a higher level of adiponectin and a low content of leptin and IL-6 was observed. With an increase in the degree of atherosclerotic lesion of the coronary bed, the expression and concentration of adiponectin decreased and the expression and levels of leptin and IL-6 increased. The maximum changes in leptin were observed in the EAT (Group 2) and PVAT (Group 3).Our results showed that in CAD patients, the expression and concentration of adiponectin in adipocytes of the EAT and PVAT decreased compared to patients without CAD. A deficiency of adiponectin in adipocytes of cardiac localization is a pathognomonic sign of CAD due to coronary atherosclerosis. This has been confirmed by the results of experimental studies, which highlighted the ability of adiponectin to limit the process of atherogenesis. Adiponectin is known to inhibit macrophage uptake of oxidized low-density lipoproteins, causes the production of metalloproteinases, reduces the destruction of the fibrous coat of atherosclerotic plaque and neoangiogenesis, reduces the expression of adhesion molecules, and activates TNF-α (induced TNF-α-activation inhibits apoptosis of endotheliocytes) .We have shown that as atherosclerosis progresses, the expression and thus the concentration of adiponectin decreases significantly and becomes minimal with extremely severe atherosclerosis. The results are consistent with data on the role of adiponectin in the progression of atherosclerotic lesions of the CA .ADIPOQ and the synthesis of adiponectin under the influence of increased pro-inflammatory IL-6 in heart fat depots. It is known that IL-6 is able to suppress the expression of ADIPOQ, not only in the SAT adipocytes, but also in the EAT and PVAT, without affecting the oligomerization of adiponectin. This hypothesis is supported by the fact that, in patients with CAD, the expression of the IL-6 gene in the EAT is higher than in the SAT [There is evidence of an inverse correlation of adiponectin levels with the progression of CA calcification. In addition, a mutation of the adiponectin gene was associated with its deficiency and with the development and progression of CAD . Logisti the SAT .IL-6 gene in fat depots of the heart increased with an increase in the degree of lesion of the CА. In addition, an increase in the level of IL-6 mRNA in the EАT and PVАT was a predictor of multivascular damage in CAD. Compared with the SAT, the expression of the IL-6 gene in extremely severe atherosclerosis was increased by 1.7 times in the PVAT and by 2.5 times in the EAT. These findings are consistent with those of Chen K.H. et al. regarding the high concentrations of IL-6 in the EAT of patients with CAD compared with people without significant coronary stenosis, according to preoperative CAG, who underwent open heart surgery, including valve replacement, correction of ventricular, and atrial septal defects [Indeed, in our study, the expression of the  defects .IL-6 gene in adipocytes is important in the implementation of its pro-inflammatory properties at the systemic level. The expression of IL-6 is characteristic of mature adipocytes, in contrast to their undifferentiated progenitor cells. The secretion of IL-6 in adipocytes is activated by β-adrenergic activation and is moderately reduced by glucocorticoids, while IL-6 itself stimulates lipolysis. The concentration of IL-6 in the АT is hundreds of times higher than in plasma, which suggests its important auto- and paracrine regulatory functions [Previous studies have suggested that an increase in the level of IL-6 in the blood is more adequate than an increase in the concentration of C-reactive protein, and that it reflects the risk of multiple atherosclerotic lesions of the CA . Our datunctions .IL-6 expression in adipocytes and its relationship with the degree of atherosclerotic lesion of the CA can be interpreted as a negative factor. IL-6 expression was found in the areas of the vascular bed most susceptible to atherosclerotic damage including the CA, cerebral vessels, and peripheral arteries.The increase in The negative effect of IL-6 is manifested by a hypertrophic effect on cardiomyocytes. Hyperproduction of IL-6 is associated with angiotensin II, which, in turn, is able to stimulate the synthesis of IL-6 and is actively involved in the regulation of vascular inflammation, and the development and progression of atherosclerotic vascular damage. In addition, the protective effect of IL-6 on cardiomyocytes, which is manifested by an antiapototic effect, is also known . IL-6 peAccording to the literature, IL-6 secretion is stimulated by leptin . The resThe data obtained are consistent with the results of other studies that demonstrated an increase in the level of leptin mRNA in the EAT in patients with multivascular atherosclerotic lesions compared with patients with 1–2 CA lesions and those without CAD. Therefore, in patients with critical CAD in the EAT, significantly higher expression of leptin and IL-6 was observed than in SAT . Zhang TLEP expression was increased in the PVAT surrounding the aortic root and the CA compared with the surrounding internal mammary artery, regardless of serum leptin levels. Additionally, the PVAT around the CA was characterized by more pronounced angiogenesis and inflammation, and a greater degree of fibrosis and hypoxia, which in turn enhances the transcription of the LEP gene and results in a significant increase in its mRNA levels [There is a scarcity of literature on the role of leptin in the PVAT. For example, Drosos I. et al. studied the expression of leptin in the PVAT surrounding the CA, in comparison with that surrounding the internal thoracic artery resistant to atherosclerosis . The stuA levels . AccordiLEP in the PVAT was observed much later and in patients with an extremely severe degree of CA atherosclerosis.It should be noted that with an increase in the degree of atherosclerosis, considering the division of patients according to the severity of the CA lesion according to the SYNTAX Score, the highest gene expression and leptin concentration were observed in the severe CA lesions, compared to those with a moderate and extremely severe degree of CA lesion. The maximum expression was found in the EAT in individuals with severe CA lesions. The maximum expression of the in vivo, forming a positive feedback loop. The feedback loop provides the autocrine/paracrine effects of leptin, significantly increasing the risk of CAD and multivascular lesions of the CA. A study regarding the prevention of coronary diseases in Scotland (WOSCOPS) showed a moderate increase in a leptin associated risk of developing CAD [In addition to the pleiotropic effects that regulate metabolic, immune, and endocrine functions, leptin is undoubtedly involved in the pathogenesis of atherosclerosis, which is confirmed in both experimental and clinical studies . Hyperleping CAD .LEP in atherosclerotic plaques of the carotid arteries in patients with clinical symptoms suggest that locally produced leptin contributes to pro-atherogenic and remodeling processes leading to destabilization of atherosclerotic plaques [The role of leptin in atherosclerosis was confirmed in an experiment on ob/ob mice with the absence of the atherosclerosis-resistant leptin gene, despite obesity and diabetes. The introduction of leptin led to atherosclerotic changes . Availab plaques . Our resIn general, an increase in leptin in the AT localized in the epicardium and CAs is considered as an unfavorable factor associated with the progression of atherosclerosis. It is interesting to note that cardiomyocytes are capable of synthesizing leptin themselves and have leptin resistance, which is considered as a protective mechanism against the negative effects of this adipokine. Moreover, leptin can reduce myocardial contractility, which implies another possible relationship between the secretion of epicardial leptin and heart function .There were limitations to our study. First, it was a single-center retrospective study. Second, our sample size was small and there was no intermediate sensitivity analysis.Thus, the results of the study indicate that an adipocytokine imbalance of the AT depends on its location. Therefore, adipocytes of the EAT in patients with CAD are characterized by a pronounced decrease in adiponectin mRNA against the background of increased leptin and IL-6. This feature of the EAT can have a negative effect on both adipocytes and cardiomyocytes, which possibly contributes to the aggravation of atherosclerotic processes and related complications.


The Z-phase precipitates were observed inside the grains, whereas M23C6 carbides - at the boundaries where they formed the so-called continuous grid. The service of the test steel contributed to the growth of the strength properties, determined both at room and elevated temperature , compared to the as-received condition. Moreover, the creep properties of HR3C steel after service were higher than those of the material in the as-received condition. The increase in the strength properties and creep resistance was connected with the growth of strengthening of the test steel by the precipitation of Z-phase and M23C6 carbides.The physical metallurgical tests were performed on the test samples made of HR3C steel, taken from a section of a pipeline in the as-received condition and after approximately 26,000 h of service at 550 °C. In the as-received condition, the test material had austenitic microstructure with numerous large primary Z-phase precipitates inside the grains. The service of the test steel mainly contributed to the precipitation processes inside the grains and at the grain boundaries. After service, the following precipitates were identified in the microstructure of the test steel: Z-phase (NbCrN) and M The HR3C steel belongs to a modern group of creep-resistant austenitic steels. This steel was developed as a result of modification of the chemical composition of steel 310 by adding the niobium and nitrogen microadditions and by optimizing the nickel content, which resulted in the growth of high-temperature creep strength and creep resistance while maintaining very high heat resistance. High creep resistance and very good resistance to high-temperature corrosion and oxidation in steam make the HR3C steel the recommended material for the elements of supercritical power units, such as, but not limited to, boiler superheaters working at 650–660 °C .23C6 carbides—precipitated at the grain boundaries, as well as the coarse-grained structure of the steel. Quick loss of ductility of HR3C steel indicates that the recommendation of the steel as the material for the boiler superheater pipes requires a certain amount of providence [The laboratory tests of HR3C steel made so far confirmed the assumed high corrosion resistance, but at the same time showed its susceptibility to very fast decrease in impact strength, with the cracking mechanism changed from ductile to brittle-intercrystalline ,5,6,7. Tovidence ,6,7. HowThe tests were carried out on 25Cr – 20Ni – Nb – N (HR3C) creep-resistant austenitic steel. The tests samples were taken from a section of the steam superheater of 45 mm by 5.7 mm. The tests were carried out on the material in the as-received condition and after approximately 26,000 h service at 550 °C. The chemical composition of the test steel was determined using the SpectroLab spark spectrometer and are presented in o = 10 mm—the testing machine Zwick/Roell Z250, and the accelerated creep tests at the test stress of 100 MPa and temperatures of: 700, 720, 740, 760, and 780 °C. The detailed description of the accelerated creep test methodology is presented elsewhere, inter alia in [The microscopic tests were performed on metallographic specimens etched with the Mi19Fe reagent, using the scanning electron microscope Jeol 6610LV (SEM) compatible with the chemical composition analyser X-Max Oxford Instruments (EDS). The metallographic specimens were taken perpendicularly to the axis of the pipe section. The analysis of precipitates was performed with the transmission electron microscope TITAN 80–300 using the selected area electron diffraction with thin foils. The 3 mm discs with thickness of 100–120 μm were electrolytically thinned to perforation using a solution of 20% perchloric acid in ethanol at −30 °C and the applied voltage of 20 V. The scope of the tests of mechanical properties included: Static tensile tests at room temperature and elevated temperature  using flat test pieces with the original gauge width of bIn the as-received condition, the HR3C steel was characterised by a coarse-grained austenitic microstructure with irregular shape and large primary precipitates a,b. The These particles were identified as undissolved primary Z-phase. The typical morphology of the primary Z-phase is showed in The microstructure of HR3C steel after service is presented in 23C6 carbides (23C6 carbides at the grain boundaries. The M23C6 carbide precipitation process in austenitic steels is related to the reduction of carbon solubility with temperature [23C6 carbides is a process of redistribution and reduction of the strain energy [23C6 carbides precipitated at the grain boundaries in the austenitic steel can be observed as early as after around 1-h creeping at 600 °C [23C6 particles precipitated at the grain boundaries increase the creep resistance of austenitic steels by impeding the grain boundary sliding [23C6 carbides could provide good creep resistance due to pinning effects of grain boundaries. The positive influence of this interaction depends on the stability of the particles precipitated at the boundaries and disappears with the growth of the particles.At the grain boundaries, these precipitates were identified as Cr-rich Mcarbides , whereascarbides . In the perature . Moreovet 600 °C ,16. The  sliding ,10. Prat sliding  found th23C6 carbides are characterised by low thermodynamic stability [23C6 carbides greatly widened the grain boundaries (23C6 carbides at the grain boundaries is very harmful to the properties of the materials—increase in embrittlement and loss of the strengthening effect of particles [23C6 carbides, Cr-rich particles, at the grain boundaries may lead to the formation of chromium-depleted region near the grain boundaries [However, Mtability ,15,19,20undaries . The coaarticles . The preundaries ,18. Whenundaries  suggests23C6 particles can also gradually precipitate at the incoherent twin boundaries, coherent twin boundaries, and inside the grains. In the test steel after service, these precipitates were not observed at the twin boundaries (23C6 precipitates were also not revealed inside the grains, which probably results from the relatively short time of service of the test steel.Apart from the grain boundaries, the Mundaries c,d. The Inside the grains, the secondary dispersive Z-phase precipitations were observed in the steel . The Z-pIn general, the purpose of the high-temperature solution treatment of the creep-resistant austenitic steels by dissolving the secondary phases was to obtain a single-phase structure. The structure of austenitic steels in the as-received condition a,b provi23C6 carbides and Z-phase (23C6 carbides, according to [23C6 carbide—39 MPa [23C6 carbides, the Z-phase precipitates are characterised by a relatively more dispersive form and higher stability [23C6 carbides on YS at elevated temperature was pointed out by the authors of [23C6 carbides. The strengthening effect associated with the Z-phase particles, and also probably with the M23C6 carbides, prevents the softening of the steel due to depletion of solid solution. The extent of strengthening will depend on the dispersion of these precipitates—the number, size, and shape. Trotter and Baker [The total strength of austenitic steels is governed by different strengthening mechanisms: Mainly precipitation and also solid solution strengthening ,10. The  Z-phase , therefo Z-phase  and the rding to ,24, is re—39 MPa . Comparetability ,27 and [tability . Howeverthors of . At the thors of , which tnd Baker  show thand Baker , one of nd Baker , the relThe rise in test temperature results in the reduction in TS value by almost half compared to the as-received condition . Wang etThe factor deciding about the fitness of the material used, among other things, for the steam pipelines is the resistance to creep. The results of short-term creep tests of the test steel are presented in 23C6 carbides. The dispersive form of the Z-phase particles often precipitates at the dislocations [23C6 precipitates at the grain boundaries probably also have an influence on the increase in the creep rate limiting through the slide on the boundaries of grains. However, at elevated/high temperature, the mobility of dislocations grows and they can bypass the precipitates through climbing and cross slip, which limits the precipitation strengthening by Orowan mechanism. In addition to the precipitation hardening, an important factor that affects the creep properties of austenitic stainless steel is, according to [The creep strength of the elements of power units made of HR3C steel determined in the short-term creep tests, while maintaining the previous parameters, was higher than that of the material in the as-received condition. This effect, similarly, as in the case of the determined strength properties, was related to the occurrence of precipitation strengthening. In case of creep properties of the HR3C steel, it is determined by the dispersion and stability of the dominant precipitates in this alloy, i.e., the Z-phase particles, as well as the Mocations ,11,23,28ocations ,10 ensurrding to , the sol23C6 carbides at the grain boundaries and the dispersive Z-phase precipitates inside the grains was observed. In the test steel, the precipitation processes resulted in the growth of strength properties and creep resistance through the precipitation strengthening mechanism. The effect of this strengthening mechanism depends on the stability and dispersion of the secondary precipitates. Controlling the precipitations and growth of the Z-phase and M23C6 carbides is beneficial to the enhancement of the strength and creep properties. The service of HR3C steel at the temperature lower than the long-term service temperature expected for this grade contributed to changes in the microstructure, reflected mostly in the precipitation processes. In the microstructure, the precipitation processes were observed at the grain boundaries and inside the grains. However, no precipitates at the twin boundaries were revealed. The precipitates at the grain boundaries formed the so-called continuous grid of precipitates. The presence of numerous chromium-rich precipitates in the microstructure of the test steel, the M


In recent years, the role of vitamin D (VD) as a protective factor in cardiovascular disease has been recognized. Thus, there is a need to study the effect of vitamin D supplementation in the control of different cardiovascular risk factors and metabolic syndrome, especially in young populations where few studies have been conducted.Pilot study of a randomized, parallel two-arm, triple-blind clinical controlled trial in 150 adolescents and young adults in the city of Bucaramanga-Colombia. The intervention group will receive 1000 IU of VD and the control group 200 IU of VD daily for 15 weeks. The main outcomes are: serum calcifediol levels (25(OH) D), body mass index and lipid profile; secondary outcomes are complementary to the previous ones . Other variables will be analyzed such as assessment of dietary intake, physical activity, sun exposure, cigarette and tobacco consumption and compliance with VD supplementation.This study is innovative since there is little evidence from clinical trials in adolescents and young adults; similar studies are not known in our context. The results of this study may facilitate the recommendation of oral vitamin D supplementation in the population of interest. In addition, it is a low-cost and easy-to-apply intervention that could contribute to the formulation and implementation of health policies.NCT04377386 It is estimated that more than 42 million children worldwide had overweight or obesity in 2016. Colombia is not alien to this problematic; by 2015, 24.4% of school children and 17.9% of adolescents had excess weight.Specifically, obesity increases constantly in the child population becoming a threat by the risk of developing a number of chronic diseases in adult life, particularly CVD.,12 A prevalence of MS of 9.5% was determined on the baseline (95% CI: 8.0–11.3%) following the criteria of the Adult Treatment Panel III (ATP III) and 8.0% (95% CI: 6.6–9.7%) based on the International Diabetes Federation (IDF). Subsequently, the SIMBA II project was conducted between 2013 and 2017, which established a prevalence of MS of 13.1% and 14.8% according to ATP III and IDF, respectively; evidencing an increase in the prevalence of MS between 3.7% and 6.8% from school age to adolescence, in accordance with each criterion.Given this scenario, in 2006 a group of researchers in Bucaramanga, Colombia, set out to study the risk factors for metabolic syndrome (MS) in a group of children between 6 and 10 years of age and to initiate the SIMBA project .Consequently, research has recently begun on the efficacy of VD supplementation in children. Thus, Rajakumar et al, found that the correction of VD levels in overweight and obese children, by administering vitamin D3 with 1000 or 2000 IU/day versus 600 IU/day, had no statistically significant effect on measures of arterial endothelial function or stiffness, systemic inflammation or lipid profile, however, they were able to evidence a reduction in blood pressure, glucose levels and improvement in insulin sensitivity, suggesting that optimization of the VD status of children can improve their cardiovascular health.Likewise, Marwaha et al, showed that VD supplementation with the three daily doses of vitamin D3  lead to a significant increase on the serum levels of 25 (OH) D in school children with VDD and the secondary hyperparathyroidism decreased from 31.7% to 8.4% after supplementation.A significant aspect to consider in the vitamin D supplementation interventions is that they are low cost, easy to implement and very safe; consequently, if a positive effect is achieved, a problem of great impact and increasing prevalence, such as the metabolic syndrome and cardiovascular risk, would be intervened.2To evaluate the efficacy of oral vitamin D supplementation in the reduction of the body mass index (BMI) and the lipid profile in adolescents and young adults of the SIMBA cohort in Bucaramanga, Colombia.3Design: Two-arm, triple-blind, parallel randomized controlled clinical trial.3.1 Between 2013 and 2017 the SIMBA II project was carried out, which managed to contact and follow up 494 adolescents. Finally, in 2019, 217 participants were re-contacted by telephone. The latter constitute the population eligible for this study protocol  up to 1 month before lab sample taking.Current supplementation with VD (any presentation).3.3The simple size was calculated considering the following parameters: an expected difference in the study outcomes  of 20% between the intervention group and the control group; a power of 90%, an alfa of 5%, an intervention group/control group ratio of 1:1, and a 20% adjustment for losses to follow-up, resulting in a sample of 270 participants (n = 135 intervention and n = 135 control group). The OpenEpi software was used for the calculation. Since this is a pilot study and considering the feasibility, the research team decided on a sample size of 150 participants (n = 75 intervention group and n = 75 control group).3.4The randomization process will take place in 2 stages. An engineer from the data central will conduct the randomization of the list of the 217 potentially eligible participants by means of a computer program with random numbers and it will select 150 individuals to participate in the study. Subsequently, a nurse will make phone calls to schedule appointments and formalize the participation in the study, the signature of the informed consent, and the taking of baseline measures. Once these stages are concluded, the assignment of treatment in real time will be made with the support of a computer program. The procedure will take place by means of a single assignment sequence that determines the assignment code for each participant's treatment. This process allows all participants in the study to be assigned to any of the treatment groups. The intervention group will receive 1000 IU of VD while the control group will receive 200 IU of VD.Supplements will be packaged in individual packages with the total number of doses per participant (105 doses). The coding of the packages will be in charge of the laboratory in charge of providing the supplements, which in turn will send to the designated person at the data center by institutional e-mail, a document with the list of codes and the dose of the supplement.The 1000 IU and 200 IU doses of VD will be provided in white containers and will be identical in terms of physical and organoleptic characteristics, to ensure that both participants and investigators are blinded to the treatment. To maximize adherence to the intervention, participants will be required to cross out daily supplementation on a calendar with the study period, which they will be required to return at the end of the study.The results of the assignment will only be known by the systems engineer at the data center. In other words, this information “will not be visible” to the coordinating nurse, laboratory personnel in charge of processing biological samples, pediatrician, principal investigator of the study, or the epidemiologist in charge of quality control and data analysis. This will ensure the masking of the people in charge of measuring the outcomes, administering the intervention and analyzing the study data.3.5For recruitment, a study nurse in charge of enrollment will contact by phone the 217 successful participants of the third re-contact, explain the objective of the study and inquire about the interest to participate; if there is a positive response, inclusion and exclusion criteria will be verified. A list of eligible participants will be generated from the above process and sent to the person in charge of the randomization process.After the randomization process, the study nurse will receive from the data center the list of the 150 participants selected, who will be invited to participate in the clinical trial. The nurse will call them on the pone for a face-to-face appointment where the details of the study will be informed, doubts will be clarified, and the informed consent form will be signed; a copy of the form will be given to the participant.During that appointment, the collection of demographic and clinical data will take place, as well as a blood simple for further measurement of VD, lipid profile and glycaemia; the anthropometric nutritional, dietary and physical activity assessment will also be carried out. Once the baseline measurements are taken, the assignment to the intervention will be made in real time through software designed for the study.Finally, the supplementation intervention will be explained in detail and the package corresponding to the participant's code will be delivered according to the process of assignment to the group (intervention/control), it will be clarified that the supplementation will last 15 weeks and then the second meeting will be scheduled to carry out again the measures taken at the beginning of the study. At the end, a third meeting will be scheduled for the delivery of results and recommendations.3.6Farma de Colombia and is commercially named as Farma D. Its commercial presentation is soft gelatin capsules.The intervention group will receive 1000 IU of VD and the control group 200 IU of VD daily for 15 weeks. All participants will be given 105 doses of VD. The supplementation will be provided by the laboratory  On the other hand, the 75 participants in the control group will take 1 capsule of VD of 200 IU daily for 15 weeks, since the benefits of VD for the health of people have been demonstrated, this being the minimum recommended dose for children. The above, considering that it is unethical for the control group not to receive any type of supplementation.The 75 participants assigned to the intervention group will take one (1) 1000 IU VD capsule daily for 15 weeks. The daily dose selected is based on the amount required for replenishment over a period of approximately 3 months, and is well below the intake levels associated with toxicity.The participants in both the intervention and the control group must record in a calendar the time of the daily intake of the supplement during the 15 weeks.3.7Follow-up will be done 15 weeks after the start of the study (after the end of the intervention).In addition, all participants will be followed up with a telephone call at weeks 1, 2, 5, 7, and 12. These calls will inquire about any “potential” adverse effects related to the intervention and assess adherence to DV sampling by means of a self-reporting instrument  is 600 IU/day, a value equivalent to a nutritional density of 40 IU/1000 Kcal. In adolescence, plasma levels decrease and needs increase; however, the recommendation is the same as for adults.Normally there is no toxicity by VD since it is a fat-soluble vitamin and the organism excretes it regularly. Thus, the causes of toxicity are not related to the diet or sun exposure, but to the chronic consumption of high doses of VD supplements. This is because the body regulates the amount of vitamin D produced by sun exposure and, and even fortified foods do not have large quantities of this vitamin. On the other hand, the doses that have been documented to lead to toxicity are above 40,000 IU to 50,000 IU per day.,17 This is considered as potentially severe condition whose symptoms are associated to secondary hypercalcemia and are mainly of a gastrointestinal nature  and polydipsia, polyuria, muscular weakness and fatigue, among the most relevant.Although the recommended doses are below 2000 IU, the maximum level of daily consumption which is considered tolerable is 4000 IU for people between the ages of 1 and 18, and 10,000 IU for people over the age of 19.Therefore, the supplementation with an orally administered dose of 1000 IU/day of vitamin D is completely safe for the participants and it does not have adverse effects.3.9Primary outcome: These are biochemical and anthropometric measurements that allow to respond to the purpose of the study. These include:Total BMI. This requires taking the size in meters (m) and weight in kilograms (kg).Lipid profile: Measurements will be made of the serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides.Serum levels of 25(OH) D.Secondary outcomes: These are complementary measurements for the primary outcomes.Waist-hip ratio: determines the intra-abdominal fat levels and is obtained by dividing the waist perimeter by the hip perimeter.Skin folds: These are taken for the indirect estimation of body fat percentage by means of measuring the bicipital, tricipital, abdominal, and subscapular folds.Fasting glycemia.3.10Taking samples, measurements, and data collection will be done by following the operating procedures manual which describes in detail each one of the procedures. Data will be digitally uploaded in real time by means of a digital questionnaire.3.10.1m) to 2 decimal places. From these measurements the BMI will be obtained using the formula: BMI = Weight (kg) / size (m)2.The procedure will be conducted by a trained nurse. Participants must be fasting, wearing minimum clothes, without shoes, belts or other accessories that may alter the measurements. The measure of body weight will be in kilograms (kg) to one decimal place, and the size in meters  with features that allow an accurate reading. Weight will be measured using a SECA 813 digital scale which has a steel frame as reinforcement, fit for people weighing up to 200 kg (440 lb); the measurement is performed twice to ensure a more reliable measurement .3.10.2Hospital Internacional de Colombia, which is certified and has a high-quality registry.After a 10 to 12 hour fast, a laboratory assistant will draw a sample of peripheral venous blood through a puncture of the basilic cephalic vein or its medians and extract approximately 15 cc to 20 cc of blood. The processing and analysis of the samples will be done respectively through enzymatic technique, selective liquid detergent, selective detergent accelerator and Glycerol Phosphate Oxidase in the clinical laboratory of 3.10.325-hydroxyvitamin D are measured from the same blood samples drawn for lipid profile and quantified in serum by chemiluminescent microparticle immunoassay (CMIA).3.10.4Measurements will be made by the trained nurse with an inelastic tape measure in centimeters (cm) to one decimal place, directly on the skin of the abdomen and bare hip or with soft garments that do not make volume or put pressure on the tissues. The person should have both of his or her hemispheres aligned and preferably be barefoot or wear flat shoes.The circumference of the waist shall be measured at the midpoint between the edge of the lower sack (10th rib) and the upper edge of the iliac crest, without adjusting or stopping touching the skin. With the person relaxed, 2 measurements shall be taken without removing the tape, just checking the position. If the difference between the two measurements is less than or equal to 1 cm, the average of the 2 will be taken and if the difference is greater, a third measurement will be taken and the intermediate value between the three measurements will be recorded.For the measurement of the hip, the knees and the heels must be together; the most prominent part of the hip on both sides shall be located and the tape measure shall be passed following the same recommendations as for the circumference of the waist.3.10.5These measurements will be taken by a trained nurse using a Harpender skinfold caliper. The skinfold will be taken with the index and thumb, and the caliper will be placed 1 cm inwards the fold. It will be applied for 3 seconds before taking the reading while the needle stops oscillating.Bicipital fold: It shall be taken parallel to the longitudinal axis of the arm above the acromial-radial midline, on the anterior face of the arm above the mid-portion of the bicep.Tricipital fold: It shall be taken parallel to the longitudinal axis of the arm on the acromial-radial midline, in the posterior region of the arm on the mid-portion of the triceps.Abdominal fold: it shall be taken vertically, parallel to the longitudinal axis of the body, at the level of the navel, approximately five centimeters from the navel on the right side of the rectus abdominisSubscapular fold: the lower angle of the scapula shall be felt to determine the most prominent lower point; the fold shall be taken two centimeters from the lower angle of the scapula, in an oblique direction, downwards and outwards, forming an angle of 45 degrees with the horizontal axis.The percentage body fat (PBF) is taken for the indirect estimation by means of measuring the bicipital, tricipital, abdominal, and subscapular folds. Percentage of body fat (%BF) calculated with the Siri equation for four skin folds (SF), like so: % BF SIRI = ((4.95/ D) − 4.5) × 100. Body density (D) is obtained using the linear regression equation proposed by Durnin and Womersley (C and D). D = C − M × log10 ∑ 4SF .3.10.6After a 10 to 12 hour fast, blood glucose levels are measured in serum from the same blood samples drawn for lipid profile, using the hexokinase/G-6-PDH technique.3.11An analysis will be made by intention to treat. The description of the categorical variables will be made by means of absolute and relative values. Quantitative variables that present a normal distribution in Shapiro Wilk's test will be reported as mean and standard deviation, otherwise the median and interquartile range will be presented. The comparison of the basal characteristics of the study groups (intervention and control) will be done using the ratio comparison test (Chi-square or Fischer's exact test) and the Student's t-test or Mann-Whitney's U-test.P value is less than .05.Quantitative outcome variables will be contrasted through paired t-tests or Wilcoxon tests for quantitative variables, methods of longitudinal data analysis will also be explored and for categorical ones the Mc Nemar test will be used. Statistical significance will be considered for all hypothesis tests when the 3.12The research will be carried out following the principles established in the Good Clinical Practice in Clinical Trials GPC/ICH. It is considered a minimum risk study according to resolution 008430 of October 4, 1993 of the Colombian Ministry of Health, since it includes the administration of a commonly used vitamin supplement with a wide therapeutic margin and for its administration the indications, doses and routes of administration established by the Institute for Drug and Food Surveillance  are considered. The vitamin supplement is supplied by the laboratory Farma de Colombia, commercially known as Farma D, whose presentation is in soft gelatin capsules and with registration number 2017 M-0012231-R1.The processing of personal and clinical data and biological samples will be handled according to the Habeas Data Act (Act 1266 of 2008) of the government of Colombia.Fundacion Cardiovascular de Colombia (FCV) according to minute N°133 of May 2018 and has the approval of the Research Ethics Committee (IEC) of the FCV according to minute N°480 of July 16, 2019.The study was reviewed and endorsed by the Technical Scientific Committee (CTC) of The study nurse will explain the objectives, importance, risks, benefits of the research and the confidentiality of the data. Written informed consent will be given to study participants and for participants under the age of 18 we will obtain from a parent or guardian.4,3 For consideration, vitamin D supplementation is being widely studied to determine its effect on the control of cardiovascular risk factors and metabolic syndrome, including obesity, dyslipidemia, and impaired blood glucose.The role of vitamin D as a protector against cardiovascular disease is widely recognized.,15 Notwithstanding this, more clinical trials are required to confirm these findings.Studies on the effect of supplementation in adolescents and young adults are scarce; however, the favorable effect of supplementation in the serum levels of 25 (OH) D in school-age children with VDD and the reduction in blood pressure, the concentration of fasting glucose, and improvements in sensitivity to insulin in children with overweight and obesity is widely known.,15 Consequently, if this trial provides positive results, it will be possible to recommend oral vitamin D supplementation for the reduction of BMI and lipid profile in the studied population. In addition, it is a low-cost and easy-to-apply intervention that could contribute to the formulation and implementation of health policies.This research is innovative considering that there are few studies on adolescent and young adult populations and that these have not been carried out in Latin America.NCS, EMG, MF, EG, and DCQ conceived the study and requested the funding; LZR, SLR, DPS, and DCQ made adjustments and refined the protocol; SLR, LZR, and DPS drafted the paper; NCS, EMG, EG, and MF reviewed the manuscript. All authors read and approved the manuscript's final draft.


Bioscience Reports at the request of the authors following receipt of a notification from a reader, alerting the Journal to repeated features in Figures 3A, 3B, 9A and 10A.This article is being retracted from The authors wish to retract the article. The Editor-in-Chief and Editorial Board agree with the retraction


Scroll compressors are popularly applied in air-conditioning systems. The conventional fabrication process causes gas and shrinkage porosity in the scroll. In this paper, the electromagnetic stirring (EMS)-based semisolid multicavity squeeze casting (SMSC) process is proposed for effectively manufacturing wrought aluminum alloy scrolls. Insulation temperature, squeeze pressure, and the treatment of the micromorphology and mechanical properties of the scroll were investigated experimentally. It was found that reducing the insulation temperature can decrease the grain size, increase the shape factor, and improve mechanical properties. The minimum grain size was found as 111 ± 3 μm at the insulation temperature of 595 °C. The maximum tensile strength, yield strength, and hardness were observed as 386 ± 8 MPa, 228 ± 5 MPa, and 117 ± 5 HV, respectively, at the squeeze pressure of 100 MPa. The tensile strength and hardness of the scroll could be improved, and the elongation was reduced by the T6 heat treatment. The optimal process parameters are recommended at an insulation temperature in the range of 595–600 °C and a squeeze pressure of 100 MPa. Under the optimal process parameters, scroll casting was completely filled, and there was no obvious shrinkage defect observed inside. Its microstructure is composed of fine and spherical grains. Scroll compressors are popularly applied in air-conditioning systems because of numerous benefits, including high volumetric efficiency, low noise, low leakage, and low vibrations ,2. Due tGas and shrinkage porosity can be effectively eliminated by squeeze casting technology, which has been recommended to manufacture the complex component from aluminum alloys and aluminum metal–matrix composites ,13,14. T97Zn1Y2 alloy. It was found that the structure of LPSO and α-Mg grains in the studied alloy can be dramatically improved by the SSSC process. Wang et al. [In recent decades, research on the SSSC process has drawn the attention of scholars. Lü et al.  investigg et al.  proposedg et al.  studied g et al.  studied The preparation of a semisolid billet is an indispensable step for the SSSC process. Electromagnetic stirring (EMS) is a contactless technique commonly applied to produce forced convection and adjust fluid flow during the solidification of the metal melt, which has become one of the main methods for the production of semisolid slurry or billets ,26. EMS Due to the drawbacks of the conventional process method and the advantages of the SSSC and EMS techniques, the EMS-based semisolid multicavity squeeze casting (SMSC) process is proposed in this paper for manufacturing aluminum alloy scrolls. This work aims to effectively improve the production efficiency, microstructure, and mechanical properties of the scroll. Firstly, the near-final forming of the scroll can be realized via the processed process, significantly improving the material utilization rate. Secondly, the concept of one mold for four castings can be verified, visibly improving the production efficiency. Thirdly, the semisolid billet with fine and spherical grains can be prepared by the EMS process, improving the mechanical properties of the scroll. The effects of insulation temperature, squeeze pressure, and the heat treatment of the micromorphology and the mechanical properties of the scroll were investigated experimentally, based on which optimal process parameters were obtained for the manufacturing of scrolls by the EMS-based SMSC process.The commercial wrought aluminum alloy 2A50  was used as the experimental material in this work. Its chemical components are summarized in The EMS-based SMSC process of one die with four aluminum alloy scrolls proposed in this paper mainly includes four stages, as shown in In this paper, 8 multicavity squeeze experiments were performed to investigate the effects of the operating parameters on the microstructure evolution of the scrolls. As shown in A schematic diagram of the whole semisolid multicavity squeeze process for fabricating four scrolls under one mold is illustrated in D is the average equivalent diameter of the crystal grains, A is the area of the crystal grain, P is the circumference of the crystal grain, N is the number of the crystal grains, and F is the average shape factor of the crystal grains. Considering the symmetry of the proposed semisolid multicavity squeeze method, one of the four scrolls was sampled for the investigation in this work. Three samples from the scrolls processed at different operating parameters were collected to study the microstructures. These samples were located at the inner gate (Position A1), the central region of the scroll (Position A2), and the bottom region of the scroll (Position A3), as shown in The microstructures of the sample collected from Position A2 formed at liquid temperature (645 °C), near-liquidus temperature (615 °C), and semisolid temperatures (600 and 595 °C) are shown in The effects of the insulation temperature in Stage II on the average grain size and shape factor are summarized in d is the average grain size and The mechanical properties investigated in this study are tensile strength, yield strength, elongation, and hardness. The mechanical properties of the scroll after the T6 heat treatment at different insulation temperatures in Stage II are presented in According to the analysis in The effects of the squeeze pressure on the average grain size and shape factor of the scroll are presented in P is the squeeze pressure, MPa.In the process of semisolid squeeze casting, the liquidus temperature of the metal slightly increases, and the cooling for the slurry is improved with the increase in the squeeze pressure, which consequently influences the microstructure of the scroll. The influence of squeeze pressure on the liquidus line of the alloy can be illustrated by the Clausius–Clapeyron equation, as shown in Equation (4) .(4)ΔTfΔThe results of The mechanical properties of the scroll samples under different squeeze pressures after the T6 heat treatment are shown in Based on the experimental results presented in A comparison of the mechanical properties between the scrolls before and after the T6 heat treatment is shown in 2, have extremely poor plasticity, which is prone to stress concentration. This stress concentration worked as the crack source, which caused the fracture of the strengthening phase on the matrix and the fusion of the microcrack. Therefore, the toughness and elongation decreased after the T6 treatment.However, the elongation of the scroll decreased after the T6 heat treatment, which reduced from 12.3 ± 0.4% to 7.6 ± 0.5%. The partial dispersion-strengthening phase generated during the T6 heat treatment split the continuity of the microstructure. During the stretching process, although the α-Al matrix has high plasticity and undergoes the macroscopic deformation with the sample, the hard and brittle particles, such as CuAlThe macro morphology of the scroll obtained under the optimal process parameters  is shown in It can be found in (1)The microstructures of the scroll at the liquid, near-liquid, and semisolid insulation temperature are composed of coarse dendrites, rose-like crystal grains, and near-spherical crystal grains, respectively. Reducing the insulation temperature can significantly reduce the grain size, improve the grain morphology, and enhance the mechanical properties.(2)Reducing the insulation temperature to the semisolid range can decrease the grain size, increase the shape factor, and improve the mechanical properties. The minimum grain size was found as 111 ± 3 μm at the insulation temperature of 595 °C.(3)Increasing the squeeze pressure is beneficial to reduce the microscopic pores of the microstructure, increase the compactness of the crystal grains, and improve the mechanical properties. However, the improvement in the mechanical properties is not obvious when the squeeze pressure exceeds 100 MPa. The maximum tensile strength, yield strength, and hardness were observed as 386 ± 8 MPa, 228 ± 5 MPa, and 117 ± 5 HV, respectively, at the squeeze pressure of 100 MPa.(4)Although the tensile strength and hardness of the scroll can be improved by the T6 heat treatment, the elongation was reduced after the T6 heat treatment. The morphology of the grains is relatively round, and no obvious deformation was observed at the bottom part of the scroll casting due to the attenuation of the squeeze pressure.(5)Based on the experimental results, the optimal process parameters are recommended as an insulation temperature of 595–600 °C and a squeeze pressure of 100 MPa.(6)Under the optimal process parameters, the scroll casting is completely filled, and there is no obvious shrinkage defect observed inside. Its microstructure is composed of fine and spherical grains. Some of the grains in the central region of the scroll are deformed by contact showing obvious flow direction. A large number of grains at the top region of the scroll casting are elongated or flattened and formed a cluster of crystal grains with strong orientation under the direct action of the squeeze pressure.This paper proposes the EMS-based SMSC process for manufacturing aluminum alloy scrolls. The insulation temperature, squeeze pressure, and heat treatment of the micromorphology and the mechanical properties of the scroll are investigated experimentally. The main conclusions can be drawn as follows:


In topic-related literature pertaining to the treatment of water, there is a lack of information on the influence of iron ions in highly basic polyaluminum chlorides on the efficiency of purifying water with increased contents of organic substance. The aim of this work was to determine the changes in the content of organic substances as well as iron compounds in water intended for human consumption following unit treatment processes with particular attention paid to the coagulation process. As coagulants, polyaluminium chloride PAXXL10 with an alkalinity of 70%, as well as polyaluminium chloride PAXXL1911 with an alkalinity of 85% the composition of which also contained iron, were tested. The analysis of the obtained results showed that iron compounds and organic substances were removed to the greatest extent by the coagulation process, which also had a significant influence on the final efficiency of water treatment. The effectiveness of water treatment was determined by the type of tested polyaluminum chloride, which influenced the formation of iron-organic complexes. The reason behind the formation of colored iron-organic complexes during coagulation using PAXXL1911 coagulant was the high pH (approx. 8), at which the functional groups of organic substances, due to their dissociation, are more reactive in relation to iron, and possibly the fact of introducing additional iron ions along with the coagulant. The necessity of removing organic substances from water is essential, ideally in the first processes of its treatment, seeing as how organic substances are the precursors of oxidation and disinfection by-products, and in the case of groundwater—also make it difficult to remove iron compounds, forming colored and stable iron-organic complexes with iron (II) and iron (III) ,2,3,4.Depending on the type and content of organic substances, as well as the pH and the oxidation-reduction potential, iron compounds, along with organic ligands, may form iron-organic complexes characterized by various degrees of solubility, which are difficult to remove during the conventional technological groundwater treatment system ,6,7.+ ions when compared to metals, which occurs in an acidic environment /[Al3+]).In solutions of polyaluminium chlorides, there are more polymerized forms with a high positive charge than among the products of the hydrolysis of coagulants that had not been subjected to pre-hydrolysis. The amount of monomers and polymers in polyaluminium chlorides varies and depends mainly on the value of the alkalinity coefficient of coagulants (r = [OH13O4(OH)24]7+ called the “Al13” polymer, whereas for r > 2.1, the share of Al13 polymers begins to decrease, since they are precipitated in aluminum hydroxide. The maximum share of Al13 is indicated for an alkalinity of approx. 70 to 80%, which corresponds to an r value of 2.1 /[Al3+]). It was also assumed that the increase in pH during the coagulation process with highly-basic polyaluminium chlorides and the presence of iron in the composition of coagulant, as well as in the raw water, may result in the formation of iron–organic complexes. The same coagulants were also tested on a technical scale. The aim of the studies conducted on the technical scale was to determine whether the type of coagulant that may contribute to the formation of iron–organic complexes during the coagulation process has an impact on the final effectiveness of water treatment.The research was conducted on a laboratory and technical scale. During the research of studies carried out on a laboratory scale, the efficiency of the coagulation process was carried out with the use of the jar test. As a coagulant, the commercial average and highly alkaline polyaluminium chlorides were tested because the amount of monomers and polymers in polyaluminium chlorides solutions varies and depends mainly on the value of the alkalinity coefficient of coagulants . Coagulation was carried out in water samples of 1 L through 1 min fast mixing at a speed of 250 rpm and 25 min flocculation with an intensity of mixing of 30 rpm. As a coagulant, the commercial pre-hydrolyzed polyaluminium chloride PAXXL10 with an alkalinity of 70% and alkalinity coefficient of r = 2.10, as well as PAXXL1911 polyaluminium chloride with an alkalinity of 85% and alkalinity coefficient of r = 2.55, which, in its composition, also contained iron in the amount of approx. 0.7%. were tested . Polyalub), amounting to as much as 40%, than the PAXXL10 coagulant, in which the content of polymer forms of aluminum was 29%.The characteristics of the tested coagulants are presented in 3/h. The scheme of the water treatment process train applied in the “Zawada” Zielona Góra water treatment plant is presented in During research conducted on a technical scale, water samples for carrying out physical and chemical analyses were collected after subsequent stages of purifying the water—a mixture of groundwater and surface water. Sample collection was carried out weekly in the summer for a period of two months. The efficiency of microfiltration was determined in relation to surface water . The water treatment process is carried out in two of the same process lines. The maximum output of each production process is 750 m3/h each. Water, following aeration, flows into two reservoirs with a capacity of approx. 250 m3 each.The aeration process of groundwater takes place in four cascades, with forced airflow with a maximum output of 220 mSurface water, after being subjected to microfiltration using microscreen drum filters with 10 µm pores and a coagulation process, was also channeled to these chambers, as well as the returned post-coagulation sludge.High-speed mixers are found in fast mixing chambers, which mix both the waters and the coagulant. The post-coagulation sludge is partially returned to the coagulation process with the aim of improving the conditions in which floccules form and increasing the effectiveness of the process. Water mixed with the coagulant flows into two serially connected slow-mix chambers. Stirrers with diagonally constructed paddles are found in the slow-mix chambers, giving the water in the chambers horizontal and vertical rotational movement. The speed of mixing is regulated and amounts to a maximum of 20 rotations/min. The sediments which are formed in the contact chambers and mixing chambers are carried away gravitationally to process wastewater collectors. The sludge is discharged periodically according to need. Water with formed post-coagulation floccules flows into the chambers of the sedimentation tanks. In the first part of the sedimentation tanks, the clarification process takes place as it does in the horizontal sedimentation chambers, whereas in the second part, lamella separators are integrated with the system of receiving troughs. The sediment which collects at the bottom of the chamber is gathered into sludge hoppers with the use of mechanical sweepers.Al/L.During technological studies carried out on a technical scale, the following were tested as coagulants: PAXXL10 with an alkalinity of 70% as well as PAXXL1911 polyaluminium chloride with an alkalinity of 85% which, in its composition, also contained iron . The dos3·MgO). Disinfectant, which is a chlorine dioxide solution, is added to the purified water flowing into the tank. In The subsequent stage in the water purification process is filtration using open rapid filters through a sand filter bed covered by manganese (IV) and iron (III) oxides i.e., the so-called catalytic-oxidative filtration bed. Following the filtration process on the catalytic-oxidative filter bed, water is additionally purified during the second stage of filtration on dolomite filters, where the filter bed is activated dolomite (CaCO254) and at 272 nm (UV272) was measured by a UV-VIS spectrophotometer Agilent Cary 60 using a quartz cell with 1 cm path length after filtration through a 0.45 µm membrane. DOC and UV254 are used in the calculation of the specific UV absorbance (SUVA254).−1) and DOC is dissolved organic carbon (gC/m3) [The physical-chemical composition of both the raw water as well as treated water was determined according to the International Standard methods. The organic substances in all samples were determined by measuring total (TOC) and dissolved organic carbon (DOC) concentration, color (absorbance of 410 and 320 nm wavelength), and absorbance at 254 and 272 nm. TOC (DOC) concentration is the most reliable method for determining the total amount of NOM, UV absorption at 254 nm monitors the amount of NOM fractions containing aromatic structures in their molecules ,32. The  (gC/m3) .3+ reacts with Ferron reagent to form an Al-Ferron complex at pH = 5, λ = 370 nm. An Agilent Cary 60  spectrophotometer was used to measure the Al-Ferron kinetics. Based on the kinetic difference of reactions between Ferron reagent (8-hydroxy-7-iodo-5-quinoline sulfonic acid) with different hydrolyzed species, hydrolyzed Al species can be divided into three types: monomeric Al species (Ala) (instantaneous reaction: 0 to 1 min), medium polymerized Al species (Alb) (reaction within 120 min), and species of colloidal (Alc) (no reaction in 120 min). The results are shown in True color was indicated in accordance with ISO 7887-Method C , using aIron compounds, as well as organic substances, but also color and turbidity, were removed at the highest levels in the coagulation process, which also had a significant effect on the final effectiveness of water purification. The efficiency of iron removal during the coagulation process was 66.7 and 88.4%, and of organic substances: 28.0 and 37.0% (TOC), 27.8 and 36.1% (DOC).b = 40%) than PAXXL10 (Alb = 29%). The reason behind the lower effectiveness of water purification in the coagulation process upon applying PAXXL1911 was the formation of iron-organic connections, most likely in the form of protective colloids.The effectiveness of purifying water in the coagulation process was determined by the type of tested polyaluminium chloride. Polyaluminium chloride PAXXL1911, which is characterized by a higher alkalinity and additionally contains iron ions in its composition, caused a significantly lower effectiveness of removing iron compounds (66.7%) and organic substances , and also decreasing the color , and turbidity (77.0%) as well as the zeta potential (23.0%), despite the fact that it contained higher amounts of polymer forms of aluminum , as well as decreasing color  turbidity (5.0 and 9.6%) and organic substances  was also increased, though manganese compounds were removed to the largest extent (70.82 and 74.65%).254; 9.08 and 9.27%-UV272), as well as lowering the color measured at a wavelength of 340 nm (11.5 and 15.4%), at which they absorb mainly organic substances containing chromophoric groups. The processes of removing organic substances from water as a result of filtration through a dolomite bed, and especially removing organic substances containing aromatic rings, is connected with the ability of these substances to create complexes with calcium and magnesium ions.The second level of filtration on a dolomite bed mainly increased the effectiveness of removing organic substances containing aromatic rings . The analyses of the obtained results also showed that only after the disinfection process in water purified with highly-alkaline polyaluminium chloride (Z = 85%) containing iron compounds in its composition, water quality parameters of water intended for human consumption were not met due to iron (0.22 mgFe/L), turbidity (1.10 NTU) and total organic carbon (5.145 mgC/L), while the calculated value of the SUVA254 indicator was over 2, thus not fulfilling the production criterion for safe water, as a result of the presence of precursors of oxidation and disinfection by-products. Therefore, the use of highly alkaline polyaluminum chlorides, which additionally contain iron ions in their composition, should not be recommended for the treatment of water containing excessively high concentrations of organic substances, including humic substances, due to the possibility of creating colored iron-organic connections difficult to remove in the entire technological system.The disinfection process using chlorine dioxide caused the partial oxidation of organic substances containing aromatic rings (4.20 and 5.80%-UVThe analysis of the test results leads to the following conclusions:


The first design stage uses the steady state simulation model and determines equipment sizes for different constant-value solar radiation intensities with the objective of minimizing total annual cost. The second design stage is implemented on the SDMD systems with process control to automatically adjust the operating flow rates using the dynamic simulation model. Operated with the yearly solar radiation intensity of Taiwan, the unit production costs (UPCs) of the optimal SDMD systems using AGMD, DCMD, and VMD are $2.71, 5.38, and 10.41 per m3 of water produced, respectively. When the membrane unit cost is decreased from $90/m2 to $36/m2, the UPC of the optimal solar-driven AGMD system can be reduced from $2.71/m3 to $2.04/m3.Solar-driven membrane distillation (SDMD) for desalination is a feasible method to solve water and energy resource issues. The design and operation of SDMD is different from continuous and steady state processes, such as common chemical plants, due to the intermittent and unpredictive characteristics of solar radiation. Employing the steady state and dynamic simulation models developed on the platform of Aspen Custom Modeler Climate change due to greenhouse effects has caused the re-distribution of worldwide water resources ,2,3. TheThe four basic configurations of membrane distillation are direct contact (DCMD), air gap (AGMD), vacuum (VMD), and sweeping gas membrane distillation (SGMD) . In a co3 and $18/m3, respectively. Recently, an economic optimization of solar powered SGMD desalination system has been reported [3. Miladi et al. [For the solar-driven membrane distillation (SDMD) desalination, Banat and Jwaied  designedreported . The stui et al. ,18 were The dynamic simulation and operation of solar MD desalination system are important due to the time variant nature of solar radiation. Chang et al. ,19 builtAs the SDMD system is powered by the solar radiation, both design and operation of the system must take into account the unpredictive and intermittent feature of solar radiation. This work presents a systematic two-stage design approach for the SDMD system. The design considers actual radiation intensity, utilizes a dynamic simulation model, and includes a control system for continuous operation. In the following sections, the process description and simulation model are presented first, followed by the explanation of the process control, the introduction of the two-stage design procedure, and the results of the design for the solar radiation of Taiwan.This section includes four parts. First, the overall SDMD systems are illustrated. Secondly, the mathematic models of the individual units are explained. The third part presents the validation of the mathematic models of membrane distillation modules using experimental operation conditions and results from literature. The last part gives the simulation results of representative cases for the overall SDMD systems.The major process units of a SDMD system for desalination are the solar collector and the membrane distillation module. The processes employing AGMD, DCMD, and VMD are different and explained in detail in this section.The process flow diagram of the solar-driven AGMD desalination system, which comprises a membrane distillation subsystem and a solar subsystem, is shown in In the solar subsystem, water (Stream 7) enters the solar collector (SC) and absorbs the solar radiation. The hot water leaving SC (Stream 8) is partly sent directed to HX-1 (Stream 9) and partly sent to a thermal storage tank (D-1) (Stream 10) before being withdrawn to HX-1 (Stream 11). The split (T-1) is adjusted by a valve (V-1). The overflow design of D-1 tank allows the operation with the same inlet and outlet flowrates. The initial temperature of D-1 is 50 °C. The temperature of D-1 increases with the increase of the radiation energy provided to the solar collector.The process flow diagram of the solar-driven DCMD desalination system is shown in The process flow diagram of the solar-driven VMD desalination system is shown in For the solar-driven AGMD, DCMD, and VMD systems for desalination, the dynamic mass and heat balance equations for each unit equipment are listed in The solar collector consists of an absorption plate and a working fluid channel. The solar collector utilizes an absorption plate to absorb the solar radiation and uses water as the working fluid. We assume well insulation of the solar collector. Therefore, the working fluid of the solar collector is adiabatic. However, the absorption plate of the solar collector contacts with surrounding, the energy will loss due to convection. The assumptions of the model include : (1) The2-K, respectively. The model consists of the dynamic energy balance equations for the hot fluid and cold fluid.Heat exchangers are of the countercurrent shell and tube type. The model assumptions are: (1) The heat capacity of the working fluid is constant considering the temperature range of operation. (2) The energy loss to the surrounding is negligible. (3) No phase change occurs during operation. The heat capacity of the working fluid and the overall heat transfer coefficient of the heat exchanger are 4180 J/kg-K and 280 W/mThe excess thermal energy during the day time operation is stored in the thermal storage tank D-1 in a. The woThe AGMD module consists of hot and cold seawater flow channels, a membrane layer, an air gap layer, and a metal layer. The DCMD module consists of a hot seawater channel, a cold water flow channels, and a membrane layer. The VMD module consists of a hot seawater flow channel, a membrane layer, and a vacuum layer. The detailed drawing of each module and variable notations are shown in Because of the small holdup volume of the membrane module, steady state models were employed. The model equations for each type of the membrane modules are summarized in The experimental data of AGMD, DCMD, and VMD modules taken from Koschikowski et al.  and Laws® (ACM). For each SDMD system, the specifications and simulation results of a representative case are summarized in For each of the SDMD system, the unit models illustrated above were developed and simultaneously solved using the solvers provided on Aspen Custom ModelerD) in the studied range. The objective is to minimize the total annual cost (TAC). The second stage is to determine the optimal design for the dynamic operation using the yearly solar radiation intensity of Taiwan. For each of the optimal solution determined from the first stage, the second optimization stage starts by the simulation of that design (equipment sizes) under dynamic operation with a control system proposed by this study. The UPCs (unit production costs) of the distillate water for all the designs from the first stage are then compared to determine the design with the minimum UPC. The two-stage procedure for optimal design of the SDMD system is depicted by the flow chart shown in A two-stage optimization approach for the SDMD system is proposed. The first stage determines optimal equipment sizes and flow rates for each of the specified constant-value solar radiation intensities  method provided in ACM was employed. For the second stage, dynamic simulation must be implemented. The details of the two-stage method are explained in this section.SC/WSC) of the solar collector [SC) [MD/WMD) and the flow channel thickness (δMD) of the membrane module [3, 153 m3, and 225 m3, respectively. The ambient temperature (Ta) and feed temperature of the seawater (Tsea) are set at 25 °C. The final design DOFs of the solar-driven AGMD, DCMD, and VMD systems are reduced to 5, 6, and 6, respectively. The common design variables of these SDMD systems are constant-value solar radiation intensities ( D), solar collector area (ASC), membrane area (AMD), seawater flowrate (Fsea) and solar collector circulation flowrate (Fsc). The additional design variables of the DCMD and VMD modules are the MD circulation stream flowrate (FMD) and the vacuum pressure (Pv), respectively.For each SDMD system operated under specified constant-value solar radiation intensity, the first design stage is to determine the equipment sizes and the stream operation conditions. The design degree of freedom (DOF) analysis method  was usedollector  and the tor [SC)  are set e module ,37 are s2. Taking into account the government incentive of $50/m2 for solar energy utilization in Taiwan, the cost of solar collector is adjusted to be $50/m2. The membrane costs of AGMD, DCMD, and VMD modules are set to $90/m2 [The cost functions of the SDMD systems are referred to Banat and Jwaied . Tax rato $90/m2 ,37. The (1)The distillate water production rate during day-time operation is 2000 kg/h.(2)The maximum temperature of the hot water from the solar collector is 95 °C.(3)min) is 10 °C.The minimum approach temperature of the heat exchanger (ΔT(4)The vacuum side pressure of the VMD system is larger than 3 kPa.The objective of the first design stage is to minimize the TAC of the system. The design DOFs of the SDMD system mentioned in D), the optimization problems of the SDMD systems are formulated as:For a given constant-value solar radiation intensities 22) of the hot water entering the heat exchanger (HX-1) is controlled by manipulating the inlet flowrate (F17) of D-1. The purpose of this control loop is to maintain constant water production rate.The temperature (T(2)15) of the solar collector is controlled at 95 °C by manipulating the make-up water flowrate (F13) from D-2. The control loop was used to avoid the working fluid boiling problem.The outlet stream temperature (T(3)19) from D-2 to the thermal storage tank is used to maintain the temperature of the thermal storage tank (T20) below T22. As the temperature control loop of T22 cannot work when T20 approaches T22.The make-up water flow  and integral time (τI) for the PI temperature controllers.The Auto-tuning variation method (ATV) ,40 was etotal), which is obtained by dividing the TAC to the annual production rate of water. The distillate water can be blended with raw water to provide potable water. The dilution ratio is the ratio of the distillate water to the raw water. Here, the dilution ratio of the water production is set at 1:1 [D) and operated with the control structure shown in The objective function in the second design stage is the unit production cost (UPC = TAC/Dt at 1:1 . For eacD) ranged from 355 to 445 W/m2, the optimal equipment sizes and stream flow rates are determined from the first optimization stage. The TAC and the costs of SC, HX, and all other units of the optimal solutions are shown in For constant-value solar radiation intensities  under dynamic control for the three SDMD systems are shown in D are used.The simulation results of UPC and annual water production rate  simulator is used to build and solve for the steady state and dynamic models of the SDMD systems. The simulation results of the membrane distillation models fit well with the literature experimental data. For better operation of the system to cope with the unpredictive and intermittent characteristics of solar radiation, a control structure was designed for the solar subsystem.In this work, the solar-driven membrane distillation (SDMD) systems utilizing AGMD, DCMD, and VMD for desalination are investigated. The Aspen Custom Molder3, $5.38/m3, and $10.41/m3, respectively. Both TAC and UPC of the solar-driven AGMD system are the lowest. The effects of the membrane unit cost on the optimal design and the water production cost are not significant. With a decrease of membrane unit cost from $90/m2 to $36/m2, the UPC of the optimal solar-driven AGMD system reduces from $2.71/m2 to $2.04/m2.Optimal designs of the SDMD systems were determined by the two-stage design approach proposed in this study. The first stage design determines the equipment sizes for constant-value solar radiation intensity using the steady state model. The second stage analyzes the operation with the control structure for the yearly solar radiation intensity of Taiwan using the dynamic model. The comparison of the optimal designs of the solar-driven AGMD, DCMD, and VMD systems indicates that the AGMD system requires the largest membrane distillation module, the DCMD system calls for the largest heat exchanger, and the VMD system needs the largest solar collector. The unit production costs (UPCs) of the optimal solar-driven AGMD, DCMD, and VMD systems for desalination are $2.71/m