The developments in the cisvil engineering fields have led to an increased demand for structural reinforcements. Therefore, designing an effective, green, convenient, and low-cost reinforcement method is considerably important. Nylon ties have high strength and good heat resistance, and they can retain good tensile properties after high-temperature cooling. Further, they are inexpensive and can be recycled. Thus, they are considered suitable for structural reinforcement engineering. In this study, the core concrete was reinforced by the active confinement of prestressed nylon ties. A uniaxial compression test was performed to evaluate the reinforcement effect of the preload generated by the high-temperature cooling of the tie rod on the core concrete. The results show that nylon ties can effectively improve the mechanical properties of the core concrete. Combined with numerical simulation technology, a damage model of a confined concrete column (CC) was established, and the damage evolution law of CC under uniaxial axial compression was analyzed. Combined with numerical simulation and experimental research, the effectiveness of nylon tie reinforced concrete and the reliability of the damage model were verified, providing a reference for research on engineering reinforcement. The reinforcement of engineering structures is a major challenge in civil engineering. The steel pasting method can effectively improve the structural stiffness. However, steel materials are heavy, easily corroded, and inconvenient to construct ,2,3. MorPolymer materials include thermoplastics and thermosetting materials . Among tWhen a structure is in a state of multidirectional compression, the lateral pressure on the confined concrete can effectively limit the expansion of the microcracks in the structure. This can effectively restrain the transverse and longitudinal deformations, as well as effectively improve the compressive strength and ductility of concrete structures. There are two types of concrete confinement methods: active and passive ,22,23,24In summary, each constraint case has its own characteristics, but effective, environmentally friendly, cheap, and convenient constraint methods have been rarely reported. Moreover, most cases are limited to the study of the constitutive relationship of confined concrete, and there the research on the damage evolution law of confined concrete is scarce. Therefore, a novel confined concrete with heated nylon ties is proposed. In this study, the active confined stress due to heated nylon ties was investigated to determine whether the nylon ties were effective in enhancing the mechanical properties of the core concrete, to provide an effective, green, and low-cost reinforcement method for civil engineering projects. The damage model of confined concrete columns (CCs) was established, and the damage law of uniaxial-compression CCs and the breakage of nylon ties were analyzed. The results provide a reference for engineering structural reinforcements.Nylon ties  have theThe tie-wraps were heated in an electric blast drying oven at 80 °C, 100 °C, and 120 °C. After the heated nylon ties were cooled, a pre-tightening test with a load ring and tensile test were conducted.The heating time was 3 h a. The laThe mechanical properties of the nylon ties were determined via tensile testing. The screw clamp of the tensile testing machine in the laboratory was difficult to use for winding the ties. Binding was wrapped using a customized winding fixture .A total of 12 specimens were used in this test . The effTaking Y35-100 and Y35 as examples, to use the numerical method combined with the test results to explore the damage evolution law of concrete, a uniaxial compression test was conducted. Therefore, the uniaxial compression model was selected for the simulation, which did not consider other types of deformation. The Y35-100 model size was as follows: the tie thickness was 1 mm and the model element type was C3D8R, which was divided into 68,508 elements. The Y35 concrete model size was ϕ150 mm × 300 mm. Hexahedral elements and sweep methods were used for mesh generation. The element type was C3D8R, and 52,800 elements were used.In the uniaxial compression simulation, the bottom of the model was constrained vertically, and the upper surface was compressed by displacement control. The maximum displacement of the loading was 30 mm and the loading rate was controlled at 0.083 mm/s .The hardening process was divided into strengthening and softening stages. When the concrete stress reached the peak stress (1−dt)E0 .Figure Nylon ties have a certain strengthening effect on concrete. In addition to the strength of the concrete core, this is mainly determined by the size of the confined force; that is, the stronger the confined force, the greater the compressive strength of the concrete.The strength formula of CC is as follows :(1)σcc′=The stress-strain curve of confined concrete can be expressed by the following formulae :(2)σcc′=To simulate the damage process of concrete under uniaxial compression, a damage model of concrete was established using the element damage function provided by ABAQUS. The damage criterion of concrete is:After the concrete bears the axial load, the tie bears the tensile force exerted by the concrete core. When the tensile stress reaches a maximum value, the tie is destroyed. The maximum tensile stress failure criterion is embedded in the VUMAT subroutine. The failure element deletion algorithm was introduced to simulate the failure process of ties.The maximum tensile stress criterion of the element is as follows:Under the action of an external force, when the stress state of an element of the tie model satisfies the criterion condition of Equation (11), the element is identified as a failure and removed from the iterative calculation of the next load step. The iterative calculation is repeated until the residual error of the internal force of all elements meet the convergence criterion. When the calculation is terminated, the stress and deformation results of the element are output . The valThe glass transition temperature of nylon is 55–58 °C, and the heating temperature is 80–120 °C. With an increase in temperature, the shrinkage deformation increased; however, the toughness decreased, leading to a decrease in the tensile strength. The cooling deformation increased with increasing temperature , Table 2After taking the ties out of the oven, the ties quickly cooled. The cooling rate was the fastest at 0–1 min. After 4 min, no cooling deformation was observed. The higher the temperature, the greater the prestress produced by the cooling shrinkage of the ties. When the stress area of radial winding was smaller than that of circumferential winding, the prestress produced by radial winding was larger than that produced by circumferential winding at the same temperature .The stress-strain curve of concrete under uniaxial compression reflects the process of material failure and can reflect the important performance parameters of the materials. In this test, 12 groups of specimens were used to measure the uniaxial compression stress-strain curves of CC with different concrete strength grades and heating grades of the nylon ties, as shown in −3, and the average peak stress was 28.64 MPa. The average peak stresses of 80 °C-CC, 100 °C-CC, and 120 °C-CC were 31.64 MPa, 33.99 MPa, and 35.83 MPa, which were 9.46%, 15.73%, and 20.06% higher than that of UC, respectively. The reason for this is that confined concrete can increase the energy damage release rate required for concrete microcrack propagation. When the confined concrete bears an axial load, the volume of the core concrete expands and the cross-sectional area increases. The nylon ties bear the tensile force and the core concrete bears the lateral binding force imposed by the ties to restrain the cracking degree of the core concrete. According to the force balance relationship, the crack suppression force provided by the tie, The compressive strength of the CC was significantly higher than that of the UC. The effect of the 120 °C confinement scheme (120 °C-CC) was the best. The average peak strain of UC was 4.72 × 10The initial elastic modulus of the confined concrete was positively correlated with the heating grade of the tie. The higher the prestress grade, the greater the initial elastic modulus of the concrete, the greater the structural stiffness, and the stronger the ability of the structure to resist deformation.In the early stage of loading, owing to the existence of prestress, when the concrete block was under pressure, the prestress restrained the growth of the internal force of the block. The cracks appeared late, and volume expansion slowly developed.When the applied stress reached the peak stress, the surface cracks of the concrete columns rapidly expanded. The ties that reached tensile strength broke and lost the restraint of the core concrete column. The volume swelling of the concrete block was visible to the naked eye, mainly in the middle and upper parts. The crack width increased and the concrete surface blocks peeled off. The crack width decreased significantly when the crack propagation path passed through the tie region, indicating that the ties could effectively inhibit crack development. In addition, compared with UC, the integrity of CC was better after failure. The crack and the cross section of the concrete were approximately 45°.During the test, the fracture of the ties occurred suddenly and rapidly. With an increase in the loading stress, the concrete column expanded, and the increase in the cross-sectional area led to an increase in the tensile stress. When the ties reached the maximum tensile strength, they lost their restraining ability and broke. The damage of concrete can be seen in Most of the research is limited to the constitutive or seismic research of confined concrete , and resA Y35 cylinder with a strength grade of C35 was selected as the study object. When the vertical displacement was U < 0.48 mm, the damage factor of the model was very small. The damage factor of each element of the column body exhibited a slight difference. In the range of U > 0.81 mm, with the increase in load, the damage factors of the column end and column body elements gradually increased. Thus, the cross-sectional area of the concrete increased. When the stress applied by the model was close to the peak stress, element damage appeared on the surface and inside the concrete model, first at the end of the column. Microcracks then appeared on the column. At a later stage of loading, the earlier microcracks gradually expanded and connected. Finally, the concrete model was sheared. The shear crack was approximately 45° to the concrete cross section. The shear cracks ran through the entire model .The damage evolution law of the UC was at the early stage of loading; the damage factor of each part of the concrete did not differ significantly, and the stress-strain development was uniform. At the middle of loading, the damage factor of the concrete column body unit increased more than that of the other parts, and at this time, no damaged had appeared at the unit. At the later stage of loading, damage first appeared at the end of the column, and the column body exhibited “sporadic” damage. With an increase in load, sporadic damage gradually expanded and connected, and shear cracks formed. The cracks were wide and penetrated the column body at 45° to the column cross section. Cracks extended perpendicular to the principal stress and along the plane of the maximum shear stress, which was similar to the diagonal propagation of cracks in the structure.Here, we take the Y35-100 specimen as an example. The CC was restrained by prestressing after its completion. When the loading displacement was small, the damage factors of the confined CCs were similar, and the lateral pressure slowly increased. An increase in the axial load of the confined CC resulted in an increase in the concrete volume. Owing to the interaction of forces, nylon ties bore tension from the concrete. When U = 1.63 mm, the tensile stress of the ties reached the tensile strength value and were then destroyed. However, there was residual restraint stress on the surface of the concrete restrained by ties. With an increase in displacement, the element reached the critical value of the damage and was removed. The cloud images show that the damage of the element located at the ties was lower, and that of the other parts of the model was greater. This is because the residual restraint stress on the surface of the model still restrained the crack propagation after the straps lost their restraint ability. Finally, shear failure occurred in the confined concrete. The shear crack was approximately 45° to the concrete cross section. Compared with the failure characteristics of UC, the failure development of CC was slow, its integrity was better, and the crack width was narrower .The damage evolution law of CC was at the early stage of loading; the prestress provided by the ties effectively prevented the concrete unit damage factor from increasing, and the unit damage factor grew slowly. In the mid-loading period, the restraining ties reached the tensile strength, and lost their damage-restraining effect. Residual stresses existed on the concrete surface and inhibited crack expansion. At a later stage of loading, the column unit damage formed a shear crack. The crack was at an angle of 45° to the column section and penetrated the main body with a narrow crack width.The reliability of the damage failure model was verified by the stress-strain curve and failure characteristics.The numerical results were consistent with the test results . The comTo obtain the tensile stress distribution of the nylon ties, the calculation results of the maximum principal stress in each integral step state were assigned to the state variables in the VUMAT subroutine. They appear in the form of an SDV in the visualization module of ABAQUS software. SDV3 represents the maximum principal stress in each integral state .When the prestress was applied, the average lateral force and tensile stress of the ties were 20 N and 48.43 MPa, respectively. At this stage, the lateral restraint of the ties was caused by the cooling shrinkage of their own material. Before the vertical displacement of the concrete reached 1.63 mm, the lateral force on the ties increased slowly. The prestressing force exerted by the ties on the concrete restrained the expansion of concrete volume. When the cross-sectional area of the concrete increased to a certain extent, the prestressing force exerted by the ties on the concrete lost its effect. After this stage, the lateral force of the ties increased rapidly. When U = 1.63 mm, the ties in the middle of the CC first reached the tensile stress strength (127.64 MPa) and broke. The lateral force of the unbroken ties at the column end continued to increase. Under monotonic axial compression, bulging in the middle of the confined CC was more severe than that at both ends. The tensile stress of the tie in the middle was the largest and also the first to break . As can Based on the advantages of nylon, which include maintaining good strength after high-temperature cooling, this study explored the effect of prestressed nylon ties on the reinforcement of CCs. Combined with the test results, a numerical model was established to explore the damage evolution law of the CCs. The conclusions are as follows.The tensile strength of the nylon ties decreased with increasing temperature, but the preload caused by the cold shrinkage of the ties increased. After high temperature cooling at 80 °C, 100 °C, and 120 °C, the tensile strengths of the tie were 138 MPa, 127.64 MPa, and 113.41 MPa, respectively, and the average pre-tightening forces generated by the ties were 27.82 kPa, 33.33 kPa, and 44.29 kPa, respectively.The prestress produced by nylon ties with different heating temperatures owing to the decrease in temperature can enhance the bearing capacity, compressive strength, and initial elastic modulus of CCs; the higher the heating temperature, the higher the prestress and the more evident the restraint effect. Compared with the UC, the compressive strength of specimens with 80 °C, 100 °C, and 120 °C confinement schemes increased by 9.46%, 15.73%, and 20.06%, respectively.The finite element software ABAQUS was used to establish the damage-failure model of the CC. The damage laws of confined CCs under uniaxial compression were analyzed from the aspects of maximum principal strain, equivalent plastic strain, and compression damage, which can effectively improve the ductility and elastic modulus of members. At the initial loading stage, the prestress applied by the ties effectively inhibited the volume expansion of the concrete, and the lateral pressure on the ties increased slowly. With the increase in load, the effect of the prestressed restraint decreased, and the growth rate of the lateral force of the tie belts accelerated. Combined with the results of the numerical simulation and test, the reliability of the damage model was verified, providing a theoretical reference for the study of the damage law of engineering reinforcements.


In this research, experimental research and finite element modelling of glulam-concrete composite (GCC) beams were undertaken to study the flexural properties of composite beams containing timber board interlayers. The experimental results demonstrated that the failure mechanism of the GCC beam was the combination of bend and tensile failure of the glulam beam. The three-dimensional non linear finite element model was confirmed by comparing the load-deflection curve and load-interface slip curve with the experimental results. Parametric analyses were completed to explore the impacts of the glulam beam height, shear connector spacing, timber board interlayer thickness and concrete slab thickness on the flexural properties of composite beams. The numerical outcomes revealed that with an increase of glulam beam height, the bending bearing capacity and flexural stiffness of the composite beams were significantly improved. The timber boards were placed on top of the glulam members and used as the formwork for concrete slab casting. In addition, the flexural properties of composite beams were improved with the increase of the timber board thickness. With the elevation of the shear connector spacing, the ultimate bearing capacity and bending stiffness of composite beams were decreased. The bending bearing capacity and flexural rigidity of the GCC beams were ameliorated with the increase of concrete slab thickness. The glulam-concrete composite (GCC) beam is a novel structural element in which the glulam member and the concrete slab fit together through shear connections. Due to the sufficient composite effect provided by shear connections, the material properties of the glulam and concrete are better utilized, as tensile forces from bending are primarily resisted by the glulam and compressive forces are resisted by the concrete ,2. The GUp to now, substantial experimental studies on the structural behaviors of GCC beams have been published ,8,9,10. There are multiple numerical research and theoretical analyses regarding the structural behavior of GCC beams. The existent finite element (FE) models for GCC beams can be separated into 1D, 2D, and 3D. Lukaszewska et al.  establisUp to now, few researches on the structural performance of GCC beams containing timber board interlayers have been completed. Here, the experimental research on glulam-concrete composite beams was undertaken to study the flexural properties of composite beams containing timber board interlayer. Then, the three-dimensional non-linear finite element model was developed and confirmed by comparing the load-deflection curve and load-interface slip curve with the experimental results. Based on the finite element studies, the influences of the glulam beam height, shear connector spacing, timber board interlayer thickness and concrete slab thickness on the flexural properties of composite beams were investigated.3, and the mean water content was 12.8%. The compressive elasticity modulus and compressive strength of the lumber were obtained through material tests according to ISO 3787 [2, the compressive strength parallel to the timber grain was 39.6 N/mm2, and the tensile strength parallel to the timber grain was 84.89 N/mm2. The mean compressive strength of the concrete was 35.8 N/mm2.One full-scale GCC beam with inclined fasteners was constructed and loaded by the four-point bending approach. In the composite beam sample, the glulam beam was connected to the concrete slab using shear connectors . The gluISO 3787 . The aveThe four-point bending loads were applied to the beam specimen using a 300 kN hydraulic jack. Firstly, the applied loads were applied at a rate of 0.2 kN/s to 10% of the anticipated ultimate load, and then the loads were released to verify the efficiency of the bending test setup and measurement equipment. After that, the load increased at a rate of 0.2 kN/s until it reached the ultimate load. For obtaining the relative slips between the concrete slab and the glulam beam, two displacement meters were mounted at the end of the GCC specimen.SLS was based on GB 50,005 [SLS = l/250. At the beginning of loading, the GCC beam displayed linear elasticity behavior. When the load was elevated to about 60% of the maximum load, the applied loads presented an analogous parabolic increase with the elevation of the mid-span deflections. The flexural stiffness of GCC beam was lower, and diminished continuously. When it attained the maximal load, with the elevation of deflections, the loads decreased remarkably because of the brittle failure of the glulam beam. At the beginning of loading period, there was no observable relative slip because of the strong bonding effect at the interfacial region. With an increased level of the applied load, a small relative slip was identified. For the composite beam sample, when the applied load was elevated to approximately 85% of the ultimate load, cone expulsion failure happened on the concrete layer around inclined screw fasteners a. The toB 50,005 , ΔSLS = ft = ’fc/10. According to Eurocode 2 [η = εc/εc1; εc1 = the strain at peak stress; Ecm = elasticity modulus of concrete; fcm = cylinder compression strength of concrete.To sufficiently consider the effect of the failure mechanisms on the flexural behavior of GCC beams containing interlayers, three-dimensional (3D) FE models were established by the commercially available FE software ABAQUS. In the FE models, the damage plasticity model was utilized to realize the modeling of the physical performances of concrete. The concrete damage elicited by cracking or crushing causes a decrease in the elasticity modulus of the concrete. The tensile behavior of concrete was hypothesized to be linear up to the uniaxial tensile strength equal to rocode 2 , the comThe timber was simulated as an orthotropic material. It was hypothesized that both rigidity and intensity in the radial or tangential orientations were identical. The association between elasticity modulus in the grain and cross grain orientation as well as the association between elastic modulus and shearing modulus are specified in standard EN 338 . The ortThe steel material properties of screw fasteners were defined as isotropic elastic-plastic constitutive. The yield strength and ultimate tensile strength of screw fasteners were 375 MPa and 462 MPa, which were measured from material tests.The composite beam specimen was mainly composed of the concrete slab, glulam beam, screw fasteners and steel bars. The screw section cutting of the threaded section was considered in the screw modeling. The net section diameter was used for the screw modeling. The 8-node solid linear elements with reduced integration C3D8R were utilized to model the concrete slab, glulam beam and screw fasteners. The T3D2 truss element was utilized to simulate the steel reinforcement in the concrete slab. The global size of the element meshed in the connection model was 10 mm, and for the beam model, the relevant size was 100 mm. The interplay between the steel bars and concrete were analyzed through the ‘‘Embedded region” option. The longitudinal spacing and transverse spacing of screw fasteners were 200 mm and 50 mm, respectively. Both tangential and normal contact behaviours were identified in the FE model to simulate interaction among screw fasteners, concrete slab and glulam beam. The option ‘‘Hard Contact” was selected to identify the normal contact behaviours, and ‘‘Penalty” was chosen for identifying tangential behaviourd through postulating the timber-concrete frictional coefficient of 0.7. The model diagram of the GCC beam after defining boundary and load conditions is shown in To reveal the impact of the glulam beam section size on the flexural performance of composite beams, different sizes of the glulam beams  were simulated. The numerical simulation results of the composite beam with different glulam beam section size are presented in The shear connections play an important role in GCC beams through transferring shear forces among the glulam and concrete members and preventing detachment mechanisms. Four finite element models of the GCC beams with 100, 200, 300 and 400 mm spacing of inclined screw fasteners were simulated and analyzed to research the influence of shear connector ratio on the flexural properties. The load-deflection curves of GCC beams with different shear connector spacings are displayed by Timber boards may be utilized as the permanent formwork for concrete casting. This can not only create convenience for the construction, but also keep the integral beauty of the timber structures. Five finite element models of GCC beams with various timber board thicknesses were established to study the impacts of timber board thickness on the structural properties. The load-deflection curves of the GCC beams are presented in Five finite element models of GCC beams with various concrete slab thicknesses were established to study the impact of concrete slab thickness on the mechanical properties. The load-deflection curves of the GCC beams with 60, 70, 80, 90 and 100 mm concrete slab thickness are displayed in (1)The experimental results demonstrated that the failure mechanism of the GCC beam was the combination of bend and tensile failure in the glulam beam. At the beginning of loading, the slip displacement was small because of the strong bonding effect at the concrete-timber interfacial region. When the loading was elevated to approximately 28% of the maximum load, with the applied loads increased, the attenuated composite actions at the interfacial region led to a rapid increase of the interface slips.(2)The finite element results showed that the numerical simulation could precisely predict the failure mode and the change characteristics of the composite beam in the loading process. The developed finite element model adequately predicted the load-deflection relationship and load-interface slip curve, particularly in the elasticity range. For the elastic-plastic stage, the predicted deflection of the GCC beam deviated from the test results due to the nonlinear bending performance. The elastic-plastic damage constitutive model of glulam needs to be optimized.(3)The parametric study results showed that with increase of the glulam beam height, the bending bearing capacity and flexural stiffness of the GCC beam were significantly improved. With the shear connectors spacing increased, the ultimate bearing capacity and bending stiffness of the composite beam were decreased. The existence of timber board had no significant effect on the flexural performance of the composite beams. The bending bearing capacity and flexural stiffness of the composite beams were enhanced with the increase of the concrete slab thickness.To study the flexural performance of GCC beam containing interlayer, experimental research and finite element modelling of the composite beam were conducted. The finite element studies were performed to investigate the impacts of the glulam beam height, shear connector spacing, timber board thickness and concrete slab thickness on the structural properties of GCC beam.


The results showed that MET and RAPA combinations lowered cell viability after exposure to MPP+. Increased LC3-II levels by MPP+ were not altered by MET and RAPA pretreatment. In normal neuronal cells, MET and RAPA pretreatment inhibited the phosphorylation of both Akt and S6K1, and the phosphorylation remained suppressed after MPP+ exposure. These findings suggest that when cells were exposed to MPP+, suppressed phosphorylation of both Akt and S6K1 by the MET and RAPA combination may lead to an inappropriate autophagic response, resulting in increased cell death.Metformin (MET) and rapamycin (RAPA) have been reported to protect against neurodegeneration in cellular and animal models of Parkinson's disease (PD). MET, which is a first-line drug for type 2 diabetes, and RAPA are known as mTORC1 inhibitors. MET also acts as an AMPK activator, which leads to the inhibition of mTORC1 activity. mTORC1 is a downstream target of Akt signaling. Inactivation of Akt/mTORC1 and its downstream S6K1 can promote autophagy, a process involved in PD pathogenesis. Based on their mechanisms and potential benefits, we evaluated the potential protective effect of pretreatment with combinations of MET and RAPA in a 1-methyl-4-phenylpyridinium ion (MPP Cells were seeded in 96‐well plates at a density of 5 × 10β-actin . For TH, undifferentiated and differentiated cells were incubated with rabbit anti-TH . Next, membranes were washed in TBS-T buffer and incubated with HRP conjugated antirabbit  or HRP conjugated antimouse IgG  in blocking buffer for 2 hours at room temperature. Immunoreactive proteins were detected using the ECL chemiluminescence system (UVITEC). The immunoblot density was quantitated using ImageJ software .After treatment, cells were washed with PBS, trypsinized, and centrifuged. Cells were lysed in lysis buffer containing a 1% protease inhibitor cocktail (Sigma‐Aldrich) and incubated on ice, followed by centrifugation at 14,000 rpm for 20 minutes. The supernatant was collected and the protein concentrations were determined using the BCA Protein Assay Kit (Thermo Fisher Scientific). Protein samples were separated on a 4–15% SDS-PAGE and transferred onto a PVDF membrane. After blocking with 5% skim milk for 2 hours, membranes were incubated with the following primary antibodies at 4°C overnight: rabbit anti-LC3 , rabbit antiAkt , rabbit antiphospho-Akt , rabbit anti-p70S6K1 , rabbit antiphospho-p70S6K1 , and mouse anti-t-test. For multiple comparisons, data were analyzed using a one-way analysis of variance (ANOVA) followed by a post-hoc analysis (Tukey's multiple comparison test) using GraphPad Prism 5 software. A value of p < 0.05 was considered statistically significant.Results were expressed as mean ± standard error of the mean (SEM). Mean comparisons between the two samples were determined by Student's μM RA to induce neuronal differentiation. After 10 days of induction, SH-SY5Y cells showed marked neuritic extension .As mentioned earlier, studies have suggested that MET or RAPA protects against neurotoxicity in cellular and animal models of PD. Here, we started with an MTT assay to assess the effect of 24-hour exposure of MET or RAPA on SH-SY5Y cells that were induced by RA for 10 days to differentiate into a neuronal phenotype prior to exposure to 700 0.01; μM . Howeverll death . The res+ exposure was associated with the magnitude of autophagy, we determined cellular LC3-I and LC3-II levels by performing Western blotting analysis. Treatment with MET and RAPA combinations did not affect basal levels of LC3; however, after MPP+ exposure, LC3 conversion was increased, and the LC3-II/LC3-I ratios were at a similar level observed in cells that received MPP+ alone , which was also seen in our previous study [To evaluate whether increased death in neuronal cells treated with MET and RAPA combinations and MPPP+ alone . MPP+ alus study . Althougus study , excessi+ exposure (+ alone increased Akt phosphorylation. The findings suggested that the combination of MET and RAPA suppressed Akt activation at the basal level, rendering the cells unable to respond to MPP+. MET and RAPA combination also significantly suppressed the phosphorylation of S6K1 in both normal neuronal cells and cells after MPP+ exposure (+ alone decreased S6K1 phosphorylation, which is consistent with a previous study in a PD in vitro model [+-induced toxicity.It is known that activation of the Akt/mTORC1/S6K1 pathway regulates autophagy , 9. We dexposure . MPP+ alexposure . Althougro model . OverallMET and RAPA have been investigated as a potential neuroprotective agent in PD. Increasing evidence suggests that dysregulation of the autophagy process in the accumulation of alpha-synuclein and/or damaged mitochondria, which is commonly observed in PD , 13. In +-treated SH-SY5Y neuronal cells were used as a PD model to evaluate the effects of MET and RAPA combinations on cell viability and an autophagy marker, LC3-II, including the autophagy-related Akt/S6K1 pathway. The results showed that pretreatment of combinations of 1 mM MET and 0.5, 2, and 10 μM RAPA before MPP+ exposure did not protect against cell death, compared with the MPP+ alone group. In addition, increased LC3-II levels by MPP+ were not altered by MET and RAPA combination. It is plausible that the drug combination may influence the basal levels of autophagy. Increasing evidence supports that dysregulated or inadequate autophagy is closely related to PD pathogenesis [+ exposure after MET and RAPA treatment may promote excessive activation of the autophagic pathway, resulting in increased neuronal death, as shown in + exposure in our study [In our study, MPPogenesis , 13. Howur study .+ decreased S6K1 phosphorylation and reduced neuronal cell viability [+ increases Akt activation, as also seen in our results. In most cellular systems, Akt activation inhibits autophagy; however, increased LC3 conversion by MPP+ could be a result of S6K1 inhibition that is mediated through AMPK activation. A previous study demonstrated that suppression of S6K1 activity led to the activation of AMPK, which then phosphorylated ULK1 and induced autophagy [+ exposure. Decreased phosphorylation of both Akt and S6K1 by MET and RAPA combinations may lead to an increase in autophagy when cells were exposed to MPP+, as shown by increased LC3-II levels in +, the activation of Akt that is typically induced by MPP+ remains suppressed by MET and RAPA, leading to increasing of autophagy in the cells, and excessive autophagy due to the continued presence of the stress may trigger a death response.We assessed the activation of the Akt/S6K1 pathway, which is known to regulate autophagy , 9. A priability . S6K1 isiability . Thus, dutophagy . In our +-induced cell death. MET and RAPA combinations may affect mTORC1 inhibition, AMPK activation, and the S6K1 feedback loop in a complicated way. Determining the interactions of multiple signaling proteins induced by MET and RAPA, which influence the level of autophagy, must be considered for further studies.In conclusion, the combination of MET and RAPA may lead to an inappropriate autophagic response and cannot protect neuronal cells against MPP


Click here to listen to the PodcastRecent data have presented intriguing information about the treatment of patients with oesophageal adenocarcinoma. However, the actual standard of care in the neoadjuvant treatment for nonmetastatic tumour remains one of the hottest controversial topics in upper gastrointestinal tumours.In this podcast, Dr Angelica Petrillo interviews Prof. Hanneke WM van Laarhoven and Prof. Sylvie Lorenzen about the best choice for neoadjuvant treatment for nonmetastatic oesophageal adenocarcinoma: chemoradiotherapy or chemotherapy? The two experts debate about the pros and cons of each approach alongside future perspectives, biomarkers and implication for patients’ selection.Prof. van Laarhoven comments in favour of neoadjuvant chemoradiotherapy in this setting, referring to the data from the CROSS trial and its update after 10 years. Those data clearly showed that neoadjuvant chemoradiotherapy improved the survival outcomes, along with good tolerability, when compared with neoadjuvant chemotherapy in patients with oesophageal adenocarcinoma even after long-term follow-up.By contrast, Prof. Lorenzen discusses about the role of neoadjuvant chemotherapy, commenting on the data from the FLOT-4 trial, which also showed a benefit in survival in this subgroup of patients with a manageable safety profile.They then discuss about the role of immunotherapy in this field, based on the results from the CHECKMATE 577 trial, and the use of biomarkers, such as human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), circulating tumour DNA (ctDNA) and microsatellite status.However, direct comparisons between the two debated strategies do not exist yet. Recently, the preliminary results from the NEO-AEGIS trial, which compared perioperative chemotherapy with chemoradiotherapy in this setting, were presented at the American Society of Clinical Oncology (ASCO) congress. The trial showed similar results in both arms in terms of disease-free survival. Of note, 85% of patients were treated with the insufficient MAGIC regimen epirubicin, cisplatin and fluorouracil or capecitabine (ECF/EOX) and not according to the current treatment recommendations with the docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) protocol. However, several phase III trials comparing head-to-head the two neoadjuvant strategies in oesophageal adenocarcinoma are ongoing; their results are awaited to provide a definitive recommendation about the best treatment choice, if any, in this setting.


Effect of social determinants on antibiotic prescribing rates is poorly studied in modern literature. The objective of this study was to explore the effect of the prevalence of poverty  in each state on antibiotic prescribing rates in outpatient settings per 1,000 population through chronic health conditions  while also adjusting for confounders .Ecological study.Entire US population.Prevalence estimates from all 51 states were used to calculate direct, indirect, and total effects of poverty on the rates of antibiotic prescribing through parallel mediation analysis using linear regression with chronic health conditions  as mediators. I obtained these data from point-prevalence estimates of 2020 survey results from the Behavioral Risk Factor Surveillance System for rates on poverty, obesity, diabetes, chronic obstructive pulmonary disease, and population aged ≥ 65 years. I also used the Antibiotic Resistance & Patient Safety Portal for antibiotic prescribing rates per 1,000 population and the Association of American Medical Colleges database for the physician density per 100,000 population.For every percentage increase in prevalence of poverty in each state, the antibiotic prescribing rate increased by 17.4 courses per 1,000 population  using indirect effects of poverty through mediators.Antibiotic stewardship programs should consider targeting social determinants of health along with underlying health conditions of patients being treated with antibiotics. Treating infections becomes more and more challenging because antibiotic-resistant bacteria leave very few options to clinicians and are essentially untreatable. The problem is truly worrisome given the fact that new antibiotics are unlikely to emerge on the market, and old antibiotics are no longer effective against drug-resistant bacteria. The development of resistance to antibiotics is a natural process; however, using antibiotics in clinical practice accelerates the process and generates drug-resistant strains. Decades ago, antibiotic use was recognized as the strongest driving force for resistance development, and higher frequency of prescribing increases the chances of resistance development. Therefore, the modern discourse of antibiotic stewardship programs aims to reduce the amount of antibiotics prescribed. The goal of antibiotic stewardship has been to promote prescribing only when needed, at right time, at right doses, and at a right duration. In other words, it is intended to prevent inappropriate prescribing.According to the Centers for Disease Control and Prevention (CDC) every year 2.8 million infections are caused by drug-resistant bacteria, and 35,000 people die from these infections. Inappropriate prescribing significantly increases the amount of antibiotics prescribed and therefore, increases the chances of resistance development. Antibiotic stewardship as a new initiative aiming to reduce antibiotic prescribing rates, has traditionally focused on physician behavior and organizational factors to reduce overall prescribing rates through preventing inappropriate prescribing.Inappropriate prescribing is a serious public health issue given that ∼30% of all antibiotics are prescribed inappropriately . Alternatively, patients diagnosed with obesity or diabetes, who are predisposed to frequent bacterial infections, may also require antibiotic prescriptions at a higher rate compared to healthy patients without those conditions. Populations with higher prevalences of those conditions may also receive more antibiotics through appropriate prescribing mechanisms. In this context, the role of social determinants that “create” and propagate chronic health conditions also remains largely uncharacterized and underappreciated by public health community. This fact is reflected in the current discourse of antibiotic stewardship programs which focuses strictly on prescriber behavior without considering the broader problems. The goal of the current study was to characterize relationship between poverty and antibiotic prescribing rates through mediating effects of underlying health conditions (1) to evaluate the effects of underlying health conditions on prescribing rates and (2) to evaluate the effects of poverty on prescribing rate through mediators .Although inappropriate prescribing may account for a significant chunk of antibiotics being prescribed, patient-specific factors may also contribute to high prescribing rates through appropriate prescribing mechanism, but this has not been studied recently. Scientific knowledge about patient-specific factors that may also increase or decrease antibiotic prescribing rates in clinical settings is limited. Situations may arise in which prescribers encounter patients with multiple underlying health conditions who may, in fact, benefit from antibiotics. For example, patients diagnosed with chronic obstructive pulmonary disease (COPD) may benefit from antibiotics during episodes of exacerbation.In the current study, I used ecological design to explore relationships between selected group of variables. The outcome variable for analysis was outpatient antibiotic prescriptions per 1,000 population for each state dispensed from community pharmacies in calendar year 2020. Because outpatient antibiotics dispensed reflects the number of antibiotic courses prescribed, I have used the term “antibiotic prescribing rate per 1,000 population.” Data on rates of outpatient antibiotics dispensed from community pharmacies per 1,000 population were obtained from the CDC website (IQVIA Xponent data). This threshold for poverty was based on the 2020 Federal poverty level for a household with 3 members, which was $21,720; however, the average household size in 2020 was 2.53 according to the US Census. Thus, the poverty threshold for a household with 2.53 persons was calculated as $18,317, which was within the range of $0–$24,999 provided by the BRFSS. Mediating variable data, such as prevalence of COPD, diabetes, and obesity per 100 inhabitants for each state, were also obtained from BRFSS survey results of 2020.The independent variable “poverty” was defined as a prevalence of population with annual household income <$24,999 for each state per 100 inhabitants, and these data were obtained from Behavioral Risk Factor Surveillance System (BRFSS) survey results of 2020.Confounders, such as physician density per 100,000 population and the prevalence of population aged ≥65 years per 100 inhabitants, have been included in the model. In previous studies, physician density has been shown to increase or decrease the services provided and improve access to care, although no study has specifically reported the impact of physician density on antibiotic prescribing rates. To account for those confounding effects, prevalence data for the elderly population (aged ≥65 years) for each state were obtained from BRFSS survey results for 2020, and the data on physician density were obtained from recent report published by the Association of American Medical Colleges . Although certain specialties have been shown to have higher prescribing rates than others, only 1 variable was included in the model to show all specialties combined per 100,000 population for each state.Prevalence of aging population was also considered a potential confounder based on previous research showing that elderly patients have higher rates of antibiotics prescribed. The analysis was conducted using 5,000 bootstrap samples that no longer required normal distribution of scores nor the Sobel test. Because ecological design encompassed all 51 states including District of Columbia, no power analysis nor sample size calculations were made.Mediation analysis was based on linear regression using the ordinary least squares method and was conducted using SPSS version 27 software  with the macro PROCESS (version 4.1). Parallel mediation analysis was conducted using model number 4, which allowed the selection of an independent variable  along with dependent variable , multiple mediators  linking independent and dependent variables, and several confounders   and was regressed against antibiotic prescribing rates while also adjusting for confounders . In the second step, the relationships between independent variable  and each mediator  were explored while also adjusting for confounders . In the third step, an independent variable  was regressed against a dependent variable  adjusted for all 3 mediators and confounders.Simple mediation analysis usually involves analyzing data in 3 consecutive steps.Descriptive statistics showed that average prescribing rate of antibiotics in outpatient setting was 619.86 per 1,000 population in 2020 with high variability among the states: West Virginia reported the highest rate of 974 courses per 1,000 population, and Alaska reported the lowest rate of 348 courses per 1,000 population (Table  = 0.39), indicating that for every percentage increase in prevalence of poverty in each state, the antibiotic prescribing rate increased by 18 courses per 1,000 population (P < .01) (Table P < .01), the prevalence of diabetes increased by 0.29% (P < .01), and the prevalence of obesity increased by 0.34% (P < .01). All 3 models showed statistically significant relationships, with R values of 0.48, 0.64, and 0.45, respectively. The third step in mediation analysis also demonstrated strong relationships between all 3 mediators and the antibiotic prescribing rate, whereas the effect size of poverty decreased to a statistically nonsignificant level .The first step of mediation analysis indicated the existence of a strong linear relationship between the prevalence of poverty in each state and the antibiotic prescribing rate per 1,000 population  Table . The sec In the current study, the data analysis showed that ∼96% of total effects were caused by indirect effects of poverty on antibiotic prescribing rates through mediators , with unstandardized β of total indirect effects of 17.4 of 18.1  (Table P = .85). Although all 3 mediators exerted a statistically significant association on antibiotic prescribing rates in an indirect fashion, the effect of diabetes was the strongest . Overall, this mediation analysis showed that the antibiotic prescribing rate increased by 17.4 courses per 1,000 population through mediators for every percentage increase in the prevalence of poverty in each state.In mediation analysis, total effects are the summary of direct and indirect effects of independent variable on dependent variable.s) Table . On the  Although much has been written about those factors, there is a significant gap in the literature when it comes to documenting the impact of underlying health conditions on prescribing rates and the impact of social factors that inflate prescribing rates. In the current study, I considered antibiotic use from a mediation analysis perspective. There is a temporal relationship between the variables studied and antibiotic prescribing rates. This temporal relationship is a cornerstone of mediation analysis. Based on current knowledge, social determinants largely “create” chronic health conditions such as obesity, diabetes, and COPD. In other words, chronic health conditions cluster in the same areas due to the social and environmental conditions, a phenomenon called “syndemics.” For example, several researchers have documented that obesity is more prevalent among residents of poor communities. The same clustering has been observed for diabetes. Although COPD has been commonly associated with smoking, which is also more prevalent among underserved and poor populations, several researchers have documented a high prevalence of COPD among nonsmoking populations in rural and economically disadvantaged areas. Thus, the relationship between the poverty and mediators is well known. In fact, the chronic health conditions  examined in this study as mediators have been selected due to their high prevalence and syndemic association with the independent variable (poverty). The mediators in the current study have direct and linear relationship with outcome variables  through direct or indirect mechanisms. For example, patients diagnosed with COPD may benefit from antibiotics and therefore, should receive antibiotics during episodes of exacerbation. On the other hand, patients diagnosed with diabetes and obesity may have a higher exposure rate to antibiotics because they are predisposed to bacterial infections, which may indirectly increase the need for antibiotic therapy. In current study, those relationships have been explored under steps 2 and 3 of mediation analysis. Each step demonstrated a strong, linear relationship with the outcome variable. In step 2, poverty was regressed against mediators, and in step 3 mediators were regressed against antibiotic prescribing rates. The relationship between prevalence of poverty and antibiotic prescribing rate was also statistically significant and showed a fully mediated process (96%), indicating that the entire effect of poverty on antibiotic prescribing was fully mediated by chronic health conditions  did not show a statistically significant association with antibiotic prescribing rates, even though several studies have documented higher prescribing rates among elderly populations.The current study had several strengths. These results clearly demonstrate strong, linear relationship between poverty and outpatient antibiotic prescribing rate with ∼39% of variability in prescribing explained by the prevalence of poverty in a state. I capitalized on the strengths of ecological studies and used community characteristics to explore relationships among the variables. Another strength of the study is that it has exposed the association of poverty with antibiotic prescribing through mediators. This association would have gone undetected if multiple regression analysis with prevalence of poverty had been used as one of the confounders because the effect of poverty becomes negligible due to the fully mediated process . Also, the rates presented in this study may have been influenced by the COVID-19 pandemic. And finally, IQVIA Xponent data used in the current study do not differentiate appropriately prescribed antibiotics from inappropriately prescribed ones.For the outcome variable in this study, the IQVIA Xponent data presented on the CDC website do not include outpatient antibiotics dispensed from the federal facilities nor inpatient medications dispensed. Thus, these data may underestimate the true amount of antibiotics dispensed from community pharmacies. Although reductions in prescribing rates are desirable, the drawback of this approach in stewardship programs may be the fact that those comparisons do not consider underlying health conditions of patients being treated by individual physicians. Also, physicians with higher prescribing rates may have patients with multiple underlying health conditions that in fact, require antibiotic therapy. Assuming that top prescribers are the ones who prescribe inappropriately and asking them to reduce their prescribing may not be quite desirable approach without considering patient-specific factors. The process of standardization, which would consider patient-specific characteristics, has yet to occur in the National Healthcare Safety Network (NHSN). The standardized antibiotic administration ratio, usually used for facility comparisons proposed by the CDC, does not account for patient mix. On the other hand, looking at antibiotic prescribing process without considering a broader context of social determinants is also detrimental to stewardship programs because without improving social determinants of populations under care, prescribing rates are unlikely to be reduced.Current discourse regarding antibiotic stewardship does not consider patient-specific factors and may in fact penalize physicians or organizations with higher prescribing rates. For example, peer-to-peer comparison has been shown to reduce antibiotic prescribing rates among top prescribers.


Many existing and newly constructed bridges are made of reinforced and prestressed concrete. Advanced concrete materials play an increasingly important role in concrete bridges, facilitating the strengthening and repair of existing bridges, fast replacement solutions for parts of existing bridges, and for the design of novel challenging bridge projects. The development of advanced concrete materials and their structural applications is, thus, an important topic in the built environment.The articles presented in this Special Issue bring together research insights, practical applications, and discussions on how to develop better structural concrete materials for bridge engineering practices. Since articles were written both by materials scientists and bridge engineers, a wide view on the topic is presented.One example of an advanced structural concrete material is ultra-high-performance fiber-reinforced concrete (UHPFRC). With research on this topic having reached a high level of maturity, practical applications of this material are becoming increasingly more common. A key practical issue is related to the resulting fiber content, fiber orientation, and efficiency factor of the structural elements, particularly relevant for thin elements. This property determines the post-cracking tensile strength of the UHPFRC. In , the autAdvances in steel-fiber-reinforced concrete include the development of steel-fiber-reinforced expanded-shale lightweight concrete (SFRELC) . In partAnother example of an advanced structural concrete material is concrete with an MgO expansive agent and steel fibers added to the mix. This improved concrete mix  was applFor the prefabrication industry, a better understanding of the structural behavior can result in the optimization of the resulting prefabricated elements. A topic of particular interest is the interface bond strength and anchorage performance of the steel reinforcement (ribbed and plain bars) in the prefabricated concrete. The experimental study of  resultedFor existing bridges, the first challenge is often the proper assessment of the structure; the information is important for the evaluation of various possible solutions, such as for the strengthening of the structure. In , the autOn the topic of strengthening existing bridges, various advanced structural concrete materials are proposed. Experiments on reinforced concrete beams strengthened with textile-reinforced concrete (TRC) and fiber–textile-reinforced concrete (F/TRC) showed the beneficial effects of this strengthening technique at the ultimate limit state, as well as in the serviceability limit state . A seconUHPFRC is also proposed for the strengthening of existing bridges . ExperimPolyvinyl alcohol fiber-reinforced engineering cementitious composites (PVA-ECCs) are proposed in another paper , where tAnother novel method for strengthening was proposed in , in whicUltimately,  proposesMaterials, who helped handle the manuscripts of this Special Issue, as well as the journal staff, who provided expert assistance to the development of this Special Issue at every step of the way.These presented papers provide insight into the current state-of-the-art of advanced structural concrete materials in bridge applications, and show the way towards the practical application of these materials. I appreciate all author contributions and sincerely value the time and effort spent in preparing these articles. I would also like to thank all reviewers who contributed to this Special Issue for their time, effort, and valuable remarks to the articles. Finally, I would like to thank the academic editors of


We analyzed the etiological classification and clinical characteristics of patients with abnormal liver function indices and elevated serum IgG4 levels and investigated the effects of intrahepatic follicular helper T cell (Tfh) infiltration and serum IL-21.  Clinical data  and etiology of liver injury from 136 patients were analyzed. We compared the general condition, clinical characteristics, and laboratory tests of 19 AIH (autoimmune hepatitis) patients with elevated serum IgG4 levels with those of 20 AIH patients with normal serum IgG4 levels admitted at the same time. Five patients with AIH and elevated serum IgG4 levels and five AIH patients with normal IgG4 levels were matched by sex, age, and liver function, and Tfh infiltration in liver biopsy tissues of patients in both groups was determined by immunofluorescence staining. Five AIH patients with elevated serum IgG4 levels were selected for measurement of serum interleukin-21 (IL-21) levels by enzyme-linked immunosorbent assay (ELISA), seventeen AIH patients with normal serum IgG4 were matched by sex, age, and liver function indices, and 29 physically healthy individuals matched by sex and age were selected as the control group. The changes in patients with IgG4-RD and abnormal liver function before and after glucocorticoid treatment were measured. n = 28) with abnormal liver function indices and IgG4-related disease received glucocorticoid therapy for six months, and ALT, AST, ALKP, GGT, TBil, DBil, IgG, IgG4, and IgE were significantly lower after treatment.  Patients (136) with abnormal liver function indices and elevated serum IgG4 levels were diagnosed with liver disease of different etiologies. IgG4-related disease was the most frequent, followed by AIH and malignancy. Abnormal liver function indices with high serum IgG4 were most commonly seen as elevated gamma glutamyl transferase (GGT). The AIH group with elevated serum IgG4 had increased intrahepatic levels of Tfh. IL-21 in AIH patients with elevated IgG4 was higher than in patients with normal IgG4 and healthy controls. Patients ( Elevated serum IgG4 was seen in patients with abnormal liver function indices with diverse causes. Tfh infiltration and increased IL-21 production may be related to the pathogenesis of AIH with elevated serum IgG4. Glucocorticoid therapy is effective in patients with abnormal liver function indices and IgG4-related disease. Assessing immune function in patients with abnormal liver function indices and elevated serum IgG4 levels should facilitate diagnosis and treatment of the disease. HoweverT (Tfh) cells are an immune cell type that has received much attention in the last decade. As a subclass of T helper (Th) cells, Tfh cells differentiate upon stimulation by IL-21, secrete large quantities of IL-21, and promote the conversion of B cells to plasma cells, thereby elevating IgG4 [Follicular helper ing IgG4 . In thisThe flowchart of patient enrollment and study design is provided in The clinical data of 136 patients with abnormal liver function indices and elevated serum IgG4 level (>2.01 g/L) who were hospitalized at Tianjin Medical University General Hospital from May 2012 to August 2020 with complete medical records and follow-up data were analyzed retrospectively. Physically healthy individuals and autoimmune hepatitis (AIH) patients with normal serum IgG4 levels were included as controls. This study was approved by the Ethics Committee of the General Hospital of Tianjin Medical University (IRB2015-YX-002).Clinical data  and etiologies of liver injury from 136 patients were obtained. We compared the general condition, clinical characteristics, and laboratory tests of 19 AIH patients with elevated serum IgG4 levels with those of 20 AIH patients with normal serum IgG4 levels admitted at the same time. Five patients with AIH and elevated serum IgG4 levels and five AIH patients with normal IgG4 levels were matched by sex, age, and liver function. Tfh infiltration in liver biopsy tissues of patients in both groups was determined by immunofluorescence staining. Five AIH patients with elevated serum IgG4 levels were selected for measurement of serum interleukin-21 (IL-21) levels by enzyme-linked immunosorbent assay (ELISA). Seventeen AIH patients with normal serum IgG4 were matched by sex, age, and liver function indices, and 29 physically healthy individuals matched by sex and age were selected as the control group. The changes in patients with IgG4-RD complicated with abnormal liver function before and after glucocorticoid treatment were measured.IgG4-RD was diagnosed according to the diagnostic criteria published in Japan in 2012 . Due to t-test, and the Fisher exact probability method was used for comparison of the count data between groups. P < 0.05 was set as the threshold for statistical significance.Statistical analysis was performed using SPSS 22.0 and GraphPad Prism 7.0 software. For measurement data, the mean ± standard deviation (SD) was used to represent normally distributed data, while the median (quartile range), M(Q), was used to represent non-normally distributed data. The number of cases or percentages was used to describe the count data. Measurement data that conformed to the normal distribution were analyzed by n = 136) were screened using the medical record management system or clinical records and classified according to sex, age, medical history, laboratory tests, histopathology, and immunological examinations. The patients were also categorized according to etiology: IgG4-related diseases , autoimmune hepatitis , malignancy , nonalcoholic fatty liver disease , viral hepatitis , alcoholic liver disease , and primary biliary cholangitis . There was one case each (0.7%) of primary sclerosing cholangitis, drug-related liver injury, liver abscess, and gallstones, and 26 patients (19.1%) had hepatic impairment of unknown etiology.Patients with abnormal liver function indices and elevated serum IgG4  were male and 24 (46.2%) were ≥65 years of age. Organ involvement included pancreas (31), bile duct (16), retroperitoneum (7), salivary gland (3), kidney (4), submandibular gland (3), lacrimal gland (2), lung (2), and other organs (3).n = 136), patients with elevated GGT were the most common, accounting for 86.8% (118), of which 76 were elevated 1- to 5-fold (64.4%) and 24 were elevated 10-fold (20.3%) .Among the patients with abnormal liver function indices and elevated serum IgG4 ( (20.3%) .P < 0.05) more patients in the group with elevated serum IgG4 were male, had elevated IgE, AST ≥ 10 ULN, ALT ≥ 10 ULN, decreased C4, concomitant allergic disease, and constipation.Details of the general condition, clinical symptoms, and laboratory test results of 19 AIH patients with elevated serum IgG4 and 20 AIH patients with normal serum IgG4 are shown in Five patients with AIH and elevated serum IgG4 and five AIH patients with normal IgG4 levels were matched according to sex, age, and liver function. The intrahepatic Tfh cell infiltration in liver biopsy tissue was visualized by immunofluorescence staining. The group with AIH and elevated serum IgG4 had increased infiltration of Tfh in the confluent areas compared to patients with normal IgG4 levels .n = 5) were significantly higher than those in 17 AIH patients with normal IgG4  and 29 sex- and age-matched healthy controls selected during the same visit period , with no significant difference between the latter two groups  (The IL-21 levels in five AIH patients with elevated serum IgG4 (P=0.167) .P=0.0041; P=0.0002; P=0.0002; P=0.0409; P=0.0011; P=0.0003; The effects of six months of glucocorticoid therapy were analyzed in 28 first-treated patients. Compared with pretreatment levels, significantly lower levels of ALT .Statistical analysis of the changes of IgG, IgG4, and IgE in first-treated patients with IgG4-RD combined with abnormal liver function indices before and after glucocorticoid therapy is shown in Elevated serum IgG4 levels in patients can be accompanied by varying degrees of abnormal liver function , 13. TheAnalysis of the clinical data of AIH patients with elevated serum IgG4 levels and AIH patients with normal serum IgG4 levels revealed significant differences. A comparison of 19 AIH patients with elevated serum IgG4 with 20 cases of AIH with normal serum IgG4 revealed that male patients and those with elevated IgE, AST ≥ 10 ULN, ALT ≥ 10 ULN, reduced C4, allergic disease, or constipation were more commonly seen in the AIH group with elevated serum IgG4. Therefore, we suggest that allergy, constipation, C4, and IgE may be associated with the development and progression of the diseases. We further infer that different immune mechanisms may underlie the condition of AIH patients with elevated serum IgG4 levels compared to those without elevated serum IgG4. Therefore, combined IgG4-associated AIH should be considered for male AIH patients presenting clinically with elevated ALT and AST levels.Comparing the changes in liver function before and after the use of glucocorticoids in patients with IgG4-RD and abnormal liver function indices revealed that glucocorticoid therapy was effective, which is consistent with previous reports . To furtIn summary, elevated IgG4 levels in patients with liver injury are commonly seen in almost all liver diseases, and the prominent liver damage is characterized by elevated GGT, indicating susceptibility to combined bile duct injury. Glucocorticoid therapy is effective in patients with liver damage caused by IgG4-RD. The concomitant diseases, changes in liver function, and complement in AIH patients with elevated serum IgG4 differed from those of AIH patients with normal serum IgG4, indicating different immune responses and different targets of action; Tfh cells and IL-21 may contribute to the pathogenesis of AIH with elevated serum IgG4. Studies on immune function in patients with liver injury and elevated serum IgG4 may be useful for diagnosis and treatment of the associated diseases. Further studies are required to fully elucidate the mechanisms of Tfh cell activation, IL-21 production, and liver injury caused by the target cells of the immune response. In addition, it remains to be determined whether the pathogenesis of liver injury with elevated serum IgG4 is the same as that of IgG4-RD. The information presented here should prove useful and effective for improving the diagnosis and treatment of abnormal liver function with elevated serum IgG4 levels.


In this paper, the environmental characteristics and corrosion damage degree of concrete in a 7-year-old coking ammonium sulfate workshop were investigated, and the neutralization life prediction of the concrete structure was carried out. Besides, the corrosion products were analyzed through concrete neutralization simulation test. The average temperature and relative humidity in the workshop were 34.7 °C and 43.4%, and they were 1.40 times higher and 1.70 times less than those of the general atmospheric environment, respectively. Both the concentrations of CO2 and SO2 were significantly different in various sections of the workshop, and they were much higher than those of the general atmospheric environment. The appearance corrosion and compressive strength loss of concrete were more serious in the sections with high SO2 concentration, such as vulcanization bed section and crystallization tank section. The neutralization depth of concrete in the crystallization tank section was the largest, with an average value of 19.86 mm. The corrosion products gypsum and CaCO3 were obviously visible in the surface layer of concrete, while only CaCO3 could be observed at 5 mm. The prediction model of concrete neutralization depth was established, and the remaining neutralization service life in the warehouse, synthesis section (indoor), synthesis section (outdoor), vulcanization bed section, and crystallization tank section were 69.21 a, 52.01 a, 88.56 a, 29.62 a, and 7.84 a, respectively.Iron and steel plants emit a large amount of CO CO2 converts Ca(OH)2, calcium silicate hydrate (C–S–H) and calcium aluminate into CaCO34. SO2 reacts with all calcium compounds of hydration products, including CaCO3, and converts them into sulfur-bearing compounds7. The list of sulfur-bearing compounds mainly includes calcium sulfite (CaSO3·1/2H2O), calcium sulfates  and calcium sulfoaluminates (3CaO·Al2O3·CaSO4 12H2O and 3CaO·Al2O3·3CaSO4·31–32H2O)7.CO9, and calcium sulfoaluminates are difficult to exist stably due to the decrease of pore-solution pH10. It was reported that the disappearance of ettringite (3CaO·Al2O3·3CaSO4·31–32H2O) and monosulfoaluminate hydrate (3CaO·Al2O3·CaSO4·12H2O) at 20 °C were at pH ≤ 10.7 and pH ≤ 11.6, respectively11. The pH ranges of ettringite that could stably exist at 25 °C, 50 °C, and 85 °C were 10.43–12.52, 10.52–12.41, and 10.87–12.25, respectively12. The decomposition of ettringite due to concrete carbonation was reported by authors15, and the reaction products were CaCO3, gypsum and alumina gel.Both carbonation and sulfuration of concrete can reduce the pore-solution pH18, where the thin protective film of iron oxides around rebar is stable. The decrease of pore-solution pH due to carbonation and sulfuration leads to the destabilization of passive film on the rebar. Once pH falls to about 9, the rebar begins to corrode due to the breakdown of passive film19. Therefore, it is necessary to development technologies and strategies for CO2 and SO2 resistance of concrete. To achieve this target, the experimental study and field investigation on the neutralization of concrete under the combined action of CO2 and SO2 should be carried out.The pore-solution pH of concrete is usually in the range of 12.5–13.82 and SO2, and they are exposed to an artificial atmosphere with the high concentrations of corrosion media21. The diffusion rate of CO2 in concrete was higher than that of SO2 under the combined action of CO2 and SO2. The main reason was that the CO2 concentration was much higher than that of SO2 in the industrial environment20. Meanwhile, the diffusion rate of CO2 with the same volume concentration was faster than that of SO2. Leah21 observed the gas diffusion process in concrete under the condition of CO2 and SO2 with the same volume concentration. It was found that concrete combined with CO2 at the initial stage of the reaction, and the carbonation product CaCO3 was generated continuously. Subsequently, SO2 converted CaCO3 into gypsum. Therefore, CO2 reacted with hydration products at first, and the essence of concrete sulfuration was the reaction between SO2 and carbonation product.There are a few experimental studies on the neutralization of concrete under the combined action of CO2 and SO2. Pavlik7 evaluated the degradation of concrete by flue gas from coal combustion in a power plant stack. It was observed that the concrete was divided into soft disintegrated zone, sulfated zone, carbonated zone, and un-neutralized zone. The pH, corrosion products, and microstructure in various zones were analyzed, respectively. Ren22 found that the concrete cover of underground stovepipe in a sintering plant was partially cracked or even peeled off, and the steel bars were seriously corroded.There is few field investigation on the concrete neutralization under the combined action of CO2 and SO2 mainly focus on the neutralization mechanism, and the performance deterioration and life prediction of concrete should be carried out. The environmental characteristics of the local industrial environment should be monitored, and the concrete neutralization simulation test method should be proposed according to these environmental characteristics. Moreover, the corrosion damage degree, corrosion mechanism and life prediction of concrete under the action of CO2 and SO2 should also be accomplished.In conclusion, the research results on the concrete neutralization under the combined action of CO2 concentration, and SO2 concentration were surveyed. Besides, the appearance, neutralization depth, and compressive strength of concrete were analyzed in various sections of the workshop. The concrete neutralization simulation test method was proposed according to the environmental characteristics, and the corrosion products were analyzed by using X-ray diffraction (XRD) and thermogravimetric analysis (TG). The prediction model of neutralization depth of concrete in the ammonium sulfate workshop was established, and the remaining neutralization service life in various sections was predicted.In this paper, the environmental characteristics and corrosion damage of the concrete structures in a 7-year-old coking ammonium sulfate workshop of Wuhan Iron and Steel Corporation (WISCO) were investigated. The environmental characteristics such as temperature, relative humidity, CO2 and SO2 in the process of coking. Taking a 7-year-old coking ammonium sulfate workshop of WISCO as an example, the environmental characteristics and corrosion damage of concrete were investigated from August to October 2013. WISCO was located in Qingshan District, Wuhan City. The ammonium sulfate workshop was built in 2006, and the structural style was a three-layers concrete frame structure.The iron and steel industry emits a large amount of COThe structure plan is shown in Fig. The concrete consisted of P.O. 42.5 ordinary Portland cement, with natural river sand as the fine aggregate and crushed limestone as the coarse aggregate. The pumping agent was used with a water reducing rate of 18%. The mixture proportion of concrete is listed in Table 23 and GB/T 18204.14-200024. There were five measuring points in each section, and they were arranged in two diagonals with the shape of plum blossom. The height of measuring points was 0.8–1.6 m from the ground, and the distance between the measuring points and the heat source or wall was not less than 0.5 m. The average values of all measuring points were the average temperature and average relative humidity in the ammonium sulfate workshop, respectively.The temperature and relative humidity in the ammonium sulfate workshop were tested by using a temperature and humidity recorder, and the data were collected hourly. The layout of measuring points was based on Chinese standard GB/T 18204.13-20002 and SO2 in various sections of the ammonium sulfate workshop were monitored by using a portable carbon dioxide detector and a portable sulfur dioxide detector, respectively. The layout of measuring points was the same as that for temperature and relative humidity monitoring, and the average values of all measuring points in various sections were the average CO2 concentration and average SO2 concentration, respectively.The concentrations of CO25. Concrete columns were randomly selected to test neutralization depth, and each column had 3–7 testing zones. Take a hole with a diameter of 15 mm in each testing zone, and the depth of the hole should be larger than its neutralization depth. The neutralization depth was measured with a 1% phenolphthalein alcohol solution . Use a carbonation depth meter for measurement. Each hole was measured three times, and the average of three measurements was considered as the neutralization depth of the testing zone. The average of all testing zones for each column was the neutralization depth of concrete column.The neutralization depth test method of concrete was adopted according to Chinese standard JCJ/T 23-201125. The selection of concrete column was the same as that of column for testing the neutralization depth. Ten testing zones were selected for each column, and they were arranged on two symmetrical measurable surfaces of the column. The measuring points in each testing zone were not less than 16. The measuring points should be evenly distributed, and the distance between two adjacent measuring points should not be less than 20 mm. The distance between the measuring points and the exposed steel bars or embedded parts was not less than 30 mm. The measuring points should not appear on stones and pores, and each measuring point only bounced once. Ignoring three maximum values and three minimum values, the mean value of the remaining measuring points was the average rebound value of the testing zone. The average rebound value of ten testing zones was the strength of the concrete column. The equivalent value of compressive strength of concrete was converted according to the rebound value of compressive strength and the neutralization depth.The compressive strength of concrete was tested by the rebound method according to JCJ/T 23-20112 and SO2 were studied by concrete neutralization simulation test. The raw materials and mixture proportion of concrete in the simulation test were the same as those in the ammonium sulfate workshop. The concrete neutralization simulation test method was proposed according to the concrete carbonation test method in Chinese standard GB/T 50082-200926.In order to analyze the corrosion mechanism of concrete in the ammonium sulfate workshop, the corrosion products of concrete under the combined action of CO2 concentration in the simulation test was 20% according to GB/T 50082-200926. The concentration of CO2 was 649 times higher than that of SO2 in the ammonium sulfate workshop. Therefore, the SO2 concentration in the simulation test was 0.03%. According to concrete carbonation test method in GB/T 50082-200926, 4 days of the simulation test is equivalent to 7 years of the actual environment. Therefore, the test period was 4 days.The environmental parameters in the simulation test were set according to the actual environment of the ammonium sulfate workshop. The settings of the temperature and relative humidity in the simulation test were the same as the actual temperature and relative humidity in the workshop. Therefore, the temperature and relative humidity in the simulation test were 35 °C and 45%, respectively. The COThe cube specimens were dried at 60 °C for 48 h before the test.2 and SO2 in concrete was one-dimensional.Each specimen was covered (except its two opposite sides) with epoxy resin to ensure that the diffusion of COThe specimens were placed in the concrete carbonation test chamber, and the distance between adjacent specimens was at least 50 mm.2 concentration = 20%.The environmental parameters in the concrete carbonation test chamber were set as follows: temperature = 35 °C, relative humidity = 45%, and COThe specimens were taken out after 4 days.The carbonated specimens were placed in the concrete sulfuration test chamber.2 concentration = 0.03%.The environmental parameters in the concrete sulfuration test chamber were set as follows: temperature = 35 °C, relative humidity = 45%, and SOThe test period of sulfuration test was 4 days.The test procedure included the following steps:The pulverizer was used to extract concrete powder. The specimen was powdered in different layers (1 mm/layer). The powder was passed through a 0.16 mm sieve. The powder was dried at 50 °C for 24 h before the test. The prepared powder was used in the XRD and TG test. XRD analysis was used to examine the phase composition of concrete. The diffraction used a Cu-Kα source, and the diffraction angle was from 5° to 45° at a step of 0.02°.TG method was used to measure the composition of concrete. The test was carried out at a temperature range from 30 to 900 °C, and the heating rate was 10 °C/min. The experimental atmosphere was nitrogen.Both the temperatures in the ammonium sulfate workshop and general atmospheric environment are shown in Fig. Both the relative humidity in the ammonium sulfate workshop and general atmospheric environment are shown in Fig. 2 concentrations in the ammonium sulfate workshop are shown in Fig. 2 concentration in the workshop was 986.2 mg/m3. Besides, the CO2 concentrations in various sections were significantly different, and the CO2 concentrations in the warehouse, synthesis section (indoor), synthesis section (outdoor), vulcanization bed section, and crystallization tank section were 927 mg/m3, 886 mg/m3, 805 mg/m3, 1207 mg/m3, and 1106 mg/m3, respectively. According to the relevant information from the Wuhan Environmental Protection Bureau (WHEPB), the average CO2 concentration of the atmospheric environment in Qingshan District was 740.5 mg/m3. Therefore, the CO2 concentration in the ammonium sulfate workshop was larger, and the maximum value was 1.49 times higher than that of the general atmospheric environment.The CO2 concentrations in the ammonium sulfate workshop are shown in Fig. 2 concentration in the workshop was 2.11 mg/m3. There were significant differences in SO2 concentrations in various sections, and the SO2 concentrations in the warehouse, synthesis section (indoor), synthesis section (outdoor), vulcanization bed section, and crystallization tank section were 1.29 mg/m3, 1.64 mg/m3, 1.03 mg/m3, 2.30 mg/m3 and 4.29 mg/m3, respectively. According to the relevant information from the WHEPB, the average SO2 concentration of the atmospheric environment in Qingshan District was 0.056 mg/m3. Therefore, the SO2 concentration in the ammonium sulfate workshop was higher, and the maximum value was 76.6 times higher than that of the general atmospheric environment. In addition, the SO2 concentration was much lower than CO2 concentration in the ammonium sulfate workshop.The SOThe appearance of concrete in the ammonium sulfate workshop is shown in Fig. 2 reacted with hydration products of concrete to form CaCO3, which made the pore structure denser than that of uncarbonated concrete. Therefore, carbonation could not change the appearance of concrete. However, SO2 converted CaCO3 into gypsum, which rapidly increased the solid-phase volume of concrete. A large amount of gypsum produced excessive internal stress in concrete, resulting in expansion and cracking on the concrete surface6. Therefore, the degree of appearance change of concrete increased as the SO2 concentration increased.CO2 concentration in the outdoor synthesis section was not high, but the outdoor environment was affected by rainwater. Water played a key role in the corrosion reaction. Water provided a medium for ion transport, and it was a necessary condition for reaction between SO2 and CaCO3. Moreover, the reaction products calcium sulfates were the substances containing crystal water. Calcium sulfates containing more crystal water increased the solid-phase volume of concrete, and concrete was more likely to crack. Relevant research showed that SO2 could cause serious corrosion damage of concrete when there was liquid water on the concrete surface21. Therefore, the appearance change in the outdoor synthesis section was relatively large.The SOThe neutralization depth of concrete in the ammonium sulfate workshop is listed in Table 2 concentrations in the vulcanization bed section and crystallization tank section were relatively high, and the neutralization depths were larger than those in the warehouse and synthesis section. In addition, the SO2 concentration in the crystallization tank section was higher than that in the vulcanization bed section, and the damage of concrete was more serious. CO2 diffused from mic-cracks into concrete, and the neutralization rate increased. Therefore, the neutralization depth of concrete in the crystallization tank section was 1.57 times larger than that in the vulcanization bed section.The frequency distribution histograms of concrete neutralization depth in various sections of the workshop are shown in Fig. As shown in Fig. Compressive strength of concrete in the ammonium sulfate workshop is shown in Table 28, while concrete sulfuration decreased the strength29. Therefore, the compressive strength of concrete in the crystallization tank section and vulcanization bed section was low due to the high concentration of SO2. Although the SO2 concentration in the synthesis section (outdoor) was the lowest, the strength dropped greatly due to the influence of rainwater, with an average value of 23.60 MPa.As shown in Table 4·2H2O), calcite (CaCO3), portlandite (Ca(OH)2) and quartz (SiO2). Among them, Ca(OH)2 was the hydration product, and gypsum and CaCO3 were the corrosion products of concrete under the action of CO2 and SO2. The diffraction peaks of gypsum and CaCO3 were obviously visible in the surface layer of concrete, while the Ca(OH)2 diffraction peak was not obvious. The gypsum diffraction peak could not be observed at the depth of 5 mm, and the Ca(OH)2 peak appeared.The XRD patterns of concrete with different depths are shown in Fig. 2 concentration in the workshop was much higher than that of SO2, and therefore, the diffusion rate of CO2 in concrete was faster than that of SO2. CO2 reacted with the hydration product Ca(OH)2 to form CaCO3, and SO2 reacted with the carbonation product CaCO3 to form gypsum. Only CO2 could diffuse to a depth of 5 mm from the concrete surface, so CaCO3 was observed in the interior concrete. The concentrations of CO2 and SO2 in the surface layer were higher than those in the interior concrete, so Ca(OH)2 could not exist in the surface layer.The CO32, while ettringite could not be observed in concrete under the action of CO2 and SO2. This was because CO2 and SO2 were dissolved in the pore solution and ionized into H+, which reacted with alkaline hydration products. Because of the decrease of pore-solution pH, ettringite could not exist stably, and it was decomposed into gypsum and an aluminum-containing gel30. Therefore, the sulfated product of concrete was only gypsum.It might be well known that gypsum reacted with aluminate phase to form ettringite in concrete under sulfate attack2 and CaCO3, respectively. Among them, CaCO3 and gypsum were the corrosion products of concrete under the action of CO2 and SO2. The height of CaCO3 endothermic peak in the surface layer of concrete was higher than that at the depth of 5 mm. This might be due to the maximum CO2 concentration was in the surface layer of concrete. Therefore, although some CaCO3 in the surface layer of concrete reacted with SO2 to form gypsum, the content of CaCO3 was still larger than that at 5 mm.The TG analysis results of concrete with different depths are shown in Fig. 36. The carbonation depth of concrete is affected by temperature, relative humidity, CO2 concentration, and compressive strength of concrete in this experiment. According to the literature36, the carbonation depth of concrete in the ammonium sulfate workshop can be expressed as:XC is the carbonation depth of concrete, mm; kmc is the calculation mode parameter, kmc = 0.996; ke, kCO2 and kf are the carbonation influence coefficients of temperature and humidity, CO2 concentration and compressive strength, respectively; t is the carbonation exposure time, d.A large number of researchers have verified that the carbonation depth of concrete is proportional to the square root of exposure time2 concentration, and compressive strength can be calculated in Eqs.  into into4) i2 concentration, concrete compressive strength, and exposure time into Eq. 2, and neutralization reaction occurs in concrete. Once the concrete cover is completely neutralized, passivation film of rebar is destroyed, and therefore, the rebar begins to corrode. The end of the neutralization service life of concrete is the initial time of steel bar corrosion. Therefore, the limit state function of the neutralization service life of concrete is shown in Eq.  is the neutralization depth of concrete, mm; and t is the exposure time, a.The high alkalinity inside the concrete forms a passivation film for the rebar to protect it from being corroded. COn in Eq. .8\docume36, the neutralization remain of concrete is shown in Eq.   9) into 2 and SO2 were studied. The main conclusions are as follows:The temperature in the workshop increased with the increase in that of the general atmospheric environment. The average temperature in the workshop was 34.7 °C, and it was 1.40 times higher than that of the general atmospheric environment. Both the relative humidity in the workshop and general atmospheric environment barely changed. The average relative humidity in the workshop was 43.4%, and the relative humidity of the general atmospheric environment was 1.70 times higher than that in the workshop.2 concentration and SO2 concentration in the workshop were 986.2 mg/m3 and 2.11 mg/m3, and they were 1.31 times and 37.68 times higher than those of the general atmospheric environment, respectively. In addition, both the concentrations of CO2 and SO2 in various sections of the workshop were significantly different.The average COThe appearance of concrete in various sections of the workshop was significantly different. There were only some damage on the concrete surface caused by mechanical collision in the warehouse, and a large amount of white crystals were precipitated on the concrete surface in the synthesis section (outdoor). Platform cornice concrete was completely corroded and peeled off in the vulcanization bed section. The coating of the floor in the crystallization tank section was partially damaged, and the damaged part was severely corroded.2 and SO2, and the neutralization depth in the crystallization tank section was the largest, with an average value of 19.86 mm.The neutralization depth of concrete in various sections of the workshop was significantly different and followed the normal distribution. The neutralization depth of concrete increased with the increase in the concentrations of CO2. The strength dropped greatly in the synthesis section (outdoor) due to the influence of the rainwater.The compressive strength of concrete in various sections of the workshop decreased. The compressive strength of concrete in the crystallization tank section and vulcanization bed section was low due to the high concentration of SO3 were the corrosion products of concrete under the action of CO2 and SO2. Gypsum and CaCO3 were obviously visible in the surface layer of concrete, while only CaCO3 could be observed at the depth of 5 mm. The content of CaCO3 in the surface layer of concrete was larger than that at the depth of 5 mm.Gypsum and CaCOThe prediction model of the neutralization depth of concrete was established, and the remaining neutralization service life of concrete in the warehouse, synthesis section (indoor), synthesis section (outdoor), vulcanization bed section, and crystallization tank section were 69.21 a, 52.01 a, 88.56 a, 29.62 a, and 7.84 a, respectively.In this study, the environmental characteristics and corrosion degree of concrete in a 7-year-old coking ammonium sulfate workshop were analyzed, and the neutralization life prediction of the concrete structure was carried out. Besides, the corrosion products of concrete under the action of CO