In this study, the mechanical properties, heat of hydration, and pore structure of early-age cast-in-situ concrete with different sodium sulfate (Na2SO4) concentrations were studied. The mechanism of SO42− internal corrosion was evaluated by measuring the dynamic elastic modulus, compressive strength, and heat of hydration rate. Scanning electron microscopy, energy dispersive spectroscopy, X-ray computed tomography, X-ray diffraction, thermogravimetry-derivative thermogravimetry, and differential scanning calorimetry were applied to analyze microstructural variations and complex mineral assemblages of concrete samples. The results indicated that during the hardening process of cast-in-situ concrete, Na2SO4 first promoted and then hindered the hydration rate of cement, and also hindered the early strength development of the cement. As the concentration of Na2SO4 solution increases, the corrosion products of ettringite (AFt) and gypsum (Gyp) gradually increase, causing cross cracks in the concrete. The proportion of small and medium pores first increases and then decreases, and the large pores first decrease and then increase. The mechanical properties of concrete gradually decrease and diminish the mechanical properties of the concrete (thereby accelerating the damage to the concrete).The deterioration of early-age concrete performance caused by SO In sulfate-rich soil, rivers, lakes, groundwater, and sea water [42− ions [42− ions.Sulfate ion 2), tricalcium aluminate (C3A), or aluminum-phase water in the cement base. The chemical products react to produce ettringite (AFt) and gypsum (Gyp) crystals which fill the pores and cracks in the concrete [Numerous studies have focused on the external sulfate attack (ESA) test and the concrete mechanical properties  after 28 days of standard curing under sulfate attack . The degradation law and mechanism have also been studied ,7, and iconcrete . The SO4concrete ,13,14,15concrete ,17,18, t2SO4 into fresh concrete as Na+ and SO42−, and directly participates in the entire concrete hydration process. To date, research on the mechanism governing internal sulfate corrosion damage is relatively rare, and there is not enough experimental data to verify the relevant theoretical models. Therefore, herein, we systematically discuss the evolution of hydration heat, compressive strength, dynamic elastic modulus, and pore changes in early-age concrete under ISA conditions, and compare the impacts of corrosive environments (ISA versus ESA) on concrete durability to improve the robustness of concrete. The service performance of concrete structures in salt-rich environments is of great significance; therefore, it is crucial to study the damage evolution of early-age concrete under the action of sodium sulfate ISA.When pouring underground cast-in-situ concrete structures in a salt-rich environment, it is inevitable that salt-containing media are mixed into the fresh concrete, causing internal corrosion  in concrete. Mielenz et al.  first pr2SO4 to reveal the deterioration mechanism of early-age concrete via sodium sulfate ISA. In this study, varying concentrations of Na2SO4 solutions were used, with mass ratios of 0%, 3%, 5%, and 10%. The evolution process of the heat of hydration, relative dynamic elastic modulus, and compressive strength of the Na2SO4-corroded concrete were analyzed in the early stages. X-ray computed tomography was used to examine the pore structure of concrete subjected to different concentrations of Na2SO4 after 28 days of standard curing. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric (TG) difference analyses were used to investigate the changes in the microstructure, corrosion products, and crack evolution of concrete with different concentrations of Na2SO4.The purpose of this work was to study the hydration heat, mechanical properties, and microstructural evolution process of early-age concrete in the presence of various concentrations of Na2SO4 reagent  was obtained from Tianjin Beichen Fangzheng Reagent Factory .This study used PO42.5 Portland cement, produced by Jidong Heidelberg Jingyang Cement Co., Ltd. , which was similar to ASTM Type I in the USA ,26,27. T2SO4 contents: a control group (Q), which did not contain Na2SO4, and groups 3N, 5N, and 10N. The numbers in the latter three codes represent the proportion of Na2SO4 in the concrete, which were 5.85, 9.75, and 19.5 kg, accounting for 3%, 5%, and 10% of the water mass. The group numbers and mixing ratios of the investigated concrete samples are presented in Four types of concrete samples were poured with varying Na2SO4 powder weighed, mixed with water, and added to the mixer in three doses. Finally, the samples were constructed into 100 mm × 100 mm × 100 mm and 100 mm × 100 mm × 400 mm test blocks. The samples in the molds were placed in a controlled environment at room temperature  and 95% relative humidity to cure for 24 h before being removed from the molds.Before concrete pouring, raw materials were weighed out. First, coarse aggregate, river sand, and cement were stirred in a mixer for 3 min, and then, distilled water was added, and the mixture was stirred for an additional 3 min. For the 3N, 5N, and 10N samples, the concrete was poured in different batches, with Na2SO4 content were removed, and the accumulated surface moisture was dried with a rag. An HYE-2000BS electro-hydraulic servo pressure testing machine was used to test the compressive strength of concrete samples. The average value was considered as the concrete compressive strength, and the loading speed was controlled to 5 kN/s.After curing in a standard curing room for 1, 3, 7, 14, or 28 d, samples with varying Na2SO4. Each sample was measured every two days. For this test, the surface moisture of the 100 mm × 100 mm × 400 mm sample was removed with a rag, and the sample mass was measured using an electronic scale with accuracy to 0.1 g. Three tests were performed for each sample, and the average value was considered the dynamic elastic modulus of the concrete. The test frequency was set to 1000–3000 Hz.A NELD-DTV dynamic elastic modulus tester  was used to test the dynamic elastic modulus of concrete samples containing different concentrations of Na2SO4 solutions. A U.S. TAM Air thermal conductivity isothermal calorimeter (Waters Technology (Shanghai) Co., Ltd., Shanghai, China) was used to test the hydration heat release and hydration rate of cement containing different concentrations of sodium sulfate over 0–7 days. These tests were carried out in accordance with ASTM C1679-2007 [According to the type of concrete, the uniform water–binder ratio of 0.485 was used, mixed with different concentrations of 0%, 3%, 5%, and 10% Na679-2007 .The pore structures of the 100 mm × 100 mm × 100 mm concrete samples with different concentrations of sodium sulfate after 28 days of standard curing were investigated using a German Siemens 64-row X-ray computer tomography scanner . During the scanning process, the voltage was 120 kV, the current was 300 mA, the scanning thickness of the sample was 0.6 mm, and the interval was 0.6 mm. The AVIZO 9.0.1 software program  was used to perform post-processing of the concrete scan slices.2SO4 on concrete, SEM and energy dispersive X-ray spectroscopic (EDS) analyses were carried out on the 28-day standard curing concrete sample. The SEM/EDS investigations employed a German Zeiss Sigma 300 field emission scanning electron microscope  to take pictures and perform elemental analysis of the samples were magnified 20,000 times and 5000 times, respectively. The samples were obtained from smashed concrete blocks, and representative fragments were selected for the analysis. The X-ray diffractometer was equipped with Bruker D8 Advance equipment . During the experiments, the voltage was 40 kV, the scanning rate was 50 scans/min, and the minimum current was 100 mA. The powder sample analyzed by X-ray diffraction was drilled 10 mm from the surface with an electric hammer and filtered through a 0.075 mm sieve.To study the internal corrosion mechanism of Na2SO4 was analyzed using an SDT Q600 thermogravimetric/differential heat combined thermal analyzer . In this experiment, the heating rate was 10 °C/min from 30 °C to 900 °C, and the nitrogen flow rate was 50 mL/min. The powder sample was drilled 10 mm from the concrete surface with an electric hammer and filtered through a 0.075 mm sieve.After 28 days of standard curing, the thermogravimetry of concrete powder from samples with different concentrations of Na2SO4 concentrations on the compressive strength and dynamic elastic modulus of early-age concrete, these parameters were measured for concrete samples after natural curing for one day after pouring , and after the concrete samples were placed in a standard environment  for designated amounts of time; the compressive strength values of concrete were evaluated after 3, 7, 14, and 28 days, and the dynamic elastic modulus of concrete was tested every 2 days, and the average value was reported.To analyze the influence of different Na2SO4 over time. In general, the compressive strength of concrete increased gradually throughout the standard curing process. The compressive strength of the Q sample was consistently higher than those of concrete samples containing Na2SO4.2SO4. The compressive strength of concrete increased significantly in the first three days, and then continued to increase slowly thereafter. After one day of natural curing, the compressive strengths of the 3N, 5N, and 10N concrete samples were about 82.28%, 81.93%, and 78.84% of the Q sample, respectively. After standard 28-day curing, the compressive strength of the Q, 3N, 5N, and 10N concrete samples were 47.278, 44.624, 41.527, and 37.416 MPa, respectively. Therefore, the compressive strength of the 3N, 5N, and 10N concrete samples were 94.4%, 81.93%, and 78.84% of that of the Q sample, respectively. These results indicated that the presence of Na2SO4 in fresh concrete hindered the establishment of the concrete’s compressive strength. As the concentration of Na2SO4 increased, the compressive strength of the concrete gradually decreased.There were observable differences in the compressive strength augmentation of concrete with different curing ages and concentrations of Na2SO4 solution into fresh concrete can inhibit the hydration rate of the cement, thereby affecting the internal skeletal structure and porosity of the concrete, and causing the relatively low strength of the Na2SO4 corrosion products. As the concentration of the Na2SO4 solution increases, the quantity of corrosion products also gradually increases, which may have a more substantial impact on the distribution of concrete pores and cracks.The concrete’s compressive strength is mainly related to the degree of hydration, porosity, and cracks. The results showed that the addition of Na2SO4 can be calculated using Equation (1).En is the change in the concrete’s dynamic elastic modulus after n days of standard curing, E0 is the dynamic elastic modulus of concrete one day after pouring (MPa), and En is the dynamic elastic modulus of concrete after n days of standard curing (MPa).Changes in the dynamic elastic modulus can reflect changes in the concrete’s integrity, compactness, and hydration degree to a certain extent. The propagation of microcracks in the concrete and the associated reduction in compactness effectively decrease the resonance frequency, i.e., decrease the dynamic elastic modulus. The relative changes in the dynamic elastic modulus of concrete samples containing different concentrations of Na2SO4. The relative dynamic elastic moduli of the Q, 3N, 5N, and 10N concrete samples after 28 days were 1.341, 1.287, 1.272, and 1.254 times that of the samples after natural curing for 24 h, respectively. These results indicate that as the concentration of Na2SO4 in concrete increases, the relative dynamic elastic modulus of the concrete gradually decreases.It is clear from 2SO4 are basically the same. This verified that as the concentration of Na2SO4 solution increases, the impact of concrete density, hydration rate, porosity, and cracks are more significant.In general, the relative dynamic elastic modulus and compressive strength of concrete samples containing different concentrations of Na2SO4 concrete samples. Based on 2SO4-containing samples were higher than that of Q sample, but after about 90 h, they were all lower than that of the Q sample. Up to two days, as the concentration of Na2SO4 increased, the heat of hydration gradually increased, but after two days, the heats of hydration of samples with different concentrations of Na2SO4 were basically the same and lower than that of the Q sample.2SO4. The first peak corresponding to the heat release rate from the Q, 3N, 5N, and 10N samples corresponded to 1.112, 1.261, 1.33, and 1.41 mW/g, and occurred at 6.99, 6.36, 6.075, and 5.925 h, respectively. The peak heat release rate of 3N, 5N, and 10N cements occurred earlier than that of the Q sample by 1.072, 0.922, and 0.636 h, respectively. As the concentration of Na2SO4 increased, the peak of the hydration heat exotherm gradually increased and tended to occur later.Based on 2SO4 entered the deceleration period, during which, the hydration heat release of different concentrations of Na2SO4 decreased at different rates. At about 16 h, the hydration heat release rate of the 10N sample was larger, and that of the 3N sample became larger between 16 h and 35 h, indicating that the Na2SO4 concentrations and hydration time before the deceleration period impacted the cement hydration. The heat rate also had a certain effect. After about 35 h, the heat release rate of the Q sample was higher than that of cement mixed with Na2SO4. These results indicate that before the acceleration period, Na2SO4 can promote cement hydration, and as the concentration of Na2SO4 increases, the hydration heat release rate of cement is faster. In the late deceleration period and stable period, Na2SO4 content inhibited cement hydration. Therefore, in the standard curing environment of different concentrations of Na2SO4 concrete, the Na2SO4 solution inhibits the hydration rate of the cement. As the concentration of Na2SO4 increases, the compressive strength and dynamic elastic modulus of the concrete gradually decrease.Subsequently, cementitious materials containing different concentrations of Na2SO4  after 28 days of standard curing. 2SO4, and 2SO4 confirmed that the main corrosion products were AFt, Gyp, and sodium hydrate. The main corrosion reactions caused by Na2SO4 are shown in Equations (2)–(7) [The mechanical properties of early-age concrete are related to the hydration products, mineral composition, pores, and cracks in the concrete. To examine their microstructures, XRD, SEM, and EDS analyses were performed on concrete samples with different concentrations of Na (2)–(7) ,32,33,342SO4 increased, the intensity of the AFt, Gyp, and Na2SO4 diffraction peaks in the concrete gradually increased, while the intensity of the Ca(OH)2 and C-S-H diffraction peaks gradually decreased. In part of the XRD patterns in 2SO4 were about 9.248° and 11.638°, but there was no corrosion product peak in the Q sample at the same 2θ. It was also observed that the intensity of the AFt and Gyp diffraction peaks gradually increased as the concentration of Na2SO4 increased. This indicated that as the concentration of Na2SO4 increases, the amounts of AFt and Gyp corrosion products in the concrete gradually increase, Na2SO4 hydration products appear, and Ca(OH)2 consumption gradually increases.Based on 2 crystals. As the concentration of Na2SO4 increased, the concrete became covered with small pores and part of the honeycomb structure. Additionally, the amount of AFt in the pores and cracks  curves determine the temperature range corresponding to the weight loss of corrosion products. The crystalline composition of corrosion products of Na2SO4 concrete was thus verified.2SO4 concrete appeared in TG/DTG analysis, the first weight loss stage or peak temperature was 80–105 °C [2. The final weight loss stage or peak temperature was 600–800 °C, which was due to the decomposition of calcium carbonate [2SO4 increased, the absorption peak areas of Gyp and AFt gradually increased, while the absorption peak areas of Ca(OH)2 gradually decreased. These results confirmed that the damage to the mechanical properties of concrete is mainly caused by the corrosion products Gyp and AFt. At the same time, as the concentration of Na2SO4 increases, the production of Gyp and AFt corrosion products increased, and the Ca(OH)2 concentration in concrete decreased. The mechanical properties of concrete mainly show the rapid decline of compressive strength and dynamic elastic modulus.It is clear from 0–105 °C ,36,37, warbonate ,39,40. B2SO4 on the pore structure of concrete, X-ray computed tomography was applied for the samples cured for 28 days. Owing to the complexity and irregularity of the internal pore structure of concrete, the shape of the pores can be standardized as spheres, and the equivalent diameter of the pores can be determined by calculating the pixel volume of each sphere. Equivalent diameters <2000 μm are regarded as small pores, diameters of 2000–4000 μm are mesopores, and those ≥4000 μm are macropores.The porosity of concrete has always been considered as the main factor governing the mechanical properties of concrete. To study the influence of different concentrations  of Na2SO4; the red areas represent the pore structure. 2SO4 increased, the pore volume ratio in the concrete first decreased and then increased, and the pore area in the 5N sample was the smallest. It is clear from 2SO4 changed from 0% to 5%, the area and density of the red area in the concrete decreased. When the Na2SO4 concentration was greater than 5%, the red area of the concrete became denser and more obvious with increasing concentrations of Na2SO4; additionally, the red pores became connected.2SO4 on the pores of early-age concrete the pores with equivalent diameters of 0–1000, 1000–2000, 2000–3000, 3000–4000, 4000–5000, and ≥5000 μm were analyzed. A histogram depicting the relationship between the equivalent diameters of concrete pores and their Na2SO4 content is shown in 2SO4. Among the concretes containing Na2SO4, the proportion of small pores in sample 5N was the largest. When the content of Na2SO4 was 10%, the proportion of small and medium pores was significantly less than that in 5N. This indicated that the reason of the low-concentration Na2SO4 concrete damage is mainly the corrosion products of gypsum and AFt. As the concentration of Na2SO4 increases, the corrosion products of Gyp and AFt in concrete gradually increase, and the proportion of small and medium pores increases significantly. Excessive concentration of Na2SO4 produces a large amount of corrosion products of Gyp and AFt in concrete, which is expansion stress generated by corrosion products much higher than the resistance of the matrix. Expansion stress causes new cracks in the concrete. At the same time, there are interconnected pores in the concrete, which reduces the small and medium pores and increases the large pores, so that the mechanical properties of concrete gradually decrease with the increase of sodium sulfate concentration [To evaluate the effect of different concentrations of Nantration ,42,43,442SO4 on early-age concrete. Analysis of XRD, SEM, EDS, TG (DTG/DSC), and X-ray computed tomography results revealed how various concentrations of Na2SO4 impacted concrete minerals, microstructures, and pores. Previous studies generally indicated that Na2SO4 is consumed in the process of cement hydration, resulting in little or no effect on the mechanical properties and microstructure of concrete [2SO4 on concrete is mainly via ESA; however, to date, there are few studies on ISA in early-age concrete.In this study, tests of compressive strength, relative dynamic elastic modulus, and heat of hydration showed the damaging effects of different concentrations of Naconcrete ,22,45. A2SO4 solutions to fresh concrete, the Na2SO4 exists in the form of Na+ and SO42−. Na2SO4 can react with Ca(OH)2 precipitated during cement hydration to form Gyp. This process consumes a large amount of Ca(OH)2, which promotes the hydration of tricalcium silicate(C3S) and dicalcium silicate(C2S) [3A) reacts with Gyp to form a swelling product AFt. When hydrated for a certain period of time, Na2SO4 reacts with Ca(OH)2 to generate NaOH, which increases the OH− concentration in the environment, thus increasing the alkalinity and inhibiting the continued formation of Ca(OH)2. Simultaneously, the unconsumed Gyp and the over-corrosion product AFt wrap the surface of the cement particles, reducing the hydration rate of the cement.After adding Naate(C2S) , and the2SO4 increased, XRD results indicated that the intensity of the Gyp and AFt diffraction peaks gradually increased. This shows that the AFt and Gyp corrosion products in concrete gradually increased in concentration with greater amounts of Na2SO4. As the concentration of Na2SO4 increased, the hindrance of cement hydration became clearer in the late deceleration and stable periods. As shown in 2SO4 concentration in the concrete increased, the cement hydration rate gradually increased. From the late deceleration period into the stable period, the cement hydration rate of the Q sample was higher than that of the Na2SO4-containing cement samples, which further verified that Na2SO4 promoted cement hydration in the early stage and inhibited the development of cement hydration later.When the concentration of Na2SO4, it can be concluded that the overall mechanical properties of the Q sample were greater than those of concrete samples containing Na2SO4. The XRD, XRD, SEM, EDS, TG (DTG/DSC), and X-ray computed tomography analytical results showed that the addition of Na2SO4 was the main cause of damage to the mechanical properties of concrete.By evaluating the compressive strength and dynamic elastic modulus of concrete samples containing different concentrations of Na4 in the cement, which delayed the cement setting process. At this time, there were small amounts of Gyp and AFt in Q, which filled the pores and cracks formed by hydration, the proportion of mesopores is higher than that of large and small pores, causing no damage to the mechanical properties or microstructure of the concrete [2SO4 to the fresh concrete, it immediately participated in the corrosion reaction. In the Na2SO4 ISA, the concrete itself needs to be provided with Ca2+. Generally, the Ca2+ in concrete comes from silicate and C-S-H. In fact, C-S-H has the most direct impact on the compressive strength and elastic modulus of concrete. Therefore, the mechanical properties of concrete decrease after Na2SO4 erosion. In addition, the strength of the AFt and Gyp corrosion products was much lower than the strength of the concrete matrix.The Q sample contained Gyp and AFt, mainly because of the addition of CaSOconcrete . After a2SO4 was less than 5%, the corrosion products in concrete were mainly AFt and Gyp crystals, and the volume of the Gyp crystals increased by about 1.24 times [2SO4 increased, corrosion products gradually accumulated and were stored in the pores and cracks. The large pores in the concrete gradually change to mesopores, resulting in a significant decrease in the proportion of large pores in the concrete and a significant increase in the proportion of mesopores in the concrete. At the same time, more Gyp and AFt crystals were found in pores and cracks. At the same time, the expansion stress and water-absorbing expansion caused by the deposition of AFt and Gyp [2SO4 solution consumed a large amount of Ca2+, causing the C-S-H crystals to change from a block structure to a honeycomb shape, which reduced the compactness and compression resistance of the concrete. At the same time, the pores and cracks were filled with a large amount of corrosion products. The proportion of internal small and medium pores was relatively high. Meanwhile, although the internal pore volume ratio of the concrete is reduced to a certain extent, the compressive strength of the corrosion products Gyp and AFt is lower than the strength of the matrix as a whole, making the mechanical properties of the concrete lower than the Q sample as a whole. Therefore, the deterioration rate of the mechanical properties of concrete in a low-concentration environment was relatively small.When the concentration of Na24 times ,49. Corr and Gyp  exceeded2SO4 was greater than 5%, a significant number of Gyp and AFt crystals were produced inside the concrete. The volume expansion of Gyp was larger than that of AFt, and Na2SO4 crystals also precipitated. The expansion stress generated at this time was much greater than the tensile strength of the matrix, which created new cracks and caused the original cracks in the concrete wider. Besides, a large number of connected pores appear, resulting in intersecting cracks inside the concrete. Further analysis revealed that the corrosion products Gyp and AFt cannot completely fill the internal pores and cracks of the concrete, so that the small and medium pores in the concrete gradually shift to the large pores, and the proportion of the equivalent diameter pores greater than ≥4000 μm increases significantly. In addition, there is a significant increase in the internal mortar and aggregates. The bond strength of the interface transition zone is reduced, which leads to the acceleration of the concrete mechanical properties deterioration.When the concentration of Na2SO4 on the mechanical properties of early-age cast-in-situ concrete from multiple perspectives. The main conclusions obtained in this work can be summarized as follows:This study revealed the damaging potential of different concentrations of Na2SO4-containing concrete was lower than that of the control sample, and the mechanical properties of concrete gradually decreased with increasing Na2SO4 concentrations.Under a standard curing environment, the compressive strength of Na2SO4 was mainly due to the impacts of corrosion products on pores and cracks, which changed the internal microstructure of the concrete and reduced the integrity of the matrix.The deterioration of concrete by Na2SO4 in concrete increased, C-S-H structures changed from blocks to honeycombs, thus reducing the strength of the concrete matrix. Simultaneously, the proportion of small and medium pores first increased and then decreased, while the proportion of large pores first decreased and then increased with increasing Na2SO4 concentration. This result reflected the degree of damage that Na2SO4 can have on the microstructure of concrete.As the concentration of Na2SO4 first promoted and then hindered the hydration rate of cement, and Na2SO4 was unfavorable in terms of the early strength development of the cement. Therefore, Na2SO4 contamination in cast-in-situ concrete should be strictly prevented.During the hardening process of cast-in-situ concrete, Na2SO4 solution on the early-age mechanical properties, cement hydration rate, pores, and microstructure of cast-in-situ concrete, and it can also help engineers deal with saline soil and salt lake, which provide a reliable reference basis for cast-in-place concrete structures in the region.The research conclusions of this article can make up for the gap in the study of the influence mechanism of different concentrations of Na


Modification of concrete with waste materials is an increasingly common process, and they are primarily used as a partial substitution for cement. In the case of inert or nearly inert additions according to EN 206, the effectiveness of such a modification mainly concerns ecological aspects and, only to a small extent, mechanical properties. This article analyses the effect of modifying cement concrete with waste limestone powder as a partial substitution for fine aggregate. The analysed waste arises as a result of the accumulation of dust produced during the initial preparation of aggregate for the production of hot mix asphalt (HMA). In order to analyse the effect of waste on compressive strength, an experimental design was prepared with variable substitution levels and variable water/cement ratios. Compressive strength tests were performed after 28 to 90 days. Statistical analysis of the results was performed. Microscopic evaluation of the fractures of the samples was carried out to clarify the mechanism of transition zone enhancement, which resulted in an increase of compressive strength of the composite.  The requirements of sustainability imply, not only the appropriate use of natural resources, but also the design of structures with adequate mechanical properties and durability . Both st2 crystal (CH) content, large ettringite (Aft) crystal content, and CH-oriented growth [This is due to interfacial transition zone (ITZ) high water-binding ratio, as well as its large Ca(OH)d growth . In thisd growth ,8. There3 is low and therefore the reaction products occur only in the boundary zone. The formation of hydration products in the boundary increases the surface roughness of aggregate grains, which consequently leads to increased adhesion between paste and aggregate. Additionally, it has been reported [There are two general methods for improving the transition zone microstructure: pozzolanic additives which react with portlandite, or fine-grained inert material that is used to obtain the compacted–densified micro-structure of the transition zone ,10. Smalreported , that, wreported .Research on the effects of limestone powder is still ongoing, but most studies show that it has a positive effect on the strength and durability of concrete. ,16,17,18In the present study, the influence of the dosage level of waste limestone powder on compressive strength was investigated with the consideration of different water/cement ratios. In order to clarify the mechanism of waste limestone powder effect on the enhancement of the mechanical properties of concrete, a detailed analysis of the microstructure of the paste–aggregate transition zone was carried out.The aim of the research presented in this paper was to illustrate and justify numerically the influence of waste limestone powder on the strength and durability characteristics of concrete. Basic tests of the potential activity of this additive give negative results, yet concrete strengthening is observed. Therefore, observation of the transition zone was undertaken, and its structure was analysed, in terms of what part consisted of portlandite and what part consisted of C-S-H gel. Observations and measurements were made of crack width along the aggregate grain surface and scratches perpendicular to the aggregate grain surface. By analysing the microscopic images and measuring the mentioned features, the reason for the increase in compressive strength of concretes modified with waste limestone dust was presented.The research part of the presented work can be divided into stages: (1) Analysis of the extracted limestone dust as a potential additive to cement concrete; (2) Potential activity analysis; (3) Analysis of the effect of substitution of sand by waste limestone dust on the compressive strength of concrete; (4) Analysis of the microstructure of selected concretes to locate the causes of the observed effect on strength. In the first two stages, the material analysed is resting limestone powder, and in the next two stages, the concrete is a result of the modification.3, is 84.85%wt. The content of SiO2 is 7.06%wt. and Al2O3 is 2.38%wt.  [2/cm3, and the blaine fineness of approximately 3000 cm2/g are values not differing from typical waste mineral additives such as fly ash or rice hull ash. These values indicate that waste limestone powder is potentially a good microfiller for cement concrete.The analysed waste powder  is generated from the coarse aggregate preparation process for HMA mixtures. Therefore, its chemical and mineral composition will be the same as that of the base aggregate. Because of its price and its good adhesion with asphalt, limestone is a very common aggregate in HMA production. Because one regime of the production is used continuously for large quantities of HMA, it is well known that the waste collected in the filters is chemically quite homogeneous for one recipe of the mix and season of the year . The che quartz) . Due to In order to analyse the activity of the tested mineral powder, the determination of the pozzolanic activity index was performed by two complementary methods. The methods used were: the Jarrige and Decreux chemical method and the EN 450-1  physicalThe purpose of the conducted research was to determine the impact of partial substitution of the fine aggregate with the waste limestone powder on the compressive strength of cement concrete. Substitution levels were 2.93% up to 20% of cement mass. Substitution levels were expressed as a percent of cement mass because this manner is more informative. The water/cement ratio values scope was 0.35–0.5.3; the crushed granite aggregate of the group of fractions 2/16   and river sand  (0/2–37%); the air-entraining admixture in a constant amount of 0.2% of cement mass and water reducing admixture in a variable amount dosed to obtain a constant consistency of S3 , amounting to 375 kg/m 12350-2 , 100–150The determination of the effect of waste mineral powder concrete modification on strength was based on the statistical design of the experiment. This approach is justified by minimizing the necessary trials while allowing the regression function to have a high correlation coefficient. The independent variables were as follows: water/cement ratio (W/C) in the range of 0.35–0.55 and the level of sand substitution with the waste powder, expressed as a mass ratio of waste to cement in the range of 0–20% (P/C), which means 0–10.8% of natural sand mass. Due to the planned statistical analysis, a bi-factorial polyseck-rotal-quasiuniformal plan  was adop3. The crushed granite aggregate of the group of fractions 2/16 and river sand were used. The grain size curve was selected according to the standard composition by EN 1766:2001 . An air-entraining admixture was used in a constant amount and the water reducing admixture was used in a variable amount, dosed to obtain a constant consistency of S3 for all mixes.In order for the study to have applicability and reference composition, unmodified concrete mix  was adopted in accordance with standard EN 1766:2001. This adoption of the reference composition makes the designed concrete suitable for most exposure classes according to EN 206. Therefore, the concrete mixes were prepared with the use of a fixed amount of cement, CEM I 42.5 R NA HSR, amounting to 375 kg/mCompressive strength was tested according to EN 12390-3 , after dAccording to EN 12390-2 , for eac2·s). After the application of the initial load, which did not exceed approximately 30% of the failure load, the load was increased continuously until no greater load could be sustained. The maximum load, indicated in kN, was recorded. Compressive strength was calculated as the quotient of recorded load and cross section area and expressed in the nearest 0.1 MPa.According to EN 12390-3 after removal of the specimen from curing, specimens was tested for strength as soon as practicable, within 1 h. The test facility was (20 ± 5) °C. Before being placed in the testing machine , the excess moisture from the surface of the specimen was wiped off. The cube specimens were positioned so that the load was applied perpendicular to the direction of casting. The constant rate of loading was 0.5 MPa/s  with an EDS probe  was used. The experiment was carried out on the samples sprayed with a conductive carbon layer at an accelerating voltage of 15 keV.The comparison of the results of dust activity tests with both methods shows that its chemical  activity is unlikely to be sufficient in this case . This isThe compressive strength (fc) of the concretes after varying times of care was investigated in this study. The strength test results are summarized in For concretes with a constant level of sand substitution by lime powder, the strength gain over time followed a similar pattern, regardless of the W/C ratio. The compressive strength was higher the lower the W/C ratio. For higher W/C ratios, the change in strength over time was greater than for lower W/C ratios a.The increase in compressive strength of concretes of compositions with constant W/C ratio varied with the level of sand substitution with waste. The increase in strength over time was greatest for P/C = 10%. As the W/C ratio increased, the concretes had higher compressive strengths b. The coTests of the paste–aggregate transition zone were carried out for concrete compositions with constant W/C = 0.45 and varying levels of substitution of sand for waste limestone dust. Concretes of compositions were numbered: 5 (P/C = 0%), 6 (P/C = 20%) and 7 (P/C = 10%) according to the experimental plan. The tests were carried out on freshly made fractures using a scanning microscope with an EDS X-ray microanalyzer . From the observation of the transition zone in the unmodified concrete, it is also possible to observe quite large cracks of the paste–aggregate zone  and micrWithin the analysed sample with P/C = 10%, no cracks perpendicular to the aggregate surface were observed. In contrast, cracks along the fine aggregate were either imperceptibly small or within 0.2 µm . At the Image analysis of concrete with 20% waste sand substitution—composition No. 6 , which indicated very good adhesion of aggregate to paste. The transition zone with increased portlandite content, typical for concrete, was not present in the sample .No cracks perpendicular to the aggregate surface were located in the analysed concrete sample with a powder substitution level of 20%. The scratches parallel to the surface were much smaller than in the other analysed concretes . The widSummarizing the analysis of the microstructure of concrete fractures with constant W/C and variable levels of sand substitution by waste limestone powder, it can be concluded that the addition of waste has a beneficial effect on the microstructure of the transition zone between paste and aggregate . In the Due to the growing interest in the strategy of sustainable development in the construction industry and the need for rational waste management, new ways of utilizing waste are being sought. The basic requirements for cement concretes are their technological and mechanical properties, one of the most important of which is compressive strength. The research presented in this article demonstrates the significant potential of waste lime powder from aggregate dusting as a partial replacement for fine aggregate in concrete and has indicated a new direction for research in the use of this waste. By using waste limestone powder, the paste–aggregate transition zone is changed. It is strengthened, which results in the increased strength and durability of cement concretes modified in this way.


Long-term continuous monocropping negatively influences the physicochemical and biological characteristics of cultivated soil, especially for the economically important crop of flue-cured tobacco that is intolerant to continuous monocropping. The underlying mechanism of soil sickness under continuous monoculture and the temporal dynamic changes over the tobacco life cycle among different monoculture time spans remain poorly characterized. In this study, high-throughput sequencing targeting the 16S rRNA gene phylogenetic marker was performed on 60 soil samples of rhizosphere soil from flue−cured tobacco in the replanting, growth and harvest period across 5, 10, and 20 years of a continuous monocropping system. Bacterial community diversity decreased with the increase in duration of continuous monocropping, and the rhizosphere microbiota was highly dynamic in the harvest period. The random forests algorithm identified 17 taxa as biomarkers and a model was established to correlate root microbiota with continuous monocropping time of flue-cured tobacco. Molecular ecological network analysis elaborated the differences and interactions in bacterial co-occurrence patterns under different monocropping systems. The co-occurrence microbial network was larger in size but there were fewer interactions among microbial communities with the increase in continuous monocropping duration. These results provide insights into the changes of flue−cured tobacco root microbiome diversity in response to continuous monocropping and suggest a model for successional dynamics of the root-associated microbiota over continuous monocropping time and development stage. This study may help elucidate the theoretical basis underlying obstacles to continuous monocropping and could contribute to improving guidance for tobacco production. Arabidopsis  of continuous monocropping. Consequently, there were three main objectives in the current study to explore the underlying mechanism(s) of continuous monocropping in flue-cured tobacco: (1) to understand microbial ecological patterns and their relationships with soil physicochemical properties and environmental factors in response to continuous monocropping; (2) to examine the characterized microorganisms as biomarkers in the rhizosphere to predict the prevailing models that reflect the soil conditions during continuous monocropping; and (3) to determine if continuous monocropping affects the root-associated microbiota in different development stages of the crop, and if it does, how the root microbiota change over the full life cycle of the crop among the different monoculture time spans.To understand temporal dynamic changes in the rhizosphere bacterial community in continuous monoculture, high-throughput 16S rRNA gene sequencing was performed in bulk on rhizosphere soil samples of flue−cured tobacco that was non-cropped (CK) or continuously monocropped for 5, 10, and 20 years  at the same geographical location. In addition, to increase knowledge of the response of bacterial community structure to the continuous cropping of flue−cured tobacco, a spatiotemporal approach was employed to detail the successional progression of the microbiota in the periods of transplanting, growth, and harvest across 5–20 years of a continuous monocropping system. This study provides insights into root microbiome assembly of flue−cured tobacco in response to continuous monocropping and may help elucidate the theoretical basis of the mechanism underlying continuous monocropping obstacles, allowing artificial interventions and replanting improvements of this important crop in the future.–1 annually, the formulation of the fertilizer was as follows: N:P2O5:K2O = 10:12:18. Along with the expansion of the cultivated base, fresh fields were constantly being used for flue-cured tobacco cultivation during the past few decades. Samples defined as 5, 10, and 20 yrCC were collected from the rhizosphere of flue-cured tobacco material named “Honghuadajinyuan” (HD) after the fifth, tenth, and twentieth years of continuous monocropping, respectively, and control soil samples defined as CK were collected from non-planting areas around the tobacco-planted areas. Rhizosphere soil of flue−cured tobacco was sampled at three development stages of the crop, including transplanting, growth (70 days after transplanting), and harvest (118 days after transplanting) in each field of the different continuous monocropping systems.Samples were collected from a commercially long-term cultivated tobacco field, the standardized raw material planting base of flue-cured tobacco named “Kuan&Zhai Garden” established by China Tobacco Sichuan Industrial Co., Ltd. This site is located at Wudongde town, Huidong County, Liangshan, southwest China . There is a long history of flue-cured tobacco cultivation in this area, with some sites having spent more than 30 years under the continuous monocropping system. Soil type in the experimental fields was ACfa (Alumi-Ferric Alisols) according to the FAO-UNESCO Soil Map of the World, and the fields were flat with uniform fertility in the long-term and had compound fertilizer applied at the rate of 750 kg ha2 under each defined year of monocropping and was separated into six regions represented by replications. Each sample was collected from five individual tobacco within a field region of 110 m2, at distances of approximately 10 m from each other. To collect rhizosphere soil, roots were firstly shaken to remove large clumps of soil (the clumps were retained), then the roots with tightly adhering soil were placed into 50-mL falcon tubes containing 15 mL autoclaved phosphate-buffered saline (PBS) solution and transported on ice to the laboratory. The roots with soil attached were vortexed in PBS solution with cyclical washing in fresh PBS solution until no soil particles were visible in the solution. All the collected PBS solutions were centrifuged at 12,000 r.p.m. for 10 min, the supernatants were removed, and 10 mL of the resuspended slurry was used for DNA extraction. Large clumps shaken from the roots at each sampling site with six replications were air-dried and analyzed for physical and chemical indexes.The area of sampling was restricted to a field of 667 m3–-N), total phosphorus (TP), available phosphorus (AP), total potassium (TK), and available potassium (AK) were assayed. Soil pH was measured using a pH meter  in a soil water suspension  after shaking for 30 min. OM was determined by the potassium dichromate method , total nitrogen (TN), nitrate-nitrogen -ACTCCTACGGGAGGCAGCAG-3′), (R5′)-GGACTACHVGGGTWTCTAAT-3′) . The resRaw sequence data were demultiplexed using the barcode sequences by in-house Python scripts, then quality filtered and assembled into full contigs using Trimmomatic  and FLASP-values were corrected for multiple tests using a false discovery rate (FDR) set at 0.05. Alpha rarefaction diversity was calculated a QIIME diversity analyses workflow script core_diversity_analyses.py and unconstrained principal coordinates analysis (PCoA) was performed using the vegan capscale function in R by specifying an intercept-only model -1], and permutational multivariate analysis of variance (PERMANOVA) was conducted using the adonis function from the vegan package .To model continuous monocropping years as a function of microbiota composition, a random forest model was generated by regressing the relative abundance of all OTUs against the continuous monocropping years from which the soil samples were collected. Random Forests approach is one of the most robust ensemble machine learning methods for classification and regression. Multiple weak classifiers were assembled to produce a strong classifier. Random Forests tries to grow multiple decision (CART) trees with different samples and different initial variables based on the construction of single classification trees, like a bootstrapping algorithm. Each tree gives a classification. Multiple trees choose the classification with the most votes to perform the final prediction  was both ≥ 0.6 and statistically significant at P < 0.01 . Nodes iP < 0.01 .To define the topological roles of different OTUs (nodes), the connectivity of nodes within (Zi) and among modules (Pi) was calculated using in-house R script according to the functions proposed by 3–-N, and AK in continuous cropping soil were significantly lower than those in CK samples. However, the AP content was lowest in CK soil and accumulated with the increase in cropping years.The edaphic physicochemical properties among different continuous monocropping systems are shown in A bacterial community profile was generated based on 60 samples collected from the bulk and rhizosphere soil of CK and 5, 10, and 20 years of continuous monocropping, in the periods of transplanting, growth (70 days after transplanting), and harvest (118 days after transplanting) respectively. Through amplification of the V3–V4 region of the 16S rRNA gene followed by Illumina sequencing, 4,973,193 high-quality sequences were obtained from the 60 samples .2FC) between continuous cropping and CK decreased with the increase in continuous monocropping time  revealed significant differences among samples exposed to different continuous monocropping times. Rarefaction plots of OTUs, Faith PD and Shannon . Divergences in β-diversity were still identified among 5, 10, and 20 yrCC rhizosphere samples within each cluster separated by distinct growing period, and this observation was supported by the PERMANOVA statistic . This suggested the composition of the tobacco rhizosphere bacterial community was affected by the development stage time-spans in the full life-cycle of the plants and marginally influenced by the continuous monocropping time-spans.To elucidate the degree by which bacterial communities were influenced by the continuous monocropping system and the development stage of tobacco, and which factor(s) could be the underlying driving forces of bacterial community variation in the data, PCoA was conducted based on the weighted UniFrac distance matrix in combination with PERMANOVA. PCoA revealed that the root microbiota of flue−cured tobacco formed three distinct clusters with the development stages, which separated along the first coordinate . This in3–-N, AP, and AK) were explanatory factors determining the observed clustering pattern of bacterial communities for different continuous monocropping times and development stages. RDA was conducted to determine the main environmental factors responsible for the variation of bacterial phylogenetic structure .In order to clarify the changes in bacterial community functionality with continuous cropping duration, we further predict the ecological functions of the rhizosphere soil bacterial community during continuous cropping of flue-cured tobacco. Forty-seven ecological functions were annotated by FaProTax software, in which chemoheterotrophy (33.87% ± 1.02%), aerobic chemoheterotrophy (31.63% ± 1.37%), chloroplasts (5.93% ± 2.32%), nitrification (4.15% ± 2.14%), aerobic ammonia oxidation (2.77% ± 1.17%), were the predominant functional groups in the rhizosphere soil of flue-cured tobacco . FurtherTo test whether root microbiota members can be used as biomarkers to differentiate the soil under different years of a continuous monocropping system, the relative abundance of root bacteria at the class, order, family, and genus levels were further regressed against continuous monocropping years of tobacco in the field using the Random forest machine learning algorithm. Using samples collected in the transplanting period, the model established in this study could correlate root microbiota composition with continuous monocropping years. In relation to different cropping times, the model based on bacterial family level explained 74.61% variance of root microbiota classification, the highest within the four tested taxonomic levels. Based on the model, a 10-fold cross-validation with five repeats was performed to evaluate the importance of indicator bacterial families. The minimum cross-validation error curve was obtained when the 17 most relevant families were chosen, which were defined as the biomarker taxa. The top 17 bacterial taxa at the family level across corresponding continuous monocropping time of flue-cured tobacco, in order of time-discriminatory importance, is shown in Most biomarker taxa showed high relative abundance in the corresponding continuous monocropping time of flue-cured tobacco in the field. Solibacteraceae, Myxobacteria (Blfdi19), and KF-JG30-C25  were defined as the featured biomarkers in soil continuously monocropped for 5 years . PedosphDifferences and interactions in bacterial co-occurrence patterns under different cropping systems were further revealed by co-occurrence network analysis at the phylum level . TopologAs shown in the To identify keystone microorganisms in the networks, the connectivity of OTUs (nodes) within (Zi) and among (Pi) modules were calculated and the OTUs were classified into peripherals, connectors, module hubs, and network hubs according to the threshold values of 2.5 (Zi) and 0.62 (Pi) proposed by Arabidopsis and tomato  leading to the shift of community structure in soils under prolonged tobacco monocropping. The Zi-Pi relationship of each individual OTU revealed that four supergeneralists existed in the network of short-term continuous monocropping (5 yrCC network) as well as 34 generalists (10 module hubs and 24 connectors) connected within and among modules respectively. However, in the long-term continuous monocropping system (20 yrCC network), the number of generalists decreased to 21 and consisted of 8 module hubs and 13 connectors. This suggested that the roles of some nodes shifted in the two networks and that prolonged monocropping changed the ecological roles of key microorganisms in soils, especially decreasing the generalists across different modules. As previously reported, more generalists in networks are favorable for maintaining the balance of microbial communities and are important for promoting exchanges of energy, information, and materials among species in networks . CompareFive nodes classified as generalists were present in both 5 yrCC and 20 yrCC networks and four of these nodes belonged to subgroup 6 of Acidobacteria , demonsthttps://www.ncbi.nlm.nih.gov/, PRJNA684032.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: LY, WYZ, and XL designed the research. WYZ and WD prepared the plant samples. LY extracted the DNA and amplified the V3–V4 region of the 16S rRNA gene. LY, WZ, and XL performed the data analysis. LY and WYZ wrote the initial draft. YZ, WD, and XL revised the manuscript. All authors read and approved the final manuscript.WD is employed by the company China Tobacco Sichuan Industrial Co., Ltd. The remaining 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.


Discussion. c-MET represents a useful molecular target for novel engineered drugs. Several clinical trials are underway for various solid tumors and the development of new specific monoclonal antibodies depends on the recent knowledge about the definite c-MET role in each different malignance. Recent clinical trials based on c-MET molecular targets result in good safety profile and represent a promising therapeutic strategy for solid cancers, in monotherapy or in combination with other target drugs.  c-MET is a receptor tyrosine kinase receptor (RTK) for the hepatocyte growth factor (HGF). The binding of HGF to c-MET regulates several cellular functions: differentiation, proliferation, epithelial cell motility, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, it is known to be involved in carcinogenesis. Comprehension of HGF-c-MET signaling pathway might have important clinical consequences allowing to predict prognosis, response to treatment, and survival rates based on its expression and dysregulation.  The list of cell surface receptors crosslinking with the c-MET signaling is constantly growing, highlighting the importance of this pathway for personalized target therapy. Research on the combination of c-MET inhibitors with other drugs will hopefully lead to discovery of new effective treatment options. MET  is a N-methyl-N′-nitro-N-nitrosoguanidine gene aberrantly overexpressed in human osteosarcoma, located in the 7q21-31 loci of chromosome 7. It encodes for a tyrosine kinase receptor and its ligand is the Hepatocyte Growth Factor (HGF). During embryogenesis, MET is essential for several processes including gastrulation, angiogenesis, migration of myoblasts, bone remodeling, and nerve germination , 5, and β chain (145 kDa) and an extracellular α chain (50 kDa). The α chain heterodimerizes with the aminoterminal extremity of the β chain. When Human Growth Factor (HGF) is recognized by c-MET immunoglobulin-like domains and binds the extracellular portion of MET β domain, two c-MET heterodimers dimerize, leading to self-phosphorylation of two tyrosine residues within the kinase catalytic domain . The heterodimerization leads to the assembling of SEMA domain, the main binding site for the HGF ligand. The extracellular portion of the β chain is composed of a cysteine-rich domain, known as the “MET-related sequence” (MRS), and four immunoglobulin-plexin-transcription (IPT) domains. The intracellular portion of the receptor is composed by the catalytic site and a C-terminal tail containing two tyrosines essential for c-MET receptor functions and its oncogenic potential. Ser-985 and Tyr 1003 sites in the juxta-membrane domain play an important role in the negative regulation of c-MET [S985 phosphorylation negatively regulates receptorial kinase activity.Cbl ligases anchor to the phosphorylated tyrosine Y1003 facilitating receptor ubiquitination and degradation.Binding of tyrosine phosphatase (PTPs), including density enhanced phosphatase 1 (Dep1), LAR (leukocyte common-related molecule), PTP1B and T-cell protein tyrosine phosphatase, modulates signal dephosphorylating tyrosines both in the kinase domain and in the docking site .PLCy activates protein kinase C which decreases phosphorylation and ultimately c-MET activity .c-MET gene has a total length of 125 kb with 21 exons , 18. Itsof c-MET , 20. Theα- and β-chain held together by a disulphide bond. The α-chain contains an N-terminal hairpin loop followed by four kringle domains  and includes a high affinity binding domain for c-MET receptor. The β-chain is homologous to serine proteases involved in blood-clotting cascade, but it lacks proteolytic activity [HGF, also known as Scatter Factor (SF), plays a role in cells motility by disrupting intracellular junctions, and it is located on chromosome 7q21 . Its seqactivity .As well known, c-MET can be active by either HGF or its natural isoform NK1. Recently, Uchikawa et al.  reportedγ1 (PLCγ1), signal transducer and activator of transcription 3 (STAT3), and RAS GTPase p120 [α and the inhibition of PKCα resulted in a reduction of c-MET signaling. They also found in 2004 that PKC regulates both c-MET traffic from early endosomes to perinuclear compartments and c-MET control of ERK in endosomes responsible for the cellular migration [γ-ear binding protein-3 containing Golgi (GGA3), and Rab coupling protein (RCP) [The linkage between c-MET and HGF promotes the autophosphorylation of two intracellular tyrosine-domains Tyr1349, Tyr1356), like the adapter molecule GRB2-associated-binding protein 1 (GAB1) , a scaffase p120 –31. Downase p120  is facilase p120  activatease p120 , 37. Y13ase p120 . Howeverase p120 , 40. In ase p120 , 42. Conase p120 . Degradaase p120  and endoase p120 . Li et aase p120  showed tase p120 . Kermorgase p120  showed t, Tyr1356igration . Endosomin (RCP) , 52. A cin (RCP) .EGFR and c-MET are frequently coexpressed in tumors and these pathways converge on the same downstream signaling mediators such as ERK/MAPK and PI3K/AKT. Crosstalk between EGFR and c-MET in lung cancer has been widely reported . Becauseβ-catenin. RON receptor, known as macrophage stimulating 1 receptor (MST1R) or stem cell-derived tyrosine kinase (Stk) in mouse, belongs to the family of tyrosine-kinase receptors. It is made of 1400 amino acids including a signal peptide, an extracellular domain, a single transmembrane domain, and an intracellular tyrosine kinase domain. The extracellular domain and the kinase domain have a 25% and 63% degree of homology respectively with the corresponding domains found in MET receptor. RON expression was found in CNS, kidney, testicles, bones, lungs, and breast and in the GI epithelium. This signaling regulates cytokines and chemokines production in response to inflammatory stimuli [RON (Recepteur d'Origine Nantais) receptor is synthesized as a 185 kDa single chain precursor which is cleaved proteolytically and exposed on cell surface as a heterodimeric glycoprotein including an alpha chain (35 kDa) and a beta chain (150 kDa) . The act stimuli –79. RON  stimuli . The nam stimuli . HGFLP i stimuli . It has  stimuli . Recentl stimuli . c-MET a stimuli  and are  stimuli . Interes stimuli .th September 2022. The combination of a third-generation selective EGFR inhibitor, as Osimertinib, with a selective c-MET inhibitor, as savolitinib, resulted in a good therapeutic strategy with an acceptable tolerability profile [Several comparative studies detected c-MET overexpression in 60% of NSCLC cases. MET amplification and its most relevant somatic splice-site mutation that results in a skipping of exon 14 are both potential predictive biomarkers for non-small-cell lung cancer (NSCLC) –93. The  profile . Telisot profile . In a re profile . For wha profile . Taniguc profile . HoweverHGF and c-MET are frequently coexpressed in invasive breast cancer. Coexpression is often stronger at the infiltrative margins. Moreover, there is a significant correlation with high tumor grade, an increased proliferation index and reduced survival, compared with cancers that are negative for coexpression. A truncating mutation in the deoxyadenosine tract element hyperactivates the HGF promoter leading to the formation of an HGF/c-MET autocrine loop . MutatioGerminal mutations in c-MET gene were identified in hereditary and sporadic renal cell carcinoma (RCC). Specifically, c-MET is overexpressed in Von Hippel Lindau Syndrome due to upregulation of hypoxic induced factors which can enhance MET signaling . VHL mutHGF was found to be elevated in head and neck squamous cell carcinoma (HNSCC) patients compared to healthy individuals. Lymph-nodal invasion is a common feature of clinical HNSCC and is predictive of patient mortality. c-MET gene is highly expressed in lymph node metastases in HNSCC . It tendA lot of causes of inappropriate MET-activation in gastrointestinal cancers can be identified: amplification and mutation of c-MET gene, with subsequent protein overexpression and kinase activation; transcriptional upregulation from other oncogenes (K-RAS); reduced c-MET receptor degradation; ligand-independent activation; autocrine overexpression of HGF; and environmental conditions such as hypoxia and inflammation. Additionally, RNA silencing of c-MET using lentivirus in gastric cancer cells, leads to suppression of peritoneal dissemination showing a proliferative and metastatic role of c-MET . DownregHepatocellular carcinoma (HCC) is the fifth most common cancer and is the second leading cause of cancer death. HGF/c-MET pathway is activated in about 50% of HCC and the expression levels of these proteins are associated with a poor clinical prognosis. Garcia-Vilas et al. argued that HGF is expressed and released by stellate cells. Data suggest that HGF acts by a paracrine mechanism binding c-MET receptor located on hepatocytes cell membrane . Currentβ-catenin and the adaptor protein Sos, which activates the RAS/RAF/ERK/MAPK cascade, and consequently increases cell growth, migration, and metastasis. This process involves astrocytoma and glioblastoma progression [in vivo and in vitro glioblastoma model, the role of a MicroRNA (miRNA) called miR-410. They demonstrated by FISH and IHC assay that, as a small non-protein coding RNA, miR-410 negatively modulates MET expression and MET/Akt transduction, because of its binding to the 3′ Untranslated Region (UTR) of MET. As well known, miRNAs can recognize target mRNA by imperfect base pairing to the 3′ UTR and they may induce their degradation or translational repression [p=0.025), an early resistance and a worse response to antiangiogenic therapies [HGF/MET interaction is frequently committed in human gliomas and high levels of these molecules correlate with high tumor grade and poor prognosis , 141. Ingression , 142. Ingression , 144. Asgression  studied pression . Chen's pression . Anotherpression , has dempression . Howeverpression . As knowherapies . The weeherapies . HoweverMany achievements have been made in our understanding of clinical importance and biological mechanisms of c-MET/HGF pathway. However, many questions still reclaim an answer to find the definitive way to implement this detailed knowledge and change the clinical practice. Aberrant HGF/MET pathway plays as an oncogenic driver, since dysregulation of c-MET and HGF has been implicated in cancer pathogenesis as it is involved in the mechanisms of cell proliferation and survival, invasion, and metastasis. Increased c-MET expression has been observed in various solid cancers and it is responsible for resistance in most of them. Strategies targeting this pathway, such as monoclonal antibodies (mAbs), have been shown only to achieve stable disease but not to prolong survival in advanced cancers –154. Rat


Damage initiation and crack propagation in concrete are associated with localisation of energy dissipation by the concrete meso-structure. Meso-scale models are, therefore, required for realistic analysis of concrete non-linear behaviour. Such models are constructed either from X-ray Computed Tomography images (image-based modelling) or by in silico meso-structure generation (parametric modelling), while both approaches are widely used and their advantages and disadvantages are recognised, little work is done on comparing their performance in predicting measured macroscopic behaviour with equivalent constitutive relations for meso-structural features. This work uses microstructure characterisation and mechanical behaviour data to construct, validate and compare the two modelling approaches. The macroscopic behaviour obtained with both meso-structural models is found to be in good agreement with experimental data. Differences are observed only between the predicted distributions of damage within specimens. These outcomes suggest that the computationally simpler parametric meso-structures are sufficient to derive stress–strain behaviour for engineering-scale models in the absence of other environmental factors. The observed differences in damage distribution could be important for analysis of coupled behaviour, e.g., mass transport and chemical reactions affecting local mechanical properties and being affected by local damage. Establishing the importance of damage distribution is such cases requires further research. The macro-cracks of concrete are developed through micro-crack initiation, propagation and coalescence. The reliable prediction of concrete component failure requires in-depth understanding of the localized crack evolution of concrete heterogeneous composition. Compared with the homogeneity at macro-scale, meso-scale concrete consists of heterogeneous phases, including coarse aggregates, mortar (cement paste with sand and fine aggregates embedded) as matrix, and entrapped air voids. Interfacial transition zone (ITZ) is not observable at meso-scale, but provides both preferable locations for crack initiation and easier pathways in the damage evolution. ITZ has lower stiffness and strength compared with mortar, because it is a thin layer of higher-porosity mortar coating around aggregates with thickness between 10 and 100 μm .The aggregate distribution of meso-scale concrete can be obtained by digital image acquisition of realistic size and location of aggregates or by random spatial distribution of aggregates of given shapes with prescribed size distribution. As a non-destructive imaging method, X-ray computed tomography (XCT), has been widely used for acquisition of concrete meso-structures ,4,5. DifThe advantage of image-based models is that accurate geometry of aggregates and voids can be obtained. However, the image processing is time-consuming and usage of XCT equipment is expensive. Moreover, the imaged regions may not be statistically representative in terms of size and spatial distribution of aggregates. On the other hand, parametric models have the capacity to cover larger engineering component volumes statistically, where aggregates with presribed size distribution and volume density can be included. The limitation is that the randomly generated aggregates differ from the natural ones of the tested specimen in terms of both position and shape. One approach for using the XCT images in constructing synthetic models is to replace natural aggregates observed by XCT with circular ones of equivalent volumes at the same locations ,21. SuchIn most of previous models, as well as in the present work, aggregates have been assigned with elastic behaviour, because their strength is higher than concrete failure stresses. Micro-cracks initiate in ITZ and propagate through mortar, which form macro-cracks in concrete structure. Mortar has been considered as inelastic homogeneous continuum with elastic-damage ,22,23,24The appropriate representation of ITZ is mostly debated. The first option is to neglect ITZ and attribute inelastic behaviour of concrete to mortar via elastic-plastic ,26,27 orParametrically generated meso-structures are appropriate for covering regions of large-scale engineering structures where damage/fracture is expected to initiate due to stress concentrators. This cannot be accomplished with image-based meso-structures due to the limited sizes of the CT scanned specimens. It is therefore necessary to understand how reliable the parametric meso-structures are in predicting the macroscopic response of concrete so that they can be used in analysis of large-scale engineering structures. The aim of this work is to established the areas of applicability of the two approaches for meso-structure construction, image-based and parametric/synthetic, by comparing their predictions for deformation behaviour and damage, supported by experimental data. One novel element of the work is the efficient segmentation of concrete constituents using artificial intelligent based segmentation tool—a trainable Weka segmentation plugin of ImageJ. Comparisons with own experimental data show that the synthetic meso-structures are sufficient for predicting the macroscopic stress–strain behaviour. However, damage is shown to develop differently in different meso-structures, suggesting that non-mechanical processes that depend on damage, such as diffusion and chemical reaction, require further investigation to demonstrate reliability of parametric models.According to British Standard , the C30The test rig and different specimen types used are shown in The X-ray Computed Tomography (XCT) scanning was carried out prior to mechanical testing on one cylinder of each aggregate content at the Henry Moseley X-ray Imaging Facility, the University of Manchester with the Nikon XTH 225  custom bay see . The XCTThe core (D50*100 mm) was cropped from the whole cylinder (D100*200 mm) to reduce data processing time and edge effect. Non-local means filter was applied to remove noise and unify grey value in different phases. Due to the enormous amount of aggregates in 2000 slice images, the trainable Weka segmentation (TWS) plugin was adopted in software Fiji , which can segment selected image features based on machine learning algorithms. The TWS plugin can automatically identify the regions of interest when the users define different phases and mark the identical features in each phase. After several trainings, TWS plugin can identify almost all of the regions of interest, as shown in Statistical analysis of each phase was carried out. The aggregate volume fractions of image-based concrete were found to be 19%, 33% and 39% respectively, in agreement with the concrete mix designs of 20%, 30% and 40% aggregate content. The porosities of the three mixtures were found to be 1.4%, 1.3% and 0.9%, respectively. Most of the voids were between 2 and 4 mm in diameter. Notably, the voids observed on the outer surface of the lab cast concrete cylinders, were not replicated in the parametric concrete meso-structures. Therefore, the porosity of parametric models was set to be 1% for all three aggregate contents.The image-based meso-scale concrete model was obtained after XCT scanning, 3D reconstruction and phase segmentation. The other approach to generate concrete meso-structure is via synthetic parametrization. Aggregate particles are randomly distributed in the concrete volume without overlapping each other, but follow the designed aggregate size distribution. Although the shape and location of synthetic aggregates do not correspond to a particular real meso-structure, the potentially different macroscopic behaviours can be assessed by Monte Carlo simulations . Coarse The take-and-place method to generate the randomly distributed aggregate and pore particles is similar to Wang et al. , where aThe meshing of concrete meso-structures obtained from XCT scan and generated by the take-and-place method was performed with common approach, by tessellating the domain into voxels and generating finite element mesh in the commercial code ScanIP  . TetraheZero-thickness cohesive elements, representing ITZ, were inserted along the interfaces between aggregates and mortar phases by an in-house code. This was achieved by duplicating the exact node sets at the interface of aggregate and mortar. The original node set remains at the mortar continuum tetrahedral elements, while the duplicated one is attached to aggregate elements. Thus, 6-node cohesive elements with zero thickness  were generated by connecting the two node sets in 3D meso-scale concrete model.Zero-thickness cohesive element was briefly introduced in ,34, and 9 MPa/mm ,14,23,469 MPa/mm ,14,23,46Pa/mm [3 ,37.Concrete damage plasticity (CDP) model was adopted for mortar to describe its plastic-damageable behaviour under different loadings. The theory of CDP model is fully explained in ABAQUS user manual . A briefChinese Code GB50010  provides.312σt02 . The fulThe experimental and simulation results of concrete with 20%, 30% and 40% aggregate volume fractions are compared to investigate the effect of meso-structure obtained from image-based and parametric modelling. Cylindrical volumes with diameter of 50 mm and height of 100 mm are generated to reduce the computational cost. The same cylinders are used under tension. This is because direct tension test with cylinder is experimentally challenging. Therefore, dogbone specimens are used for direct tension tests.E denotes elastic modulus, t and equently ,14,23,46Displacement control is adopted to load all specimens from the direction parallel to cylinder axis prescribed at the two circular surfaces. Nodes at one surface are fixed to zero displacement, while those at the opposite surface are controlled by nodal displacements in tension, or by displacements from a rigid loading platen in compression. The friction between the rigid loading platen and the concrete sample is set to be 0.3 . ABAQUS/Full mesh sensitivity results of parametric models can be found in a previous study by the authors . The effThe stress–strain results, energy dissipation and damage patterns of meso-scale concrete obtained from XCT scan and generated synthetically, are analysed under compression and tension. The results suggest that the macro-scopic mechanical behaviour of both mesoscale concrete models subject to compression and tension has good agreement with experimental data, while the distribution of damage, rather than the dominant fracture pattern, between these models is the only substantial difference observed.The compressive failure patterns and damaged elements of image-based and parametric models with 20%, 30% and 40% aggregate content are shown in The inelastic behaviour of meso-scale concrete is represented by plastic dissipated energy (PD) of mortar and damage dissipated energy (DMD) of mortar and ITZ in current model. The energy dissipation of mortar and ITZ in 20% aggregate content image-based model is similar with that in parametric model. The only difference is that the energy dissipation rate of the former is less rapid than that of the latter, because the post-peak softening of the former is slower. The onset of plastic and damage dissipation of image-based model with 30% and 40% aggregate content is later than that of parametric model, because the critical strain of the former is larger. The energy dissipation rate is related with post-peak softening. For example, in concrete model with 30% aggregate, the rapid post-peak softening of image-based model is reflected on the rapid increase on dissipated energies of mortar and ITZ. Furthermore, more energy is dissipated through mortar plasticity and damage in image-based models with 30% and 40% aggregate compared with that in the corresponding parametric models. The reason is that the extra dissipated energy is required to achieve a higher peak strength in these image-based models. Finally, the ITZ damage dissipation of image-based models with 30% and 40% aggregate volume fractions is smaller than that of parametric models due to the smaller total surface area of ITZ in image-based model.The tension results of concrete with 20%, 30% and 40% aggregate volume fractions are shown in The concrete fracture energy in both models can be roughly estimated to be 203 J/mcrete in .As to tensile fracture patterns, one dominant crack is observed for concrete models. When aggregate content of concrete is low , the crack is located in the middle of cylinder. However, failure close to one end of cylinder is observed if concrete aggregate volume fraction is high, i.e., 40%.Both parametric and image-based concrete models are in good agreement with experimental observations except the substantial difference in the distribution of damage. Note that the construction of both models needs to meet certain requirements. Self-developed code is required to generate randomly prescribed phase particles, while XCT scanning is expensive and image processing is time consuming.Compared to image-based modelling, the advantage of the parametric modelling is that it can be used to generate meso-structures in larger material volumes while reproducing the basic statistical meso-structural characteristics - volume density and size distribution of aggregates. The size of the material volume is limited only by the computational resources. From a research perspective, the benefit of using material volumes larger than those that can be imaged is that they can be used to investigate size effects in concrete, arising from the ratio between the average aggregate size and a component size, and more generally to clarify the notion of representative volume element for a given concrete composition. From a more practical perspective, parametric meso-structures can be used to cover either whole structural elements or regions of such elements where damage is expected to initiate and propagate due to presence of stress concentrators. As a result, it can be used in advanced integrity assessments of critical components of engineering structures.The advantage of image-based models is that they represent more realistically the shape, size, and spatial distribution of aggregates and pores. The benefit of this is that such models can be used to test different hypotheses regarding the constitutive behaviour of different phases, particularly when 4D imaging is used, i.e., when the scanning is performed during mechanical testing. A disadvantage is that the imaged volume is limited and there is no guarantee that the behaviour measured with such a volume is representative for a concrete specimen of a larger size. It has been demonstrated with the present work, that the selected constitutive behaviours for different phases with parameters calibrated by testing of mortar or selected from previous experience, lead to good predictions of the macroscopic stress–strain behaviour and damage evolution with both the image-based and the parametric models. This suggests that the imaged volumes have been close to representative for the concrete compositions studied.Artificial intelligent based segmentation tool, trainable Weka segmentation plugin of ImageJ, is effective and efficient in identifying various features of heterogeneous materials.Modelling meso-scale concrete inelastic behaviour with plastic-damageable mortar and damageable ITZ represented by zero-thickness cohesive elements is a practical and effective approach to deal with uniaxial compression, tension and potentially other complex loading conditions.The mechanical response of both image-based and parametric mesoscale models shows good agreement with compressive and tensile experimental data; differences between the two modelling approaches are observed only in the distributions of damage.Parametric models are recommended for analysis of size effects in concrete, as well as for modelling critical components or parts of such components in engineering structures.Image-based models are recommended for testing hypothesis for constitutive behaviour of concrete constituents, as well as for analysis of coupled behaviour, such as mass transport and deformation, where the realistic shape, size, and spatial distribution of constituents could have significant effect on the coupling.Concrete specimens with 20%, 30% and 40% aggregate volume fractions are simulated with both image-based and parametric meso-structures under compression and tension. Stress-strain curves and failure patterns are analysed to assess the effect of aggregate distribution on concrete mechanical behaviour, while energy output is compared to explain the mechanisms. The main findings and recommendations of this work are: