The pathogenesis of immunoglobulin G4-related disease (IgG4-RD) remains unclear. IgG4-RD often mimics other diseases, including pancreatic cancer (PC) and Sjogren’s syndrome (SS), which may easily lead to misdiagnosis. This study was performed to explore the metabolite changes and potential biomarkers of IgG4-RD and other misdiagnosed diseases.n = 87), PC (n = 33), and SS (n = 31) was performed. A random forest machine learning model was used to verify the relevance of the identified metabolites in the diagnosis of different diseases and the prediction of disease prognosis.Untargeted liquid chromatography–tandem mass spectrometry metabolomics profiling of plasma samples from a cohort comprising healthy controls (HCs) and patients with IgG4-RD  = 1]. A combination of phenylalanine betaine, 1-(1z-hexadecenyl)-sn-glycero-3-phosphocholine, Pi 40:8, uracil, and N1-methyl-2-pyridone-5-carboxamide showed a moderate value in predicting relapse in patients with IgG4-RD (AUC = 0.8).The ATP-binding cassette transporter pathway was found to be most closely related to IgG4-RD, which was significantly up-regulated in the IgG4-RD group than in all the matched groups. Five metabolites were proved to be valuable biomarkers for IgG4-RD. Caftaric acid, maltotetraose, Our findings revealed the metabolite changes of IgG4-RD and provide new insights for deepening our understanding of IgG4-RD despite the lack of validation in external cohorts. Metabolomic biomarkers have significance in the clinical diagnosis and disease prognosis of IgG4-RD.The online version contains supplementary material available at 10.1186/s12916-022-02700-x. Immunoglobulin G4-related disease (IgG4-RD) is a complex immune-mediated fibroinflammatory condition of unknown etiology and can affect multiple organs , 2. It oBiomarkers for the diagnosis and differential diagnosis of IgG4-RD are urgently needed. Serum IgG4  and IgE The advances in liquid chromatography–mass spectrometry (LC-MS) have revolutionized untargeted metabolomics . MetabolIgG4-RD is gradually being considered as an immune-mediated disease with metabolic disorders. Our previous plasma metabolomics study found some differentially expressed metabolites in patients with IgG4-RD compared with healthy volunteers, some of which have potential diagnostic value . A recenregistered onClinicalTrails.gov, NCT01670695; study start date: June 2012) that was recruited at the Peking Union Medical College Hospital. Patients with untreated IgG4-RD, PC, and SS as well as HCs were enrolled in this study from January 2012 to October 2021. IgG4-RD was diagnosed based on the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria [This study was based on a prospective cohort . Each aliquot (150 μL) of the plasma sample was stored at −80°C until ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). The plasma samples were thawed at 4°C, and 100-μL aliquots were mixed with 400 μL of cold methanol/acetonitrile  to remove proteins. The mixture was then centrifuged for 15 min . The supernatant was dried in a vacuum centrifuge. The samples were redissolved in 100 μL of acetonitrile/water  solvent for LC-MS analysis.Analysis was performed using UHPLC  coupled to Q-TOF-MS . Further details on the LC-MS/MS analysis and data processing can be found in Additional file http://csbg.cnb.csic.es/mbrole2/).The enrichment analysis of the KEGG metabolic pathway was applied by the KEGG library. Fisher’s exact test was used to analyze and calculate the significance level of the enrichment pathway by MBROLE version 2.0  method for multiple testing. VIP > 1 and P-value < 0.05 were used to screen for significantly changed metabolites. Spearman’s correlation analysis was performed to determine the correlation between two variables. A two-sided α of < 0.05 was considered to indicate statistical significance. In the random forest analysis, a thousand trees were built using the R package randomForest (version 4.6.14) with 10-fold cross-validation. This was repeated 100 times. Then, in the training set, to reduce the impact of the randomness of the data and reduce the overfitting of the model, a 10-fold cross-validation was used for the training set. After the model was established, the test set was used for verification. For each tree, the classification accuracy of the out-of-bag samples was determined both with and without random permutation of the values of the variable. The prediction accuracy after permutation was subtracted from the prediction accuracy before permutation and averaged over all trees in the forest to obtain the importance scores. The importance scores were used to identify biomarkers and remove non-informative variables.Statistical analyses were performed by R V.4.0.2. The original data was initially divided into the training set and test set according to 7:3  and those with IgG4-related pancreatitis  according to their organ involvements  and 30 age- and sex-matched HCs were included in the study  transporter pathway was found to be most closely related to the pathogenesis of IgG4-RD, which was up-regulated in the IgG4-RD group. Thirteen differential metabolites were involved in this pathway, including uridine, taurine, ine Fig. A–C. Addid-glutamic acid and 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoserine can adequately distinguish IgG4-RP from PC  analysis was used to verify the relevance of the identified metabolites in the differential diagnosis of IgG4-RD, HC, SS, and PC. The importance score of each metabolite was calculated by random forest, and sorted metabolites  and non-relapsed (n = 30) groups  according to their prognosis after treatment . Random forest analysis revealed that the combination of phenylalanine betaine . Also, d-glutamic acid, which is not endogenously produced in higher mammals and is derived from food intake in humans, was found to be the most potent natural inhibitor of glutathione (GSH) synthesis [The imaging findings and serum IgG4 levels of patients with IgG4-RD and pancreatitis often overlap with those of patients with PC , 25. In ynthesis , which iynthesis . Specifiynthesis . Metabolynthesis . HoweverAs an immune-mediated disease, IgG4-RD often mimics the symptoms of other autoimmune diseases. To distinguish them, we chose SS as the control disease in this study. Metabolomics revealed that IgG4-RSD had a metabolic pattern distinct from that of SS, and hydroxyproline can adequately distinguish IgG4-RD from SS. Hydroxyproline is a nonessential amino acid mainly found in collagen. It is significantly increased during the fibrosis process of systemic sclerosis , which iOur study also found five metabolic biomarkers -sn-glycero-3-phosphocholine, Pi 40:8, uracil, and N1-methyl-2-pyridone-5-carboxamide) that can predict the relapse of IgG4-RD by comparing the metabolomics of relapsed and non-relapsed patients (AUC = 0.8). Few articles have been published on these metabolites. Phenylalanine betaine is an amino acid betaine derived from phenylalanine and it has been reported to significantly increase urinary excretion in mice fed rye brans . 1-(1Z-hKEGG analysis revealed that the metabolic disorders in IgG4-RD were mainly related to amino acid metabolism and glycolysis pathways. In these pathways, ABC transporters were the most significantly enriched. ABC transporters are a family of membrane proteins found in all domains of life. They contain a pair of ABC or nucleotide-binding domains . MultiplIn summary, distinct metabolic patterns were observed in patients with IgG4-RD. Five valuable metabolic biomarkers were identified for the diagnosis of IgG4-RD and distinguishing it from PC and SS. Additionally, we found five metabolic biomarkers with moderate values for predicting disease relapse. Amino acid metabolism and glycolysis pathways, especially ABC transporters, have potential roles in the pathogenesis and treatment of IgG4-RD. Despite the limitations mentioned above, we believe that our study further comprehensively uncovered the metabolic mechanisms and the metabolic biomarkers of IgG4-RD.Additional file 1. LC-MS/MS analysis and Data processing.Additional file 2: Fig. S1. Flow diagram of data analysis. Fig. S2. The disease distribution of enrolled subjects in this study. Fig. S3. Volcano plot representation of the differently expressed metabolites between IgG4-RD and other paired groups. Fig. S4. ESI+ and ESI- mode of PCA between groups. Fig. S5. Permutation test of OPLS-DA model showing the stability of the model in ESI+ and ESI- mode. Fig. S6. The expression level of the selected metabolic biomarkers in all the enrolled subjects. Fig. S7. The correlation between metabolic biomarkers and clinical features.Additional file 3: Table S1. Detailed clinical features for the enrolled IgG4-RD patients and healthy controls. Table S2. Detailed summary of clinical features for the enrolled Sjogren’s syndrome patients. Table S3. Clinical features of pancreatic cancer patients. Table S4. Clinical features of IgG4-RSD and IgG4-RP patients. Table S5. Differential metabolites between IgG4-RD and HC. Table S6. Differential metabolites between IgG4-RP and PC. Table S7. Differential metabolites between IgG4-RSD and SS. Table S8. Clinical features of relapsed and non-relapsed IgG4-RD.


The Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence.This study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline to the treating clinicians. We simulated varying adherence to guideline recommendations for low procalcitonin levels and determined which threshold adherence rate could have resulted in rejection of the null hypothesis of no difference between groups at alpha = 0.05. We also performed sensitivity analyses within specific clinical settings and grouped patients initially prescribed antibiotics despite low procalcitonin into low, medium, and high risk of illness severity or bacterial infection.Our primary outcome was number of antibiotic-days by day 30 using an intention-to-treat approach and a null hypothesis of no difference in antibiotic use. We determined that an 84% adherence rate in the hospital setting (emergency department and inpatient) for low procalcitonin could have allowed rejection of the null hypothesis . The threshold adherence rate was 76% for continued guideline adherence after discharge. Even 100% adherence in the emergency department alone failed to reduce antibiotic-days. Of the 218 patients prescribed antibiotics in the emergency department despite low procalcitonin, 153 (70.2%) were categorized as low or medium risk.High adherence in the hospital setting to a procalcitonin antibiotic prescribing guideline is necessary to reduce antibiotic use in suspected lower respiratory tract infection. Continued guideline adherence after discharge and withholding of antibiotics in low and medium risk patients with low procalcitonin may offer impactful potential opportunities for antibiotic reduction.Trial registration Procalcitonin Antibiotic Consensus Trial (ProACT), ClinicalTrials.gov Identifier: NCT02130986. First posted May 6, 2014. Procalcitonin is a circulating peptide typically elevated in bacterial but not viral infection. Several European randomized trials found that provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians safely reduced antibiotic use in suspected lower respiratory tract infection –4. TheseWe sought to determine what guideline adherence rate to antibiotic withholding recommendations at low procalcitonin levels would have resulted in less antibiotic use in the ProACT trial and in which settings. We also explored how clinically challenging it would be for clinicians to achieve guideline adherence based on predictors of illness severity and bacterial infection.ProACT was a patient-level, 1:1 randomized trial in 14 hospitals in the United States. We enrolled 1656 adult patients presenting with an initial diagnosis of acute lower respiratory tract infection. Treating clinicians estimated the likelihood of bacterial etiology before any experimental actions. Patients randomly received usual care (no other interventions or guides) or an intervention where the treating clinicians received procalcitonin results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels. The guideline used the same cutoff values as in previous trials and as approved by the U.S. Food and Drug Administration . On discharge, we provided patients with a letter for their primary care provider that included their last procalcitonin assay result, a trial synopsis, and the procalcitonin guideline. The primary outcome was total antibiotic exposure to day 30 and data were obtained through chart review and by telephone calls at days 15 and 30 made by coordinating center staff who were unaware of the treatment-group assignments. Using baseline characteristics and published criteria, we categorized the initial diagnosis of lower respiratory tract infection into final diagnoses of acute exacerbation of chronic obstructive pulmonary disease (COPD), asthma exacerbation, acute bronchitis, community-acquired pneumonia, and other.To evaluate the impact of adherence on the primary outcome of antibiotic-days by day 30, we varied adherence between 65% and 100% and determined which threshold adherence rate for low procalcitonin levels (≤ 0.25 mcg/L) in the intervention arm could have allowed rejection of the null hypothesis (no difference between groups) at a significance level of 0.05. The usual care control arm (n = 830) was used for comparison and was not altered in simulations. In the procalcitonin intervention arm we identified all patients who had guideline nonadherent antibiotic prescriptions. To examine 100% adherence, we set antibiotic use to zero at each timepoint when procalcitonin levels were under guideline cutoffs in all intervention arm patients (n = 826). To examine adherence rates < 100%, we simulated an intervention arm population of the same size (n = 826) with the given adherence rate. To account for variability in sampling, we present the mean results of repeating this sampling process 1000 times.To create each simulated intervention arm population we first included all patients who had only guideline-adherent antibiotic prescriptions. We then used random selection without replacement in R version 3.6 to sample the requisite number of patients with nonadherent prescriptions needed to simulate the given adherence rate. For each of these sampled patients we set their antibiotic use to zero for the timepoints where their procalcitonin levels were below the guideline cutoff. For the patients with nonadherent prescriptions who were not selected and for the patients with only guideline-adherent prescriptions we used their observed antibiotic-days. As with the original report of the ProACT trial, we compared the mean number of antibiotic-days between usual care and intervention groups using two-sample t-tests, following an intention-to-treat approach with multiple imputation to account for patients lost to follow-up after discharge.Our primary analysis focused on the protocol period in the hospital including both emergency department (ED) and inpatient, where clinicians received procalcitonin results. In sensitivity analyses, we also determined the threshold adherence rate for rejection of the null hypothesis for adherence only in the emergency department, or in the hospital (ED and inpatient) for only for the lowest procalcitonin levels (< 0.1 mcg/L). These analyses addressed whether hospital clinician adherence to procalcitonin guidance only in the emergency department, or only for the lowest procalcitonin levels, could be sufficient to reduce antibiotic use.We also determined the threshold rate for continued guideline adherence after discharge. For this analysis, we selected patients whose last procalcitonin level prior to discharge was low and who did not receive antibiotics on the day this procalcitonin level was reported. This analysis addressed whether avoidance of overruling in the outpatient setting of initial decisions to withhold antibiotics could be sufficient to reduce antibiotic use.To explore the second question of how challenging it would be to achieve adherence, we examined the characteristics of patients presenting with a low procalcitonin who were initially prescribed antibiotics on presentation in the emergency department. We then grouped these patients into low, medium, and high risk of illness severity or bacterial infection based on published risk criteria and the treating clinician’s estimate of the likelihood of bacterial etiology –9. Our iWe categorized as high risk all patients with a new infiltrate on chest imaging or > 1 risk criterion of illness severity or bacterial infection. We defined risk criteria based on the systemic inflammatory response syndrome (SIRS), quick Sepsis Related Organ Failure Assessment (qSOFA), the Center for Medicare and Medicaid Services SEP-1 criteria, baseline demographics , clinician estimate of likelihood of bacterial etiology, oxygen saturation, and hospitalization status –9. We liThe threshold hospital (ED and inpatient) adherence rate for rejection of the null hypothesis was 84% for low procalcitonin levels in intervention arm patients  Table . CompletOf patients with low procalcitonin levels in whom antibiotics were initially withheld, 36.7% 172 of 469) subsequently received antibiotics after discharge. The threshold adherence rate to reduce antibiotic use was 76% for continued guideline adherence after discharge  were categorized as low, 136 (62.4%) as medium, and 65 (29.8%) as high risk of illness severity or bacterial infection.The impact of a novel diagnostic test depends on the characteristics of the healthcare environment in which it is implemented. Efforts to study and implement novel tests should examine the entire epoch of care from initial encounter through the outpatient period to fully characterize the impact of testing on care. Our main finding was that a high adherence rate to procalcitonin guidance in the hospital setting (ED and inpatient) would have been necessary to observe a reduction in antibiotic use in the ProACT trial. Our results also indicated that continuing guideline adherence post-discharge could have a greater impact on antibiotic reduction, with more than one in three patients with low procalcitonin and no initial antibiotic prescription later receiving antibiotics after discharge.Withholding antibiotics can be a source of anxiety to both clinicians and patients. Both groups may be more willing to forego antibiotics when procalcitonin is low and clinical risk factors are low to moderate versus when procalcitonin is low but clinical risk is high. Our simulations demonstrated that continuing guideline adherence after discharge would have resulted in the greatest reduction in antibiotic use, and that a large proportion of patients prescribed antibiotics despite low procalcitonin levels had low to moderate risk of severe disease. We found that of patients initially prescribed antibiotics despite low procalcitonin, less than one in three were deemed to be at high risk of severe disease or bacterial etiology. These patients represent a potentially amenable target for improving adherence to a procalcitonin antibiotic prescribing guideline either in limiting initial prescriptions or for earlier cessation of antibiotics.Complete guideline adherence is generally unachievable in medicine and may not even be desirable as it would eliminate clinical judgment. These issues raise the question of what level of adherence is achievable and reasonable to target. In the ProACT trial procalcitonin guidelines were implemented using quality improvement principles and adherence varied from 39.5% to 83.3% between centers . Our simOur results are limited to the setting of the ProACT trial including patients with suspected lower respiratory tract infection and using serial testing. Results are also limited to patients and sites similar to those enrolled in ProACT; relatively young, non-critically ill patients with low comorbidity burden, presenting to predominantly urban tertiary care academic centers with low baseline antibiotic use. We assumed no harm would have resulted from lower antibiotic use due to increased adherence, as prior procalcitonin trials that resulted in lower antibiotic use found no harm –4. AdditOur simulations demonstrate that high adherence in the hospital (ED and inpatient) to a procalcitonin antibiotic prescribing guideline is necessary to reduce antibiotic use in suspected lower respiratory tract infection. Continued guideline adherence after discharge and withholding of antibiotics in low and medium risk patients with low procalcitonin may offer impactful potential opportunities for antibiotic reduction.


The most frequently used construction material in buildings is concrete exhibiting a brittle behaviour. Adding fibers to concrete can improve its ductility and mechanical properties. To this end, a laboratory study was conducted to present an experimental model for the specimens’ size effect of on macro-synthetic fiber-reinforced concrete using variations in fracture energy. Composite concrete beams with different thicknesses and widths were made and tested under mode I to obtain (1) fracture toughness, (2) fracture energy, and (3) critical stress intensity factor values. Results indicated that by increasing the thickness and the width, fracture toughness and fracture energy were enhanced. Moreover, increasing the thickness and width of the beam led to critical stress intensity factors enhancement respectively by 35.01–41.43% and 7.77–8.09%. Fiber-reinforced concrete is a type of composite material made of concrete mixed with fibers of various types and sizes, which can additionally include glass, polymer, carbon, and steel .Studies have been conducted to investigate the effect of fibers on concrete, such as its mechanical properties, fatigue life, and durability, which indicate the positive effect of fibers on concrete performance ,3,4,5. APakravan et al. focused on the use of hybrid fibers in concrete and reported that combining various types of fibers would yield better results in terms of concrete toughness and energy absorption . BordeloA summary of recent studies on the effects of different types of fibers on concrete’s mechanical properties is presented in There are numerous studies on the mechanical properties of fiber-reinforced concrete and the size effect of concrete specimens. However, most of the studies related to the size effect increased the thickness and span of the beam specimens. This approach does not describe the effect of thickness or width variations independently.In this study, we evaluated the effect of the size of a macro-synthetic-fiber-reinforced concrete specimen on the variations in fracture energy. The studied parameters were the fracture energy of notched concrete beams and the stress intensity factor. We used twisted fibers, which were added to the concrete mix with a volume fraction of 0.4%. Three samples were developed for each specimen, and the results were averaged and recorded in tables.The experimental model of variations in concrete fracture energy considers thickness, width, and macro-synthetic fiber content.The effect of specimen size on the fracture energy of concrete specimens is explained.The effect of fibers on the stress intensity factor of concrete specimens with three different thicknesses and widths is described.This research was conducted to achieve the following goals:3), fine aggregate 789 (kg/m3), cement 442 (kg/m3), water 199 (kg/m3), superplasticizer 2.2 (kg/m3) m3), and fibers with two doses of 3.6 and 5.4 (kg/m3). The fibers used in this research were selected according to the specifications of ASTM D7508/D7508M-10, with a length of 3.8 cm [To evaluate the fracture energy and stress intensity factor of notched concrete beams, a concrete mixture was designed based on the ACI 211 standard . All thef 3.8 cm . Figure KIc) of fiber-reinforced concrete, concrete beam samples were fabricated based on the JCI-S-001-2003 standard [To evaluate the fracture energy and critical stress intensity factor  and (2).Fracture energy is defined as the amount of energy required for crack growth per unit area along the ligament. The fracture energy of the manufactured concrete specimens was measured based on the Japan Concrete Institute’s standard . In thisGF—the fracture energy (N/mm2),W0—the area below the CMOD curve up to rupture of the specimen (Nmm),W1—the work done by the deadweight of the specimen and loading jig ,Alig—the area of the broken ligament ,m1—the mass of the specimen (kg),S—the loading span (mm),L—the total length of the specimen (mm),m2—the mass of the jig not attached to the testing machine but placed on the specimen.The adjustment of the device and specimen is presented in KIc) [P, H, T, and S are shown in As an important parameter in fracture mechanics, the critical value of the stress intensity factor shows the resistance of a material to crack growth. When a cracked specimen is exposed to remote load, high-stress intensity occurs around the tip of the crack, and when this stress reaches its critical value, the fracture process is initiated in the specimen. The value of the stress intensity coefficient, which is calculated based on this critical stress, is known as the critical stress intensity factor (KIc) ,32. The To calculate the fracture energy of fiber-reinforced concrete specimens, notched specimens with three different thicknesses  and widths  were manufactured based on the JCI-S-001-2003 standard  and loadTo study the effect of independent variables, including the thickness of concrete specimens, and fiber dosage on fracture energy, multiple linear regressions were used. The initial equation considered for analysis is shown in Equation (4).GF—fracture energy (N/mm2)H—thickness of concrete specimens (CM)Fiberdosage—fiber volume fraction (%)H) and the linear term for fiber dosage was meaningful if the p-values were less than 0.05 with 95% reliability. In the final model, the interactive term was eliminated due to insignificance, which means that the thickness (H) and percentage of the fibers do not interact with each other. According to R2 value of 0.98 indicates that two variables, thickness (H) and fiber dosage, explain about 98% of the fracture energy variations; hence, the model is suitable to predict fracture energy.After fitting, coefficients of their significance values were less than the present significance level and were eliminated by the stepwise regression and backward elimination method, and the final model was obtained according to 2 was equal to 0.00122. Therefore, if the change in fracture energy for thickness (H), holding other factors fixed, is considered, the equation 2, the greater the effect of the thickness variable (H) relative to the fiber dosage on the fracture energy.As shown in According to the model, the relationship between the three mentioned variables is graphically plotted in T with H.To study the effect of independent variables, including the width of concrete specimens and fiber dosage, on fracture energy, multiple linear regressions were used. The initial equation considered for analysis is shown in Equation (4) by replacing F indicates the overall significance of the model at a high confidence level. However, the adjusted R2 value of 0.98 indicates that two variables, width (T) and Fiberdosage, explain about 96% of the fracture energy variations; hence, the model is suitable to predict fracture energy.Similar to the method used for thickness variations, a width change was also made and the final model was obtained according to 2 was equal to 0.00051. Therefore, if the change in fracture energy for width (T), holding other factors fixed, is considered, the equation T) on the fracture energy.As shown in According to the model, the relationship between the three mentioned variables is graphically plotted in The critical stress intensity factors of different notched macro-synthetic fiber-reinforced concrete specimens were calculated based on Equation (3) and are presented in KIc increases by increasing the thickness H and width T of concrete beams.As seen from these results, generally, the value of After the tests, the cross-sectional area of the sample was broken and the tip of the fiber was examined..The experimental model of the effect of specimen size was presented by testing specimens with three different thicknesses and widths for normal and fiber-reinforced concrete.The results in The results in The results in of The results in The results in The results in In this study, we calculated the fracture energy for macro-synthetic fiber-reinforced concrete specimens with different thicknesses and widths tested using notched beam specimens. The main concluding remarks are:


Geopolymer recycled aggregate concrete (GPRAC) is a new type of green material with broad application prospects by replacing ordinary Portland cement with geopolymer and natural aggregates with recycled aggregates. This paper summarizes the research about the mechanical properties, durability, and microscopic aspects of GPRAC. The reviewed contents include compressive strength, elastic modulus, flexural strength, splitting tensile strength, freeze–thaw resistance, abrasion resistance, sulfate corrosion resistance, and chloride penetration resistance. It is found that GPRAC can be made to work better by changing the curing temperature, using different precursor materials, adding fibers and nanoparticles, and setting optimal mix ratios. Among them, using multiple precursor materials in synergy tended to show better performance compared to a single precursor material. In addition, using modified recycled aggregates, the porosity and water absorption decreased by 18.97% and 25.33%, respectively, and the apparent density was similar to that of natural aggregates. The current results show that the performance of GPRAC can meet engineering requirements. In addition, compared with traditional concrete, the use of GPRAC can effectively reduce carbon emissions, energy loss, and environmental pollution, which is in line with the concept of green and low-carbon development in modern society. In general, GPRAC has good prospects and development space. This paper reviews the effects of factors such as recycled aggregate admixture and curing temperature on the performance of GPRAC, which helps to optimize the ratio design and curing conditions, as well as provide guidance for the application of recycled aggregate in geopolymer concrete, and also supply theoretical support for the subsequent application of GPRAC in practical engineering. About 30 billion tons of concrete are used worldwide every year [2. Moreover, about 7% CO2 all over the world comes from the manufacture and use of cement [As the population in the world continues to grow and urbanization continues, carbon dioxide emissions are increasing. According to British Petroleum, the energy giant, the carbon emissions of the world could reach 34,169 million tons of carbon dioxide, and China leads the world in carbon emissions with a total of 9826 million tons (2019) [f cement ,6,7.Davidovits proposed the concept of geopolymers as early as 1978. Materials containing silica-aluminate substances with alkaline activators to form Si–O–Al–O bonds. This is the hardening process of the geopolymer, which is completely different from the reaction mechanism of conventional concrete (CC) (hydration reaction between water and cement) . GeopolyNatural aggregates (NAs) are still the main aggregate component in both GPC and CC. Since aggregates make up 75 to 80 percent of the total volume of concrete, they are in high demand for the preparation of concrete. The current over-exploitation of NA has caused a shortage of natural sand and gravel resources in some areas, and has also caused damage to the ecological environment. Moreover, the unreasonable disposal of large amount of construction waste has caused certain environmental problems . TherefoIn view of its promising development and environmental protection concept, many scholars have conducted in-depth studies on RAs. First, Kim and Jeonghyun  concludeIn addition, the temperature and humidity of carbonation have an effect on the modification of RA. The carbonation reaction increases with the increase in carbonation temperature. The optimum relative humidity for carbonation should be between 40% and 80%. It is demonstrated that at 28 days, the modified RA with 100% substitution has a 14.2% improvement in compressive strength . Ouyang Both GPC and RA have promising application prospects, so geopolymer recycled aggregate concrete (GPRAC) can be prepared by replacing cement with geopolymer and NAs with RAs. There are two modes of substitution for the replacement of NAs by RAs. One is to replace all sizes of NAs, and the other is to replace only larger particles of NAs. The latter has been shown to have an enhanced effect on the strength and crack resistance of GPRAC beams . In addiCurrently, the performance of GPRAC has been studied through different research methods. Many scholars have conducted macroscopic studies on the performance of GPRAC through basic mechanical tests and durability tests. For example, Ren and Zhang  investigAs research on GPRAC has become more advanced, it has been found that improving the internal materials in GPRAC or adding fiber materials and nanoparticles has an impact on the performance of GPRAC. In this paper, the effects of using different precursor materials, RA admixture, curing temperature, and nanoparticle admixture on the mechanical properties and durability of GPRAC are reviewed. This provides guidance for subsequent studies on the application of RAs in GPC and to make GPRAC more widely used in the construction industry and to narrow the gap between theoretical research and practical engineering. However, there are few reviews on GPRAC. Therefore, this paper reviews the mechanical properties and durability of GPRAC under various influencing factors, so as to continuously optimize the mix ratio and derive the optimum nano-doping, which may help the subsequent research on GPRAC.Workability of the concrete includes flowability, adhesion, and water retention. Among of these, flowability affects the ease of construction and quality of concrete. The flowability is usually evaluated by slump and slump flow. Nuaklong et al.  found th2 content, in order to ensure that NS and RHA have the same SiO2/Al2O3, RHA needs to be added more. It can be seen from the Younis  presente2+ in GGBFS can provide nucleation centers to reduce the setting time [Setting time plays an important role in concrete construction. When the initial setting time is short, it is able to affect the transportation and watering of the concrete mix. When the final setting time is too long, the construction speed of a concrete project can be affected. The use of RA causes the aerated geopolymer concrete to set faster. Pasupathy et al.  investiging time . 3, which was lower than that of pressed geopolymer concretes containing limestone dust. This is because the bulk density of limestone dust is higher than that of recycled concrete block aggregate and RC. It is inferred that the type of RA also affects the density. He also noted that the dry density of pressed geopolymer concretes increased with the aggregate/FA ratio increasing. Posi et al. [It has been confirmed that the addition of FA decreases the maximum dry density . When thi et al.  performe3 were obtained for geopolymer mortars containing 20% and 30% polyethylene terephthalate (PET) waste, respectively. Utilizing PET waste leads to a decrease in density, which may contribute to the production of lightweight materials and thus reduce the constant load of the building. Nevertheless, the effect of the molar concentration of SH solution on density is confirmed to be insignificant and does not affect the density values regardless of the type of RA used [The use of RAs in GPC inevitably leads to a decrease in the density due to their own low density ,71,72,73 RA used ,74. However, an increase in the liquid alkali/solid binder ratio is effective in increasing the density values. Posi et al.  found thPorosity and water absorption are closely related. Generally speaking, the greater the porosity, the stronger the water absorption, which in turn has an impact on the density, impermeability and frost resistance properties. Hu et al.  discoverIn addition to changing the materials inside the concrete, water absorption and porosity can be reduced by adding nanoparticles. The addition of NS and RHA reduces the water absorption, while NS is less effective in reducing porosity compared to RHA. Because NS has a tendency to agglomerate . When thThe compressive strength of concrete represents its ability to resist failure under external forces. The strength of the concrete needs to meet the requirements to ensure the safety of the buildings. When the aggregates in the pressed geopolymer concrete were replaced with RA for NA, it caused a reduction in compressive strength. For pressed geopolymer concrete containing NA, the compressive strength ranged from 11.9 to 13.6 MPa. For pressed geopolymer concrete containing RA, the compressive strength was from 7.0 to 10.3 MPa. This is due to the weakness of the mortar attached in the RA, which has the lower abrasion resistance and dry density than the NA ,74. The Since RA has many shortcomings, some scholars have improved the compressive strength of RA by using different types of RA or by treating them. Compared to recycled brick aggregate, the compressive strength is higher using RCA . Junak aIn addition, the compressive strength is intimately associated with the curing time, curing temperature, alkali concentration, and the large number of pores in the ITZ and the binder. Wang et al.  was cond− ions determine the formation of gels. The chemical reaction is weak when the concentration of OH− ions is low. At this time, increasing the concentration of alkali ions can enhance the compressive strength of the geopolymer material. However, beyond a certain value, the excess OH− can cause precipitation of aluminosilicate products and decrease the strength [According to strength ,75,78. Tstrength ,71,82,87strength . Moreovestrength . 2/Al2O3 molar ratio and silica content of the system, which causes an increase in the Si–O–Si bond. This promotes an increase in compressive strength [Premkumar et al.  used silstrength . Howeverstrength ,90. The strength . The advstrength . Modulus of elasticity and compressive strength generally have a positive relationship. Unlike compressive strength, age has little influence on the elasticity modulus ,82. CompArulrajah et al.  evaluateThe use of RA reduced the flexural strength of GPC compared to the use of NA. Kunthawatwong et al.  found thThe splitting tensile strength of GPRAC decreases with the increase of RA content due to the defects in reclaimed aggregate. Kunthawatwong et al.  found thThe percentage increase of splitting tensile strength for specimens with 50% RCA was 0.8%, 38%, and 21% for CF contents of 0.1%, 0.2%, and 0.3%, respectively, which indicated that CF could increase the splitting tensile strength. However, at higher content, the dispersion of the fibers is inappropriate, which reduces the splitting tensile strength . It was When the water in the concrete freezes at low temperature, it can lead to volume expansion. Microcracks appear when the tensile strength is exceeded. After a freeze–thaw cycle, cracks gradually increase and expand, which reduce the strength. Sahin et al.  investig2/Al2O3 ratio. The excessive silicate may reduce the abrasion resistance [Abrasion resistance is mainly determined by weight loss. Wang et al.  found thsistance . An earlsistance  found thSulfate erosion is a type of durability damage, so it is necessary to investigate measures to reduce acid corrosion of GPRAC. The effect of the addition of NS on acid erosion has been studied earlier. The results show that although the addition of NS decreased the permeability of GPRAC, acid erosion was more severe when the specimens were prepared with NS. The reason for such results could be that unreacted silica fills the large pores and reduces the available space for expansion products. Hence, increasing the internal stresses leading to concrete disintegration . In addif is the residual compressive strength, which is a ratio of compressive strength before and after a sulfate attack. As can be seen from f of S25, S50, and S75 increased by 5.1% and 11.1%, 6.0% and 13.6%, and 9.2% and 15.2% after 15 and 30 sulfate cycles, respectively. From the results, it can be seen that the compressive strength of the GPRAC with higher GGBFS content is higher after the initial sulfate attack. This is due to the fact that GGBFS contains more Ca2+ compared to FA, and there is more reaction between GGBFS and sulfate solution. Although the compressive strength growth rate of S75 mix is higher at the beginning of erosion (before 15 cycles), it also has a higher compressive strength decrease rate after 60 cycles than other mixes. Ugurlu et al. [2SO4 + 1.5% MgSO4 solution had a greater negative impact on the samples than the 3% MgSO4 solution, which led to more weight gain. In addition, Kunthawatwong et al. [Xie et al.  investigu et al.  found thg et al.  found thResistance to chloride ion penetration is to some extent similar to resistance to sulfate attack. Nuaklong et al.  performeSEM is mainly used to observe the morphology, composition, and structure of concrete in its microscopic state, which can explain the changes in strength and durability of concrete from a microscopic point of view. Compared to NAs, RAs contain more crushed mortar on the surface, so the porosity at ITZ is higher. This provides a convenient channel for the infiltration of water molecules, chloride ions, sulfate attacks, etc., which is reflected in the basic properties of concrete as a reduction in strength, increased permeability, etc. . Figure 3, 400 kg/m3, and 500 kg/m3, respectively, an increase in the density of the gel and a decrease in the cracks could be observed with the increase in the content, which was a microscopic explanation for the improvement of the mechanical properties with the binder content.Since RAs exhibit significant disadvantages in GPRAC performance due to their own defects. Pawluczuk et al.  first tr3 is mainly from RA [Through XRD of the material and analysis of its diffraction pattern, information such as the composition of the material and the structure of the atoms or molecules inside the material can be obtained. Studies have shown that the mullite in concrete is derived from the FA or MK, quartz is mainly from river sand, and CaCO from RA ,95. Nuak from RA  observed from RA . This alThis paper is devoted to a review of the physical properties, mechanical properties, and durability performance of GPRAC. The following conclusions are drawn by summarizing the effects of RA content and type, alkali concentration, fibers, precursor materials, etc.(1) As the content of GGBFS increases, both of the slump and the setting time decrease significantly. The increase of slag replacement rate leads to the increase of splitting flexural strength. Compared to FA, GGBFS was more resistant to sulfuric acid attack, and increasing MK content can improve the permeability resistance, surface abrasion resistance, and compressive strength of concrete.(2) The increase of SH molar concentration reduces the slump. It is proven that the abrasion resistance and mechanical properties are better when the concentration of SH is 12M. Furthermore, increasing the molar concentration of SH causes an increase in the resistance to chloride ion penetration and a decrease in porosity, but has no significant effect on density.(3) The porosity and water absorption of GPRAC decreased after adding NS and RHA. However, the effect of NS on reducing porosity is not as good as RHA. Moreover, the porosity increases with the increase in NS content. The studies show that the addition of 2% NS has a greater impact on improving the mechanical properties and durability.(4) The microstructural analysis revealed that the porosity at the ITZ of GPC containing RA was higher compared to that of NA. Macroscopic properties showed a decrease in strength and an increase in permeability of GPRAC. However, by using the modified RA, the density, compressive, the flexural strength of GPRAC increased, while the porosity and water absorption decreased.Based on the existing research results, a brief systematic summary of the basic mechanical properties and durability of GPRAC is presented, as well as a possible outlook for future efforts.There is less research on modified RA, and more research can be done in the future on the treatment of modified RA to better reinforce the old mortar of RA or to directly remove the mortar from the surface of RA. In addition, there is no clear regulation on the quality of the classified RAs. Therefore, a set of criteria can be developed for the quality of RA so that the RAs can be better used in GPC. GPRAC is not widely used in practical projects, and there is still a need to improve the mechanical properties and durability of concrete by optimizing the mix ratio. Existing studies have shown that GPRAC using a single precursor material does not perform as well as using a synergistic precursor material. Moreover, several studies have shown better performance of GPRAC with MK as a precursor material. Hence, MK can be used synergistically with HCF or with precursor materials such as GGBFS, and the ratio of multiple precursor materials can be continuously optimized in order to produce GPRAC with better performance. There are more studies on the synergistic effect of two precursor materials, but there are few studies on the simultaneous use of three precursor materials, and it is possible to investigate the mechanical properties and durability of GPRAC with the synergistic effect of three precursor materials at the same time. The mechanical properties and durability of concrete with the synergistic effect of three precursor materials can be investigated.


Carbon fiber (CF) is widely used in the preparation of carbon-fiber-reinforced polymer composites (CFRP) in which it is combined with epoxy resin due to its good mechanical properties. Thermosetting bisphenol A epoxy resin, as one of the most common polymer materials, is a non-renewable resource, leading to a heavy environmental burden and resource waste. To solve the above problems and achieve high mechanical and thermal properties comparable to those of bisphenol A, herein, a high-performance, degradable and recyclable bio-based epoxy resin was developed by reacting the lignin derivative vanillin with 4-amino cyclohexanol via Schiff base. This bio-based epoxy resin showed a Young’s modulus of 2.68 GPa and tensile strength of 44 MPa, 36.8% and 15.8% higher than those of bisphenol A epoxy, respectively. Based on the reversible exchange reaction of the imine bond, the resin exhibited good degradation in an acidic environment and was recoverable by heat treatment. Moreover, the prepared epoxy resin could be used to prepare carbon fiber (CF)-reinforced composites. By washing off the epoxy resin, the carbon fiber could be completely recycled. The recovered carbon fiber was well preserved and could be used again for the preparation of composite materials to realize the complete recovery and utilization of carbon fiber. This study opens a way for the preparation of high-performance epoxy resin and the effective recycling of carbon fiber. Carbon-fiber-reinforced polymer composites (CFRP) are widely used in aerospace, wind turbine blades, automobile parts and other fields due to their advantages of high modulus, high strength, low density and corrosion resistance ,2,3,4. TThe large number of three-dimensional networks in CFRP makes them composite materials with high stability, which is the fundamental factor hindering the recovery of CFRP composite materials. The key to solving this problem is to change the stable cross-linking structure in the material ,12. A coImproving the recovery efficiency of thermosetting resins and CFRP composites has become an urgent problem. In order to replace traditional thermosetting resins, in this paper, we aim to fabricate a bio-based epoxy resin with good mechanical properties comparable to those of DGEBA, as well as with good degradability and easy recoverability without any other catalysts. Vanillin is the only commercially available lignin aromatic derivative, and it is a renewable resource with high structural design ability, so it has attracted extensive attention in the polymer field. Herein, a novel bio-based monomer (VAN-AC) composed of vanillin (a lignin derivative) and 4-aminocyclohexanol was prepared via Schiff base reaction. After reacting the VAN-AC with epichlorohydrin (ECH), an epoxy resin (VAN-AC-EP) was obtained and further thermally cured with the commercial curing agent 4,4′-diaminodiphenylmethane (DDM). The curing kinetics, mechanical properties, thermodynamic properties, degradability and recoverability of VAN-AC-EP/DDM were systematically studied and compared with those of DGEBA/DDM. On this basis, VAN-AC-EP CFRP composites were further prepared by adding carbon fiber (CF) into the VAN-AC-EP, and the mechanical properties of the CFRP composites and the recovery of the CF were investigated.2) was purchased locally. All compounds were directly used without any treatments, unless otherwise stated.Vanillin (VAN), 4-amino-cyclohexanol (AC), 4,4-diamino-diphenylmethane (DDM), tetrabutylammonium bromide (TBAB) and potassium hydroxide (KOH) were purchased from Aladdin Corporation, China. Ethanol, epichlorohydrin (ECH), methylene chloride, hydrochloric acid (HCl) and ethylenediamine were purchased from Sinophosphoric Chemical Reagent Co, Ltd., Shanghai China. Diglycidyl ether of bisphenol A (DGEBA) epoxy resin was supplied by McLean, China. Carbon fiber  VAN-AC powder was dissolved in 92.5 g (1 mol) epichlorohydrin, and 1.6 g TBAB was added into the mixture. After stirring at 120 °C for 24 h, the mixture was rapidly cooled to 0 °C by placing the reaction flask in an ice water bath. Then, 60 g KOH aqueous solution (50 wt%) was added dropwise, and the reaction was carried out for another 2 h. At the end of the reaction, a stratified system was obtained. After separation, the underlying oil was diluted by dichloromethane, washed with deionized water three times, and rotary evaporated to obtain a yellow liquid (VAN-AC-EP). The yield was 81.4%.Quantities of 10.8 g VAN-AC-EP and 3 g DDM (1:1 molar ratio of epoxy groups to N-H groups) were heated to melting and stirred well in a beaker. After cooling at room temperature, the mixture was debubbled in a vacuum oven for 10 min and then poured into a mold. Then, it was heated at 100 °C for 3 h and subsequently cured at 110 °C, 130 °C and 150 °C for 2 h respectively. After cooling at room temperature, the thermosetting resin VAN-AC-EP/DDM was demolded. As comparison samples, DGEBA and DDM were also cured in accordance with the above ratio.VAN-AC-EP was ground into a powder, evenly spread in a steel groove 70 mm (L) × 5 mm (W) × 0.5 mm (T) with a polytetrafluoroethylene plate above and below, and placed in a plate vulcanizing machine for hot pressing at 180 °C for 0.5 h. Recycled film was obtained by demolding after cooling at room temperature.Firstly, VAN-AC-EP and DDM were fully melted and mixed at 90 °C, and 50 wt% ethanol was added to make a mixed solution. The mixture was evenly brushed onto carbon fiber (100 mm × 100 mm). Then, carbon fiber prepreg was obtained by removing the ethanol in a vacuum oven at 60 °C for 10 h. The carbon fiber composites were prepared by hot pressing at 110 °C, 130 °C and 150 °C for 2 h respectively Broken parts of CFRP were overlapped and sandwiched between two polytetrafluoroethyene plates. They were then hot pressed at 180 °C for 0.5 h. After cooling, recycled CFRP was obtained.0 was immersed in several common solvents and placed at 50 °C for 24 h. It was then removed from the solvent, and the mass Ms after the removal of excess liquid on the surface was recorded. Then, the sample was dried in a drying oven under vacuum. After the mass of the sample reached a constant, the mass was recorded as Md, and the swelling rate and gel content were calculated as follows (1)–(2) [The gel fraction of VAN-AC-EP/DDM was determined by the impregnation method. The sample with original mass M (1)–(2) :(1)Swell1H NMR) were recorded on an AVANCE III Bruker NMR spectrometer  using DMSO-d6 as a solvent. Fourier transform infrared spectra (FT-IR) were recorded using a SPECTRUM 100 spectrophotometer  from 4000 to 600 cm−1 with a resolution of 4 cm−1 and a scanning number of 32 times. Differential scanning calorimetry (DSC) curves were recorded using a NETZSCH DSC-214 . Measurements were carried out at a rate of 10 °C/min at 50–250 °C under N2 atmosphere. The tensile properties of VAN-AC-EP-DDM and CFRP at room temperature were tested on a 5967X universal testing machine. The size of the resin samples for tensile testing was 30 mm (L) × 5 mm (W) × 2 mm (T), and the stretching rate was 10 mm/min. The distance between the two clamps was 10 mm. Each tensile value was obtained from an average of 5 samples. Dynamic Mechanical Analysis (DMA) curves were recorded using a DMA Q800 under tensile mode . Test samples of size 30 mm (L) × 5 mm (W) × 2 mm (T) were prepared, and the measurement was carried out between 30 and 250 °C. The heating rate was 3 °C/min, and the oscillation frequency was 1 Hz. The stress relaxation property was determined as follows: samples were equilibrated between machine clamps for 5 min at a pre-set temperature, and then 1% strain was applied to the sample. Changes in the storage modulus over time were recorded for analysis. Thermogravimetric analysis (TGA) was performed on a TGA/1100SF device at temperatures ranging from 50 to 800 °C and at a heating rate of 10 °C/min in a nitrogen atmosphere. The morphologies of the carbon residue after TGA measurements and of the combination of carbon fiber and resin were investigated by scanning electron microscopy  at 2.0 kV. Raman spectra were measured using an inVia Reflex laser with a laser wavelength of 532 nm, an exposure time of 60 s and a laser energy of 12 mW. Proton nuclear magnetic resonance spectra (1H NMR and FT-IR spectra. In 3), 3.45 ppm , 3.10 ppm , 1.87–1.56 ppm , 1.57–1.27 ppm  and 3.39–3.33 ppm  were assigned to the protons of VAN-AC. 1H NMR spectrum of VAN-AC-EP. The characteristic peaks belonging to the hydroxyl protons at δ = 8.20 and 4.55 disappeared, and new characteristic peaks appeared at 4.44, 3.94, 1.79, 1.61, 1.23 and 1.09 ppm, which were attributed to the proton peak of the glycidyl ether. The FT-IR spectra of VAN-AC and VAN-AC-EP are shown in −1 and the appearance of the epoxy characteristic peak at 910 cm−1 also proved the successful synthesis of the VAN-AC-EP epoxy resin. The molecular structures of VAN-AC and VAN-AC-EP were determined from their b), peak curing temperature (Tp) and end curing temperature (Te) could be obtained. As a comparison, the same conditions were used to test DGEBA/DDM. For both epoxy resins, the faster the heating rate was, the higher the curing temperature was. The solidification activation energy (Ea) can be calculated according to Kissinger formula (3) [p2) plotted against 1/Tp was obtained (b), peak curing temperature (Tp) and end curing temperature (Te) of the VAN-AC-EP/DDM system were lower than those of the DGEBA/DDM system. The enthalpy of release (ΔH) of the VAN-AC-EP/DDM system was much lower than that of the DGEBA/DDM system. The curing process of VAN-AC-EP/DDM was faster and offers greater environmental protection in regard to energy savings. However, the curing activation energy was higher than that of DGEBA/DDM, possibly due to the high content of C=N double bonds in the main chain of the VAN-AC-EP/DDM system inducing an increase in steric hindrance [The curing kinetics of the VAN-AC-EP/DDM system were studied by differential scanning calorimetry (DSC) at four heating rates of 5, 10, 15 and 20 °C/min. mula (3) :(3)ln, which can be calculated via Equation (4) [d5% is the temperature at which the mass is reduced by 5% and Td30% is the temperature at which the mass is reduced by 30%. The thermal performance is shown in The thermal properties of the VAN-AC-EP/DDM and DGEBA/DDM systems were characterized by TGA under Ntion (4) :(4)Ts=0.As shown in The stress–strain curves showed that the tensile strength of VAN-AC-EP/DDM reached 44 MPa, higher than that of DGEBA/DDM (38 MPa), while the elongation at break was 2.4%, slightly lower than that of the DGEBA/DDM system, and the Young’s modulus of VAN-AC-EP/DDM was 2685 MPa, much higher than that of DGEBA/DDM (2320 MPa). The higher mechanical strength of VAN-AC-EP/DDM is provided by the large number of C=N double bonds in the molecular backbone of the VAN-AC-EP/DDM system after curing and the π–π conjugation present between the benzene ring and the imine bond. The higher molecular rigidity limited the rotation of the molecular chains, which induced the decrement in the flexibility.g) of VAN-AC-EP/DDM (146 °C) was lower than that of the DGEBA/DDM system (201 °C), according to the Tan Delta curve in The thermodynamic properties of VAN-AC-EP/DDM and DGEBA/DDM were characterized by DMA. As an important parameter of the upper limit temperature of thermosetting resin, the glass transition temperature . The data are shown in 3, lower than that of DGEBA/DDM. Generally, a system with higher cross-linking density leads to higher energy storage modulus and Tg. Tg conforms to this rule, but the energy storage modulus goes against it. This is because a large number of imine bonds exist in the molecular backbone; thus, the network structure of VAN-AC-EP/DDM is relatively harder, and the stiffness of VAN-AC-EP/DDM is nearly twice that of DGEBA/DDM. The cross-linking densities of VAN-AC-EP/DDM and DGEBA/DDM can be calculated as their rubber elasticity via Equation (5) :(5)Er=3Rg, the relaxation time τ followed Arrhenius’ law [0 is the characteristic relaxation time at infinite temperature, Ea is the activation energy of bond exchange, R is the universal gas constant (8.314 jmol−1k−1) and T is the temperature in units of K. Linear fitting was performed by the curve of ln(τ*) plotted against 1000/T (a (82.3 KJ/mol) was calculated from the slope. Apparent relaxation of the resin occurred due to the rearrangement of imine bonds. The dynamic exchange of amine bonds provided the reprocessing ability of the thermosetting resin. It only took 2 min for the stress of the material to drop to 1/e of the initial value at 190 °C. The value of Ea is noteworthy, as it is much lower than those of some other thermosetting epoxy resins without the addition of catalysts. This makes the resin more malleable at high temperature.The ductility of VAN-AC-EP/DDM was tested by stress relaxation experiments. In ius’ law :(6)τ*(T)t 1000/T b, and Ea−1) belonging to C=N was also retained. From the tensile curves in Since VAN-AC-EP/DDM had good ductility, its reprocessed performance could be explored. The cured VAN-AC-EP/DDM was ground into a powder, and resin film was obtained by hot pressing. VAN-AC-EP/DDM was expected to have hydrolyzed degradation ability in an acidic environment due to the imine bonds. The process of degradation was divided into two parts. Firstly, the thermosetting resin expanded in the degradation solution, and then the polymer chains dissociated. Therefore, the degradation rate of the thermosetting resin was mainly affected by the infiltration and hydrolysis rate. Generally speaking, the degradation solution should be in full contact with the thermosetting resin and spread into its interior. The contact angle (θ) is an important parameter for the infiltration of liquid into a solid . The smaThe degradation process is shown in VAN-AC-EP/DDM was immersed in ethylenediamine, and the degradation process is shown in 1H NMR and FT-IR spectra. In −1) belonging to C=N was also retained in 1H NMR spectrum, and a stretching vibration peak belonging to C=O (1660 cm−1) appeared in FT-IR .VAN-AC-EP/DDM was immersed in several common polar solvents at 50 °C for 12 h to characterize the chemical stability of the thermosetting resin. The specific data are shown in The carbon-fiber-reinforced composites were prepared according to the procedures shown in Bio-based epoxy resin has the characteristics of rapid curing, being already hardened when melted and mixed with a curing agent. It is thus difficult to produce finished products by pouring at room temperature. Most of the bio-based resins are prepared by pressing sheets, which greatly limits their application. SEM showed that the carbon fiber was completely encapsulated by VAN-AC-EP/DDM, rather than forming a thermosetting resin film on the surface e, which g value was 146 °C; in addition, the tensile strength was 44 MPa, and the Young’s modulus was 2.68 GPa, which were 15.8% and 36.8% higher than those of bisphenol A epoxy, respectively. In addition, the dynamic imine bond introduced by the Schiff base reaction gave the resin degradation and recycling ability. It could release deformation stress quickly at 170 °C under high temperature, and it had good reprocessing ability. Using the epoxy resin as the matrix, the resulting carbon-fiber-reinforced composite had the same excellent mechanical properties, and the tensile strength was 122 MPa. After removing the epoxy matrix efficiently, the carbon fiber could be fully recovered, and the carbon fiber could still be used in composite materials. Due to the low cost of recycling resin and carbon fiber, there is hope that this bio-based epoxy resin (VAN-AC-EP) and its CFRP composite could have considerable application prospects in wind power generation and aerospace fields.In summary, a novel epoxy resin, VAN-AC-EP, with recyclable and recoverable properties was synthesized using a bio-based vanillin monomer. This bio-based resin had good thermodynamic properties after thermal curing. The T


Background: Antimicrobial stewardship initiatives usually occur in the inpatient setting, and they are often lacking at transitions of care (TOC), including hospital discharge. We assessed the appropriateness of antibiotic treatment duration at the time of discharge from our institution. Methods: This retrospective chart review included 300 adult patients discharged on oral antibiotics for acute infections during a 3-month period in 2019. The primary outcome was the duration of antibiotic therapy (DOT). To assess appropriateness, we compared the prescribed DOT (1) to that recommended by clinical guidelines, (2) to the minimum supported by clinical trials, and (3) to the period beyond the point of clinical stability, defined as normal vital signs with improvement in symptoms present from diagnosis. Each indication and antibiotic was assessed using standards appropriate for the combination. Results: Results are shown in Tables Conclusions: Antibiotics were often given longer than necessary on hospital discharge. In this study, patients received a median 2 days of excess antibiotics compared to recommended guidelines and 6 days after reaching clinical stability. A pilot TOC stewardship program was initiated to address this problem.Funding: NoDisclosures: None


The purpose of the study was to develop a blueprint using financial documentation to describe and quantify vaccine and antibiotic usage (ABU). This method was piloted in a commercial pig farm in South Africa, with the ultimate hope to serve as a tool in a future species-specific vaccine and ABU surveillance system. Data collection was based on templates from the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) network and the World Organisation for Animal Health (WOAH). Invoices from 2016 to 2018 were used as the main data source. In addition, monthly statement of accounts were used to check for missing invoices. An inventory check was done to ensure that the correct antibiotic concentrations were used in subsequent calculations. Livestock counts and slaughter statistics were also collected to be used as denominator data. Cost calculations for the procurement of antibiotics and vaccines were also done. The study showed that veterinary medicinal products were purchased only from a single veterinary practice. A total of 291 invoices were issued over 3 years, of which 2.75% (8/291) were missing and could therefore not be used in quantification. Tetracyclines (453.65 ± 25.49 kg and 135.16 ± 3.31 mg/kg), followed by quinoxalines (258.33 ± 8.04 kg and 77.07 ± 3.93 mg/kg) were used in the highest amounts, both in terms of weight (kg) and adjusted for animal biomass (mg/kg). Vaccines used on the farm targeted seven different diseases, namely enzootic pneumonia, erysipelas, ileitis, infectious infertility, leptospirosis, neonatal pig diarrhea and porcine circovirus disease. An average of 103 546 vaccine dosages was purchased for ZAR1 302,727 ($ 84,620 Antibiotic use (ABU) is associated with antibiotic resistance (ABR) –3. It isVeterinary antibiotics are governed by two acts in South Africa, namely: (i) the Fertilizers, Farm Feeds, Agricultural and Stock Remedies Act No. 36 of 1947 regulated by the Department of Agriculture, Land Reform and Rural Development (DALRRD) and (ii) the Medicines and Related Substances Control Act No. 101 of 1965 regulated by the Department of Health (DoH) . HoweverA study by Van Boeckel and colleagues 2015) predicted that an average of 63 151 tons of antibiotics, measured in weight of active ingredient, were used in animals among 228 countries in 2010 . The aut predicteSome studies on ABU have been conducted in South Africa. Chipangura and colleagues 2017) investigated how antibiotics were used by veterinarians for small companion animals, specifically focusing on dogs through an online questionnaire, but the study did not quantify usage in terms of antibiotic active ingredients . A surve investigThe South African agriculture sector is divided into backyard subsistence and commercial farming. On-farm record keeping is generally poor in subsistence farming. However, the purpose of a commercial farm is to be profitable and detailed financial records will easily be available. Financial data may therefore be used to quantify antibiotic purchases at farm-level. This will serve as a proxy for ABU, as medicinal products will not be purchased unnecessarily. Additional information on other VMPs, such as vaccines, would also be available as the use of vaccines is an effective intervention to decrease ABU through disease control .The pork industry was chosen as a pilot of the livestock sector, as the industry is highly organized in South Africa, even though it is small . Furthermore, ABU is the highest (172 mg/kg in 2010 and 193 mg/kg in 2017) in pigs and the greatest increase in ABU is expected in pork production over the next decade , 13. TheThe study received approval from multiple research ethics committees. The study was approved by the Research and Animal Ethics Committee of the Faculty of Veterinary Science (REC0055-20) and the Research Ethics Committee of the Faculty of Humanities, University of Pretoria, Pretoria (HUM027/0620). In addition, the Animal Research Ethics Committee of the National Institute for Communicable Diseases (NICD), Johannesburg (AEC003-19) approved the study. A section 20 clearance certificate (12/11/1/1/13) was obtained from DALRRD, South Africa. The study was also approved by the Human Research Ethics Committee , University of the Witwatersrand, Johannesburg (M190244) and the Faculty of Health Sciences Research Ethics Committee, University of Pretoria, Pretoria (406/2020).The study protocol was presented to the Pig Veterinary Society (PVS), a special interest group of the South African Veterinary Association (SAVA), in May 2019. Veterinarians were requested to provide more information to their clients (i.e. farmers) and to invite them to participate by completing an online form. Three commercial farms expressed interest in the study. The owners were contacted and provided with the complete study protocol. However, only one farm was successfully enrolled into the pilot study after the completion of informed consent.The farm is located in North-West province. The farm uses an all-in, all-out, farrow-to-finish, closed production system, with a one-week continuous batch cycle and has more than 1 000 sows. Sows are impregnated through artificial insemination and no new breeding pigs have been purchased since 2011. Two pig breeds, namely the Large White and the South African Landrace, are used on the farm. The production houses are separated into four operational stages: (i) breeding, (ii) farrowing, (iii) weaning, and (iv) growing to finishing. Strict biosecurity measures are maintained at all times.Data collection was based on European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) from the European Medicines Agency (EMA) and the World Organization for Animal Health (WOAH)'s data collection templates , 25. InvAfter the site visit, every purchase of a VMP, containing an antibiotic or a vaccine, was recorded as an observation in an electronic database from the scanned invoices. The following information was captured from the invoices: (i) product name, (ii) purchasing date, (iii) quantity purchased, (iv) product packaging size , (v) purchasing price in South African Rand (ZAR) excluding value added tax (VAT) and (vi) the invoice number. A SPC sheet was compiled for every antibiotic or vaccine identified as mentioned above , 3. If tAntibiotic active ingredients were further categorized according to the World Health Organization (WHO)'s Critically Important Antibiotics (CIA) for human medicine list, the WOAHIE's list of antibiotic agents of veterinary importance, the EMA's list of antibiotics in the European Union and the PVS of SAVA's guidelines –30. The Antibiotic strengths are declared in different units of measurements on product information sheets and were therefore standardized to grams of active ingredient for each packaging size and recorded on the SPC as guided by the WOAH prior to calculations . The conAnimal biomass as denominator was calculated according to WOAH methodology with some modifications , 31. ModThe total live weight of all pigs slaughtered per month was recorded by the farmer. These monthly values were summed to obtain the total live weight of all pigs slaughtered (kg) per year . The monAntibiotic use per year was calculated as indicated in the equation below , 31:Antibiotic use was reported in mg/kg  and summed per antibiotic class, route of administration, production stage and per month to investigate seasonality.The total number of vaccine dosages was calculated by multiplying the total dosages per vial as stated on the SPC with the total number of vials purchased and summed per vaccine according to disease targeted, per year, as shown in the equation below.The ratio of vaccine dosages purchased over the pig population eligible for vaccination  was calculated to serve as a proxy for vaccine administration. One would expect the ratio to be as close as possible to one, as a single animal will receive a single dose. If a primary and a booster shot were required by the vaccination schedule, the yearly average livestock count was multiplied by two. The vaccine administration ratio was adjusted according to the pig population eligible for vaccination by dividing the vaccine purchases per year by the yearly average physical livestock count as shown in the equation below.The actual livestock counts were available for every month for the following pig populations: i) the number of sows disaggregated by the total number of dry sows, lactating sows and pregnant sows, ii) boars, iii) piglets, and iv) weaners disaggregated by replacement weaner gilts and weaners destined for slaughter . The yeaThe total cost of antibiotics and vaccines purchased was summed per year and reported in ZAR. Value added tax (14% in 2016–2017 and 15% from April 2018 onwards) were excluded, as farming inputs are zero-rated. The average exchange rate for 2016 , 2017  and 2018 (11.5445) were used to convert the cost of antibiotics and vaccines in ZAR to United States dollar ($), rounded to the closest unit . A singlData capturing, data cleaning and summary calculations were done in Excel . Continuous variables were reported as means and standard deviations. Data visualization was done in R software using the dplyr, ggplot2, ggpubr and scales packages –37.A total of 291 invoices  were issued. It is unknown if all invoices for January 2016 were available for capturing, as the monthly statement of account were missing, but seven invoices were captured for January 2016. However, all other monthly statement of accounts from 2016 to 2018 were available to check for missing invoices. Overall, 2.75% (8/291)  of invoices were missing and could therefore not be used to quantify vaccine and ABU.The farmer only purchased antibiotics from a single veterinary practice and not from cooperatives or feeding mills. The compiled SPC for each antibiotic is listed in A total of 19 different VMPs containing antibiotics were identified from the invoices, of which 63.16% (12/19) were verified through the stock take. The composition of the remaining VMPs  were retrieved from MIMS IVS. Among the 19 products, five products contained two active ingredients, whereas each of the remaining products contained a single active ingredient. The statute of registration was unknown for a single product, but 72.22% (13/18) of the remaining antibiotics were registered under Medicines Act. Injectable tetracyclines and antibiotic growth promoters  were registered under Stock Remedies Act, except for pleuromutilin , which were registered under the Medicines Act. A single product was associated with off-label use . However, this was an isolated occurrence, where the VMP was used either for a specific infectious event or as an alternative product due to a supply chain problem. The same antibiotic active ingredients  were listed in different products. Results are further reported per active ingredient to anonymise the distributing pharmaceutical company. A total of 19 different active ingredients were identified, which grouped into 11 different antibiotic classes. The antibiotic class distribution per active ingredient is shown in via three different routes, which included (i) injectable medication (predominantly for treatment), (ii) orally via feed and (iii) orally via drinking water. Two antibiotics (i.e. lincomycin and amoxicillin) were administered through two different administration routes . The most common route of administration was through injection , followed orally via feeding  and orally via drinking water . The classification of antibiotic active ingredients according to the WHO, EMA, WOAH and PVS are indicated in Antibiotics were administered The average ABU over 3 years (2016–2018) are reported in If ABU per year was adjusted according to animal biomass, on average 275.89 mg/kg (± 16.35 mg/kg) of antibiotics were used, of which tetracyclines (135.16 ± 3.31 mg/kg), quinoxalines (77.07 ± 3.93 mg/kg), β-lactams (34.36 ± 2.68 mg/kg) and streptogramins (14.87 ± 12.75 mg/kg), were the antibiotic classes used in the highest amounts  Supplem. In-feedSeasonal variation for antibiotics purchased per month according to volume (kg) and adjusted per animal biomass (mg/kg) in relation to the number of sows present (livestock count) and the live weight (kg) of the pigs slaughtered per month for 2016, 2017, and 2018 are shown in The average expenditure to procure antibiotics equated to ZAR 907 371.60  , of which antibiotic growth promoters made up 62%  of the total average cost over the three-year period .Escherichia coli , Erysipelothrix rhusiopathiae, Clostridium perfringes type C, Lawsonia intracellularis, Leptospira species, and Mycoplasma hyopneumoniae. Porcine circovirus (PCV) type 2 and porcine parvovirus (PPV) were the targeted viral pathogens.Characteristics of the farm's vaccination programme are summarized in The same five commercial vaccines were used throughout the study period. However, two competitor products were used in two instances when the preferred products were not available. Among the five commercial vaccines, two vaccines were multivalent, whereas the remaining three, each targeted a single pathogen. Pre-weaned piglets were the main population for vaccination either through direct administration  of the vaccine or through passive maternal immunization  obtained from the lactating sows that were vaccinated 2 weeks prior to farrowing. The remaining vaccine targeted breeding animals  .E. coli and C. perfringes), where the average administration ratio was 0.41 (± 0.16).The average total number of vaccine dosages, vaccine dosages adjusted per eligible pig population and vaccine procurement cost, are shown in Methodological variation to quantify ABU is high . There avs. actual) had a considerable impact on the quantification of ABU  of antibiotics sold are administered in-feed] , which means that not all breeding animals present on the farm received this vaccination based on procurement records. This could be due to cost containment strategies, due to the Listeriosis crisis in 2017/2018 that had a devastating impact on the profitability of pork production in South Africa . Furthervet) as the exact number of animals treated were unknown and the DDDvet is also not a suitable metric to quantify antibiotic growth promoters use.The study had several limitations and potential biases. Only a single farm was recruited and findings can therefore not be generalized to the rest of South Africa, as ABU is farm-specific and one can expect farm-to-farm variability , 55. FurDespite these limitations, this study had shown that invoices and monthly statement of accounts are a useful data sources to quantify vaccine and ABU at farm-level for a particular food-producing animal species. This study may in future serve as a blueprint to quantify usage in more commercial farms across different food-producing species in the absence of prescription records. This blueprint can serve as a template on how ABU can be reported, by showing which variables are required and how calculations can be performed in a future species-specific vaccine and ABU surveillance system in South Africa. A system, as such, would be important to guide risk assessments, residue monitoring and antibiotic resistance surveillance programmes, which in turn can be used the South African government in the development of evidence-based animal health policies. This system can also be used as a tool to measure the effectiveness of interventions, as antibiotic growth promoters are phased-out to ultimately improve animal health and welfare, without negatively impacting productivity and economic viability.The datasets presented in this study can be found in online repositories. The accession numbers to the repositories can be found in the The studies involving human participants were reviewed and approved by Human Research Ethics Committee , University of the Witwatersrand, Johannesburg (M190244) and the Faculty of Health Sciences Research Ethics Committee, University of Pretoria, Pretoria (406/2020). The patients/participants provided their written informed consent to participate in this study. The animal study was reviewed and approved by Research and Animal Ethics Committee of the Faculty of Veterinary Science (REC0055-20) and the Research Ethics Committee of the Faculty of Humanities, University of Pretoria, Pretoria (HUM027/0620). In addition, the Animal Research Ethics Committee of the National Institute for Communicable Diseases (NICD), Johannesburg (AEC003-19) approved the study. A section 20 clearance certificate (12/11/1/1/13) was obtained from Department of Agriculture, Land Reform and Rural Development, South Africa.WS conceptualized the idea, collected, entered, analyzed, and interpreted the data and wrote the manuscript. ML assisted in data collection and independently double-checked calculations used in the summary of product characteristics. EE provided support in statistical analysis. OP and EE provided commentary on the manuscript and interpretation of the results. All authors reviewed the manuscript.Research reported in this publication was supported by the South African Medical Research Council (SAMRC) as a sub-grant received from the Bill and Melinda Gates Foundation (Project code: 96086). The contents and findings reported/ illustrated are the sole deduction, view, and responsibility of the researcher and do not reflect the official position and sentiments of the SAMRC or the Bill and Melinda Gates Foundation. WS was also supported by a Fogarty International Center Global Infectious Disease research training grant, National Institutes of Health, to the University of Pittsburgh and the National Institute for Communicable Diseases (D43TW011255).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.