The multicomponent structure of the EPR spectra of the tested blood samples depended on the time of the healing of the burned wounds. The amount of the high-spin Fe3+ in methemoglobin (line I) in the blood decreased after 21 days of the healing of the burned wounds. The amount of the high-spin Fe3+ in transferrin (line II) slightly increased after 21 days of therapy with the basis. The amount of Cu2+ in ceruloplasmin and free radicals (line III) in the blood was very high after 10 days of therapy. At the first day of the healing of the burned wounds, the highest amount of the high-spin Fe3+ in methemoglobin (line I), the relatively lower amounts of the high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III) existed in the blood. In the medium phase (after 10 days) of the healing of the burned wounds, the extremely higher amounts of Cu2+ in ceruloplasmin and free radicals (line III) appeared in the blood. In the last phase (after 21 days), only the low differences between the amounts of the high-spin Fe3+ in methemoglobin (line I), the high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III) were observed. The present study may serve as a starting point for the development of a new technique for monitoring molecular complexes containing iron Fe3+  or copper Cu2+ ions (ceruloplasmin) and free radicals in the blood during wound healing.The multicomponent electron paramagnetic resonance spectra of the blood during healing of skin burned wounds treated with a new generation biodegradable dressings containing poly(lactide-co-glycolide) were analysed. The evolution of different types of paramagnetic centers in the blood with time of healing was determined. The EPR spectra of the blood samples at 230 K temperature were measured at 1, 10, and 21 days after burning of the pig skin. The EPR lines of the following paramagnetic centers: the high-spin Fe Thermal burns represent one of the most challenging types of trauma. Injuries range from mild reddening of the skin to severe tissue damage with additional systemic complications. The pathophysiology of thermal injury is related to the initial distribution of heat within the skin. Thermal injury is progressive and results in a spectrum of local and systemic homeostatic derangements that contribute to burn shock , 2. The κB or AP-1 and promote transcription and translation of numerous inflammatory cytokines [The release of cytokines and noncytokine inflammatory mediators, as well as the excessive formation of reactive oxygen species (ROS) at the site of injury, has a systemic effect inducing hyperdynamic and hypermetabolic state that can lead to severe progressive distant organ failure , 8. Moreytokines , 10. Theytokines , 12. Ourytokines . Free raytokines . However3+ such as transferrin and methemoglobin. Fe was postulated as beneficial in wound healing, especially due to its status as a cofactor for both lysyl and prolyl hydroxylase in collagen synthesis. In wound healing, iron deficiency results in decreased collagen synthesis in the proliferative phase as well as in impaired T cell and phagocyte function in the inflammatory phase. Finally, as a critical component of hemoglobin, iron is beneficial in wound healing providing oxygen transport to proliferating tissues [3+ ions in transferrin (g = 4.14) and methemoglobin (g = 5.89) and Cu2+ ions in ceruloplasmin and free radicals (g = 2.05) were analysed in the blood during healing of the burned wounds.On the other hand, except for the increased formation of free radicals, the local and systemic inflammatory response to thermal injury involves the increased hepatic synthesis of a number of plasma proteins, which can markedly facilitate wound healing. Plasma proteins can support tissue repair by metabolic and functional activity. Among them, ceruloplasmin (Cp), transferrin (Tf), and hemoglobin (Hb) play an important role in EPR studies. Ceruloplasmin, the primary Cu-transporting protein, is an acute phase reactant synthesized in the liver and a multifunctional enzyme, which takes part in the wound healing process . Copper  tissues , 19. WheTwo 16-week-old domestic pigs were implemented for the evaluation of wound repair because of the many similarities between porcine skin and human skin. The contact thermal injuries were inflicted according to the methods of Hoekstra et al. . The wouBiopsies, in three replications, were taken from the wound bed on postburn days 1, 10, and 21. The wounds left by the biopsy were covered with collagen dressing. Experimental animals were housed according to the Good Laboratory Practice Standards.Venous blood was collected from young animals using the marginal ear vein method. The pig was restrained, and the ear was cleaned with three alternating scrubs of 70% alcohol and betadine. Blood collection was performed on the vein puncture at the base of the lateral surface of the ear. When the vein was punctured, the emerging blood was collected directly by capillary action into EDTA vacutainer tubes. After collection, the blood was stored at low temperature (-70°C).The experimental protocol was accepted by the Ethics Committee of the Medical University of Silesia in Katowice, Poland (LKE-111/2014).For the blood samples, electron paramagnetic resonance (EPR) spectra were measured. The microwaves with a frequency of 9.3 GHz from the X-band were used. The EPR lines of paramagnetic centers in the tested blood samples were recorded by the EPR spectrometer produced by Bruker (USA) at low temperature equal to 230 K. The cryogenic system to low-temperature measurements of Bruker (USA) was used. The spectra were measured with a magnetic modulation frequency of 100 kHz as the first-derivative curves. To avoid microwave saturation of the lines, all the EPR spectra were obtained with the low microwave power of 7.9 mW. The microwave power was measured by the recorder of Bruker (USA).g factors and amplitudes (A). g values will be calculated from a resonance condition according to the following formula [h is the Planck constant, v is the microwave frequency, μB is the Bohr magneton, and Br is the resonance magnetic field.The following parameters of EPR spectra of the blood samples were analysed:  formula –26:(1)gν) was directly measured by the recorder in the Bruker (USA) spectrometer. The Br values was determined from the electron paramagnetic resonance lines.The microwave frequency (3+ ions in transferrin (g = 4.14) and methemoglobin (g = 5.89) as well as Cu2+ ions in ceruloplasmin and free radicals (g = 2.05) were recorded in the blood during the burn wound healing.Wound healing, physiologic response to tissue injury, proceeds as a complex pathway of biochemical reactions and cellular events, secreted growth factors, cytokines, and noncytokine mediators of inflammation. Throughout four distinct but overlapping phases, free radicals and some proteins and trace elements, their care has been shown to play an important role in each wounding stage, including inflammation, proliferation, angiogenesis, and maturation. Oxygen free radicals are contributory agents to local tissue damage following burn injury. Moreover, thermal injury initiates systemic inflammatory reactions producing oxygen radicals –3. The r3+ in methemoglobin (line I), high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III) were visible in the complex spectra. The measured EPR spectra of the blood were superposition of these three signals. The third EPR component line (line III) was unresolved, and it was the sum of EPR lines of paramagnetic Cu2+ ions and free radicals (S = 1/2). The EPR signals of Cu2+ and free radicals overlapped, and they give complex line III in the whole spectrum of the tested blood samples. The paramagnetic centers with the individual EPR components  absorbed different amounts of microwaves that reflected their different fractions in the whole paramagnetic system in the tested blood. The low field signals  of the EPR spectra of the blood samples in the experimental measure for the bandage containing only the basis for 1 day, 10 days, and 21 days of therapy are presented in Figures Several lines were observed in the EPR spectra of the blood samples obtained from the experimental animals during different phases of burn healing covered with new generation biodegradable dressings containing poly(lactide-co-glycolide) (PLGA). The shape of these spectra clearly indicated their multicomponent character. The component lines appeared at different magnetic fields. The EPR spectra of the blood for skin burned wounds treated with the new generation PLGA-containing dressing for 1 day, 10 days, and 21 days of therapy are shown in Figures g = 5.89, g = 4.14, and g = 2.05, they represent typical signals of paramagnetic centers in the blood: the high-spin Fe3+ in methemoglobin (line I), high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III), respectively [Taking to account that obtained EPR were recorded at ectively , 19. In A) of the individual EPR component lines in the spectral changes during the healing process. The amplitudes (A) of the individual lines  changed differently with time of therapy. Such conclusion was done from the analysis of line I, line II, and line III, in the EPR spectra of the blood. Their amplitudes were compared in the diagram in A) of the individual component lines  were presented for the spectral observations at the 1 day, 10 days, and 21 days of the healing of the burned wounds dressed by nanofiber dressing containing poly(lactide-co-glycolide).Comparing the multicomponent structures of the EPR spectra of the tested blood samples presented in Figures 3+ in methemoglobin responsible for the first line (line I) in the EPR spectra of blood samples remains stable up to 10 days of the experiment  was only the low changes of the amount of these types of paramagnetic centers in the blood during the healing of the burned wounds (3+ in transferrin (line II) existed in the blood samples obtained during days 1 and 10 of the experiment. The slight increase of the amount of the high-spin Fe3+ in transferrin (line II) was observed after 21 days of therapy of the burned wounds with the nanofiber coverage  in the blood samples were similar on the 1st and 21st days of the healing of the burned wounds  was noticed on the 10th day of healing. It was reflected by the extremely strong increase of the amplitude of the EPR line of Cu2+ in ceruloplasmin and free radicals (line III) in the blood . Moreover, Cu has been recognized as a regulator of angiogenesis; however, specific targets of Cu action and detailed mechanism remain unknown [2+ ions in ceruloplasmin and from free radicals (g = 2.05) recorded in the blood on the 10th day of the burn healing process was found in our study, indicating that copper and free radical are essential participants in the late phase of inflammation, and the early phase of proliferation and remodeling, which occur at this time.Ceruloplasmin, the primary Cu-transport protein, takes part in the wound healing process as an acute phase reactant and multifunctional enzyme, which shows aminooxidase, superoxide-dismutase, and ferrooxidase activities. Copper is known to be a critical component in lysyl oxidase (LOX), the enzyme required for the cross-linking and maturation of collagen , 30. Cer unknown . A signiOn the other hand, due to its potential toxicity in excess, metabolism of copper should be under tight control, in order to maintain free copper concentrations at very low levels. The intracellular copper is regulated by transmembrane copper transporters such as CTR1, ATP7A, and ATP7B, as well as the copper chaperones, including CCS: chaperone for superoxide dismutase 1; Cox17: chaperone for cytochrome C oxygenase; and Atox1 antioxidant-1: chaperone for the ATPases, ATP7A, and ATP7B. It has been found by Das et al.  that wouThe comparative analysis of the EPR spectra resulting from different types of paramagnetic centers in the blood was useful to describe the evolution of paramagnetic centers during the healing process in the example of the burned wounds. Information about paramagnetic centers as the units with unpaired electrons was helpful to describe the healing process of the burned wounds.3+ in methemoglobin (line I), high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III) were characteristic for the analysed blood samples and were dependent on the time of the healing of the burned woundsThe multicomponent EPR spectra as the superposition of the lines of the high-spin Fe3+ in methemoglobin (line I) in the blood did not change up to 10 days, and it decreased after 21 days of the healing of the burned woundsThe amount of the high-spin Fe3+ in transferrin, which was responsible for the second EPR component (line II), slightly increased on the 21st day of therapy with the use of biodegradable dressingThe amount of the high-spin Fe2+ in ceruloplasmin and free radicals (line III) in the blood on the 1st and 21st postburn days of the healing of the burned wounds were similar. The amplitude of the EPR line (line III) and the amount of Cu2+ in ceruloplasmin and free radicals (line III) in the blood were strongly the highest on the 10th postburn dayThe amounts of Cu3+ in methemoglobin (line I) existed in the blood. The relatively lower amounts of the high-spin Fe3+ in transferrin (line II) and Cu2+ in ceruloplasmin and free radicals (line III) were observedAt the first day of the healing of the burned wounds, the highest amount of paramagnetic centers in the form of the high-spin Fe2+ in ceruloplasmin and free radicals (line III) existed in the blood. The lowest amount of the high-spin Fe3+ in transferrin (line II) compared to the Cu2+ in ceruloplasmin and free radicals (line III) and the high-spin Fe3+ in methemoglobin (line I) was present in the bloodIn the medium phase of the healing (10 days after burn), extremely high amounts of Cu3+ in methemoglobin (line I), the high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III) were observedIn the last phase of the repairing process (21 days after burn), only the low differences between the amounts of paramagnetic centers in the form of the high-spin FeThe results of the research may contribute to a more complete assessment of biochemical changes taking place in the process of repairing tissue damage after burn insult, in the scope of mechanisms regulating the metabolism of iron and copper ion complexes as well as free radicals in the bloodThe X-band (9.3 GHz) electron paramagnetic resonance (EPR) examination of the paramagnetic centers in the blood obtained from the pig during healing the burned wounds dressed with a new generation biodegradable dressings containing poly(lactide-co-glycolide) indicated the following:


Our methodology is applicable to study areas for which meteorological data are accessible, and is, therefore, useful for decision making if land-use planning schemes specify the objects of airborne pollutant concentration.As an important contributor to pollutant emissions to the atmosphere, land use can degrade environmental quality. In order to assess the impact of land-use planning on the atmosphere, we propose a methodology combining the land-use-based emission inventories of airborne pollutants and the long-term air pollution multi-source dispersion (LAPMD) model in this study. Through a case study of the eastern Chinese city of Lianyungang, we conclude that (1) land-use-based emission inventorying is a more economical way to assess the overall pollutant emissions compared with the industry-based method, and the LAPMD model can map the spatial variability of airborne pollutant concentrations that directly reflects how the implementation of the land-use planning (LUP) scheme impacts on the atmosphere; (2) the environmental friendliness of the LUP scheme can be assessed by an overlay analysis based on the pollution concentration maps and land-use planning maps; (3) decreases in the emissions of SO Land resources are vital to support human survival and social development. In recent decades, however, they have been significantly influenced by human activities due largely to rapid demographic growth. Those activities directly related to land use include agriculture and urbanization, which have intensified changes in environmental quality on both regional and global scales . Some laIn order to assess the land use and land-use planning’s impact on the atmospheric environment, a variety of assessment methodologies have been developed. Emission inventories prove useful for assessing atmospheric quality ,11,12,13Previous studies have used land-use regression models to characterize the variability of airborne pollutants ,20,21,22In order to assess the impact of LUP implementation on the atmospheric environment, it is practical to use an airborne pollutant dispersion model if key factors contributing to pollution are determined. The long-term air pollution multi-source dispersion (LAPMD) model has, therefore, been developed, based on the prediction of pollutant dispersion in the reference year . The assIn this study, we propose a new methodology combing land-use-based emission inventory and LAPMD model for assessing LUP impact on the atmospheric environment. The specific objectives of this study are (1) to establish a land-use-based emission inventory to support the assessment of the LUP impact on the atmosphere; (2) to develop a method for assessing the LUP impact on the atmospheric environment by combining a land-use-based emission inventory and the LAPMD model; and (3) to demonstrate the application of the methodology through a case study of Lianyungang, an eastern Chinese city in Jiangsu province.An emission inventory of airborne pollutants can provide spatial source intensity for dispersion assessment. Emissions from individual land-use types in the reference and target years can be estimated using their respective inventories. By means of the LAPMD model, spatial variability of airborne pollutants in the reference and target years can be quantified, and the LUP impact on the atmospheric environment can be assessed. As emissions of airborne pollutants are closely associated with land use ,28, we cBased on the land-use type, emission sources can be classified as three types, namely point, line, and area. For a city/county level LUP environmental assessment, point sources refer mainly to key plots for primary plants, line sources mostly include roads or rivers used for shipping, and area sources are residential land for both urban and rural populations. Because straw burning has been a widespread occurrence across China, particularly since the 2000s ,30, agri2 from land use can be obtained using Formula 1 according to the principle of the mass balance-based method:E is the emission intensity of SO2 (unit: kg), 2 equaling 64, S the rate of sulfur content in fuel, Given the possibility and efficiency of data acquisition, we used the mass balance and emission factor-based methods ,32,33,34iE is the emission intensity of pollutant i (unit: kg), jP the holding quantity of vehicle j, jM the annual average running mileage of vehicle j (unit: km/per vehicle), i,jEF the emission factor of pollutant i from vehicle j (unit: g/km⋅per vehicle). The emission factor-based method calculates the emissions based on the average emission rate from a particular activity generating emissions . For exaAfter estimating the emission intensity, the spatial distribution of pollutant emissions for each year can be mapped in ArcGIS , by assigning average emissions for individual land-use types  to their respective raster cells. The LAPMD model was used in this study to calculate the long-term land-use airborne pollutant multi-source concentration. This model can predict the annual dispersion of airborne pollutants based on a Gaussian dispersion model . For theus study . In the Long-term land-use airborne pollutant multi-source concentrations, which directly reflect the land-use impact on the atmospheric environment, were calculated using the LAPMD model for the reference and target years, respectively. The impact assessment can be performed by the spatial comparison of the airborne pollutant dispersion results between the reference and target years. In addition, the environmental friendliness of the land-use planning scheme can be evaluated through the overlay analysis of the land-use planning map with the concentrations map.To demonstrate the application of the proposed methodology, the land-use planning scheme of Lianyungang (2010–2020) was used to assess its LUP impact on the atmosphere for the reference year (2010) and target year (2020). As a coastal city in Jiangsu province in Eastern China , Lianyun2 and PM10, attenuation parameter of pollutants, and pollutant source height  were collected from local environmental authorities. Note that the pollutant source height is the sum of the ground height of the pollutant source and the chimney height.To predict the spatial variability of airborne pollutants and assess LUP impact on the atmospheric environment, the study area was limited to the entire geographical area of Lianyungang  and its adjacent areas  and SO2.5 emission has been widely considered as severe pollution in China, with the most serious effects in metropolises like Beijing [2.5 monitoring sites are sparse, and were even more so in the past [2.5 emission in all city-level administrative regions has been required to be monitored and published only since 2015 [2.5 data available in Lianyungang in 2010. Despite this, to some extent, the emissions of PM10 and SO2 which reflect that of PM2.5 [10 and SO2 were selected as significant airborne pollutants in the emission inventory for our assessment.PM Beijing  and Shan Beijing . Howeverthe past . In Chinnce 2015 —there waof PM2.5 , have beAs mentioned in 2 from the point sources of key plots and the area sources of urban residential land (Formula 1) [2 emission data of some plants that we investigated. The The mass balance method was used to estimate the emission of SOrmula 1)  except f10 from the point sources of key plots and the area sources of urban and rural residential land were built using the emission factor-based method. The emission factor value of point sources was assigned as the average rate derived based on the coal consumption and PM10 emission data of the investigated plants. The emission factor values of urban and rural residential land were derived from Kong et al. (2014) [2 and PM10. The emission inventories of SO2 and PM10 from agricultural land were based on the agricultural crop residues combustion and emission factor values of SO2 and PM10 reported by Zhu et al. (2012) [An emission inventory of PM. (2014)  (Table 1. (2012)   (AQSC) [The long-term airborne pollutant concentration in the target year demonstrates the impact of LUP on the atmospheric environment. For better comparison, the concentration was classified into three levels according to the ) (AQSC) . The env2 and PM10 from urban residential land, all the other point and area sources in Lianyungang would expect declining emissions. In total, both SO2 and PM10 emissions would decrease remarkably over the ten years. The SO2 emissions from transportation land  are basically distributed in the city center and around key plots both in 2010 and 2020. There is a decrease in the average concentration of SO2 from 0.97 to 0.48 mg/m3 and of PM10 from 1.68 to 1.15 × 10−3 mg/m3  are usually quite accessible—this allows the methodology presented to be easily applied to other study areas, particularly those with restricted data acquisition. Equally importantly, a high spatial resolution is not required for an atmospheric assessment of a region covering thousands of square kilometers. 2 and PM10 emissions from point sources from 2010 to 2020 illustrates the improvement of atmospheric quality based on the land-use planning for ten years. The significant decline in emissions from agricultural land might be attributed to the implementation of the no-straw-burning policy in China from 2010. The minimum utilization rate is estimated at 90% as the goal of Lianyungang in 2020 by the government of Lianyungang. The contrasting trends in SO2 and PM10 emissions from urban and rural residential lands over the 10 years . it is understood that that the overall impact of the layout of new rural residential land is environmentally friendly. A small part of that newly planned urban land with SO2 concentrations <0.005 mg/m3 in 2020 (69.43%) reveals noticeable differences in emissions from urban land and rural land, with the former releasing more SO2. The overlay analysis also reveals that all the area has PM10 concentrations <0.04 mg/m3 both in 2010 and 2020 and that the PM10 pollution would have little negative influence on the newly planned residential land. In examining the newly planned urban and rural lands, we note that the new urban residential land will be more affected by air pollution than new rural residential land, and that specific efforts are therefore needed to control emissions for these two types of newly planned land. The concentration maps are also useful in evaluating the environmental friendliness of LUP. By overlaying the concentration maps with the vector data representing the newly planned urban and rural land in GIS, we obtained the affected area at different levels . As mostLand use can increase the emissions of airborne pollutants into the atmosphere and degrade environmental quality; it is, therefore, essential to consider the impact on the atmospheric environment during land-use planning. In this study, we proposed a methodology combining the land-use-based emission inventories of airborne pollutants and the LAPMD model to assess the land-use planning atmospheric impact. Land-use-based emission inventories prove effective and feasible in collecting the overall pollutant emissions at a low cost when compared with the industrially based method, and a moderate spatial resolution is appropriate to a city-scale LUPEA. Through the land-use-based emission inventories, the LAPMD model allows a characterization of the spatial variability directly reflecting the impact of the LUP on the atmosphere. The environmental friendliness of LUP can also be assessed by overlaying the concentration maps with the newly planned urban and rural land map.2 and PM10 concentrations from the reference year of 2010 to the target year of 2020 suggest that improved atmospheric quality would be expected thanks to the implementation of land-use planning. High concentrations are mostly distributed in the city center and around key plots. There is, therefore, a concern that urban population in the affected areas will be exposed to high pollution concentrations. Although the overlay analysis reveals that the layout of newly planned urban and rural lands is environmentally friendly, emission reduction measures should be in place for the newly planned urban lands located in the areas of high SO2 and PM10 concentrations (>0.005 mg/m3). In the case study of Lianyungang, some land-use types such as urban residential and transportation land are related to higher emissions. The overall decreases in average SO2.5. Moreover, by means of the correlation of the exploration of PM10 and PM2.5 found in other studies, it is possible to assess PM2.5 based on the PM10 data. Findings from this study are helpful for decision making if land-use planning schemes specify the objectives of airborne pollutant concentration explicitly.The methodology proposed in this study highlights the assessment of the land-use planning impact on the atmosphere from a land-use point of view. It promises a low cost of data acquisition and investigation and is applicable to other areas for which data availability is restricted and, in the case of similar dispersion, to the studies which focus on airborne pollutants such as NOx and PM


Artemia salina, and showed a CL50 equal to 97 µg/mL to azo dye orange II. Additionally, the methodology was effective in removing the maximum of orange II using BSA by adsorption at pH 3.5 which mainly attracted ions to the azo dye during the adsorption process. This suggests that this form of treatment is economical and easy to use which potentially could lead to bovine serum albumin being used as a sorbent for azo dyes.Azo dyes are generally resistant to biodegradation due to their complex structures. Acid orange II is one of the most widely used dyes in the textile industry. The influence of bovine serum albumin (BSA) in different concentrations, pH, and time of contact on Orange II was investigated using kinetics and adsorption-isotherm experiments. The results showed that the maximum colour removed from dye/albumin was 99.50% and that a stable dye-protein complex had been formed at pH 3.5 and in a proportion of 1:3 (v/v), respectively. The synthetic effluent did not show toxicity to the microcrustacean  The release of colored wastewaters from the textile industry is a current problem encountered in developed and under developed countries all over the World, and this phenomenon is particularly notable for toxic products such as azo dye pigments which are known for their efficiency in the dyeing process. Azo dyes, which mostly consist of aromatic moieties linked together by -N=N- bonding (a type of chromophore), represent the largest class among these pollutants which are water soluble. Their release into the natural environment, mainly in an aqueous medium, is undesirable because of the adverse effect of these toxic and carcinogenic compounds on aquatic life that thus causes the destruction of ecosystems ,2,3,4.Currently, the textile industry uses more than 10,000 ± types of dyes, and 6,000 of these pigments are mono-azo or polyazoic azo dyes. In Brazil the textile industry accounts for 2.6% of the global demand for these azo dyes ,6. HowevVarious physical-chemical processes and biological methods  were used in the past to remove dye coloration from wastewater. However, a lack of efficiency was observed in this process because the pollution is simply transferred from one phase to another which leads to the treatment of textile effluents being costly. The presence of heavy metals associated with the dyes may also cause chronic toxicity and human health problems ,13,14,15Previous studies describing the use of proteins for adsorption processes focused on the physico-chemical process. Additionally, the process of membrane filtration was investigated in biomedical research using a physico-chemical process to adsorb proteins, and for their subsequent separation . One musStudies on filtration membranes are often applied to the movement of extracorporeal and macromolecules, such as polysaccharides or proteins, and this phenomenon has been observed in haemodialysis studies, when considering the interaction between heparin and plasmatic proteins ,19. BoviArtemia salina.This paper investigates the effect of pH on the adsorption process of the azo dye Orange II using bovine serum albumin (BSA), focusing on the possible interactions associated with the decolorization process, given the principle of the interaction between the dye molecules (cationic system) and albumin. The physical process of vacuum filtration was used to evaluate the decolourization of the effluent, and the complex albumin-Orange II formed, followed by evaluation of the toxicity of the decolorized effluent using the microcrustacean In order to find the optimal contact time and albumin (BSA) concentrations, the experiments were conducted at a pH of 3.0. The relative proportions of dye to albumin were maintained (at 1:3 v/v). The results indicated that the highest contact time (90 min) of dye and albumin led to the removal of Orange II .2 full factorial designs are shown in The effects of dye and BSA on decolorization, as well as the interaction between them, in the first 2In addition, the results of our experiments show that BSA adsorption is superior to non-conventional methods, such as tangential flow filtration with membranes and bioelectrochemical systems, for the removal of azo dye with a view to totally removing the dye ,28.The initial parameters obtained from the phenomenon of chemical precipitation of Orange II-BSA observed at both the beginning and the end by separation of and the end of separating the membrane filter are shown. For this, the interaction time was set to 20 to 90 min, the dye/albumin ratio was 1:3, and the pH was varied from 3.0 to 4.0. The pH value with the highest decolorization (92.91%) was pH 3.0 . The resThe data obtained from the experiments were analysed to evaluate the efficiency of the method (ability of BSA to remove Orange II). The effects of pH, contact time and albumin/Orange II volume ratio on Orange II removal are presented .Parameters such as pH, agitation and the v/v relationship of the dye/albumin may be affected by the interaction . The effThe Langmuir isotherm has an equilibrium concentration area between the concentrations of the dye (0.1 g/L), depending on the adsorbed mass, and the mass of adsorbent in relation to the concentration in the adsorbed system. These results described the concentration of the azo dye remaining in the water at the adsorption equilibrium point depends on a variety of factors, such as efficiency of interaction of the sorbent and the pH. The literature data are essentially corroborated with the results obtained with the decolorization process ,21,36.Artemia salina as the test organism for the toxic azo dye Orange II in order to determine if the species is an appropriate indicator of pollution in aquatic environments.The filtrates that achieved 99.50% and 90.33% removal of azo dye by albumin, in both pH conditions was similar at the start and end of the process. On the other hand, the results showed a higher removal (99.50%) of the proportion of azo dye and albumin 1:3 (v/v). All of these results were attributed mainly to the ionic attraction of albumin associated with Orange II pH [Artemia salina remained viable when it was exposed to all filtrates after colour removal, and suggests an absence of toxicity. The results indicated that a lethal concentration (LC50) is equal to 79 µg/mL of the azo dye Orange II.A chronic toxicity bioassay was conducted with the microcrustacean ge II pH ,38,39,40max) is 485 nm. A schematic of the chemical structure of the anionic monoazo species is shown in Class II Orange monoazo dye was obtained from Sigma-Aldrich. The molecular mass of Orange II is 350 Da (g/mol), and the polyamide wavelength maximum absorption .2 area of filtration; 0.2 µm porosity) [The protein solution used in the experiment was bovine serum albumin , which was used in a concentration of 0.1 g/L and 0.25 g/L diluted in ultrapure water, pH 11 and was maintained at 5 °C. The membrane used for vacuum filtration was cellulose acetate, which was supplied by Millipore  .The tests were performed in batches with distilled water, using the effluent prepared in laboratory with Orange II. The filtration unit consisted of the Millipore kit for vacuum filtration, the membrane filter and a CIENTEC vacuum pump with negative pressure flow of 28 inches of Hg. The interaction between the dye and the albumin was promoted by stirring using a magnetic stir plate (FANEM model 258) at 220 rpm. The experimental processes of separation using the vacuum filtration unit were performed at room temperature (30 °C). The tests were performed using various concentration of albumin to determine the best conditions for adsorption regarding the pH, incubation time for the formation of electrostatic complex and the formation of the permeate.Colours measurements were performed with a Spectronic Genesis, model 2 UV-visible spectrophotometer. The wavelengths for the measurements were set at the values of the azo dye concentrations and were calculated using an absorbance at 485 nm as per the calibration curve. The percentage of the solute retention time of the membrane was calculated from the readings taken for the samples before and after filtration.The albumin concentration was determined using biuret reagent (Labstest) and was measured on a spectrophotometer (λ = 545 nm).® software version 7.0 was used to conduct the ANOVA so as to determine the regression coefficients and produce the graphs [To determine the effects of the azo dye and albumin decolorization, an analysis of variance (ANOVA), with 95% confidence limits was conducted; the results are shown in e graphs .The experiments were conducted on a vortexer (200 Hz) at 28 °C. The samples were collected after addition of azo dye albumin over a period of 90 min ,42,43. TThe new methodology that was investigated in this study proved to be an innovative and promising adsorption process for removing recalcitrant azo dyes from textile industry wastewater. The high removal rates achieved suggest that the treated effluent may be reused. Furthermore, the new process was reproducible, effective, and low cost and should be considered as a method for treating dyes.


We attempted to clarify the severity of the risk of diabetes mellitus (DM) in the individuals who repeatedly fulfill the criteria for prediabetes in both fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). The subjects were 2347 individuals who underwent annual health checkup at our hospital. They were classified as normal glucose tolerance or prediabetes as their yearly status of glucose tolerance for three years; furthermore, the individuals classified as prediabetes were subclassified into 3 groups. Among them, we focused the individuals who fulfilled the criteria for prediabetes in both FPG and HbA1c, and this group was named as PD3. Similarly, all subjects were categorized into 4 groups by the frequency of the status of PD3 during three years. Moreover, all subjects were categorized into 8 patterns when PD3 status was positive. Then, we surveyed the development of diabetes for 5 years, and the incidence rates (IRs) and the age- and sex-adjusted odds ratios (ORs) were obtained. A total of 188 subjects developed diabetes. The individuals in the group of PD3 showed the highest IR of DM (33.6%). The values of ORs were 11.5, 20.0, and 63.5 when the frequencies of PD3 were one, two, and three, respectively. In the group whose frequency of PD3 was two, the individuals who had repeated the status of PD3 twice then moved to the status other than PD3 showed smaller risk of DM than the others in the same group. In conclusion, individuals who fulfill the criteria for prediabetes in both FPG and HbA1c were at a high risk of developing DM, and the risk was enhanced by repeating this status. On the other hand, changing the status from PD3 to others might reduce the risk of DM. The worldwide prevalence of diabetes mellitus (DM) is increasing; therefore, the importance of preventing DM is emphasized , 2. A prThis study has been approved by the ethics committee of Chugoku Rosai Hospital . All participants were informed that their clinical data would be used for analysis and that they had the option to withdraw their consent at any time.We collected and reviewed the records of annual health checkup of 3193 individuals who were conducted at Chugoku Rosai Hospital without missing in 2009, 2010, and 2011 (entry period). Most of the examinees were healthy employees of nearby companies around our hospital. We excluded 451 individuals who could not be followed up for five years . Furthermore, 304 individuals were excluded due to existing DM or a new diagnosis of DM by examination results upon entry into the study. Only one individual withdrew the consent to participate in this study and thus was excluded. Moreover, we attempted to find the individuals who had the disease or the medication affecting the examination results of FPG and HbA1c , 14. AftIn the entry period, each participant was classified as PD or NGT according to our criteria shown in  which fo2. All of the subjects completed proper overnight fasting, and blood samples were taken from their antecubital vein. Blood samples were immediately measured in the hospital's laboratory which is accredited by Japan Medical Association. The values of HbA1c as defined by the Japan Diabetes Society (JDS) in 2009 were converted to those of the National Glycohemoglobin Standardization Program (NGSP) according to the former report [Height and weight were measured while a participant wore a hospital's uniform for health checkup. Body mass index (BMI) was calculated according to the established procedure: BMI = body weight(kg)/[body height(m)]r report . Our hosP value of less than 0.05 was considered to be significant.Statistical analyses were performed using JMP12 . Differences in group characteristics were compared by the chi-square test for categorical variables. The one-way ANOVA and Tukey-Kramer test were used to compare differences of continuous variables. The age- and sex-adjusted odds ratios (ORs) of developing DM were obtained by logistic regression analyses for the identification of the severity of the risk in the groups of NGT, PD1, PD2, and PD3. Similarly, all subjects were categorized by the frequency of PD3 status during the entry period, and then the age- and sex-adjusted ORs of DM were calculated in these groups. Moreover, all subjects were categorized into eight patterns when the status of PD3 was positive during the entry period, and then the age- and sex-adjusted ORs of DM during the survey period were obtained by logistic regression analyses. Firstly, we surveyed the association between the status of glucose tolerance in the first year (2009) and the outcome during the survey period. In 2009, 1014 individuals were classified as PD and 1333 as NGT. Furthermore, we categorized individuals with PD into three subgroups . The numWe concluded the individuals classified as PD3 had the highest risk of developing DM among three subcategories of PD. Next, we examined the association between the repetition of this status (PD3) and the incidence of DM. In order to clarify the features of the groups of Frequency-1, Frequency-2, and Frequency-3, we performed statistical analyses about anthropometry and clinical factors which were reported to concern glucose tolerance –18.  TabThe group of Frequency-3 showed the highest risk of developing DM. However, the groups of Frequency-1 and Frequency-2 also showed severe risk of DM when compared with the group consisting of PD2, PD1, and NGT (Frequency-0). We analyzed the severity of the risk in eight patterns when PD3 was positive during the entry period . In the In the group of Frequency-2, the individuals who were PD3-positive in 2009 and 2010 but negative in 2011 apparently showed the small risk. Their IR and OR of DM during the survey period were 11.5% and 10.3, respectively. These values were almost half of the values of the other individuals in the same group and comparable to those in the group of Frequency-1. The individuals who were PD3-positive in 2010 and 2011 had the rather large risk of DM when compared with the individuals who were PD3-positive in 2009 and 2011.In the present study, a risk of developing DM was estimated using the values of FPG and HbA1c. Therefore, the risk might be erroneous when an individual had comorbidity or medication which affected the examination results of FPG and HbA1c. Iron deficiency anemia, hemolytic anemia, and renal anemia affect the value of HbA1c because the red blood cell turnover is not normal . In casePD is the status indicating relatively high risk of the future development of DM , 7. In tWe know some individuals repeat the status of PD3. Therefore, we examined whether such individuals had severer risk of DM . The IRsFocusing the features of the groups of Frequency-0, Frequency-1, Frequency-2, and Frequency-3, we could find the significant difference in the values of FPG and HbA1c . The meaWe found interesting possibility in the results shown in In conclusion, the present study confirms that individuals in the status fulfilling the criteria for PD in both FPG and HbA1c have the high risk of DM progression and shows that repetition of this status will enhance the risk of DM. Furthermore, many of new DM cases are considered to go through PD3 status to develop DM, but the risk of DM is not so severe when an individual stays the status other than PD3. Moreover, changing the status from PD3 to others by intervention may reduce the risk of DM. In order to ensure our conclusions, similar studies in a large cohort and in a different ethnic group will be necessary, and prospective studies will also be needed to examine whether intervention to this status can actually reduce the risk of DM. Nevertheless, we recommend that an individual in the status of PD3, especially repeating this status at the time of annual health checkup, should be proactively treated to prevent DM.


The tribological performance of copper-based powder metallurgical material is much influenced by the interfacial bonding between the components and matrix. By adding Cu-coated or uncoated graphite particles as a lubricant, two types of copper-based powder metallurgical materials were prepared via spark plasma sintering (SPS). The hardness, relative density, and thermal conductivity of the two specimens were firstly measured. Using an inertial braking test bench and temperature measuring instrument, the average friction coefficients, instantaneous friction coefficients, and friction temperatures of the two specimens were tested under different test conditions, and the wear rates were calculated accordingly. Based on the analysis of surface morphologies and elements distribution after the tests, the mechanisms of wear and formation of friction films were discussed. The results show that with the lubricant of Cu-coated graphite, the hardness, relative density, thermal conductivity, and interfacial bonding between the graphite and matrix can be greatly improved. Under the same test condition, the average friction coefficient, wear rate, and friction temperature of the specimen with added Cu-coated graphite are both lower than those of the specimen with added uncoated graphite. The two specimens show different variation trends in the instantaneous friction coefficient during the tests, and the variation of the instantaneous friction coefficient at a high initial test speed is also different from that at a low initial test speed for each specimen. The two specimens also show differences in the continuity of friction film and the content of graphite and oxide in the friction film. The requirements for friction materials in high-speed braking applications are strict. They demand that the friction materials can provide not only a high and stable friction coefficient, but also good wear resistance during braking ,2,3. AmoFor copper-based powder metallurgical materials, it is an effective measure to enhance the interfacial bonding between the graphite and matrix in sintering by using metal-coated graphite ,15,16,17In this work, two types of copper-based powder metallurgical materials were prepared with Cu-coated and uncoated graphite. The hardness, relative density, and thermal conductivity of the two specimens were measured and compared. In the friction and wear tests under different braking conditions, the differences between the two specimens in the average friction coefficient and wear rate were studied. By measuring the temperatures near the friction surface and instantaneous friction coefficients during the braking processes of different conditions, the variation characteristics of friction temperature and friction coefficient with test time and the relationship between them for the two specimens were also discussed. Based on the analysis of microstructures, surface morphologies, elements distribution, and phases composition after friction tests, the interfacial bonding, formation mechanisms of friction film, and wear mechanisms of the two specimens were explored.Two types of friction specimens were prepared via SPS, and the sintering temperature and pressure were 780 °C and 30 MPa, respectively. The sintering process is shown in a) of the disk were 37 HRC and 1.0 µm, respectively. The structure of the test bench and the friction pair are shown schematically in 2 after computation (Equation (A1)). Test groups are shown in 0) were 100, 150, 200, and 250 km/h. During the tests, the instantaneous friction torque, friction speed, and pressure were measured by the sensors, and the instantaneous friction coefficient could be calculated by the computer equipped on the test bench (Equation (A2)) accordingly. For each group, the test was repeated five times, the average friction coefficient and braking time of each test were recorded, and the material loss per unit of energy consumed  was computed (Equation (A3)). For the test groups 1, 4, 5, and 8 for specimen S1 and groups 9, 12, 13, and 16 for specimen S2, the temperature near the friction surface was also measured to study its variation during the tests. The measurement position was 1.5 mm beneath the friction surface. An electronic thermometer (TES1384)  with a memory function and a K-type thermocouple were used in the tests. The data collection interval was set as 2 s. Meanwhile, the instantaneous power input during the test process was also computed (Equation (A4)).The friction and wear properties of the two specimens were tested on an inertial braking test bench (MM 1000-II) . The braking disk (25Cr2MoVA steel) with a diameter of 160 mm and thickness of 9 mm was chosen. The hardness and surface roughness  were analyzed and compared using SEM and x-ray diffraction (XRD) patterns. For better comparing the surface morphologies and wear mechanisms of the two specimens, several cylindrical samples were shaped to inclined-plane form, as shown in The hardness, relative density, and thermal conductivity coefficient of the two specimens are given in 2, as indicated by the white arrow. The components distribution of specimen S2 (cimen S2 b is the The friction and wear test results are shown in The variations of average friction coefficient and wear rate of the two specimens with the initial test speed at two different pressures are shown in Due to the differences between the two specimens in the friction coefficient and thermal conductivity, the power inputs and friction temperatures of them show different variation features during test processes. It is evident that both the temperature rising rate of the beginning stage and the temperature value at the same test time of specimen S1 are lower than those of specimen S2 under the same condition. For each condition, before the friction process reaches a certain time (10, 6, 22, and 16 s indicated by the black arrow in r is the real contact area and P is the pressure. As shown in the formula, it is seen that the increase of the real contact area and meshing degree of the friction pair is helpful to increase the friction coefficient. As the test time goes on, the contact area, meshing degree, and adhesion of friction pair are gradually increasing, so the friction coefficient of specimen S1 increases [The friction coefficient of the surface is much influenced by the mechanical property and friction temperature, and they also have strong impacts on the formation of the surface friction film. As shown in ncreases ,25, as sncreases , so the ncreases ,26. The However, for specimen S2, at 100 km/h, the instantaneous friction coefficient generally shows a downtrend a,b. HoweFirstly, based on the analysis of the friction surface morphologies of the two specimens, the wear mechanisms under different conditions were studied. As shown in For specimen S1, at 100 km/h and 0.4 MPa, it is seen in Compared with specimen S1, the wear of specimen S2 is obviously increased under the four same conditions, as shown in Based on the analysis of morphologies and elements distribution of inclined-plane samples, the differences of friction films on the surface of specimen S1 and S2 were further studied. For specimen S1, it is seen that the difference between the surface and subsurface in the distribution of C is small b; howeve3O4 obviously arises at 250 km/h, indicating that the oxide friction films have formed on the surface at this high speed. Due to the isolation effect of the oxide films on the friction pair, the diffraction intensity of Cu at 250 km is much lower than that at 100 km/h. However, for specimen S2, the diffraction peak of oxide is not found at each speed, but the diffraction peak of C is obviously stronger than that of specimen S1, indicating that the content of graphite in friction films of specimen S1 is higher, especially at the speed of 250 km/h, and the diffraction intensity of Cu at 250 km is also lower than that at 100 km/h for specimen S1, which is due to the fact that the friction films can easily form at a high speed. The above analysis shows that the increase of speed is favorable to the formation of the friction film on the surface for both of the specimens.After the friction and wear tests, we performed XRD analysis for the two specimens to test the phase composition on the surfaces. The analysis results of the friction surfaces at 0.4 MPa and two speeds are shown in Under the same content of graphite, with the lubricant of Cu-coated graphite, the hardness, relative density, thermal conductivity, and interfacial bonding between the graphite and matrix of the copper-based powder metallurgical material can be greatly improved.Under the same test condition, the average friction coefficient and wear rate of specimen S1 are both lower than those of specimen S2. The higher friction coefficient of specimen S2 is beneficial for braking, but it can also increase the wear of material.Under a low initial test speed, the variations of the instantaneous friction coefficient for specimen S1 at two pressures both show an uptrend, but the variations of it for specimen S2 at two pressures almost show a downtrend. Under a high initial test speed, when the braking process reaches a certain stage, the decrease in the instantaneous friction coefficient occurs obviously in specimen S1 at each pressure, and the friction coefficient then increases again. For specimen S2 at each pressure, the instantaneous friction coefficient firstly decreases, and then after a stage of fluctuation, it keeps decreasing to the end.The friction temperature of specimen S1 at each condition is much lower than that of specimen S2. At a low initial test speed, for the two specimens at each pressure, the friction temperature increases with time. At a high initial test speed, when the braking process reaches a certain stage, the temperature decline arises in both of the two specimens at each pressure.Due to the great delamination effect on the surface of specimen S2, the wear of it is more serious than that of specimen S1. A high speed is favorable to the formation of friction films on the surface for the two specimens. The friction films of specimen S1 contain more graphite and less oxide, and show low continuity; however, the friction films of specimen S1 mainly consist of oxide and show high continuity.Based on the investigation of the tribological performance of copper-based powder metallurgical friction material with the lubricant of Cu-coated or uncoated graphite particles, the following conclusions can be drawn:


Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II) complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds. There have been several ruthenium-based complexes synthesized as anticancer drugs ,2,3 to sIn our previous work ,13, we hIn this paper the binding affinities and conformations of 30 metallocompounds including their hydrated forms  are repo1, 1a, 8, 8a, 9, 9a, 10, 10a, 11 and 12 (2 and 3) are found to be highly competitive with the co-crystallized compounds in their binding affinities  and hydrated RAPTA  complexes are predicted to have stronger binding affinity to many of the receptors  is DNA as they are found having higher binding energy with DNA compare to other receptors. The hydrated cisplatin, especially the doubly hydrated form (Cisp-W2) has the highest DNA binding compared to the other forms of cisplatin which further confirmed the need for hydration before activation ,28. Howexicology  is bette12 binding to DNA-2 from both the relaxed and covalent constrained dockings is perfectly superimposed (12 with the two based pair nitrogen atoms (N7) of the guanine in DNA-2 by both relaxed and constrained docking as shown in 10a and 12 by both the relaxed and covalent constrained docking. Autodock also predicted complex 10a among the best five inhibitors of DNA within the interval of 0.60 Kcal/mol. The features of complex 10a in Autodock docking to CatB shows a very strong H-bond interaction of one of its carboxylic groups with the SG of the CYS 29, which supposed to be, center of metal-residue covalent interaction  and Autodock (magenta) fits properly into the hydrophobic pocket of the CatB as shown in 12 as one of the best binding metallocompounds to CatB. Also, the orientation and the interactions suggested Autodock and relaxed Molegro docking are the same with the structure of 12 on the binding site almost superimposed  residue CYS 64A or strong close contact van der Waal interactions with the two bridged surphur (SG) atoms of the residues CYS 64A and CYS 59A.In Autodock docking of complex f 1.78 Å . The thr1a, 8a, 9a, 10a and all the hydrated RAPTA complexes. In agreement with the literature, the best target of cisplatin is DNA [An insight into the interaction of the metallocompounds with the two types of DNA (DNA-1 and DNA-2) is given for the Autodock , relaxedn is DNA ,28 as thn is DNA ,15.12, 1 and 1a, 10 and 10a, 9 and 9a and 11 bind strongly to CatB than its co-crystallized compound. Both Molegro and Autodock included the hydrated RAPTA complexes as part of the best binding metallocompounds to CatB while only Molegro ranked bidentate RAPTA complexes 2 and 3 better than the hydrated ones. In ranking, we give preference to the Molegro dockings than the Autodock ones, especially where there is a very close binding affinity prediction from the Autodock docking considering the standard error margin of ~2.177 kcal/mol [3 and 2) and the hydrated RAPTA complexes. The features of the predicted binding affinities of RAPTA complexes give a better insight into their reported experimental activities in CatB and TrXR. The experimental activities of the RAPTA complexes against CatB follow the order 15, 14, 2, while 3 and 13 rarely show any appreciable binding affinity and that of TrXR followed the order 2, 3, 14 and 15 while 13 has the lowest activity  have better binding than its co-crystallized compound. This is also applicable to the RAPTA complexes.The features of the binding affinities of the metallocompounds against gyrase from both docking methods show that co-crystallized compound still preferentially bind to gyrase better than any of the metallocompounds, even though the activities of the new modeled metallocompounds are competitively close to that of its co-crystallized compound. The metallocompounds that have the best binding to gyrase using Molegro are 1 and 12 . Autodoca and 5a . The bin1, 9, 10, 11, 12 and their hydrated forms (where applicable) are predicted to bind better than RAPTA complexes by all three methods of docking. The crystal structure of HP-NCP shows RAPTA-C  binding to two different sites on chain G and H of the receptor  are predicted among those that have the best binding to BRAF kinase . The rHA is predicted as an average target, suggesting that many of the Ru(II)-based complexes that are considered will on average be kinetically favourable which further support the experimental findings [There have been experimental reports on HP-NCP also being a possible target of RAPTA complexes , but thereceptor e. In ordtructure e. The neF kinase . BRAF kiF kinase  to have findings ,27.1, 10, 8, 11, 12 and 9 including the bidentate RAPTA complexes 3, 2 and hydrated 14a. The suggested best binding metallocompounds to TopII after the co-crystallized compound are 1, 10, 9, 12, 11 and the RAPTA complexes 2, 3, 14a and 16a. Commonly predicted best binding metallocompounds to TS by the three methods of docking are 12, 10, 11, 9 and the bidentate RAPTA complexes 2 and 3 while only Molegro rated 1 as part of the best for TS.In the interaction of the metallocompounds with RNR, the binding site co-crystallized compound is found to bind preferentially to all the metallocompounds. The predicted best binding metallocompounds to RNR are i.e., for protein receptors) and the N7 atom of the guanine in DNA [Since the targets of many organometallic complexes are not yet known ,6,7,8,9,e in DNA ,30. There in DNA ,31 and ie in DNA . There ie in DNA  and for e in DNA , BRAF kie in DNA , RNR  are still ranked among those that have the best binding affinities to all the receptors. The binding behaviour of many of the metallocompounds when the covalent constraint is applied or omitted shows that the functions of the metal centre of the metallocompounds are receptor dependent.The general feature is that the binding affinity is lower when the covalent constraint is applied  compare 1, 9, 10 and 12 (and their respective hydrated forms where applicable) are predicted by all the methods of docking between the best two inhibitors of all the receptors. Also, complex 11 is rated among the best three during the relaxed docking for gyrase and during the constrained docking for CatB and HDAC7. Specific to Autodock docking, the hydrated complexes 4a and 5a are suggested among the best inhibitors of DNA-1, DNA-2, HP-NCP, Kinase, TopII, TrXR and TS. Ranked high among the RAPTA complexes in many of the receptor interactions are the bidentate complexes 3 and 4 followed by the hydrated complexes 14a and 16a. This gives further insight into the reported better anticancer activities of complexes 14a [16a [In summary, the new models, especially complexes 14a [16a . ConsideThe docking method of Molegro gives a more comprehensive insight into the factors that determine the binding affinities of the metallocompounds. Their correlation The geometries of the metallocompounds were first optimized in Gaussian 03/09 ,41 using1, 9, 10 and 12 (and their respective hydrated versions where applicable) are predicted by all the methods of docking to be between the best two inhibitors of all the receptors. Ranked high among the RAPTA complexes in many of the receptor interactions are the bidentate complexes 3 and 4 followed by the hydrated complexes 14a and 16a in agreement with reported better anticancer activities of complexes 14a [16a [12 that prefers CatB to rHA. The general features are that the binding affinity is lower when the covalent constraint is applied (16 and 16a respectively are higher than that of metallocompounds 15 and 15a by the Molegro, which further agrees with the experimental reports [2, 3, 14a, 15a and 16a. The lower binding affinities of the metallocompounds in the constrained metal-residues covalent bond type of docking compare to the relaxed Molegro docking and better correlation of the relaxed Molgro to the available experimental reports show that the metal atom in these type of metallocompounds will give preference to positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects on each other than forming a covalent bond. Also from the Molegro docking, there is clear indication that the pose energy, inter protein ligand energy, intra molecular van der Waal and molecular weight strongly determine the final binding energy of the metallocompounds to the receptors.In this paper we have presented the binding affinities of new model metallocompounds and some of the experimentally available metallocompounds, especially those of RAPTA complexes using the Molegro and Autodock methods of docking. Making use of the atomic charges of the metallocompounds obtained from the optimized quantum calculation significantly improved the predicted activities and ranking of the metallocompounds, which strongly agrees with the available experimental results. In summary, the new models, especially the complexes exes 14a  and 16a 14a [16a . Conside applied  compare  applied . However reports . Those p


Dear Editor,Mycobacterium leprae. The disease is classified into two, namely paucibacillary (PB) or multibacillary (MB) leprosy. PB leprosy is a milder form of disease, characterized by several  hypopigmented, pale and reddish lesions, and hypo- or anesthetic lesions. MB leprosy is associated with several skin lesions that manifest as nodules, plaques, or diffuse skin infiltrationLeprosy remains an important health issue. The disease is characterised by a chronic granulomatous infection of the skin and peripheral nerves caused by Globally, India, Brazil, and Indonesia are the three countries with scattered populations reporting over 10,000 (81%) of new patients each year, which indicated that the world is demanded to make a great progress towards the goal of eliminating leprosyIn 2015, the prevalence of leprosy in the province was1.25 / 10.000 population, with new 275 cases of MB leprosy and 28 new cases of PB leprocy see 5. The spAlthough leprosy is the oldest disease known to manThus, this condition calls for the role of public health to set up the strategy in Indonesia, particularly in the province of SouthEast sulawesi to eliminate the increase of leprosy and to fight stigma. These focused on 1) Increasing early case detection in the community; 2) Improving the quality of leprosy services, including rehabilitation services that are integrated with basic health care and referrals; 3) Changing the image of the disease that leprosy is curable by disseminating information or media campaigns; 4) The elimination of stigma by increasing the knowledge of the disease; 5) Empowering those who have experienced leprosy in various aspects of life, and strengthening their participation in controlling leprosy; 6) Restoring self-esteem; and 7) Developing program that prevents disabilities or permanent damage


Tailing microcrystalline foam glass (TMFG) is a building material that not only has the characteristics of light weight, fire resistance, and thermal insulation, but also has decorative applications. TMFG has a broad application prospect, but there has been little research on the macroscale mechanical properties of this material. In order to analyze TMFG basic mechanical properties, a series of experimental studies were carried out by performing the four-point flexural, shear, uniaxial compression, and splitting tensile strength tests. The research showed that the foaming agent (SiC) had a great influence on the mechanical properties of the material. With the reduction of the amount of SiC, the strength of the material and brittle failure increased. The microcrystalline decoration surface improved the flexural strength and compression strength of the tailing microcrystalline foam glass. The modulus of elasticity and the Poisson’s ratio are discussed, and a formula for the modulus of elasticity is proposed. Based on the analysis of the stress and strain curves, a constitutive model is proposed for the application of tailing microcrystalline foam glass and future research on this material. St. Gubain developed a variety of silicate foam glass systems. Subsequently, the United States, Germany, Japan, the United Kingdom, and other countries also began the study of foam glass and issued a number of related patents and research reports. Foam glass has the advantages of low density, low thermal expansion coefficient, low thermal conductivity, and corrosion resistance. It enables heat insulation and sound absorption and is a lightweight, moisture-proof, and fire-proof building heat insulation material and decorative material. The development and application of foam glass will play a positive role in the recovery and utilization of glass wastes and in environmental protection [Foam glass (FG) is a porous glass material composed of waste glass and various mineral waste materials. Generally, the production process of foam glass is as follows: Firstly, a uniform mixture is formed by adding appropriate amounts of the foaming agent, cosolvent, and various modified additives, and, then, the uniform mixture is put into a specific mold and subjected to preheating, melting, foaming, cooling, and other processes ,2,3. In otection ,5,6,7.However, foam glass has a low mechanical strength, so it is rarely used as a wall material. Microcrystalline foam glass (MFG) produced by the micro-crystallization of foam glass is a lightweight, high-strength material. A large number of small bubbles and needle-like crystals are evenly distributed in the main phase of the glass. MFG has several advantages, such as being a fire-proof, non-toxic, non-radioactive, corrosion-resistant, and machinable material. Using MFG as a wall material can greatly reduce the weight of a building. Nowadays, tailing can produce not only MFG but also an MFG with a microcrystalline decorative surface by specific process, as shown in −3 and 0.9–1.8 MPa, respectively. This research found that the compressive strength of MFG is affected not only by apparent density values, but also by the internal porosity and thickness of the struts and the crystalline phase composition. Chen B. [Fernandes H.R.  used rec Chen B.  used a h Chen B. ,19,20,21The tailing microcrystalline foam glass (TMFG) used in the following tests was composed of quartz sand, waste stone residue, and glass. The batch composition was measured in terms of the weight percentage. The foaming rate was controlled by adding a foaming agent to adjust the strength and density of the TMFG. The main raw materials for all specimens were the same and were divided into three batch compositions. The specimens with microcrystalline decorative surfaces were based on the main raw materials with the addition of natural gravel. The specific batch compositions are listed in The entire production process of TMFG is shown in In The bulk density, porosity, and water absorption of Group A specimens were tested. The test methods were adopted in GB/T 3810.3-2016 standard . The sizm1) of the specimens was determined.The specimens were placed in a drying box. The temperature was slowly raised to 110 ± 5 °C to dry the specimens to a constant mass, and then the specimens were moved to the dryer and cooled to room temperature. According to the criterion of constant mass, the quality of the specimen is weighed two times in 24 h at constant temperature, and the mass change rate is less than 0.1%. The dry weight (m2).A water tank made of inert material and a wooden grille with a section of about 50 mm × 50 mm were made. The size of the water tank should allow to immerse ten specimens. The specimens were placed on the wooden grille at the bottom of the water tank so that they were not in contact. Water was added to the water tank, and a 50 mm-thick layer of water was maintained above and below the specimens. The water was heated to boiling in 2 h, then the specimens were cooled in water to room temperature. Room temperature was maintained for 4 h. The treated specimens were placed gently in the hanging basket of an electronic balance and immersed in water to weigh their buoyant weight (m3) was immediately determined in air.The specimens were removed from the water, and the excess moisture was wiped off with a wet towel. The liquid in the air hole of the specimens was not sucked out. The saturated weight (3), The bulk density, porosity, and water absorption of the specimens was calculated as follows:The bulk density, porosity, and water absorption of groups A1, A2, and A3 are shown in There has been little research on the macroscale mechanical properties of TMFG, so a reasonable experimental design is very important. The adopted test methods were as for GB/T 5486-2008 standard  and concThe size of the specimens for the four-point flexural tests was 100 mm × 100 mm × 400 mm (width × height × length). A total of 36 specimens was tested. The loading device is shown in The size of the specimens for the splitting tensile strength test was 100 mm × 100 mm × 100 mm. The specimens were TMFG without the microcrystalline decoration surface. Nine specimens were tested, and the loading device is shown in 2).The splitting tensile strength can be calculated as follows:The size of the specimens for the cubic compression test was designed to be 100 mm × 100 mm × 100 mm, while that for the prism compression test was 100 mm × 100 mm × 300 mm (width × height × length). A total of 36 specimens were tested. The surface of TMFG has many pores, therefore, plaster was used to level the upper and lower surfaces of the specimens, as shown in Considering the fragility of TMFG, the Z-shaped specimen method  was adopThe shear strength can be calculated as follows:The result of the four-point flexural strength, compressive strength, splitting tensile strength, and shear strength tests were analyzed, and constitutive equations of TMFG are proposed in this paper.The flexure specimens from group A and group ADs produced sounds, indicating broken internal pores during the loading process, and vertical penetrating cracks in the middle part of the specimens were found. The destruction process without obvious signs was rapid, resulting in brittle failure. There were two forms of damage to the specimens in the group ADt. One was the shear slanting cracks that appeared in the largest shearing area. First, the microcrystalline foam glass parent metal was damaged, and, then, the microcrystalline decoration surface was destroyed in the largest shearing area. The damage process was rapid. The specimens ADt1 and ADt2 mainly exhibited this failure mode. The other form of destruction consisted of vertical cracks appearing in the largest moment area in the middle part of the specimen. The parent material was damaged first, and, then, the microcrystalline decoration surface was destroyed. This type of damage occurred in ADt3, as shown in As shown in As shown in The various mechanical properties of A2 were about 1.22 times greater than those of A1, such as the compressive strength of A2 was 1.21 times that of A1, the splitting tensile strength of A2 was 1.24 times that of A1, the shear strength of A2 was 1.18 times that of A1, and the flexural strength of A2 was 1.24 times that of A1.The various mechanical properties of A3 were about 2.45 times greater than those of A1, such as the compressive strength of A3 was 2.29 times that of A1, the splitting tensile strength of A3 was 2.41 times that of A1, the shear strength of A3 was 2.54 times that of A1, and the flexural strength of A3 was 2.56 times that of A1.The cubic compressive strength of TMFG without the microcrystalline decoration surface was close to the prism compressive strength: the cubic compressive strength was about 1.04 times greater than the prism compressive strength. Further, the cubic compressive strength was about 4.7 times greater than the shear strength, about 6.64 times greater than the splitting tensile strength, and 2.92 times greater than the flexural strength.The conversion relations are as follows:The compression strength of the specimens with the microcrystalline decoration surface was significantly higher than that of the specimens without it. The cubic strength of group AD was 2.48 times that of group A, and the prism strength of group AD was 2.47 times that of group A. Therefore, the microcrystalline decorative surface improved the flexural and compressive strength of TMFG.The compressive stress–strain curves of each group are shown in In the dimensionless analysis of the compressive stress–strain curves, the ordinate is represented by There were initial microcracks inside the TMFG specimens. Because of the development of microcracks after stress application, the pre-peak stage curve would indicate stiffness changes in the initial stage; therefore, the 2-fold line formula was used to fit the pre-peak stage curve. The curve in the post-peak stage refers to the Hognestad concrete constitutive curve , and theThe fitting curve was in good agreement with the stress–strain curve, following the application of the segment adjustment parameter The modulus of elasticity and Poisson’s ratio are important indexes of a material. The slope of the pre-peak stage curve between Poisson’s ratio is an important index of a material’s lateral deformation. TMFG without the microcrystalline decoration surface is an isotropic material; therefore, the displacement meter was arranged on one of the symmetrical surfaces, and the transverse deformation of the specimen was recorded. For the specimens with the microcrystalline decoration surface, there was a small deformation in the direction of the decorative surface compared to the nondecorative surface; therefore, the displacement meter was arranged in the direction of the nondecorative surface. The data were processed using Formula (12) to obtain the Poisson’s ratio for each specimen, as shown in The Poisson’s ratio tended to decrease with the increase in the compressive strength of TMFG, as shown in On the basis of the data of the physical properties in With the increasing of the amount of the foaming agent (SiC), the porosity increased. As the porosity was reduced, the prism compressive strength, splitting tensile strength, shear strength, and flexural strength increased, so that TMFG acquired better mechanical properties. Similar results were also found by F. Mear .Because of the scarcity of research on the macroscopic mechanical properties of microcrystalline foamed glass, relevant studies on the modulus of elasticity of concrete are here considered. Researchers have carried out many experimental studies on the modulus of elasticity of concrete, and their results have also been adopted to formulate various standards, such as the Chinese standard (GB50010-2010)  and the Code for the design of concrete structures (GB50010-2010)Building code requirements for structural concrete (ACI318M-05)Calculation formula of DhirCalculation formula of Dhir MellmannAs can be seen from (1)With the reduction of the amount of SiC, the porosity decreased, so that the mechanical properties improved. The improvement in the various mechanical properties was similar. The cubic compressive strength of TMFG without microcrystalline decoration surfaces was close to the prism compressive strength. The cubic compressive strength was about 1.04 times the prism compressive strength. The cubic compressive strength was about 4.7 times the shear strength, about 6.64 times the splitting tensile strength, and 2.92 times the flexural strength.(2)The microcrystalline decorative surface improved the compressive and flexural strengths of TMFG. The compression strength of group AD was about twice that of group A. The flexural strengths of groups ADt and ADs were, respectively, 2.31 and 1.4 times greater than those of group A, and the orientation of the specimens significantly influenced the flexural strength of the specimens with the microcrystalline decoration surface. The flexural strength of group ADt was approximately 1.64 times that of ADs. The stress–strain curve of TMFG could be expressed by the 3-fold line equation.(3)With the reduction of the amount of SiC, the modulus of elasticity of TMFG increased. The modulus of elasticity of TMFG was lower than the calculated value obtained using the concrete-specific formulas, and the highest ratio between the experimental and the calculated results was 3.12 times. A formula is proposed to estimate the modulus of elasticity of TMFG.(4)With the increase in the compressive strength of TMFG, the Poisson’s ratio decreased. The Poisson’s ratio of the specimens with the microcrystalline decoration surface was slightly smaller than that of the specimens without the microcrystalline decoration surface.


The von Economo neurons (VEN) are characterized by a large soma, spindle-like soma, with little dendritic arborization at both, the basal and apical poles. In humans, VENs have been described in the entorhinal cortex, the hippocampal formation, the anterior cingulate cortex, the rostral portion of the insula and the dorsomedial Brodmann’s area 9 (BA9). These cortical regions have been associated with cognitive functions such as social interactions, intuition and emotional processing. Previous studies that searched for the presence of these cells in the lateral frontal poles yielded negative results. The presence of VENs in other cortical areas on the medial surface of the human prefrontal cortex which share both a common functional network and similar laminar organization, led us to examine its presence in the medial portion of the frontal pole. In the present study, we used tissue samples from five postmortem subjects taken from the polar portion of BA10, on the medial surface of both hemispheres. We found VENs in the human medial BA10, although they are very scarce and dispersed. We also observed crests and walls of the gyrus to quantitatively assess: (A) interhemispheric asymmetries, (B) the VENs/pyramidal ratio, (C) the area of the soma of VENs and (D) the difference in soma area between VENs and pyramidal and fusiform cells. We found that VENs are at least seven times more abundant on the right hemisphere and at least 2.5 times more abundant in the crest than in the walls of the gyrus. The soma size of VENs in the medial frontopolar cortex is larger than that of pyramidal and fusiform cells of layer VI, and their size is larger in the walls than in the crests. Our finding might be a contribution to the understanding of the role of these neurons in the functional networks in which all the areas in which they have been found are linked. However, the particularities of VENs in the frontal pole, as their size and quantity, may also lead us to interpret the findings in the light of other positions such as van Essen’s theory of tension-based brain morphogenesis. Although some researchers, before and after von Economo, mentioned the presence of spindle-shaped neurons in diverse cortical sectors, their first characterization in humans belongs to Constantin von Economo and Georg Koskinas  in search of VENs with negative results  in Bogotá, Colombia. The subjects  had ages ranging between 20 and 41 years old (mean of 25.8 years old), a postmortem interval that ranged between 8 h and 14 h (mean of 9.8 h) and the causes of death were: wound by firearm in the thorax (three cases) and wound by firearm in the spinal cord (two cases). None of them had antecedents of neurological or psychiatric diseases, brain injury or edema in the medical-forensic report. The procedures of this study were approved by the ethics committees for human research of the Faculty of Health of the Universidad del Valle and the NIFMFS, in accordance with the Helsinki protocol.Tissue blocks (1 cm wide × 1 cm long × 1 cm deep approximately) were taken from the freshly extracted brain, washed with 10% saline solution for 5 min and then fixed by immersion. The samples were taken from the polar portion of BA10, on the medial surface of the two hemispheres, according to the cytoarchitectonic map of  were obtained using a Initially, the sections were introduced into a mixture of 0.3% hydrogen peroxide and 30% absolute methanol to prevent the action of the endogenous peroxidase. To avoid adhesion to non-specific antigens, we used normal horse serum diluted 1.5% in phosphate buffered saline (PBS) for 40 min. The tissue was incubated in anti-NeuN antibody  for 18 h. The primary antibody was diluted in PBS with 0.5% Triton X-100 (1:2500). Then, the sections were incubated in the avidin-biotin HRP complex  for 1.5 h. Finally, they were processed in a solution of 4% 3,3′-diaminobenzidine, 2% hydrogen peroxide and 2% nickel in PBS  for 5 min. After each treatment, three washes of 5 min each were carried out with PBS. With the tissue already subjected to immunostaining, it was mounted on chrome-lighted glass plates which were then washed with distilled water and dehydrated with graded alcohols and xylols. The tissues were cover-slipped with histological mounting media . As a negative control, tissue sections were processed in the same way previously described except that the primary antibody was omitted. All procedures were carried out at room temperature.The histological observation of the tissue sections was performed with a light microscope ZEISS Scope.A1, coupled with a high-resolution camera AxioCam HRc. In total we had 57 tissue sections, 30 of the right hemisphere and 27 of the left hemisphere. Given the small size of the samples provided by the NIFMFS, we only had the crest and the walls of one gyrus per subject without the deep part of the sulci  and a deep (Vb) portion. Layer V had the presence of pyramidal cells whose density decreased going deeper (Vb); on the contrary, their soma area increased, which constituted a criterion for its subdivision  located on sublayer Vb. To establish possible differences in the distribution of VENs between portions of the same gyrus, we placed two-dimensional grids measuring 1500 μm long × 300 μm thick along the layer Vb  both on the crest and on the walls of each tissue section where VENs were found .Within these grids we also chose pyramidal neurons whose soma area was measured to compare with the VENs soma area. The fusiform cells of layer VI whose soma area was compared with pyramidal cells and VENs were located just below the grids. This procedure was performed for neurons that were overlap-free and had no defects that could have affected their measurement. The neuronal soma area was determined by delineating the perimeter of the soma in microphotographs of magnification 40× properly calibrated, and the software gave us the measurement of the bi-dimensional area of the soma in μm2, showing the average value (SD). The analysis of the data was performed with the GraphPad 5.0 software. Data were analyzed considering statistically significant differences with a minimum significance level of p < 0.05. The VEN/pyramidal ratio between crests and walls of the gyri was compared using a student’s t-test. The VEN/pyramidal ratio between hemispheres was compared using a student’s t-test. The soma area of VENs with respect to pyramidal and fusiform cells was analyzed using one-way ANOVA; and the soma area of the three types of neurons between crest and walls of the gyrus was analyzed using two-way ANOVA. For both cases, comparisons were made intra- and inter-hemispherically.In Table p < 0.05). The observed VENs exhibit the elongated bodies with a single basal process and an apical process extending symmetrically. The anti-NeuN antibody labeling showed low intensity in the soma, contrasting with the high intensity in the clearly distinguishable nucleus  as well as the morphological characteristics described in previous studies, in the present study we report for the first time the presence of VENs in sublayer Vb on the medial surface of the human frontopolar cortex . However, the VEN/pyramidal ratio differed statistically between crest and wall of the gyrus (p < 0.05).Although up to 21 VENs were found in a counting grid (from subject 1), these neurons were scattered and did not form clusters. The total number of pyramidal cells quantified in the counting grids where VENs were found was 10971. The VEN/pyramidal ratio considering the totals of each neuronal type was 1:119, that is, VENs corresponded to 0.84% of the pyramidal cells of sublayer Vb on the medial surface of the human frontopolar cortex only in those sectors where VENs were found (see Tables Table p < 0.0001 and p < 0.05 respectively). These significant differences are preserved by discriminating between the portions of the gyrus  of each hemisphere (p < 0.0001 and p < 0.05 respectively). The counts of pyramidal cells between hemispheres did not show statistically significant differences (p > 0.05).Inside the counting grids, we found 81 von Economo neurons in the right hemisphere and 11 in the left hemisphere. The VEN/pyramidal ratio was 1:92 and 1:318, respectively (see Table 2 (79.55 μm2). In the case of pyramidal cells  and that of the fusiform cells of layer VI . On average, VENs were 1.43 times (43.89%) larger than the pyramidal cells of layer Vb (p < 0.05), and 1.88 times (88.70%) larger than the fusiform cells of layer VI (p < 0.05). The soma area of VENs, pyramidal and fusiform neurons did not show significant differences between hemispheres  and 417.10 μm2 (93.45 μm2) in the walls, i.e., 19.7% larger in the latter (p < 0.01). The soma area of pyramidal and fusiform cells, between crest and walls of the gyrus, did not present statistically significant differences (see Figure With respect to the area of the neuronal soma, in VENs, the average of this item was 369.29 μmThis is the first report of VENs on the medial surface of the frontopolar cortex in humans. We had previously made a search for these cells in the frontal pole, specifically on the lateral surface, with negative results (Fajardo et al., According to previous reports, the VEN/pyramidal proportion vary from one cortical region to another ranging from 0.5% to 13% (Nimchinsky et al., Considering that our results and those reported in the frontal region of the insula, the anterior cingulate cortex and dorsomedial BA9, it is possible to suggest that in humans, VENs decrease in the postero-anterior and ventro-dorsal direction, as in that they approach the frontal pole or the dorsomedial convexity of the frontal lobe. Of course, this interpretation needs to be validated in the light of more evidence, for example, by exploring other cortical regions of the medial frontal lobe such as BA25 and BA32.Given the small size of the tissue sample obtained for the present study, there was a lack of data regarding the presence and distribution of VENs in the depth of the sulci. We found that the VEN/pyramidal ratio and the absolute number of VENs were higher in the crest than in the wall of the gyri (see Tables We also found that the VEN/pyramidal ratio and the absolute number of VENs were higher in the right hemisphere than in the left counterpart (see Table On the other hand, the connections of the medial BA10 with other cortical regions in which the presence of VENs has been reported have been associated with processes such as intuitive assessment and generation of rapid responses in social contexts (Baron-Cohen et al., In the human medial frontopolar cortex, the soma area of VENs is larger than that of pyramidal cells of layer Vb, and that of fusiform neurons of layer VI. However, the difference in soma area between VENs and pyramidal cells found in the medial BA10 is less significant than the difference reported in other human cortical regions (Nimchinsky et al., In human medial BA10, data such as the observed small number of VENs and the small differences in the soma area with respect to the pyramidal cells, would suggest that in addition to being a specific cell type, the morphology of VENs might be the product of mechanical forces experienced during the gyrification of cerebral cortex (Van Essen, CAG-A and EB conducted the experiments and carried out the data analysis. CAG-A, MIE, HP and EB designed the experiments. CAG-A, MIE, MFC, HP and EB wrote the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MV and handling Editor declared their shared affiliation.