Leishmania braziliensis (Lb), the agent responsible for cutaneous leishmaniasis (CL) in Brazil, represents an interesting model in which to evaluate the effects associated with MET. Metformin (MET) is a hypoglycemic drug used for the treatment of diabetes, despite interference in host immunity against microorganisms. Cutaneous infection caused by pathogens such as Lb infection. To evaluate the modulatory effect of MET in Lb infection and MET treatment in BALB/c mice and Raw 264.7 macrophages. Experimental study of Lb culture allow for the maintenance of stationary parasite growth phase. Lb-infected cells treated with MET exhibited increased parasite load. While both MET and Lb infection alone promoted the production of intracellular reactive oxygen species (ROS), reduced levels of ROS were seen in MET-treated Lb-infected macrophages. MET treatment interfered with lesion kinetics, increased parasite load and reduced macrophage proliferation. Low concentrations of MET in Lb parasite load, altered ROS production and modulated cellular proliferation. Our experimental results indicate that MET interfere with the evolution of CL. Experimental treatment with MET interfered with the kinetics of cutaneous ulceration, increased  Leishmania.Leishmania braziliensis (Lb) and is clinically characterised by one or more oval-shaped ulcerative lesions, or rounded, granulomatous-bottomed ulcerations with well-defined raised borders.,,,Cutaneous leishmaniasis (CL) is a clinical form of the anthropozoonotic disease complex caused by protozoa of the genus +5) are the first-line drugs for Lb infection treatment. Despite high efficacy, the numerous side effects, such as cardiac, renal and hepatic toxicity, induced by these drugs consequently restricts use to certain groups of patients.,,+5 and immunomodulators, such as pentoxifylline, an inhibitor of TNF production, which seemed to accelerate cure in patients.,In Brazil, pentavalent antimonials , has been described in cancer and infectious diseases, including tuberculosis and pneumonia caused by Experimental model design - After receiving ethical approval by the local Institutional Review Board for Animal Experimentation (protocol 013/2017), 6-week-old male isogenic BALB/c mice were obtained from the Animal Care Facility of the Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (IGM-Fiocruz) in Salvador, Bahia, and maintained under controlled conditions . Mice were divided into three groups of five according to MET treatment and Lb infection status. Group 1: Lb infection; Group 2: MET treatment alone; Group 3: Lb infection and MET treatment.Metformin hydrochloride treatment - Mice from Groups 2 and 3 received continuous pre-treatment for six weeks (prior to infection procedures) with an oral solution containing metformin hydrochloride (Hcl)  at a dosage of 500 mg/kg diluted in water. Following Lb infection procedures, mice in Groups 2 and 3 continued to receive MET solution orally for an additional six weeks.Leishmania braziliensis infection - Groups 1 and 3 were intradermally infected in the left ear using a 30G needle syringe containing 10 μL of 2 x 105 stationary-phase metacyclic Lb promastigotes (strain MHOM/BR/01/BA788). Parasites were cultivated in Schneider’s medium , supplemented with 20% inactivated foetal bovine serum (FBS) , L-glutamine (2 mM), penicillin (100U / mL) and streptomycin (100 mg / mL), for 5-7 days under 23ºC until reaching stationary phase.The diameter of the infected ear was measured weekly in Groups 1 and 3 with the aid of a digital caliper. Measurements were expressed in millimeters (mm) and used to compare between groups.Parasite load quantification - Parasitic load was determined in Groups 1 and 3 based on a limiting dilution assayCell viability testing - Raw 264.7 macrophages were plated at a concentration of 105 cells/well on a CELLSTAR® 96-well flat plate containing 200 μL/well of Dulbecco’s Modified Eagle’s medium (DMEM) (GibcoTM) supplemented with 10% FBS (Gibco), L-glutamine (2 mM), penicillin (100U/mL) and streptomycin (100 mg/mL). Experiments were performed in triplicate under the following conditions: positive control (viable cells in DMEM medium), negative control [cells grown in 1x phosphate-buffered saline (PBS)], R white control (DMEM medium) and macrophages incubated with 2, 2.5, 5 and 10 mM of MET hydrochloride for 24 h at 37ºC under 5% CO2. Next, 20 μL from each well was removed, followed by the addition of 20 μL of AlamarblueTM Cell Viability Reagent (ThermoFisher Scientific), followed by a 4-hour reincubation period under the conditions described above in the absence of light. Readings were performed on a spectrophotometer at wavelengths of 570 nm and 600 nm, with results interpreted following the manufacturer’s protocol. The selected concentration for subsequent experimentation was determined to be 2 mM of MET.Macrophage viability assays - Cell growth kinetics were investigated using a 24-well plate assay (CELLSTAR®) performed in triplicate with 105 macrophages/well under the following conditions: 1) no MET; 2) treatment with 2 mM MET, followed by incubation; 3) cells pre-treated with 2 mM of MET six days prior to receiving an additional 2 mM MET, followed by incubation. Counts were performed at 24, 48, 72 and 96 h of cultivation at 37ºC under 5% CO2 in supplemented DMEM (1 mL) (GibcoTM). At each cell counting timepoint, DMEM medium was discarded and cells were removed by enzymatic action using 1 mL 0.25% trypsin-EDTA (Sigma-Aldrich) for 1 min at 37ºC under mechanical homogenisation with a micropipette. The aspirated volume (1 mL) was inactivated with 9 mL supplemented DMEM and centrifuged at 1200 rpm under 4ºC for 10 min. The medium was discarded and obtained cellular pellet was resuspended in 1 mL of supplemented DMEM. Trypan Blue (Sigma-Aldrich) was added to the cell suspension aliquots at a ratio of 1:10. Cell viability was then assessed by counting in a Neubauer chamber at 400x magnification.Influence of metformin on L. braziliensis growth - Metacyclic Lb promastigotes (5 x 105/mL) were placed in 25 cm2 cell culture flasks (CELLSTAR®) containing 5 mL of supplemented Schneider’s medium and grown in a BOD at 23ºC. Cultivation was performed in duplicate under the following conditions: 0, 2, 5 or 10 mM of MET. Promastigote growth was measured via daily counts for six days by removing 10 μL from culture flasks, which was placed in a Neubauer chamber and observed under an E200 (Nikon) optical microscope at 400x magnification.Raw 264.7 macrophage infection with L. braziliensis - Macrophages were plated at a concentration of 105 cells/well on 24-well plates (CELLSTAR®) in 300 μL of supplemented DMEM medium, followed by the addition of circular coverslips (13 mm) for macrophage adhesion.Lb; 5) infection with Lb and 2 mM MET treatment; 6) 100 ng/mL LPS and 2 mM MET treatment; 7) infection with Lb, 100 ng/mL LPS and 2 mM MET treatment. Cells under conditions 3, 5, 6 and 7 were pretreated with 2 mM MET for five days prior to challenge, and received an additional 2 mM MET following infection procedures. The multiplicity of infection (MOI) used was 10:1 parasites/macrophage, with a 4-hour incubation at 37ºC under 5% CO2. Experimental conditions were performed in quadruplicate and the experiment was repeated twice.Cells were cultivated under the following conditions: 1) negative control without treatment or infection; 2) positive control with 100 ng/mL lipopolysaccharide (LPS) treatment; 3) 2 mM MET treatment without infection; 4) infection with Parasite infection rate and quantification - Coverslips were washed thrice with 1 mL PBS 1x and then subjected to rapid panoptic staining (Laborclin). Rapid panotic number 1 (300 μL) was added to the wells and stored for 10 min in a refrigerator at 2 to 8ºC, followed by 300 μL of panoptic number 2 for 1 minute at RT, 300 μL of panoptic number 3 for 10 seconds at RT and finally washed thrice with 1 mL of distilled water with the aid of a 1000 μL micropipette during the entire process. The coverslips were then mounted using Entellan (Sigma-Aldrich) on 26x76 mm glass slides for further evaluation under an optical microscope (Nikon) at 100x magnification. The number of infected cells (presence of parasites in intracellular medium) was totaled out of 100 counted cells, with values expressed as percentages, and the total number of parasites was counted inside infected cells.Evaluation of intracellular parasite viability - After 4 h of infection, the wells were washed thrice with 300 μL 0.9% NaCl solution at 37ºC to remove any non-internalised promastigotes. Prior to washing, 200 μL/well of supplemented Schneider medium was added and the sealed plate was incubated in a BOD at 23ºC for 96 h. The number of promastigotes in 10 μL aliquots were counted in a Neubauer chamber at 400x magnification.ROS quantification in culture supernatant - Culture supernatant was distributed on two 96-well flat-bottomed plates (Greiner Bio-One) in triplicate. To measure ROS in the supernatant, an alternative methodology involving Griess reaction (Sigma-Aldrich) was used. The Griess method allows, via colorimetric reaction, the measurement of nitric oxide (NO) production through nitrite conversion using spectrophotometry. Two experimental conditions were used: wells in one plate received the addition of hydroxylamine (NH2OH), while another did not. Optical density (OD) values were transformed in concentrations (μM) by measuring differences in OD readings between the two plates, thus allowing for an indirect evaluation of ROS in the culture supernatant, due to the inhibition of the nitrification reaction via the presence of the NH2OH intermediate substrate.Quantification of intracellular ROS - Cells were submitted to a CellROX Oxidative Stress Reagent assay (ThermoFisher Scientific). All wells containing macrophages were washed thrice with 1x PBS, and 300 μL/well of supplemented DMEM medium and CellROX reagent were added. After being incubated in the dark at 37ºC under 5% CO2 for 30 min, wells were washed three times again with 1x PBS, and the cell coverslips were fixed with 3.7% paraformaldehyde (PFA) for 15 min, then mounted on a 23x76 mm glass slide with 5 μL of 4‘, 6-diamino-2- phenyl indole (DAPI) in antifade mounting medium (ThermoFisher Scientific). Subsequently, the slides were analysed under an inverted fluorescence microscope (Leica) in the range of 485/520 nm, and images of fields containing eight cells each were captured to quantify the corrected total fluorescence coefficient (CTCF) using OlyVIA 7.0 software (Olympus). This analytic strategy consists of measuring fluorescence in the area occupied by a cell, averaging values from the eight cells analysed, and then subtracting the fluorescence background average from five extracellular spaces.Statistical analysis - The D’Agostino test was used to classify the distribution of samples as parametric or nonparametric. The Mann-Witnney or Kruskal-Wallis tests were used for nonparametric samples, while the t-test or one way analysis of variance (ANOVA) was employed for parametric distribution. The Chi-square test for trend was also used. Analyses were performed using GraphPad Prism v.7 software , and p values less than or equal to 0.05 were considered significant.MET delays the appearance of Leishmania papules and modifies lesion size - Three weeks after inoculating metacyclic promastigotes in stationary phase, G1 (Lb) animals presented a 20% larger ear thickness compared to G3 (Lb + MET): mean 0.7 mm , small ulcerated papule with acneiform aspect and cutaneous hyperemia. On the other hand, lesion size in G3 was 3.4% smaller than G2 (control) of 0.56 mm (± 0.055), ie, showing no evident tissue damage. In the 4th week of infection, lesion size in G1 decreased by 5.7%, while group G3 increased by 15.1%, demonstrating the appearance of acneiform papules without ulceration. At six weeks after infection, the absence of ulcers was seen in non-MET (G1) animals, with ear thickness averaging 0.58 mm (± 0.084), just 0.8% different from G2, the uninfected group  and G3 (n = 05). Mouse organs were macerated and then cultivated in serial dilutions for parasitic load measurement. At the site of infection (6 parasites/mL), 103 more promastigotes compared to G1 .nfection C and in nfection D, G3 preMET exerts no cytotoxic effects and inhibits Raw 264.7 macrophage growth - Cell viability following exposure to different MET concentrations was evaluated in cultures of Raw 264.7 macrophages, with an absence of any observable cytotoxic effects arising due to MET within 24 h. Cell viability values ranged from 85 to 100% relative to the positive control, i.e. cells that did not receive MET in supplemented DMEM medium.5 cells/well) was performed to quantify the number of viable cells after 24, 48, 72 and 96 h of MET exposure by comparing cells pretreated for six days in MET and those without previous drug exposure. After 96 h, cultured cells without prior exposure to MET achieved an average growth of 1.4 x 105 cells, i.e. 22.5% higher than pretreated cells. Cultures without MET yielded an average of 5.9 x 105 cells/well after 96 h, representing a 76.3% higher proliferation rate compared to macrophages not previously exposed to MET (p = 0.0024), versus 81.3% more compared to previously treated cells (p = 0.0016)  A.Low MET concentrations increase Lb promastigote growth - After verifying that MET interferes with macrophage growth in vitro, we verified the effect of this drug on Lb promastigote cultivation in vitro by growing 5 x 105 metacyclic promastigotes/mL in 5 mL of DMEM. Cultivation was quantified daily for six days until proliferation was observed to decrease. On the 6th day of culture, 34.3% higher growth was seen in cells receiving 2 mM MET compared to those that did not receive the drug, with an average of 1.7 x 108 parasites/mL and demonstrated continuance of in log phase growth. Under culture conditions involving 5 mM MET, no difference was seen compared to drug-free culture (average of 6 x 107 parasites/mL). Using 10 mM MET, 8.5% less proliferation was observed compared to drug-free culture (average of 5.5 x 107 parasites/mL) (ites/mL) B.In vitro MET treatment resulted in increased infection rate and parasitic load in Raw macrophages 264.7 - After a 4-hour infection period, the percentage of infected cells  C.Lb infection.Taken together, these data suggest that MET-treated cells may decrease the microbicidal potential of macrophages during MET suppresses the release of ROS in the extracellular environment and intracellular ROS production in Lb-infected Raw 264.7 macrophages - ROS from macrophages was quantified in culture supernatants. After infection with Lb, MET treatment suppressed ROS production by 89.6% compared to uninfected treated cells (p = 0.007) . Lb was found to induce a superior effect compared to stimulation with LPS (p = 0.01) or MET (p = 0.0008), and also resulted in higher ROS production compared to LPS-stimulated cells and treated with MET (p = 0.01). This analysis highlights differences in the production of reactive mediators compared to the negative control, under stimulation with MET treatment and Lb infection (p = 0.008), MET and LPS (p = 0.03) or MET, LPS and Lb (p = 0.006). Despite achieving statistical significance (p = 0.08), we also found that MET reduced intracellular ROS production by 34.1% in Lb infection compared untreated infected macrophages (= 0.007) . In Fig.= 0.007) A. Our rerophages B.Lb-infected mice delays the appearance of papules characteristic of Lb infection; however, this drug not found to prevent ulceration. A study by Qingin vitro keratinocyte cell proliferation, negatively impacted healing in an experimental model and worsened the clinical condition of foot ulcers in diabetic patients, suggesting that MET interferes with tissue remodeling, lesion size and lesion healing time.The present results demonstrate that MET treatment in Mycobacterium tuberculosisL. pneumophila.Plasmodium infections, MET could exert a protective effect in malaria.,Lb infection model employed herein resulted in a 1,000-fold increase in the number of parasites at the inoculation site and draining lymph nodes compared to untreated mice. These findings suggest that MET exacerbates the production of ROS, a marker of cellular oxidative stress, and results in increased susceptibility to Lb Novais et al.Leishmania parasites are sensitive to ROS, the respiratory explosion that occurs in macrophages that are not activated by adaptive immunity in response to infection is insufficient to enable parasite killing. Fukai et al.L. amazonensis, which directly favors parasite survival.MET induces AMPK activation by modulating the mitochondrial ADP / ATP balance, resulting in the production of mROS in macrophages, which increases the microbicidal potential of these cells in the context of other pathogenic infections, such as Lb growth, treatment with 2 mM MET did not affect parasite growth, which remained in stationary growth phase, however this was not the case when using higher doses or the absence of MET. The Raw 264.7 macrophage cell line presents a doubling time of 16-24 h.The pleiotropic effects of MET are also known to attenuate monocyte differentiation in macrophages, as well as inflammation-inducing events.Wang et al.Lb infection in vitro. In addition to increased numbers of infected cells and parasitic load, in intracellular parasite viability was found to increase by 36% in MET treated macrophages within 96 h of infection compared to untreated infected cells. Considering that one of the main mechanisms of pathogen intracellular death is the production of ROS,,Lb interferes with MET-induced ROS levels, which promotes increased parasite viability. In macrophage culture supernatants, we found that MET increases the release of ROS in uninfected cells; however, cells infected with Lb exhibited a significant decrease in ROS production following treatment with the drug.Following our evaluations of the effect of MET in isolated macrophage cultures, MET was investigated in Lb infection promoted a 37.8% greater synthesis compared to MET. Moreover, the introduction of MET in infected macrophage cultures was found to decrease intracellular ROS production by 34%. Quintela-Carvalho et al.L. amazonensis infection is followed by dramatic increases in SOD-1 expression and activity, which has been shown to directly favor parasite survival.The cultivation of uninfected macrophages with MET resulted in a 48.1% increase in mean intracellular ROS production, while stimulation by Lb infection and blocks the release of ROS into the extracellular medium. In addition, elevated production of ROS induced by Leishmania and the MET pathway, through the increase of AMPK-p, can generate high levels of cellular oxidative stress and promote the activation of host SOD production and its described isoforms in parasites,The data presented herein allow us to propose  that theLb infection, and may actually exacerbate viability and parasite load.Our experimental findings suggest that MET, the main hypoglycemic drug used in the treatment of diabetes, does not aid in the control of


Detection of pathogenic microbes as well as antibiotic residues in food animals, especially in chicken, has become a matter of food security worldwide. The association of various pathogenic bacteria in different diseases and selective pressure induced by accumulated antibiotic residue to develop antibiotic resistance is also emerging as the threat to human health. These challenges have made the containment of pathogenic bacteria and early detection of antibiotic residue highly crucial for robust and precise detection. However, the traditional culture-based approaches are well-comprehended for identifying microbes. Nevertheless, because they are inadequate, time-consuming and laborious, these conventional methods are not predominantly used. Therefore, it has become essential to explore alternatives for the easy and robust detection of pathogenic microbes and antibiotic residue in the food source. Presently, different monitoring, as well as detection techniques like PCR-based, assay (nucleic acid)-based, enzyme-linked immunosorbent assays (ELISA)-based, aptamer-based, biosensor-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry-based and electronic nose-based methods, have been developed for detecting the presence of bacterial contaminants and antibiotic residues. The current review intends to summarize the different techniques and underline the potential of every method used for the detection of bacterial pathogens and antibiotic residue in chicken meat. Globally, both developed and developing countries predominantly consume chicken as a meat product. According to the report of Global Livestock Counts, there are around 19 billion chickens in the world . ChickenCampylobacter and Salmonella are the common pathogenic microbes accounting for >90% cases of food poisonings associated with bacteria and are considered responsible for food safety hazards worldwide ).In the last few decades, there have been substantial improvements in the techniques used for identifying bacterial pathogens and antibiotic residue in food samples and especially in meat. Even though there are limitations associated with culture and microscopy, they are still the predominantly used detection techniques. Genetic and PCR are an effective non-culturable technique used for presently determining the bacterial pathogen, and on the other hand, MS techniques have emerged as an effective method for identifying microorganisms and detecting antibiotic residues. However, these approaches are limited to assess the pure cultures and are ineffective indeciphering the complex samples. To overcome this, chromatography-based methods like TLC and HPLC have been simplified and have eased the challenge associated with MS techniques. In the future, the progressive development and combination of these techniques and instruments will advance the ability to detect the pathogenic microbes and antibiotic residues.


A concrete-filled steel tube (CFT) combines the advantages of concrete and steel in construction and structural applications. However, research on the time-dependent deformation of the CFT under long-term sustained loading are still limited, particularly for stress transfer between the steel tube and concrete due to creep. This study investigated the creep behavior of CFT over a long period of 400 days. The creep and shrinkage strain of CFT was significantly lower than those of concrete that was not confined within a steel tube. The vertical strains of the steel tube and concrete core were almost identical, and it was shown that they were well bonded and acted as a composite. The vertical stress of steel increased by 32.7%, whereas the vertical stress of concrete decreased by 15.8% at 375 days. The stress transfer is notable and cannot be neglected in CFT design. Moreover, the results of creep and shrinkage were compared to prediction values of the B4 model and B4-TW model to verify their validity. Concrete-filled steel tubes are composite structural members made of a hollow steel tube filled with concrete. These composites have been widely used in practical fields because of their high ductility, high strength, good fireproof properties, excellent seismic resistance, low creep and shrinkage benefits in comparison with reinforced concrete or steel structures ,2,3. NevMost experiments have analyzed the time-dependent behavior of the CFT with various affecting parameters, including structure shapes, types of concrete and steel tubes, and applied stress. The creep and shrinkage of square and rectangle section specimens were tested by Uy et al.  and Han Additionally, some researchers investigated the strain and stress of the steel tube and concrete core of the CFT member. Ichinose et al.  and Y. WThe CFT is made from two materials so that the composite has different properties and the time-dependent deformation is also more complex than separated components. Although some researchers have performed analyses of the properties of long-term behaviors, the time-dependent deformation of CFT under long-term loading has not been fully studied. Notably, a few studies investigated the stress transfer between the steel tube and concrete due to creep.Long term creep tests on the time-dependent deformation behavior of CFT using high strength self-compacting concrete (SCC) embedded with a vibrating wire strain gauge (VWSG) were conducted for 400 days. The observation and estimation of the stress transfer between the concrete core and steel tube under a sustained load were also provided. The stress transfer magnitude cannot be neglected and must be taken into consideration in CFT design. Moreover, the measured creep and shrinkage values were compared to prediction values of the B4 model and B4-TW model to verify their validity.2/kg. Mineral admixtures included ground-granulated blast-furnace slag (GGBS) and silica fume (SF) with a specific surface area of 435 m2/kg and 15,000 m2/kg, respectively. The used aggregates were fine, with fineness modulus of 3.1 and sandstone was used as a coarse aggregate (CA) with a nominal maximum size of 12 mm. To enhance the workability, a high-range water-reducing agent (type F) was used as the superplasticizer (SP) admixture. An expansive additive (EA) was incorporated into all specimens to reduce the shrinkage. The mix proportion of the concrete is presented in 3 , 20kg/cm3 , respectively.The cementitious materials used in the study were cement, slag and silica fume. Type II Portland cement complying with ASTM C150  was usedA total of six CFTs used cylindrical steel tubes with an in outer diameter of 108 mm, height of 300 mm and steel tube thickness of 3 mm. The steel tube had a yield strength of 250 MPa, grade satisfied ASTM A36. The CFT specimens had a diameter to thickness ratio (D/t) of 36, and a steel ratio (proportion of steel area to concrete area) of 12.1%. The composite members were not only carried out on basic creep and autogenous shrinkage tests but also used to determine the strain and stress behavior of the steel tube and concrete core. The CFT specimens were only used for basic creep and autogenous shrinkage tests because the role of the steel tube is to act as a permanent framework to maintain an enclosed environment so that concrete core in the steel tube is considered as a sealed specimen. The creep tests of the SCC specimens were conducted on Φ100 mm × 300 mm cylinders, while the shrinkage and length change tests of SCC specimens used two different sizes: Φ100 mm × 300 mm cylinders and 100 mm × 100 mm × 285 mm prisms. Each test set included three specimens. The specimens used in creep, shrinkage and length change tests are presented in The compressive strength and elastic modulus tests were conducted with cylindrical specimens of 100 mm by 200 mm dimensions. A total of 90 specimens were prepared to determine the mechanical properties at different times. Sixty specimens were used to investigate the strength and modulus of elasticity for ages of concrete at 7, 14, 28, 56 and 91 days. Another thirty cylindrical specimens were only evaluated for compressive strength in five creep tests at loading ages of 14 days and 28 days.All test specimens were prepared in the laboratory and cured in controlled conditions. The slump test of the SCC mixture was conducted by Abrams cone, according to ASTM C143 , while tThe compressive strength and the modulus of elasticity were tested according to ASTM C39  and ASTMζ is temperature-compensated strain; −6 mm/mm), respectively; K is coefficient of strain gauge, which is 0.98; The creep tests of the CFT and SCC specimens were conducted according to ASTM C512 . All timThe bottom end of each steel tube of the CFT specimens was welded to a steel base plate of 13 cm × 13 cm in cross section. After the VWSG was installed, the concrete was filled into the mold, and immediately after casting, a plastic sheet was coated on the exposed surface to prevent evaporation. At loading ages of 14 days and 28 days from the casting, the specimens were grinded smooth, as shown in While the CFT specimens were only subjected to a basic creep test, for the SCC specimens both basic creep and total creep were measured. The VWSG was also preinstalled in the mold of the SCC specimens and then the concrete was poured in. After 24 h from the casting, all the specimens were demolded and placed in moist curing conditions until the loading ages of 14 days and 28 days. After curing, the specimens of the total creep experiment were moved to be stored in a drying room with an automatically controlled temperature of 23 ± 2 °C and relative humidity of 50 ± 2%, whereas the basic creep specimens were s = kept in the moist environment  until the end of test. The SCC specimens were connected by high strength gypsum before being put into the loading frame as presented in The concrete core of the CFT specimens only experiences autogenous shrinkage as a result of the self-desiccation process, but the SCC specimens were assessed both in terms of total shrinkage and length change up to 400 days. All shrinkage specimens were demolded 24 h after casting and cured in a standardized chamber . When the concrete ages were cured for 14 days and 28 days, the C-SCC-TS14 and P-SCC-TS28 specimens—for which total shrinkage was determined—were stored in a drying room , respectively. Moreover, for the purpose of evaluation, the length change effects of the concrete on the creep data, the C-SCC-LW14 and P-SCC-LW28 specimens were placed in the same environment as the basic creep specimens at a designated time. The shrinkage strain of the cylindrical specimens can be recorded at an initial setting time (the beginning of solidification) by the VWSG. After the initial setting time of fresh concrete was determined based on ASTM C403 , the shrMany present models predict the creep and shrinkage of concrete, for example the ACI 209R-92 ,25, fib According to the B4-TW model, the creep compliance function is given byn is the empirical parameter, .In which 3), respectively; 3); factors With 3); The B4 model has different equation details in comparison with the B4-TW model. The creep compliance function is determined bycm) is replaced by the cement content (c).The According to the B4-TW model, the total shrinkage strain is given asV/S is the volume to surface ratio.In which The autogenous shrinkage of concrete without mineral admixture is expressed asAutogenous shrinkage of concrete with mineral admixtures is calculated byThe B4 model includes total shrinkage, expressed byOther shrinkage formulae of the B4 model are the same as in the case of the concrete without the mineral admixture of the B4-TW model, only the cementitious material content of factors B4 model .50 spread time of 16 s. The initial setting time and final setting time of the concrete were 539 min and 729 min, respectively.The SCC concrete had a slump flow value of 570 mm, and TThe average compressive strength and modulus of elasticity of SCC were tested on 12 specimens for each age at 7, 14, 28, 56 and 91 days, as shown in The CFT combines concrete and steel tubes so that the stress that impacts on these specimens is not the same as plain concrete. It is well known that creep and shrinkage of the concrete core directly affect the time-dependent deformation of CFT. If the surfaces of the components are not the same level, as presented in According to the theory of elasticity, the stress of CFT is converted to find exactly applied loading values on the specimens. The theory load of CFT can be expressed asIt is assumed that the plane remains plane under axial compression, which is the essence of strain compatibility so that the steel strain is the same as the concrete strain at all locations and can be calculated by the following equationThe load applies to the steel tube can be calculated on that of the concrete core as2); In which t′ (MPa); 2).The loading force of the concrete core of the CFT can be calculated the same as with the SCC specimens.When CFT is under axial loading, various cylinder stresses appear in the composite member, including vertical stress of the steel tube ; 2).In which 2); t′.Additionally, when the specimens are embedded with the VWSG inside the specimen, the conversion area can be obtained byThe conversion stress According to the loading force equations with the designated stress ratio (−6/MPa) depending on the applied loading, expansive agent content, and steel ratios.The amount of creep reduces on with the loading age of the concrete, as shown in When the specimens were stored in the dry environment (relative humidity of 50 ± 2%), the loading age significantly affected the creep values. The total creep compliance was 49% and 40% higher than the basic creep compliance at 375 days after loading ages of 14 days and 28 days, respectively, as observed in The elastic strain, creep strain, creep compliance and creep coefficient of the basic and total creep specimens at 375 days after loading are given in The shrinkage occurs as soon as the adsorbed water from the hydrated cement paste is removed due to the effects of cement hydration and water loss, so that the shrinkage strain was normally measured from the instant when the concrete starts to harden. The shrinkage and length change values were measured at an initial setting time, as shown in As a result, the autogenous shrinkage of CFT specimens (C-CFT-AS14) increased rapidly within 14 days after molding and the value reached approximately 71% of the shrinkage strain at 400 days. The shrinkage strain of the concrete stabilized from the third week. The issue that the confining effect of steel tube not only significantly restraints the shrinkage of the concrete but also prevents the swelling because of the expansive agent, is considered. Shrinkage of the CFT specimen increases only due to the result of the self-desiccation process as the macroscopic volume reduction in cementitious materials when the cement hydrates after the initial setting. The volume of hydration products is less than the sum of the volume of water and the volume of cement that is hydrated . In comp−6 mm/mm) at 126 days, which is equal to 44% of the SCC specimen at the same time.When the temperature is stable—the same as in the testing condition—the total strain at age t can be calculated without thermal expansion by the following equation (38)ε(t)The real creep strains can be obtained by subtracting the shrinkage strains from the measured creep strains, as illustrated in −6 mm/mm); −6 mm/mm), which is elastic strain if the stress is small; −6 mm/mm), −6 mm/mm).In which The shrinkage strain of specimens was measured after the curing of concrete in addition to the creep strain and total strain presented, and these values are presented in The measured time of shrinkage and length change tests were taken at 14 days and 28 days as well as loading age of creep tests, and the data are plotted in The strains of the CFT components were measured by separate strain gauges. As can be observed in In the initial period after loading, the steel tube had a vertical strain value higher than the concrete core because the Poisson’s ratio of concrete is lower than that of the steel. The difference of vertical strains of CFT components also indicates that longitudinal slipping between the steel tube and concrete can occur in this stage. The vertical strain of the concrete was higher with time due to creep in addition to the larger lateral strain. However, the deformation of the concrete core is restrained by the confinement effect of the steel tube so that the vertical strain of the concrete increases equally with steel. The result confirms that the plane remains plane as well as compatibility between steel and concrete components. The test data compared suitably with those of Kwon et al. , who detWhen the CFT specimens were subjected to a sustained load of 325 kN with a conversion stress ratio of 0.32, the stress of the components can be evaluated according to the data of strain gauges. −6 mm/mm) at 375 days and a modulus of elasticity of 355,555 MPa, respectively, a D/t ratio of 36, and a yield strength of steel of 250 MPa, the stress transfer of the steel tube was predicted to be 7% of steel stress equal to 17.5 MPa, which is an error of 50% in comparison with the experimental data.The stress result of the composite components varied over time and was also shown by Kwon et al.  and WangThe vertical strains, vertical stresses, and stress transfer of CFT components varied at various days, as can be seen in B4 model and B4-TW model were used to predict the creep and shrinkage of the concrete. The B4-TW model extends and refines the B4 model so that the parameter values of the two models are almost the same and are given in . HoweverZ. P. Bažant  indicateq2, q3 and q4, which are factors that affect the basic creep value, predicted by the empirical formula of the B4 model was higher than the value calculated based on the B4-TW model. Therefore, the B4 model gave much higher—from 54 to 57%—long-time values of basic creep compliance than those of the B4-TW model at 375 days after different loading ages, as illustrated in As can be seen in q5—that controls the magnitude of the drying creep compliance—calculated by B4-TW model, is 1.84 times higher than for the B4 model. Furthermore, the instantaneous strain q1, which is closely related to the elastic modulus value, estimated by the B4-TW model, is also larger than that estimated by the B4 model  and the plain concrete curing in moist conditions (C-SCC-LW14 specimen), as observed in shε∞ for the B4 model is also less than that of the B4-TW model, as shown in The total shrinkage of specimens with a curing age of 14 days (C-SCC-TS14) and 28 days (P-SCC-TS28) are compared to the values of the B4 and B4-TW prediction models, as shown in In the study, the SCC was used to fill the steel tube but the shrinkage of the SCC is higher than the plain concrete due to its higher amount of paste and lower water-to-binder ratio. The addition of expansive additive to the SCC in the CFT is common to prevent the gap caused by significant autogenous shrinkage. However, the experiment shrinkage also showed large divergences in comparison with the predicted values of the models, as presented in (1)The advantage of the interaction between the steel tube and the concrete core significantly reduced the time-dependent deformation of CFT. The steel tube has a role as a restraint on the concrete, creating an enclosed environment that prevents the concrete spalling and the relaxing of the impacted stress. Therefore, the creep compliance and shrinkage strain of the CFT specimens was33% and 62%lower than that of the concrete without the steel tube, respectively.(2)The creep strain in the moisture condition was lower than that in the drying condition. Additionally, the various loading ages that affected the total creep were higher than basic creep because the basic creep is not influenced by the level of humidity, the total creep has a rapid drying process at an earlier age. However, the different curing ages negligibly affect the total shrinkage and length change of the specimens.(3)The vertical strain of the CFT components had a similar magnitude which was only 1.1% different compared to the vertical strains of the steel tube and the concrete core so they can be considered as fully composite members.(4)The vertical stress of the steel increased by 32.7% but the vertical stress of the concrete decreased by 15.8% at 375 days. This stress transfer magnitude cannot be neglected and should be considered in CFT design.(5)The B4-TW model is more consistent than the B4 model in predicting the basic creep of the concrete. The prediction values of the two models were close to the test data of the short-term total creep under about 100 days but higher than those of the long-term total creep. The B4 model does not predict the autogenous shrinkage of concrete with slow hardening cement. Additionally, both the B4 model and the B4-TW model are not suitable to estimate the shrinkage of SCC using expansive admixture.This paper tests the creep and shrinkage behavior of CFT and concrete without steel tube specimens. The SCC used an expansive admixture to fill a steel tube of 108 mm in diameter, 3 mm in thickness, and 300 mm in length. The time-dependent deformation was performed under different curing conditions over a long time period of up to 400 days. Based on the experimental results, the main conclusions of the study can be drawn as follows:


This study was designed to assess the awareness and knowledge of antibiotic usage and antibiotic resistance among the general public in the Cape Coast metropolis of Ghana. It also tries to decipher whether the level of education and the professional status of an individual has a positive association with the level of knowledge on antibiotic resistance.A population-base survey involving members of the public was conducted from August to November 2019. A structured questionnaire was developed to collect data from 632 respondents. Data were analyzed through SPSS v.21 using Chi square statistics and multivariate regression. Differences in knowledge were evaluated using ANOVA and the assumption of equal variance was tested with Levene statistics.M = 1.82, SD = 0.769), middle educational status group , and the high educational status group  were not significantly different from each other with regard to their general knowledge level on antibiotic resistance (P < 0.05). The study revealed that, working in the healthcare sector is a major contributor to the level of knowledge on antibiotic resistance.The response rate was 74.3%. Lower educational status group had a greater knowledge level (39.7%) on antibiotic resistance. Despite the high score, the lowest educational status group, (Given the scale of the issue on antibiotic resistance and the fact that attempts to resolve it will involve efforts on the part of all, it is important that the public is aware of the importance of the issue of antibiotic resistance, its implications and what they can do to address it. The level of knowledge among respondents with lower educational status should be enough evidence to introduce more educational campaigns on antibiotic resistance. Antimicrobial resistance is a serious and ever increasing public health threat , 2. AntiIn a study by Costelloe et al. and Morgan et al. , 10, theGhana as a developing country is also faced with this global crisis of antibiotic resistance and as a result, there are national plans  and strategies on antimicrobial stewardship to help tackle this problem. Despite this problem, there is still no known study addressing the level of knowledge and awareness on antibiotic resistance in the Cape Coast Metropolis and the entire country as a whole. I would highlight that, understanding public knowledge on antibiotics, is crucial in identifying the different attitudes of people which could subsequently help shape campaigns and policies addressing this problem , 14. KnoA cross-sectional survey design was used for this study. Respondents were reached through a formal electronic and paper invitation requesting them to participate in this survey. For those participants that were contacted electronically, their emails were obtained through an earlier exercise that was carried out within the Municipality. Upon accepting the invitation, the electronic questionnaire was sent to them for completion. Also, some respondents that had no access to internet or respondents that we did not have their emails were recruited via street-intercepts, home visits and through smaller local associations. Convenient, purposive and proportionate stratified random sampling were employed as sampling techniques for this study. Convenient sampling was employed for those whom we had their email addresses. The purposive sampling technique was adopted in other to ensure all participants who took part in the study fell within the age of ≥18 years. Additionally, the population (communities) was grouped into strata of four (4) and random selection was done so that each member of the population had an equal chance of being included in the study. The respondents were selected based on age (≥18 years) and nationality (Ghanaians). The respondents were then grouped according to their educational level i.e. low (≤Junior high), middle  and high . The professions of the respondents were initially blinded to the researcher but this information was elicited through the questionnaire and was then used to group the general public into health workers and non-health workers. About 99.5% of respondents were based in the coastal part of Ghana, Cape Coast to be precise.The questionnaire  was struGender, age, educational level, and profession were included as statistical controls in our regression tables. For gender, females were the reference category, whereas for age, year group 18–21 was used as the reference. Lower education level and health workers were the reference categories for educational level and profession respectively. Educational level was measured with three categories: low, middle, high. The history of antibiotic use within the last 12 months was measured with four categories: never, once, 2–5 times and more than 5 times and a dummy category for those who could not recall. Although the data were not collected anonymously, we guaranteed complete confidentiality to each respondent. Regression analysis was performed according to respondents’ attitude and general awareness on antibiotic resistance per knowledge level.All responses were coded and analyzed using SPSS version 21. The demographic data of respondents were analyzed using descriptive statistics and results were presented as frequencies and percentages. The researchers employed simple statistical analyses (Chi square test) to determine whether a relationship existed between responses to questions on antibiotic use and misuse, perception of respondents on the role of health professionals in antibiotic use and antibiotic resistance, behavior and respondents’ demographics. A regression analysis on various demographics, was performed according to their level of knowledge on antibiotic use and antibiotic resistance. The differences in knowledge on antibiotic resistance among the various groups  were tested using the analysis of variance (ANOVA) to determine if the data met the assumption of equal variance (Levene statistics). Three scores were created to measure the level of knowledge on antibiotic use and antibiotic resistance based on a 10-level structured question. Each score was defined as the proportion of questions for which the answers were correct. These three scores ranged from 0 to 100%. For each respondent, the total of the correct answers on the knowledge items was computed and the scores were summed up. Based on their scores, respondents were ranked into groups as ‘low knowledgeable’ (having a maximum of four correct answers), ‘moderate knowledgeable’ (having up to seven correct answers) and the third group, as ‘highest knowledgeable’ (getting more than seven correct answers).A total of 1000 respondents were initially invited to participate in this survey. Out of these, 851 agreed to the invitation. Six-hundred and thirty-two (632) respondents out of the 851 filled and returned the questionnaires representing a response rate of 74.3%. Among them, 323 (51%) were males whiles 309 (49%) were females and they were wildly distributed within age groups 18-21 year , 22-25 years  and above 25 years . The respondents were grouped based on their level of education with high educational status recording the highest proportion  followed by middle educational status  and low educational status  in that order. Four-hundred and twenty-four (424) of the respondents were non-health workers representing 67% of the total respondents.P < 0.05). Although the respondents had some knowledge on whether antibiotics are effective against common cold, barely few people within the different educational status, disagreed to the statement that, leftover antibiotics can be saved for personal future use; i.e. 60% (79/131) for low educational status, 33% (47/142) for middle educational status and 53% (191/359) for respondents within the higher educational status category. Responses to the various questions; 1. the body can fight mild infections on its own without antibiotics (agree) and 2. whether it is good to acquire antibiotics from relatives, without having to be examined by a doctor (disagree) were not significantly different (P < 0.05) among the various categories of educational status.From Table N = 155, 25%), the second group, the ‘moderate knowledgeable’ had up to seven answers correct  and the third, the ‘highest knowledgeable’ had more than seven answers correct . Comparing the knowledge (high knowledge) on antibiotic use and antibiotic resistance based on the educational status, Lower educational status group recorded 39.7% (52/131) followed by the higher educational status group 36.5% (131/359) and Medium educational status 28.9% (41/142) . The lowest educational status group, , middle educational status group , and the high educational status group  were not significantly different from each other with regard to their general knowledge level on antibiotic resistance (P < 0.05). The expectation that the profession of the respondents will have an effect on the level of knowledge on antibiotic resistance was tested with the multivariate regression analysis displayed in Table B = -1.724, SE = 0.289), middle knowledgeable group  and then the highest knowledgeable group had  at (P < 0.01)  opined that, when they are challenged with infections, they wait and see, i.e. rest without any medication and later monitor if the infection goes away on its own. Also 62.2% (393/632) usually use hand hygiene to reduce the risk of spreading common infections. Most importantly, the majority of them 73.1%, 462/632)  within the last 12 months. This prevalence is highly relevant to public campaigns on antibiotic resistance—both because high levels of use contribute to the problem, and because it demonstrates just how many people it could impact in a short time frame if the antibiotics they are taking become increasingly ineffective.Antibiotics and its resistance need to be given a much greater attention. From this study, approximately half of the respondents still believe that antibiotics can be saved for personal use and that, it is a good habit to acquire antibiotics from relatives without any thorough checkup by a physician. Various studies have confirmed that keeping leftover antibiotics results in poor compliance with antibiotic therapy , and thiFurthermore, one contributor to misuse of antibiotics is the lack of understanding of which conditions can or cannot be treated with antibiotics and the lack of such knowledge can lead to the development of resistance. On average, only 14.2% (90/632) of the respondents across the various gender, age, educational status and profession, disagree to the statement that antibiotics make one recover faster when having a cold. This is because the respondents are not aware that common cold and flu are not caused by bacteria but viruses and does not need an antibiotic to treat it. About three quarters (75%) of respondents believed that, people can become resistant to antibiotics and that antibiotic resistant bacteria cannot spread from person to person. It should be noted that, antibiotic-resistant bacteria can spread from person to person, with the potential to affect anyone, of any age and in any country. The majority of respondents agreed to the fact that, the more antibiotics are used in a society, the higher are the risk that resistance develops and spreads.Past and current public health campaigns on antimicrobial resistance have echoed a key assumption in the so-called ‘information deficit literature’ , that, tA lot of studies have proved that people with high level of education have much knowledge on antibiotic resistance compare to people with low level of education , 23. ThiThis study fills the paucity of information on knowledge on antibiotic use and resistance. Our findings provides a repository of data which will help shape campaigns and policies addressing this problem. The strength of this study is the fact that it employed a reasonably large number of respondents considering the fact that this is the first known population base study within the municipality. Also, respondents were sampled from the general population and not from the hospital setting as most studies do. Limitations of this study were; 1. A possible bias towards respondents who may have a fair knowledge on the subject matter and 2. By using closed-ended questions to assess the level of knowledge on antibiotic resistance, respondents may have selected the most favourable answer instead of using qualitative methods to revel misconceptions.Given the magnitude of the problem of antibiotic resistance and the fact that attempts to resolve it will involve efforts on the part of all, it is important that the public is aware of the importance of the issue of antibiotic resistance, its implications and what they can do to address it. The level of knowledge among respondents of the lower educational level is a positive direction which we can leverage on to deal with the problem of antibiotic resistance. Strategies that can be employed by healthcare workers to improve the communication between them and their patients on effective ways to use antibiotics should be a focal point by researchers and healthcare authorities.Additional file 1. Survey Instrument on antibiotic resistance.


FRFC was reinforced with the natural fiber henequen  at volume fractions of 0.5%, 1% and 1.5%. Polypropylene fiber reinforcement was also used as a reference. For all FRFCs, the inclusion of the fibers enhanced the compressive and tensile strengths and plastic behavior, which was attributed to the increase of specimen integrity. Under compressive loading, after the peak strength, there was no considerable loss in strength and a plateau-like regime was observed. Under tensile loading, the fibers significantly increased the tensile strength of the FRFCs and prevented a sudden failure of the specimens, which was in contrast to the brittle behavior of the PFC. The tensile behavior enhancement was higher when treated henequen fibers were used, which was attributed to the increase in the fiber–matrix bond produced by the alkaline treatment. The microscopic characterization showed that the inclusion of fibers did not modify the air-void size and its distribution. Higher energy absorption was observed for FRFCs when compared to the PFC, which was attributed to the enhanced toughness and ductility by the fibers. The results presented herein warrant further research of FRFC with natural henequen fibers for engineering applications.The mechanical characterization of plain foamed concrete (PFC) and fiber-reinforced foamed concrete (FRFC) with a density of 700 kg/m With the correct dosage of foam, the density of the concrete can vary between 400 and 1600 kg/m3 . It has 3. They found that this reinforcement led to increases in compressive and tensile strengths of 84.7% and 558%, respectively, when compared to the unreinforced foamed concrete. They also found that the inclusion of fibers changed the brittle failure mode of foamed concrete to elastic–plastic behavior. Jones and McCarthy [3 reinforced with polypropylene (PP) fibers at volume fractions of 0.25% and 0.5%. The most marked increases of mechanical performance were observed at 0.5% volume fraction, i.e., the compressive and flexural strengths were 52% and 58% higher than the reference, respectively. Othuman Mydin and Soleimanzadeh [3 improved with the inclusion of PP fibers using volume fractions of up to 0.4%. They also reported that for a density of 800 kg/m3, an increase in the fiber volume fraction (from 0.2 to 0.4%) produced a coarser pore structure, in particular in the areas around the fibers. Mugahed Amran et al. [3 reinforced with PP fibers at volume fractions in the range of 0.5–3%. They found that the inclusion of the fibers at volume fractions of 0.75 and 1% improved the compressive and flexural strengths of the foamed concrete.In foamed concrete, the inclusion of fibers with random orientation can improve load transfer, compressive strength, tensile strength and ductility by changing the typical brittle behavior to elastic–plastic behavior ,4. Thesen et al.  investigThe most common types of fibers to reinforce concrete are metallic  and synt3 and 0.45% kenaf fiber volume fraction, exhibited an increase in compressive strength when compared to the unreinforced foamed concrete. Othuman Mydin et al. [3 reinforced with coir fiber at volume fractions of 0.2% and 0.4%. They found that the fiber-reinforcement improved the tensile, compressive and flexural strengths and impact resistance of the foamed concrete. Liu et al. [3 improved the compressive and tensile strengths. Flores-Johnson et al. reported an improvement of the mechanical properties of foamed concrete with densities of 800 kg/m3 [3 [As aforementioned, several studies have been performed to assess the mechanical performance of natural fiber reinforced cement-based materials; however, most of these studies have been carried out on mortar and concrete. Foamed concrete reinforced with natural fibers has been scarcely studied. Mahzabin et al.  found thn et al.  reportedu et al.  found thu et al.  reported00 kg/m3  and 900 kg/m3 [3  with theAgave fourcroydes Lem.) to reinforce cement-based materials, in particular, foamed concrete, is very limited when compared to the research performed on sisal  fiber. Henequen is the main cultivated species of Agave for fiber production in the Yucatan peninsula in Mexico, endures drought better than sisal [3 is presented and discussed. Henequen (untreated and treated) fibers were analyzed as the reinforcement at fiber volume fractions of 0.5%, 1% and 1.5%. For the treated henequen fibers, an alkaline chemical treatment with an aqueous sodium hydroxide (NaOH) solution was used. Polypropylene (PP) fiber reinforcement was also used as a reference; PP fiber is a readily available construction material, which is commonly used for the reinforcement of cement-based materials. Uniaxial compression and tension tests were performed, and the results were analyzed and discussed. A microscopic characterization on the fiber-reinforced foamed concretes, showing the overall air-void size and its distribution, is also presented.The motivation for this work is the lack of knowledge on low density foamed concrete, reinforced by natural fibers. Low density foamed concrete can be used as a lightweight construction material to effectively reduce the risk of earthquake damage ,31, and an sisal  and can 3 and fiber volume fractions in the range of 0.5–1.5% demonstrates that the henequen fiber can be used to reinforce cement-based materials. The mechanical testing shows that the treated henequen fibers could potentially replace synthetic fibers in sustainable construction applications since they provide similar benefits in terms of compression properties and produce improved tensile properties. The use of natural fibers, which are low-cost sustainable materials, is of great value currently, i.e., it is increasingly important to study and develop sustainable materials for applications in the construction industry.The research significance of this work is to advance the understanding of the mechanical behavior of natural fiber reinforced foamed concrete. There is currently a knowledge gap regarding the mechanical behavior of low density foamed concrete reinforced with treated henequen fibers at different volume fractions. Compression and tension tests performed on foamed concrete with a density of 700 kg/m3 was used. For the FRFC, natural fibers extracted from the henequen plant (Agave fourcroydes Lem.) were used  for 1 h at 25 °C, using a mechanical stirrer at 550 rpm. Subsequently, the fibers were washed with water until all the sodium hydroxide was eliminated. Finally, the fibers were dried in an oven at 60 °C for 24 h [For the treated fiber-reinforced mixtures, henequen fibers were treated with a sodium hydroxide (NaOH) aqueous solution at 2%  preparation of the liquid cement mixture (mortar); (2) preparation of the foam and (3) mixing of the mortar and foam. The materials were mixed in a 60-litre mixer until a homogeneous mixture was obtained. The foam was prepared separately using a foam generator JFG200  and EABASSOC foaming agent . To prepare the foam, a mixture of the foaming agent and water was prepared (31 mL of foaming agent per liter of water). This mixture was then poured into the foam generator container. The container was pressurized to 0.689 MPa (100 psi), which produced a foam density of 50 ± 2.5 kg/m3. Finally, the foam was poured into the mixer containing the mortar until a wet density of 800 kg/m3 was achieved. The FRFC mixtures were prepared following the same procedure as above with the fibers added to the mixture after stage 3. All the different foamed concrete mixtures prepared in this study are shown in Foamed concrete with a target dry density of 700 kg/mThe compression behavior of each mixture was evaluated in accordance with the BS EN 12390 standard using a Shimadzu AG-1 universal testing machine, equipped with a load cell of 100 kN, and a cross-head speed of 2.4 mm/min. It is noted that the compressive displacement of the specimens was measured using the crosshead displacement of the universal testing machine, and consequently, the accuracy in the measurement of elastic strains is limited. Cubical specimens with dimensions of 100 mm × 100 mm × 100 mm were used. The specimens were cured in molds for 1 day after casting; then, they were demolded and cured in a plastic bag for 24 days. After that, the specimens were removed from the bag and air cured for 3 days at a temperature of 25 °C. All samples were tested 28 days after casting.Uniaxial tensile tests were performed using briquette specimens (dog-bone shaped specimens) with a length of 76 mm and a cross-section area of 25.4 mm × 25.4 mm in the middle section. All samples were tested 28 days after casting. A Shimadzu AG-1 universal testing machine with a 20-kN load cell was used. The load was applied at a constant displacement rate of 1 mm/min.mA of each air-void was measured using the image processing software ImageJ v. 1.60 , and the equivalent diameter ed was obtained using the following equation [Scanning electron microscopy (SEM) analysis of foamed concrete samples was conducted on a low vacuum scanning electron microscope JEOL JSM 6360 LV . Specimens with dimensions of 8 mm × 8 mm × 5 mm were cut from a foamed concrete briquette of each mixture. One specimen per mixture was obtained. Subsequently, the surface of the specimens was polished and cleaned with compressed air. Finally, the specimens were placed on a sample holder and coated with gold for better electron conductivity. Four SEM micrographs were taken for each specimen in order to study the cellular structure. To analyze the air-void size for each mixture, the total area equation :de =  and fiber-reinforced foamed concrete (FRFC) with a target dry density of 700 kg/m


IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL  in conjunction with protean clinical manifestations in various organs such as pancreato–hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part. IgG4-related disease (IgG4-RD) is a newly defined multiorgan immune-mediated fibroinflammatory disorder with protean clinical manifestations ,6,7,8. IIt was accepted that histopathologic findings are crucial for the diagnosis of IgG4-RD. The essential pathologic characteristics including lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis should be confirmed in the biopsy specimens ,11,12. TKLF7, FRMD4B, LOC101928923 and MPPED2 are the susceptibility genes that trigger lacrimal and salivary gland lesions in Japanese patients with type 1 AIP.IgG4-RD is regarded as a complex autoimmune-mediated fibroinflammatory disorder in which type 1 autoimmune pancreatitis (AIP) is the archetype. Although a number of genetic loci have been found associated with AIP, these genetic predispositions are not consistent with the actual features described more recently because no one of them can well define the disease entity. Here, we only cite the genetic studies after genome-wide association study (GWAS) has been published. In this regard, Oguchi et al.  by referMST1 locus contains CpG islands in its promoter region and suggested that the epigenetic regulation of MST1 could control immune responses. Fukuhara et al. ) and a diverse autoantibodies , glycoproteins  and non-fibrillary collagen (collagen IV) that can deposit in the tissue .Recently, a bunch of fibrosis-related inflammatory mediators have been successively discovered. These fibro-inflammatory mediators include IL-1 family  , Th1 cyt2 cell (Tfh2) to become CD4+- and CD8+-cytotoxic T cell (Tc) populations [fh2 cells, B cells mature to CD19+ plasmablasts, which can subsequently produce autoantibodies, proinflammatory cytokine (IL-1β) and profibrotic cytokines  to enhance collagen fiber synthesis and deposition driven by FBs and MFBs. All of these B cell-derived factors and help signals hasten tissue inflammation and consequently tissue fibrosis in patients with IgG4-RD. It is postulated that B lymphocytes and their lineages, Breg’s, participate in tissue fibrosis of IgG4-RD. In an in vitro study, Francois et al. , by co-culations . The twoulations . On the φ)/plasmacytoid dendritic cells (pDC) [fh2 and CD4+ - and CD8+-cytotoxic T cells (CD4+and CD8+ Tc) play active and critical roles in the immunopathogenesis of IgG4-RD [In addition to the crucial roles of B cell subpopulations as antigen-presenting and effector cells in the pathogenesis of tissue fibrosis in patients with IgG4-RD, recent investigations have further revealed that many innate immune cells including white blood cell lineages , and macrophage type 2 (M2–Mls (pDC) ,118 and  IgG4-RD .φ2/pDC, basophils and polymorphonuclear cells (PMN). The binding leads to release of proinflammatory cytokines (IL-1 and IL-6), B cell growth factors (BAFF and APRIL) and Th2 differentiation cytokine (IL-4) to induce B cell maturation and Igs class-switch from IgE to IgG4 by modified Th2 response. For clarifying the properties of fibroinflammatory cytokines and their individual producing cells, many authors have successively demonstrated that IL-10 and IL-13 released from Th2, B lymphocyte-activating factor of TNF family (BAFF) and a proliferating inducing ligand (APRIL) released from M2-Mφ and PMN, IL-4 and IRF-7 released from pDC, IL-33 released from antigen presenting cell (APC) and endothelial cell (EC) in patients with IgG4-RD [φ may release profibrotic cytokines (TGF-β and IL-33) to activate the production of profibrotic cytokines from Treg including TGF-β, IL-10 and IL-33. These effects can further stimulate FBs and MFBs to synthesize collagen fibers for storiform fibrosis in IgG4-RD.Triggering of innate immune responses by microbe-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs) is mediated by binding of these molecules to the TLRs and NOD-like receptors (NLRs) on innate immune cells including M IgG4-RD ,121,122.+T cell infiltration constitutes the major inflammatory cell populations in IgG4-RD lesions. Tsuboi et al. [+CD25highCD4+ surface marker and (2) naïve Treg with CD45RA+CD25+CD4+ surface marker. Miyoshi et al. [Recent studies have revealed that increased proportions of Th2 and Treg cells, with their abnormal cytokine production, are involved in IgG4-RD and CD4i et al.  have deti et al.  have repfh that expresses CXCR5 (corresponding ligand is CXCL13) chemokine receptor can help GC formation [fh cells are a distinct CD4+T cell subpopulation that can expedite B and plasma cell differentiation and finally GC formation. Aberrant expansion and function of Tfh subsets can be found associated with circulating plasmablast numbers, IgG4, IL-4 levels and tissue damage in patients with IgG4-RD [+CXCR5+PD1+Tfh cell populations. The increased Tfh cells were caused by a specific expansion of Tfh2 (CCR6-CXCR3-), and to a lesser extent, Tfh17 (CCR6+CXCR3-) subsets. Therefore, IgG4-RD is characterized by a shift of circulating T cells toward a Th2/Tfh2 and Th17/Tfh17 polarization.Histologically, ectopic germinal center (GC) formation is present in some lesional tissues of patients with IgG4-RD. Wurster et al.  have docormation . Tfh cel IgG4-RD ,127. Fur IgG4-RD  have rev+T helper cells are regarded as the most abundant cells in the GC of affected tissues in IgG4-RD, these cells are considered as a driver in the pathogenesis of the disease. Another unique CD4+T cells existing in lesional sites are CD4+ cytotoxic T cells (CD4+Tc) which secrete cytolytic molecules including perforin and granzymes A and B. Moreover, profibrotic cytokines  and Th1 cytokine (IFN- γ) are also secreted by these cells [+T cells [+SLAMF+CD8a- TEM (CD45RO), the cytotoxic T cells with effector memory phenotype, which is oligoclonally expanded in patients with active IgG4-RD and can be suppressed following glucocorticoid administration to remit disease. In short conclusion, both CD4+CTL and CD8+CTL in disease lesions of IgG4-RD may contribute to the induction of cell apoptosis and tissue fibrosis of the disease [Although CD4se cells ,130,131.+T cells . Della-T+T cells  have ide disease .+CD25high surface marker which expresses a regulatory effect to suppress proliferation of autoreactive T lymphocytes. IL-10 is believed to be the major effector molecule released from these Breg cells to exert immune-regulatory functions. Authors have also demonstrated that IL-10 is produced by both CD19+CD24highCD27+ (B10) and CD19+CD24highCD38high (immature) Breg subsets. Sumimoto et al. [Kessel et al.  have fouo et al.  and Lin o et al.  have demIgG4-RD is a complex, protean and multiorgan fibroinflammatory disease originated from overactive IgG4-producing lymphoplasmacytic cell infiltration in variable tissues. It may thus lead to bizarre clinical and histological manifestations including storiform tissue fibrosis and obliterative phlebitis. The odd properties of IgG4 molecules such as Fab–arm exchange, Fc–Fc aggregation and modified Th2 response lead to immunological paradox in IgG4-RD. A series of florid interactions among innate and adaptive immune cells result in abnormal cytokine/chemokine/growth factor modulation that may lead to fibroinflammatory cell infiltration, tissue inflammation with fibrosis and allergic conditions in patients with IgG4-RD. Many conundrums remain to be solved such as the nature of antigenic stimuli, the molecular mechanism underlying storiform fibrosis, the etiology of aberrant immunobiology, the fine-tuning of genetic/epigenetic modifications of cytokine expression, and the pathologic roles of autoantibodies relevant to immunopathogenesis of IgG4-RD.The precise epigenetic regulations, including DNA methylation/acetylation and histone modifications for the diverse immune dysfunctions in IgG4-RD;The aberrant expression of non-coding RNAs in the ontogenesis of abnormal B cell biology in IgG4-RD;4+Tc in IgG4-RD;The characterization of factors involved in the induction of CDThe elucidation of the sophisticated molecular mechanism underlying storiform fibrosis;H. pylori infection and other environmental factors, such as allergens for development of the disease;Clarification of the interactions between Immunopathologic roles of different IgG4 autoantibodies in its pathogenesis;With regards to the designation of new therapeutic strategies for IgG4-RD other than corticosteroids, nonspecific immunosuppressants and anti-CD20 therapy are mandatory in clinical practice. These strategies may include blockades of modified Th2 response and new anti-fibrogenic therapies. However, many unmet needs should be fulfilled for identifying more in-depth the cellular and molecular mechanisms underlying IgG4-RD—as well as improving its therapies. These investigations may focus on:per se. Since the disease is a relatively newly found disorder implicating the humoral immune system, a multi-arrays of work are expected to have fruitful results in the future.These are only a few points we suggest that may be helpful for understanding IgG4-RD, as well as the unique nature of IgG4,


Cracks caused by environmental temperature and humidity variation are generally considered one of the most important factors causing durability deterioration of concrete structures. The seasonal or daily variation of ambient temperature and humidity can be considered periodic. The dynamic modulus of elasticity is an important parameter used to evaluate the performance of structural concrete under periodic loads. Hence, in this paper, the dynamic elastic modulus test of concrete under simulating periodic temperature-humidity variation is carried out according to monthly meteorological data of representative areas . The dynamic elastic modulus attenuation pattern and a dynamic elastic modulus degradation model of concrete under periodic temperature-humidity are investigated. The test results show that the dynamic elastic modulus of concrete decreases and tends to be stable under the action of periodic temperature-humidity. Comparative analysis shows that the two-parameter dynamic elastic modulus degradation model is more suitable for describing the dynamic elastic modulus attenuation pattern of concrete under periodic temperature-humidity action than the single-parameter one. For most structures, durability is an important performance and a decisive factor which influences service performance during the whole life cycle ,2. EnvirDuring the construction period and service life of a concrete structure, the structure is always affected by the temperature and humidity variation of the service environment. There are also indoor and outdoor temperature and humidity differences in industrial and civil buildings which produce temperature and humidity differences between the internal and external surfaces of the concrete components. The changing temperature-humidity-induced temperature gradient and humidity gradient inside of the concrete will cause internal stress and deformation cracking of the concrete structure , especiaThe seasonal or diurnal variation of environmental temperature and humidity can be described by periodic environmental temperature and humidity ,10. CompDomestic and foreign scholars have done a lot of research on damage accumulation and performance deterioration of concrete material under temperature-humidity, but most of their works focus on the deterioration of concrete material under freeze-thaw cycles ,15,16,17From the perspective of structural design, the compressive strength and elastic modulus of concrete are the most important performance indicators of concrete. These parameters are usually determined, according to the standard procedure, by the uniaxial compression of cylindrical or cubic specimens, and are used as a reference. However, it is not always possible to use these methods in practice, due to their destructiveness and time-consuming nature, and their consumption of numerous specimens . By compThe dynamic elastic modulus is often used as the damage variable used to characterize the deterioration degree of concrete under the action of sulfate attack, freeze-thaw, and carbonation ,41,42,43Although there are many works on the damage accumulation and performance degradation of concrete under the action of temperature and humidity, most of them have been carried out for the freeze-thaw cycle. Research on the performance degradation and fatigue effect of materials under the quasi-periodic variation of temperature and humidity in a normal service environment has not attracted enough attention. It is an important factor that cannot be ignored for the performance degradation and durability of mass and overlength concrete structures in areas with large annual or daily temperature variation. Hence, this paper aimed to grasp the dynamic elastic modulus attenuation pattern and the fatigue damage accumulation model of concrete under periodic temperature and humidity. To this end, the dynamic modulus of an elasticity test of concrete with different strength grades under simulated periodic temperature-humidity variation is carried out according to monthly meteorological data of representative areas . The dynamic modulus of an elasticity attenuation pattern and the fatigue damage accumulation model of concrete under periodic temperature-humidity are investigated.Three kinds of concrete with the strength grades C20, C30, and C40 were chosen to carry out a dynamic elastic modulus test under simulated periodic temperature-humidity variation. Chinese standard ordinary Portland cement  and comThe chemical compositions of the cements PO42.5 and PC32.5R are shown in Cement, river sand, and coarse aggregate were added into 40 L compulsory mixer according to the mix proportion of concrete and stirred for one minute. After this, water was added and the mixture was mixed and stirred for 2 min. Immediately after mixing was finished, the fresh concrete mixture was placed into molds to prepare the specimens. The molds, after being poured full with fresh concrete mixture, were placed on a concrete vibration table and vibrated for one minute to make the concrete compact. All the specimens of the same mix proportion were prepared from the same batch of concrete. According to the Chinese standard GB/T 50082-2009 , the speAccording to the temperature and humidity data of Nanjing City selected from a data set of annual and monthly ground values of China (1981–2010) provided by the national meteorological science data sharing service platform of the Meteorological Data Center of China Meteorological Administration, a simulated environmental periodic temperature and humidity variation pattern was determined for a dynamic elastic modulus test of concrete. The meteorological data of Nanjing City are listed in According to the meteorological data of Nanjing City, the simulated periodic temperature-humidity parameters set for the equipment of the Temperature and Humidity Alternating Test Chamber were as follows: (1) The cycle duration was 24 h, divided into 24 sections, with each section lasting 1 h; (2) the monthly average maximum temperature and the monthly average minimum temperature from January to December, which were used as the test environmental temperature, were assigned to sections 1–24, individually; and (3) the monthly average relative humidity from January to December was assigned to every two sections as the test environmental relative humidity.The periodic temperature-humidity experimental parameters for the dynamic elastic modulus test of concrete, according to the meteorological data of Nanjing City, are shown in The temperature-humidity conversion time between each section was not included in the duration of each section. The next section started after the equipment reached the set temperature and humidity at the fastest speed.A Programmable Temperature and Humidity Alternating Test Chamber (ETE-GDJS-015L), which is shown in During the test, due to the time and accuracy deviation between the temperature-humidity inspection instrument and the temperature-humidity probe built in the temperature-humidity alternation test chamber, the actual humidity and temperature conditions in the alternation test chamber were not consistent with the set temperature-humidity parameters. Hence, humidity and temperature parameters measured by the temperature-humidity inspection instrument were selected.The dynamic elastic modulus of the concrete specimens under cyclic temperature-humidity action was measured and recorded after each temperature-humidity cycle. The measurement of the dynamic elastic modulus was conducted using a resonant frequency method according to the Chinese standard GB/T 50082-2009 . The insThe side perpendicular to the specimen molding surface was selected as the test surface and the middle point was marked as the measurement point, which avoided visible holes or cracks. The frequency range selected was from 1000 to 3000 Hz according to experience and the results of many dynamic elastic modulus tests on concrete.dE is the dynamic elastic modulus of concrete (MPa), a is the length of the cross section of the specimen (mm), L is the length of the specimen (mm), W is the weight of the specimen (kg), and f is the fundamental vibration frequency (Hz).After curing for 28 days, the specimens were put into the temperature and humidity alternating test chamber and the dynamic elastic modulus of concrete was measured after each cycle. After changing the excitation frequency to make the specimen reach the resonance state, the resonance frequency displayed at this time was measured, and each measurement was repeated more than two times. When the difference between two consecutive measurements did not exceed 0.5% of the arithmetic average of the two measurements, the average values of the two resonance frequencies was taken as the fundamental frequency of the specimen. The dynamic elastic modulus of concrete was calculated according to Equation (1) , i.e., and the weight of each specimen was recorded once after each temperature-humidity cycle.lM) of each group was able to be calculated from the average weight of three specimens by Equation (2), i.e.,lM is the weight loss rate of the concrete specimen (%), m0 is the weight of the concrete specimen before the test, and nm is the weight of the concrete specimen after n times of periodic temperature-humidity cycles.The weight loss rate . The weight loss rates in the dynamic elastic modulus test of concrete under periodic temperature-humidity, accompanied by the results of frost resistance research from relevant references are shown in Such results should be related to the consistent immersion of concrete specimens in water in the freeze-thaw test. Concrete pores, for example those in air-entrained concrete, play an important role in influencing the weight loss rate of concrete under freeze-thaw cycles. The weight loss rate is also influenced by the strength grade of concrete and decreases as the strength increases.As we all know, the dynamic elastic modulus correlates well with the strength and elastic modulus of concrete. The dynamic elastic modulus of concrete, which can be obtained by non-destructive testing, is suitable to be used as a damage variable to analyze the attenuation pattern of concrete mechanical properties under periodic temperature-humidity action.dE) of C20, C30, and C40 concrete was able to be calculated using Equation (1). To evaluate the attenuation pattern of the dynamic modulus of elasticity of concrete with different strength grades under cyclic temperature-humidity action, the relative dynamic elastic modulus is able to be defined as [drE is the relative dynamic elastic modulus of concrete (%), E0 is the initial dE of concrete, and nE is the dE of concrete after n times of periodic temperature-humidity cycles.After each periodic temperature-humidity cycle, the dynamic elastic modulus (fined as (3)Edr=EThe calculated relative dynamic elastic modulus, which was used to evaluate the degradation model of the dynamic elastic modulus of concrete under periodic temperature-humidity action, is listed in The relative dynamic elastic modulus of concrete with three strength grades under periodic temperature-humidity, accompanied by the results in frost resistance research from relevant references, is shown in Under the action of a freeze-thaw cycle, the relative dynamic elastic modulus of ordinary concrete decreases almost linearly, while that of air-entrained concrete decreases non-linearly. With the increase in fatigue duration, according to Cao’s research , the relSuch results should be related to the strength grade of concrete and should improve the dynamic elastic modulus as the strength increases. Concrete pores, especially for air-entrained concrete, also play an important role in the dynamic elastic modulus of concrete.The causes of structural damage are various, and different damage variables and evolution equations can be selected according to diverse damage mechanisms. Even if the same damage process is analyzed, different damage evolution equations will be obtained by using different damage variables.D is the damage variable (maybe the relative dynamic elastic modulus of concrete), M is the material correlation constant, and N is the number of fatigue cycles.Fatigue damage is a process of micro crack and micro pore initiation and expansion caused by irreversible evolution of the material structure. This irreversible evolution process directly affects the macro performance of materials. On the basis of continuous damage mechanics, Chaboche ,50 thougf has inseparable variables N and D in order to describe non-linear damage accumulation and sequence effects [Many other parameters can be considered within Equation (4) according to the problems studied. The damage rate in Equation (4) depends on the present damage state, permitting a non-linear evolution under periodic loading. The function  effects .When the loading parameters considered are the maximum stress and mean stress in each cycle, a common general form of the fatigue damage accumulation model is obtained ,51, i.e.fp is the material constant.Lemaitre and Plumtree have proposed the following equation to describe the fatigue damage evolution and defined the form of the function failures , i.e.,(Equation (8) for the fatigue damage equation can be obtained by simple substitution of Equation (7) into Equation (6), followed by transformation.M0, , and K are material constants, n is the number of periodic actions cycles (in this paper it is the number of periodic temperature-humidity cycles), and According to Shang’s research , if the M1 and M2 are constants relating to the materials and fatigue load experimental conditions, etc., which can be obtained via fitting analysis of the experimental results.The above models, Equations (8) and (9), are consistent with the fatigue failure mechanism and are more in line with the conditions of multi-axial and complex load action, such as freeze-thaw fatigue. However, the models are inconvenient to apply because of the inclusion of many parameters which are difficult to obtain. Obviously, the fatigue damage evolution in the form of Equations (8) and (9) can be simplified by considering the material characteristics to be constant for a certain material. Hence, Equations (8) and (9) can be simplified into Equation (10) according to the actual freeze-thaw conditions .(10)dD=D = 0 when N = 0. Equation (10) is transferred to the following form [Both sides of Equation (10) are integrated at the same time and then combined with the boundary conditions of ing form :(11)D=1−Equations (11) and (12) are empirical and cannot deeply describe the macroscopic behavior and reflect the dissipation mechanism of fatigue damage propagation . The empD = 1 − En/E0 according to Equation (3) into Equations (11) and (12), we can obtain the degradation model of the dynamic elastic modulus of concrete under periodic temperature-humidity action asN times of periodic temperature-humidity cycle.If the dynamic elastic modulus loss rate is taken as the damage variable in the analysis of damage and the degradation model of the dynamic elastic modulus of concrete under periodic temperature-humidity action, after substituting Firstly, the Curve Fitting Tools (cftools) in MATLAB software were used to fit the first eleven relative dynamic elastic modulus data  according to the relative dynamic elastic modulus degradation model (Equations (13) and (14)), and the fitting parameters (M1 and M2) in Equations (13) and (14) were obtained.Then, the relative dynamic elastic modulus obtained from the last five experimental results of the dynamic elastic modulus test under periodic temperature-humidity action was compared with the fitting curve of the relative dynamic elastic modulus degradation model , and the rationality of the attenuation model was evaluated by correlation between the curve and experimental results.The degradation models of the relative dynamic elastic modulus (Equations (13) and (14)) were used as custom equations to fit the initial and former 10 experimental results of the relative dynamic elastic modulus under periodic temperature-humidity action via cftools in MATLAB.The initial and former 10 relative dynamic elastic moduli obtained from the experimental results and the fitting results of C20, C30, and C40 concrete are shown in The fitting goodness values of the dynamic elastic modulus degradation model of C20, C30, and C40 concrete are listed in The fitting effect and practicability of the fitting function can be evaluated by the fitting goodness analysis, mainly based on the SSE and R-square, as shown in The fitting parameters (M1 and M2), which were obtained from fitting the initial and the first 10 relative dynamic elastic moduli by the degradation model of the dynamic elastic modulus under periodic temperature-humidity action as custom equations, were substituted into the two-parameter dynamic elastic modulus degradation model (Equation (14)). The degradation model curves were plotted and compared with the experimental relative dynamic elastic modulus results of the last five cycles, as shown in From It also can be seen from In addition, the verified dynamic elastic modulus degradation model can also be used to predict the relative dynamic elastic modulus after more instances of cycles under the same periodic temperature-humidity action, which can reduce the actual test times and durance to a certain extent. Moreover, the related fitting analysis methods in this paper can also be applied to analyze and solve other similar problems.The action of periodic temperature-humidity variation decreases the dynamic elastic modulus of concrete, and the dynamic elastic modulus loss rate tends to be stable after more cycles of periodic temperature-humidity. The dynamic modulus loss rate of C40 concrete is obviously lower than that of C30 and C20 after more cycles of periodic temperature-humidity, and is lower by over 12%.2 The weight loss rate of concrete increases continuously, and, later, the growth rate slows down. The weight loss rate is also influenced by the strength grade of concrete and will decrease as the strength increases. The relative dynamic elastic modulus of high-strength-grade concrete was found to decrease slightly faster in the early stage but was significantly higher than that of low-strength-grade concrete later under periodic temperature-humidity action.Taking the loss rate of the dynamic elastic modulus as the damage variable, the dynamic elastic modulus deterioration model of concrete under periodic temperature-humidity action can be established based on the theory of fatigue damage and the evolution equation of fatigue damage.The two-parameter dynamic elastic modulus degradation model (M1 ≠ 1) is more suitable for describing the dynamic elastic modulus attenuation pattern of concrete under periodic temperature-humidity action than the single-parameter model (M1 = 1).The current research in this paper is insufficient, and further research is required. The service load of the actual concrete structure is also an important factor in the deterioration of concrete performance, so the degradation of the dynamic elastic modulus and damage evolution under the combined action of the service load and periodic temperature-humidity are worthy of further study. The micromechanical mechanism of concrete cracking and elastic modulus degradation under periodic temperature and humidity needs to be further studied by means of microscopic analysis, for example via scanning electron microscopy, and finite element analysis. In addition, temperature-humidity conditions closer to the actual service environment should be considered in further research, for example by using the highest (lowest) daily temperature in a certain month as the representative value of the highest (lowest) monthly temperature. The deformation and failure micromechanism of airport or pavement concrete under the coupling effect of wheel load-temperature-humidity in areas with severe temperature and humidity changes is also worthy of attention.In this work, a dynamic elastic modulus test of concrete under periodic temperature and humidity was conducted with experimental parameters determined according to the monthly meteorological data of Nanjing City. The dynamic elastic modulus deterioration model of concrete under periodic temperature-humidity action was established based on the theory of fatigue damage and the evolution equation of fatigue damage. The conclusions and future research directions are summarized as follows: