Mixed recycled aggregate (MRA) is a kind of recycled aggregate containing discarded bricks and other impurities that is inferior to ordinary recycled concrete aggregate. To study the effect of MRA in concrete, specimens with 100% MRA under different water–cement ratios (W/C) of 0.50, 0.42, 0.36 and 0.30 were prepared, and the mechanical properties and microstructure were tested. Results show that compared with ordinary concrete, the compressive strength of mixed recycled aggregate concrete (MRAC) with the same W/C was reduced by more than 50% at 28 days, but the axial compression ratio was relatively high, reaching over 0.87. Affected by the high water absorption of MRA, the hydration rate of cement slowed, which was beneficial to the long-term development of the properties of MRAC. An appropriate increase in cement content could strengthen MRA and densify the pore structure of MRAC. The research results of this article prove that MRA has high utilization value and could be used to prepare MRAC with application potential using optimal gradation, which is of positive significance for promoting the consumption of construction waste. As a widely used building material, concrete consumes many natural resources, which has a negative impact on the environment. At the same time, the acceleration of urbanization and the demolition of old buildings generates significant quantities of construction waste. According to incomplete statistics, China’s annual construction waste is approximately 1.5 billion tons, resulting in a large amount of solid waste, including broken bricks, gravel, scrap iron, and ceramics [Regarding the issues above, some scholars considered crushing the industrial by-products and construction solid waste from which impurities have been removed into recycled aggregate (RA), then replacing natural aggregate partially or completely to prepare recycled aggregate concrete (RAC), holding that this can relieve resource pressure and effectively eliminate construction waste ,3,4,5. IAt present, research on RAC has made much progress and could be applied to real project ,27. HoweDue to disadvantages such as complex composition, low density, high crushing index, and large water absorption, it is generally recommended that the content of recycled bricks in the aggregate should not exceed 20%, and the replacement ratio of mixed recycled aggregate (MRA) should not exceed 50% ,39,40. HThrough previous studies, it can be found that the main factor limiting the utilization of MRA is the unclear effect of MRA on the properties of concrete, especially the strength development of concrete under different W/C ratios. Based on this, this paper designed and prepared four mixed recycled aggregate concretes (MRACs) under different W/C ratios of 0.30, 0.36, 0.42, and 0.50. The effects of W/C and age on the strength of MRAC were studied through macroscopic mechanical property tests. Mercury intrusion porosimetry (MIP), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were also used to verify the general influence of different W/C ratios on the mechanical properties of MRAC.The MRA used in this study was provided by Zhoushan Jinke Resources Recycling Co., Ltd.  The aggregate is divided into three fractions. The first fraction is MRA-1 with a particle size of approximately 18–32 mm; the second fraction is MRA-2 with a particle size of 10–18 mm; the last fraction is MRA-3 with a particle size of 0–10 mm and a fineness modulus of 2.9. The basic compositions of the three MRAs are shown in Standard cement (P.I 42.5) was used as the cementing material. According to the Chinese standard of Standard Cement Technical Conditions for Properties Inspection of Concrete Admixtures (GB 8076-2008), the basic properties of standard cement are shown in There are three grades of MRAs used in this article. First, the mixing ratio of MRA-1 and MRA-2 was determined by the closest packing method. The results showed that the bulk density of MRA-1 and MRA-2 reached a maximum value when the mixing amount of MRA-2 was 15%. Then, MRA-3 was added in equal proportions to the mixed aggregate, and the bulk density curve is shown in The test samples were cured in a standard curing room with a temperature of 20 ± 2 °C and a relative humidity of more than 95% after forming. The compressive strength and splitting tensile strength of concrete samples with 100% MRA corresponding to ages of 3 d, 7 d and 28 d were tested according to the Standard for Test Methods of Concrete Physical and Mechanical Properties (GB/T 50081-2019). The axial compressive strength and elastic modulus were tested at the age of 28 days according to the same standard of GB/T 50081-2019.To compare with ordinary concrete, we calculated the compressive strength of ordinary concrete under the same W/C according to the Bolomy formula used in the Specification for Mix Proportion Design of Ordinary Concrete (JGJ 55-2011):The Mercury Intrusion Porosimetry (MIP) method was used to determine the porosity and pore size distribution of MRAC. The test instrument was the AutoPore IV 9500 Mercury Porosimeter  by the National Key Laboratory of Chemical Engineering, Zhejiang University. The samples near the center area of MRAC were broken into small fragments after the compressive strength test and dried before the MIP test.X-ray Diffraction (XRD) Analysis technology was used to determine the mineral composition of MRAC under different W/C ratios at 28 d. The test instrument was a Bruker D8 ADVACNCE X-ray diffractometer  by the Analysis Center of Zhejiang University. The MRAC samples were ground into powder that could pass through a 0.08 mm square hole sieve before XRD analysis.Scanning Electron Microscope (SEM) Test was used to analyze the influence of W/C on the pore structure and cement hydration products. The test instrument was a Gemini SEM300 thermal field emission scanning electron microscope  by the Analysis Center of Zhejiang University. The hydration of small fragment samples for SEM was stopped by absolute ethanol at a specific curing time. Then, those samples were sprayed with gold for 60 s to be conductive before SEM test.Combining As shown in The results in In summary, as age increased and cement hydration continued, the large pores in each group of MRAC were gradually filled with hydration products. The total porosity showed a trend of declining continuously. At the age of 28 days, the porosity of the four groups of specimens was between 21% and 26%, which was higher than that of ordinary concrete. The proportion of most harmful pores and harmful pores cannot be further reduced, which was mainly because discarded brick is a kind of porous material that contains many closed pores. For cementitious material, it was difficult to enter these closed pores. There are also many cracks and pores between the old mortar and the MRA. It is difficult for hydration products to reach this part of the area through the old mortar. Therefore, compared with ordinary concrete, there are still a certain proportion of most harmful pores and harmful pores inside the MRAC at the age of 28 d. Pores such as these would have a certain impact on the durability of concrete, which should be considered in actual engineering.2, Ca(OH)2, CaCO3, C2S, C3S, ettringite, and anorthite. Among these, the diffraction peak of SiO2 was the highest, indicating that as the main mineral component of sand, it was also the most abundant in MRAC. The diffraction peaks of anorthite were much higher in test groups MRAC-0.42 and MRAC-0.30, while it is average in groups MRAC-0.50 and MRAC-0.36, indicating that anorthite may be an impurity component contained in MRA. C2S and C3S are unhydrated cement clinkers, and their peak intensity gradually decreases from top to bottom in the four spectral lines. In the group MRAC-0.50, the diffraction intensity of C2S and C3S was 292, while in the group MRAC-0.30 the diffraction intensity was 384, indicating that C2S and C3S still had a certain amount of residual after 28 days. The lower the W/C, the more C2S and C3S were residual. It also indicates that the hydration reaction of the cement would continue after the standard curing age, and the properties of MRAC could be improved to a certain extent.2 and ettringite were the products of cement hydration. The crystal state and growth direction of these hydrated products would have a significant impact on the macroscopic properties of concrete. In 2, except for the lower peak value in the group MRAC-0.50, there was no obvious pattern in the groups MRAC-0.42, MRAC-0.36, and MRAC-0.30. This may be because there were still some C2S and C3S inside MRAC that did not convert into Ca(OH)2 and CSH gel. 3 of the four groups were different. The peak value of group MRAC-0.42 was the highest, while that of the group MRAC-0.50 was the lowest. The peak values of the two groups MRAC-0.36 and MRAC-0.30 were similar. Considering that the samples were tested immediately after curing, the impact of carbonization was negligible. Therefore, it is believed that calcium carbonate, like anorthite, may be an impurity component in MRA.Ca(OH)2 was formed. 2 crystals were formed, and the hydration products at both ends of the cracks began to be close to each other. Generally, in the early stage of age, due to the small amount of hydration products, it was not enough to effectively fill the pores and wrap the aggregate. Therefore, the strength of MRAC was low, and the pore size of the internal pore structure was also larger. At the age of 7 d, a certain amount of CSH gel and a small amount of Ca(OH)2 crystals began to appear in group MRAC-0.50, while in group MRAC-0.30, a large piece of gel had formed, which completely wrapped the aggregate. The hydration rate of the low W/C group was faster than that of the high W/C group. At 28 d age, the degree of cement hydration increases. The aggregates of the groups MRAC-0.50 and MRAC-0.30 were surrounded by CSH gel and in close contact with each other without gaps. As a typical weak aggregate, the discarded brick shown in 2, needle-like ettringite, and flocculent CSH gel with a disordered distribution. There were still some microholes and microcracks in the interface transition zone. As the age changed, we found that the property improvement in the interface transition zone of MRAC was mainly related to the hydration process of the cement slurry. Through the growth and filling of hydration products, the original cracks and pores continuously decreased, and the density of the interface transition zone increased. The bonding strength of the gel between the old mortar and the MRA and the old mortar and new mortar was improved. Thus, the properties of MRAC were improved as well.The interface transition zone has always been regarded as the weakest zone in concrete due to its loose structure and easy cracking. It is an important factor that could affect the mechanics and durability of concrete. Therefore, it is necessary to study the properties of the interface transition zone inside MRAC. Using MRA to prepare MRAC, the maximum 28 d compressive strength can reach 37.9 MPa, which can meet the requirements of general engineering.Compared with ordinary concrete, the compressive strength of MRAC with the same W/C is greatly reduced, and the drop is over 50% at 28 d. In contrast, the axial compression ratio of MRAC is above 0.87, which means that the safety is better. Therefore, special attention should be paid to the influence of MRA when designing the mix ratio.The compressive strength of MRAC linearly decreases with increasing W/C when the W/C is higher than 0.30. When the W/C is lower than 0.30, the compressive strength of MRAC at the early stage is lower than the predicted value but is higher at the later stage. The reason is that the weakness of MRA affects the early strength of MRAC. The properties of MRA could be strengthened by cement slurry over time.The XRD results showed that the hydration rate of cement in MRAC is slow. However, the additional water absorbed by the MRA can act on the unhydrated cement clinker to form an internal curing mechanism, which is beneficial to the long-term development of the properties of the MRA.The increase in cement content can improve the mechanical properties of MRA. The main reasons are as follows: (i) Filling harmful pores effectively and then reducing the pore size of the pore structure; (ii) The wrapping of the formed hydration products strengthens the MRA more effectively.In this paper, using MRA as the raw material, four groups of MRAC under different W/C ratios were designed and prepared to study the mechanical properties and microstructure. The experimental results and discussion lead to the following conclusions:


The risk of relapse for stage III melanoma remains high. Subsequently, there has been a surge of interest in the role of contemporary therapies in the neoadjuvant setting. Results of 8 phase II trials show safety, remarkable pathologic response and relapse-free survival.Despite advances in adjuvant immuno- and targeted therapies, the risk of relapse for stage III melanoma remains high. With 43 active entries on clinicaltrials.gov (8 July 2020), there is a surge of interest in the role of contemporary therapies in the neoadjuvant setting. We conducted a systematic review of trials performed in the last decade evaluating neoadjuvant targeted, immuno- or intralesional therapy for resectable stage III or IV melanoma. Database searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception to 13 February 2020. Two reviewers assessed titles, abstracts, and full texts. Trials investigating contemporary neoadjuvant therapies in high-risk melanoma were included. Eight phase II trials (4 randomized and 4 single-arm) involving 450 patients reported on neoadjuvant anti-BRAF/MEK targeted therapy (3), anti-PD-1/CTLA-4 immunotherapy (3), and intralesional therapy (2). The safest and most efficacious regimens were dabrafenib/trametinib and combination ipilimumab (1 mg/kg) + nivolumab (3 mg/kg). Pathologic complete response (pCR) and adverse events were comparable. Ipilimumab + nivolumab exhibited longer RFS. Contemporary neoadjuvant therapies are not only safe, but also demonstrate remarkable pCR and RFS—outcomes which are regarded as meaningful surrogates for long-term survival. Studies defining predictors of pCR, its correlation with oncologic outcomes, and phase III trials comparing neoadjuvant therapy to standard of care will be crucial. With 96,480 new cases per year, melanoma is the 5th leading cause of cancer in the Unites States. Worldwide, its incidence has increased over the past 50 years ,2. AlthoIn the last decade, randomized controlled trials using anti-BRAF/MEK targeted therapies such as dabrafenib/trametinib (DAB + TRAM) or vemurafenib/cometinib, and anti-PD-1/CLTA-4 checkpoint inhibitor immunotherapy such as ipilimumab (IPI) or nivolumab (NIVO) have demonstrated dramatic improvements in progression-free survival (PFS) and OS for unresectable melanoma ,6. TradiV600E/K mutation, combination DAB + TRAM showed improved relapse-free survival (RFS) and OS when compared to placebo  ) ,13. Immu, 0.58]) ,15. Simi, 0.58]) , while N, 0.58]) . As a reAlthough advances in adjuvant therapy for stage III melanoma are remarkable, the risk of relapse remains high, especially for palpable or radiographically detected nodal disease. Furthermore, neoadjuvant therapy has become standard of care in locally advanced breast, rectal, and esophagogastric cancers ,19. The Contemporary neoadjuvant therapies are poised to change the standard of care for resectable high-risk palpable Stage III melanoma. To characterize progress in the neoadjuvant approach, we conducted a systematic review of phase II and III trials performed in the last decade evaluating neoadjuvant immuno-, targeted-, and intralesional therapy for palpable stage III or oligometastatic stage IV melanoma.Cochrane Handbook for Systematic Reviews of Interventions . Fo. Fo25]. We collected descriptive statistics for each included study. Due to the variability of the treatment arms, of the reported outcomes, and the paucity of homogeneous randomized data, a meta-analysis was not possible.A total of 971 records were identified. Six duplicates were removed. Title and abstract screening was performed on 965 records, 889 of which were deemed irrelevant by the two reviewers. Full-text screening was performed on 76 studies, and a total of 11 references were included for review ,34,35,36Four full-text publications and seven conference abstracts were included, comprising a total of 450 patients across eight trials. Two trials contained data from more than one reference. All studies were phase II trials, four of which were randomized and four of which were single-arm. Trials evaluated neoadjuvant anti-BRAF/MEK targeted therapy (3), anti-PD-1/CTLA-4 checkpoint inhibitor immunotherapy (3), and intralesional therapy (2). Results of these trials are summarized in V600E/K mutant melanoma . Seven of the 12 patients (58%) who underwent surgery in the treatment group had a pathological complete response (pCR), with a longer DMFS than those without pCR. Neoadjuvant plus adjuvant DAB + TRAM was well tolerated, with only 7% grade 3 adverse events (AEs), no grade 4 AEs, and no treatment-related deaths. Finally, the molecular and immune profiling performed in the treatment group showed tumors achieving pCR had lower baseline pERK positivity, less expression of TIM-3 and LAG-3 on CD8+ PD1 T cells, little to no remodelling of the T-cell repertoire between baseline and surgery, and strong upregulation of cytotoxic CD8 + T-cell genes between baseline and samples taken early-on treatment. Of note, this trial was stopped early following an interim analysis which demonstrated more relapse events in the standard of care group. Further predictive probability modelling showed neoadjuvant plus adjuvant DAB + TRAM would be superior to standard of care, leading to closure of the standard of care group.Neoadjuvant combination targeted therapy with DAB + TRAM was evaluated in 3 studies. Amaria et al. were the first to compare neoadjuvant plus adjuvant DAB + TRAM plus surgery  versus upfront surgery plus consideration of standard of care adjuvant therapy  . NeoadjuV600 mutant melanoma [Long et al. reported the single-arm phase II ‘NeoCombi’ trial which evaluated pathological response after neoadjuvant DAB + TRAM for resectable stage III BRAFmelanoma . Thirty-V600E/K mutation [In the ‘REDUCTOR’ trial, Blankenstein et al. evaluated the effect of short-term DAB + TRAM on the rate of conversion from unresectable to resectable disease for patients with locally advanced stage III or oligometastatic stage IV melanoma with BRAFmutation . The triNeoadjuvant checkpoint inhibitor immunotherapy has been studied in 3 phase II trials. Amaria et al. reported a randomized phase II trial with two arms: single-agent NIVO  and combination IPI plus NIVO  . NotablyIn the ‘OpACIN-neo’ trial, Rozeman et al. randomized patients with resectable stage III melanoma with nodal metastases only to three regimens of combination IPI and NIVO. The primary outcomes were pCR and grade 3–4 AEs ,31. A toThe OpACIN-neo trial provided justification for an extension cohort to tailor both the surgical approach and systemic therapy approach based on personalized tumor response after neoadjuvant IPI and NIVO in resectable stage III melanoma  . The pri©, toll-like receptor 9 agonist (CMP-001). Andtbacka et al. reported results of a randomized controlled trial evaluating the effect of neoadjuvant intralesional T-VEC on pathologic response and survival outcomes in patients with resectable stage IIIB/C/IVA melanoma and at least 1 injectable cutaneous, subcutaneous or nodal lesion [p < 0.07). Additional sensitivity analysis excluding non-R0 events showed statistically significant improvement in 2-year RFS in the neoadjuvant T-VEC arm . 2-year OS rates were 88.9% in arm 1 compared to 77.4% in arm 2  [Neoadjuvant intralesional therapy for melanoma has been studied in 2 phase II trials using talimogene laherparepvec (T-VEC) and ‘CheckMate Pharmaceuticals’l lesion . 150 patl lesion . Survival lesion . 2-year  < 0.05) . This hiDavar et al. undertook a single-arm phase II trial to evaluate neoadjuvant NIVO and intralesional CMP-001 in patients with high-risk resectable stage IIIB/C/D melanoma . 20 patiQuality assessments are summarized in The multimodal management of stage III melanoma and oligometastatic stage IV melanoma is rapidly evolving. Due to the high-risk of recurrence and death despite aggressive surgical intervention, this population is an attractive target for novel treatment paradigms. While the effectiveness of neoadjuvant treatments has been well established in many solid organ malignancies , this review highlights noteworthy preliminary evidence of the exciting potential of contemporary neoadjuvant therapies in palpable/locally advanced Stage III and resectable stage IV melanoma. Based on the established rationale for neoadjuvant therapies in other cancers, the studies reviewed suggest that: (1) neoadjuvant therapy induces frequent and substantial pathologic response; (2) pCR may be a valuable prognostic indicator for RFS, or even OS after neoadjuvant therapy; (3) neoadjuvant therapy is safe, with reasonable treatment toxicities; (4) neoadjuvant therapy may convert well-selected unresectable melanoma to resectable disease; (5) overall oncologic outcomes  may be improved with a neoadjuvant approach.International Neoadjuvant Melanoma Consortium trial design guidelines) future results from these preliminary studies should be quantitatively comparable, with similar populations and endpoints [Eight phase II trials were included in this review with a total of 450 patients. Three studies used neoadjuvant anti-BRAF/MEK targeted therapy, three used anti-PD-1/CTLA-4 immune checkpoint inhibition and two used intralesional therapy. While formal quantitative analysis was not feasible, outcomes were more homogeneous, so qualitative evaluation of pathologic response, recurrence and survival was completed. Because international consensus has grown in support of agreed standards in trial design  was most consistently observed in patients who received neoadjuvant combination IPI 1 mg/kg + NIVO 3 mg/kg, as described in arm B of the OpACIN-neo trial and the PRADO trial. Finally, in trials using intralesional therapy, pCR ranged from 21–76%.Although the rates of pCR at surgical resection seem comparable between neoadjuvant targeted therapy and immunotherapy, recurrence-free survival in patients with pCR differs. When RFS was assessed based on response to treatment, data showed that patients with a complete or near-complete pathologic response had better RFS than non-responders across all trials. However, patients who received neoadjuvant targeted therapy had a higher risk of relapse than those treated with neoadjuvant immunotherapy. In the NeoCombi trial, although the number of patients in follow-up is small, almost half of the patients with pCR had recurred at the time of data cut-off. In the neoadjuvant immunotherapy trials, pCR is strongly associated with an absence of relapse. Remarkably, of the three neoadjuvant immunotherapy trials, only one of 105 patients with pCR relapsed. While more long-term survival data is needed to determine whether pCR correlates with OS, the reviewed studies suggest that pCR likely correlates with RFS.The results of trials using intralesional therapy show that there is value in considering neoadjuvant intralesional treatment in patients with in-transit disease. When combined with systemic immunotherapy, CMP-001 increases immune activation both in the tumor and systemically. These results suggest that synergistically combining different therapy modalities offers increased treatment value for in-transit disease. Of note, AEs were minimal in intralesional trials.The lowest rates of grade 3–4 AEs and highest pCR rates were seen with the DAB + TRAM and combination IPI + NIVO at the doses of IPI 1 mg/kg + NIVO 3 mg/kg neoadjuvant regimens. When directly compared, grade 3–4 AEs and rates of pCR are similar. However, neoadjuvant immunotherapy showed longer RFS. These results provide justification for trials assessing other treatment regimen combinations, such as the ‘NeoTrio’ trial, which evaluates targeted therapy plus anti-PD-1 immune checkpoint blockade . Perhapsnot established that primary surgical resection for non-responders provides a recurrence or survival benefit, surgery in this population may provide palliation and improved quality of life.One area of concern regarding the neoadjuvant approach is losing the surgical ‘window of opportunity’ for non-responders. For that reason, careful patient selection of those likely to benefit from a neoadjuvant approach is crucial. In the trials reviewed, for T-VEC + surgery versus surgery alone, 25% of patients in the neoadjuvant T-VEC arm did not have surgery as planned versus 95% in the surgery alone arm. Notably, the trial by Amaria et al. comparing neoadjuvant NIVO versus IPI + NIVO was stopped early for safety, in part due to 17% of patients in the NIVO arm progressing on treatment and losing the opportunity for primary surgery. Interestingly, despite evidence of a lower response rate as compared to immunotherapy, no patient who was initially resectable at trial entry in the two targeted therapy trials involving this patient population progressed during neoadjuvant therapy. While it is certainly Predictive biomarker analysis of responders and non-responders may help determine which populations will benefit from neoadjuvant therapy. For example, Huang et al. discovered that in resectable stage III or IV melanoma, a single dose of anti-PD1 immunotherapy (pembrolizumab) resulted in T-cell reinvigoration at 7 days post-treatment . This seWhether neoadjuvant immunotherapy will replace adjuvant approaches in melanoma remains an open question. Ongoing trials, such as the SWOG1801 study, aim to answer this question . The varThe strengths of this systematic review include a systematic approach to study inclusion, pragmatic reporting of study results, and maximizing data capture in the setting of sparse literature. The limitations of this review relate to the significant clinical heterogeneity between studies and the absence of large phase III studies. Consequently, making firm clinically relevant conclusions is not feasible. Although the inclusion of abstracts in a systematic review may affect the appraisal of heterogeneity, risk-of-bias assessment, and the reliability of reported results, this review included abstracts due to the scarcity of available evidence on this topic . FinallyWith the remarkable success of adjuvant immuno-, targeted, and intralesional therapies for melanoma, the rationale to evaluate these contemporary therapies in the neoadjuvant setting is clear. This review highlights the encouraging preliminary results of 8 phase II trials evaluating neoadjuvant therapies for high-risk palpable stage III and resectable stage IV melanoma. Results suggest that the neoadjuvant approach is not only safe and feasible, but also dramatically improves pathologic response and very likely RFS. In the future, understanding predictors of pCR and its correlation with long-term oncologic outcomes will be paramount. More mature data of the phase II trials and future phase III trials will help determine whether contemporary neoadjuvant therapy can supplant adjuvant therapy as the standard of care for resectable stage III and IV melanoma.


The paper presents experimental investigations of the concrete covers’ protective ability to counteract rebar corrosion in reinforced concrete cubes. The concrete sample was subjected to a chloride-induced environment to get corroded and combined with an un-corroded sample. The chloride-accelerated technique can induce a high degree of corrosion within a controlled time. Moreover, detailed and thorough experimental measurements and analyses of reinforcement loss due to corrosion and its influence on concrete microstructure, were studied through 3D X-ray micro-computed tomography. The rebar outside the concrete was heavily corroded due to the chloride-accelerated test, whereas, only local surface corrosion products appeared inside the concrete. It turned out that the concrete cover showed protective ability to counteract the reinforcing-steel corrosion mechanism despite the accelerated corrosion environment. Moreover, the bond strength between the reinforcement rebar and concrete was not visibly affected since the failure force in the pull-out test and failure mechanisms, observed by 3D X-ray micro-CT, were similar for corroded and un-corroded samples. The failure occurred due to radial cracks with a maximum width equal to approximately 0.25 mm. The latest reports have shown significant economic impact due to the negative influence of corrosion. Thus, some countries are forced to spend money on repairing and maintaining steel and RC structures ,2. CorroMoreover, tensile stresses in the concrete cover, caused by the oxides on the corroded steel, lead to loss of the bond mechanism. Simultaneously, the high alkalinity of concrete pH ~ 13.0) protects the steel due to a passive zone of ferric oxides. Thus, steel reinforcement is protected by a passive layer on its surface and concrete cover. Significantly, the uncracked concrete cover is a physical barrier for corrosive factors delaying their diffusion through the concrete pores towards the reinforcement. Chlorides enter the concrete pore network by diffusion or capillary suction or combining the mechanisms as mentioned above .0 protec.2) solution. Non-destructive monitoring of the corrosion process in reinforced specimens was performed through X-ray CT scans. In addition, an innovative nanoindentation technique was used. The result indicated that some mechanical properties of rust  are highly dependent on the level of confinement provided by the surrounding cement paste to the rust layer. Cheng et al. [This process can take more than 10 or 15 years until the destructive environmental influence reaches the reinforcement. At the same time, the alkalinity of the concrete decreases (pH reduces below nine), and the thin protective layer on the reinforcement starts to depassivate. Then, oxidation occurs, and a gradual increase of rust on the steel reinforcement occurs. For the past few decades, many experimental and theoretical works have been dedicated to investigating the corrosion of steel reinforcement, however usually at the structural level . Most recent studies utilize the typical application of X-ray computed tomography and other innovative techniques to visualize phenomena such as steel corrosion and its progression in real-time, at the micrometer and even nanometer scale. In many studies, experimental work is performed on crack-induced concrete material to accelerate corrosion. In the study of Savija et al. [g et al.  presenteg et al.  determing et al.  have prog et al.  analyzedg et al.  determing et al. , shear sg et al. , and damg et al.  were carDetailed and thorough 3D experimental measurements and analyses of reinforcement loss due to corrosion and its influence on concrete microstructure using X-ray micro-computed tomography3D X-ray micro-computed 3D investigations of fractures in reinforced concrete samples subjected to pull-out tests.The main goal of this research was to better understand the protective ability of the concrete cover to counteract the reinforcing-steel corrosion mechanism that negatively affects bond strength. This knowledge is essential for enhancing the lifespan of reinforced concrete members and structures. Bond strength is the maximum bond stress, mainly resulting from friction between reinforcement rebars and the concrete, which can easily be regarded as shear stress over the bar’s surface or the interlocking mechanism, along with the reinforcing bar interface with the surrounding concrete. The bond between the concrete and reinforcement involves three effective mechanisms: adhesion, friction between concrete and steel surface, and the bearing of reinforcement ribs against concrete. To study and quantify the consequences of corrosion, laboratory methods have been developed to simulate and accelerate the natural process in reinforced concrete samples. The research procedure performed a chloride-accelerated corrosion test combined with X-ray micro-CT observations carried out at different intervals. Finally, the two main novel objectives of the study were:fys = 650 MPa, and the modulus of elasticity of steel was Es = 200 GPa. For the first seven days, blocks were stored in a climatic chamber at a temperature of about 200C and humidity 95% to avoid surface evaporation and autogenous shrinkage. Relatively small dimensions for the reinforced concrete specimens were used to enable the entire sample to be scanned in the micro-CT system.Finally, two cubic concrete samples with dimensions of 70 × 70 × 70 mm reinforced with a centrally located steel bar with a diameter of 12 mm were prepared; thus, the concrete cover was equal to 29 mm . The reiMechanical tests on the hardened concrete (on the 28th day after concreting) were conducted on six cubic specimens with the dimensions of 15 × 15 × 15 cm. The average uniaxial compressive strength  was fc =Micro-computed tomography is a non-destructive 3D imaging technique using X-ray to see the inside of objects. The micro-CT scanner makes a series of 2D planar X-ray images and reconstructs the data into 2D cross-sectional slices that are further processed into 3D models. Thus, the volumetric information about changes in the internal micro/mesostructure may be obtained. There are many examples of micro-CT systems for concrete members  with rebar, initially in a reservoir with Baltic Seawater, in order to simulate the marine environment. After seven days, no changes were observed, and due to that, to intensify the corrosion process, we increased the salinity to 3.5% by adding NaCl to the solution. Direct electric current was applied to the reinforcing steel bars through the power supply to accelerate the corrosion’s electrochemical reaction. The voltage value was set at 2.5 V. The positive-constant-current regulator electrode was connected to the rebar and the negative electrode to the stainless steel plate, which was also immersed in NaCl solution. In this way, an electric circuit was generated. The reinforcing steel bars acted as the anode of the circuit, the stainless steel plate acted as a cathode, and the saltwater was the electrolyte, which allowed ions to flow into the circuit ,7,10. FiThe ribbing of the reinforcing bar is distinguished. After 14 days the first signs of corrosion appeared, and its development is visible mainly in the rebar area outside the concrete cube. The concrete cover effectively counteracts the development of the corrosion since only limited and local areas were noticed within the concrete interior. After 42 days of the corrosion acceleration experiment, corrosion of the rebar outside the concrete visibly increased and the corrosion within the concrete interior only slightly evolved. A similar conclusion might be drawn after 70 days of the experiment. Whereas rebar outside the concrete was heavily corroded, only local surface corrosion products appeared inside the concrete. It turned out that despite the accelerated corrosion environment, the concrete cover showed the protective ability of the concrete cover to counteract reinforcing steel corrosion mechanisms.Pull-out quasi-static tests were carried out using the Zwick machine to observe if the steel corrosion mechanism negatively affects bond strength . The qua3D X-ray micro-CT investigations revealed that concrete cracking was similar for both cases . The faiCorrosion of steel reinforcement is currently one of the most critical problems in preserving concrete structures. Corrosion of reinforcement leads to the weakening of the bond strength, resulting in deterioration of the structural integrity. As a result of corrosion, the initial cross-section of the reinforcement is reduced, which weakens the mechanical properties of the steel bar. Before chloride ions reach steel reinforcement, there is an initiation period. During this period, water and chloride ions reach the appropriate level necessary to start the corrosion process. This process can take more than 10 or 15 years until the destructive environmental influence reaches the reinforcement. Corrosion accelerated tests combined with X-ray micro-computed tomography (micro-CT) of concrete reinforced samples revealed that the chloride-accelerated corrosion test allows simulation and acceleration of the natural corrosion process. This technique can induce a high degree of corrosion within a controlled time.The heterogeneity of tested material has a substantial impact on the local phenomena, such as the mechanism of the initiation, growth, and formation of fractures, which are responsible for the macroscopic behaviour of the material. Thus, concrete should be realistically described as a four-phase material composed of the cement matrix, aggregate particles, interfacial transition zones (ITZs), and macro voids assumed based on X-ray micro-CT images taken during experimental tests. Additionally, at this level of accuracy, the ribs of the steel bars should be modeled as well. The pull-out tests on uncorroded and corroded steel reinforcement concrete, allowed the material microstructure and cracking phenomenon to be observed using 3D X-ray micro-CT during the concrete splitting failure. The failure occurred due to the presence of radial cracks with a maximum width equal to approximately 0.25 mm.Whereas rebar outside the concrete was heavily corroded due to the chloride-accelerated corrosion test, only local surface corrosion products appeared inside the concrete. It turned out that the concrete cover showed protective ability to counteract the reinforcing-steel corrosion mechanism despite the accelerated corrosion environment. Moreover, the bond strength between the reinforcement rebar and concrete was not affected since the failure force and failure mechanisms were similar for corroded and un-corroded samples.Corrosion accelerated tests combined with X-ray micro-computed tomography (micro-CT) of concrete reinforced samples allow us to draw the following conclusions:X-ray micro-CT allows visualization of material micro-structure, steel rebar with ribs, and air void distribution. Thus, the measured total air volume in the non-cracked reinforced concrete specimens ranged from 2.75% to 2.81%, whereas closed porosity varied from 2.39% to 2.49% and open porosity varied from 0.55% to 0.61%, respectively.X-ray micro-CT scanning enables observation of the evolution of corrosion outside and inside the concrete sample after 14, 42, and 70 days. After 14 days of the chloride-accelerated corrosion test, noticeable corrosion changes within the rebar were noticed. Corrosion development is mainly visible in the rebar area outside the concrete cube. After 42 days of the chloride-acceleration experiment, corrosion of the rebar outside the concrete visibly increased while the corrosion within the concrete interior just slightly evolved. Similar conclusions might be drawn after 70 days of the experiment.Our experiments will be continued with different steel corrosion ratios and various steel reinforcement diameters. X-ray micro-CT will be used to investigate the corrosion phenomenon and bond failure mechanism at the aggregate level. Furthermore, the experimental tests will be simulated using an isotropic coupled elastoplastic-damage constitutive model. It will be mainly for concrete enhanced by a characteristic length of microstructure in terms of integral non-local theory. The heterogeneity of tested material has a substantial impact on the local phenomena, such as the mechanism of the initiation, growth, and formation of fractures, which are responsible for the macroscopic behaviour of the material. Thus, concrete will be realistically described as a four-phase material composed of the cement matrix, aggregate particles, interfacial transition zones (ITZs), and macro voids assumed based on X-ray micro-CT images taken during experimental tests. Additionally, at this level of accuracy, the ribs of the steel bars will be modeled as well. The final goal is to introduce a new enhanced bond law that considers material heterogeneity.


The research reported in this paper aims to evaluate the epoxy injection technique used to strengthen fiber-reinforced self-compacting concrete (FRSCC) with high strength. This method is carried out on ruptured concrete specimens to assess the efficiency of the epoxy resin adhesive injection retrofitting technique for strength and stiffness. Five FRSCC mixes were designed and placed using different types (steel and polypropylene) and contents  of fibers. The fresh and mechanical properties in addition to the microstructure of produced mixes were evaluated to assess the impact of fibers on the behavior of FRSCC. Results showed that the workability of FRSCC is reduced by increasing steel or polypropylene fiber content; however, the rheological characteristics of placed mixes satisfied the European Guidelines for Self-Compacting Concrete recommendation for fresh concrete. Also, splitting tensile, flexural, and shear strengths were enhanced by increasing fiber content. The simultaneous application of epoxy injection in FRSCC for repairing damaged concrete beams was shown to be highly effective. The versatility and efficiency of concrete as a construction material have demonstrated its ability to become the ultimate building material in the world. Despite concrete’s compression capacity, the low tensile strength and brittle characteristics of concrete have necessitated overcoming this weakness by using several types of reinforcement . Consequently, enhanced concrete service life and durability can be attained by overcoming cracks issues . The infThe utilization of steel fibers in concrete has been highly investigated in the past two decades, and the experimental results have proved its capacity for structural concrete applications. da Silva et al.  pointed Considering the disadvantages of the incorporation of steel fibers in concrete, polymer-based fibers (polypropylene fibers) are considered a good alternative. Owing to their good chemical stability and hydrophobic nature, and long-term durability, performance in harsh environments can be attained ,13. AddiDifferent cementitious and polymer materials are used for crack repair in reinforced concrete structures. Epoxy injection is considered an effective repair method. Based on the ACI 546  “ACI ConFrench et al.  approvedThe abovementioned literature review reveals that the majority of published papers on the incorporation of fibers in concrete have been restricted to the addition of fibers only; however, limited investigations have assessed the impact of epoxy injections on the flexural strengthening of FRSCC. In this regard, FRSCC mixtures modified by steel and polypropylene fibers were designed and subjected to flexural strength tests to form cracks. Consequently, the coupled effect of fibers and epoxy injection postrepairing phase to enhance the properties of FRSCC was investigated to widen the information about this type of concrete to practically apply it in the construction industry. Obtained results reveal benefits associated with the epoxy treatment of formed cracks in terms of enhancement of mechanical strength. 3) were intended for casting SCC to ensure adequate rheological properties. Ordinary Portland Cement (OPC) CEM I 42.5 N complying with the European standard [Cement, sand, coarse aggregate, water, superplasticizer, and fibers have been used to produce the FRSCC with high strength. Thus, a low w/c ratio (0.35) and high powder content  fine and coarse aggregates were used by 45% and 55% proportions, respectively. A modified polycarboxylates aqueous solution superplasticizer (Sika ViscoCrete-5 Neu) was used to achieve the required strength and workability under the European Guidelines for SCC .It is important to note that the superplasticizer was added at the same amount for all mixes to assess the effect of steel and synthetic fibers on the fresh properties of SCC; however, this amount was optimized initially for the control mix. Two types of fibers were used in the present work: steel and synthetic fibers. The steel fiber was a 3D 65/60 BG Dramix, which is known for its advantages such as 3D, combining high performance, durability, and ease of use, and it is a time-saving and cost-efficient solution . The synIt is known for its advantages, such as high tensile strength and excellent postcrack behavior, in addition to its high resistance to aggressive fluids and corrosion and that provides a longer service life with minimal maintenance requirements. In addition, it can be handled easily because of its low weight. An electric mixer was used to mix the materials; it contained a flat cylindrical tank where the concrete component can be added. The tank rotated automatically for mixing, and in addition there were three steel blades that hung on the steel cover of the mixer and rotated in the opposite direction of the tank in order to make the mixing more efficient. The total mixing time was from 5.5 to 6 min, partitioned into four stages, and after each stage, the ingredients were manually mixed to achieve the highest homogeneity. In the first stage, coarse aggregates, sand, and cement were added and mixed for about 1.5 min.3 of polypropylene and 0, 20, and 35 kg/m3 of steel fiber. Mix proportions are presented in In the second stage, fibers were added and mixed for 1 min, then in the third stage, the water was added to hold the components together and mixed for about 1.5 min, followed by the superplasticizer, and then mixed for 1.5 min. This procedure was optimized by the authors before starting the experimental program, and it helped to achieve the required workability and homogeneity of the SCC mix . Five miTo ensure that the produced mixes have satisfied the European Guidelines for SCC, slump flow diameter and V-tunnel time tests have been conducted directly after mixing. The slump flow diameter test was used to assess the workability and consistency of the concrete. The V-funnel time test was carried out on fresh FRSCC to evaluate the viscosity of the fresh concrete. Both of them were conducted per the European Guidelines for SCC . Specime2) through the equations presented in The shear strength was tested by the original experimental method: by using a notched cylindrical push-off specimen, which creates two stress-free zones. New boundary conditions were created to transform the compression stress into shear in a limited area. The shape of such a specimen (S-shape) allows for a longitudinal slip, which ensures the occurrence of shear stress in a plane by loading with two forces that equilibrate each other without necessitating the application of supplementary forces on the boundary to ensure equilibrium. The specimen was notched in two symmetrical areas of 1 cm thickness and 7.5 cm depth, and the spacing between the notch and base was 10 cm for both from each side; the used notched cylindrical push-off specimen is shown in The crack was cleaned using compressed air.The epoxy resin was prepared.The crack was filled with the epoxy resin by injecting it using a syringe c.After epoxy injection, the outer edges of the crack were painted using epoxy.The specimen was left for 24 h, then the flexural test was carried out on the repaired specimen d.By conducting the three points flexural strength test on the prism specimens, they mostly cracked on the bottom side in the middle of the span. Typically, one dominant crack appeared, as is shown in The impact of steel and polypropylene fibers on FRSCC flowability and viscosity  are shown in The compressive strength results of FRSCC mixes that include various volume fractions and types of fibers are illustrated in To assess the impact of fibers on the tensile strength of casted FRSCC, splitting tensile strength tests were carried out on specimens, and the corresponding results are plotted in According to The flexural strength test results which show the effect of using steel and polypropylene fibers with and without epoxy injection are plotted in Based on experimental observations, all tested specimens failed within the middle third section. After breakage, beams repaired with epoxy injection performed differently. Most of the repaired control specimens that split at new different places had higher flexural strength values compared to the specimens that split at the same places see . In compThe correlation between the flexural strength of the FRSCC before and after repairing by epoxy is presented in It has been recognized by Feng et al.  that the2 = 0.70). Since the results of flexural strength before using the epoxy meet the predicted values proposed in the aforementioned standards, the flexural strength results after using the epoxy will do, considering the compressive strength is the same.rf = flexural strength (MPa), cf = cylindrical compressive strength (MPa).The results of the compressive and flexural strengths of FRSCC test results are correlated in This paper is a part of a comprehensive research project undertaken to evaluate the effects of the addition of steel and polypropylene fibers on the fresh and mechanical properties of FRSCC proportioned with high strength.The research also conducted the epoxy injection technique to strengthen the FRSCC after cracking. It was carried out on ruptured concrete specimens to assess the efficiency of the epoxy resin adhesive injection retrofitting technique for strength and stiffness. The simultaneous application of epoxy injection in FRSCC for repairing damaged concrete beams was shown to be highly effective.According to the experimental results, the incorporation of steel or polypropylene fibers led to reduced responses in the workability of FRSCC. Such phenomena become aggravated when mixtures are proportioned with higher contents of fibers.The impact of polypropylene or steel fibers on the compressive strength results was marginal. The positive impact of fibers on splitting tensile strength was noticeable, given that the fiber bridging action that limits crack propagation.Steel fibers with high tensile properties could significantly improve the flexural strength and shear capacity of FRSCC, owing to the effect of fibers on the postcracking response and shear stress transfer across the cracks. Repairing FRSCC with epoxy enhances its flexural strength, unlike the normal concrete produced without fiber. The porous transition zone between the fiber and cement matrix helps to improve the strength after repair, as presented by the SEM images. Finally, the experimental results of flexural strengths were found to be predictable by several standards.


The desired effect of antibiotics is compromised by the rapid escalation of antimicrobial resistance. Children are particularly at high-risk for unnecessary antibiotic prescribing, which is owing to clinicians’ diagnostic uncertainty combined with parents’ concerns and expectations. Recent Belgian data on ambulatory antibiotic prescribing practices for children are currently lacking. Therefore, we aim to analyse different aspects of antibiotic prescriptions for children in ambulatory care.Pharmacy dispensing data on antibiotics for systematic use referring from 2010 to 2019 were retrieved from Farmanet, a database of pharmaceutical dispensations in community pharmacies. Population data were obtained from the Belgian statistical office (Statbel). Descriptive statistics were performed in Microsoft Excel. The Mann-Kendall test for trend analysis and the seasplot function for seasonality testing were conducted in R.The past decade, paediatric antibiotic use and expenditures have relatively decreased in Belgian ambulatory care with 35.5% and 44.3%, respectively. The highest volumes of antibiotics for children are prescribed by GPs working in Walloon region and rural areas, to younger children, and during winter. The most prescribed class of antibiotics for children are the penicillins and the biggest relative reduction in number of packages is seen for the sulfonamides and trimethoprim and quinolone antibacterials.Paediatric antibiotic use has decreased in Belgian ambulatory care. Further initiatives are needed to promote prudent antibiotic prescribing in ambulatory care.The online version contains supplementary material available at 10.1186/s12887-021-03047-7. Antibiotics are one of the most cost-effective, live-saving treatments and they may contribute to an extended lifespan. However, their effect is compromised by the rapid escalation of antimicrobial resistance (AMR) which is considered as a major global health threat . Drug-reChildren are particularly at high-risk for unnecessary antibiotic prescribing , 3. AcutBelgian reports on antibiotic prescribing practices deduce that the largest volumes of antibiotics are consumed in the community . These rTherefore, we aim to analyse Belgian antibiotic dispensing data on children in ambulatory care over a ten-year period regarding antibiotic subgroups, delivery month, specialty of the prescriber, age of the child, region, and rurality category.Pharmacy dispensing data on antibiotics for systematic use  referring from 2010 to 2019 were retrieved from Farmanet, a Belgian database containing data on pharmaceutical dispensations, delivered in community pharmacies and reimbursed by the compulsory health insurance . We requPopulation data were obtained from the Belgian statistical office (Statbel) . Belgiump-value ≤ 0.05 was considered significant. The function seasplot was used to construct seasonal plots of time series objects which were created through the ts function.Descriptive statistics were performed in Microsoft Excel version 21.02. Statistical analysis was conducted with R version 4.0.3. Because of non-linearity, the nonparametric Mann-Kendall test was used for trend analysis. A The results below describe the number of packages of antibiotics for systemic use ATC J01) delivered in Belgian public pharmacies to children aged zero to 12 years and associated NIHDI expenditures, calculated per 1000 inhabitants. Extensive data tables are included in Additional file  deliverep < 0.001) and 44.3% (p < 0.001), respectively , quinolone antibacterials , beta-lactam antibacterials other than penicillin , and amphenicols   and the macrolides, lincosamides, and streptogramins  , with 29.8% (p < 0.001) for paediatricians, and with 25.4% (p < 0.001) for other medical doctors . NIHDI expenditures dropped with 48.3% (p < 0.001) for GPs, with 35.60% (p < 0.001) for paediatricians, and with 37.5% (p < 0.001) for other medical doctors.During the last ten years, the number of packages of antibiotics prescribed for children and NIHDI expenditures have significantly decreased for all specialties Fig. . The nump = 0.049), as compared to the number of packages prescribed by a GP , or a paediatrician  , while this has increased for paediatricians  and other medical doctors   for zero- to one-year-olds, with 38.9% (p < 0.001) for two- to six-year-olds, and with 31.0% (p = 0.001) for seven- to 12-year-olds , 45.2% (p < 0.001), and 45.5% (p < 0.001), respectively.In 2019, 18.2% of the antibiotic use in children was represented by age group of zero- to one-year-olds, 50.6% by two- to six-year-olds, and 31.2% by seven- to 12-year-olds. Considering the number of Belgian inhabitants per age category, we can conclude that more antibiotics are prescribed in children up to 6 years, compared to seven- to 12-year-olds  . In factMoreover, our conclusions should be interpreted with caution, as correction for population growth and/or decline is imprecise. Farmanet calculates age as delivery year of the antibiotic minus birth year, overestimating the actual age of the children, while Statbel contains data for the first of January of each year. This means that data retrieved from Farmanet and Statbel cannot be perfectly aligned to perform trend analysis per 1000 inhabitants. However, correcting for alternations in the population allows generalisability to other settings.This research is a critical step in identifying where antibiotic prescribing practices can be improved. Our data suggest that physicians working in Walloon region and rural areas prescribe more antibiotics per 1000 inhabitants. Besides, in the past ten years, other medical doctors than GPs and paediatricians have proportionally prescribed more antibiotics for children.The lack of information about the indication the drug was prescribed for, the dosing frequency, and the duration of therapy, make it impossible to estimate whether the use of antibiotics was appropriate based on these data. Further research is needed to investigate the appropriateness of prescriptions.Moreover, further research should investigate temporal trends of broad and narrow spectrum antibiotic use, as we did not provide data on the individual antibiotics. Physicians prescribe broad-spectrum antibiotics because of diagnostic uncertainty, stimulating antimicrobial resistance . This diFuture studies should aim to analyse whether COVID-19 has had an impact on antibiotic use in Belgium. We hypothesize that, similarly to England , the numThe past decade, paediatric antibiotic use and expenditures have decreased in Belgian ambulatory care. The highest volumes of antibiotics for children are prescribed by GPs working in Walloon region and rural areas, to younger children, and during winter. Prudent antibiotic prescribing should be continuously promoted in ambulatory care.Additional file 1. Contains simplified tables of the requested pharmacy dispensing data, corrected for the number of inhabitants. This can be found online.Additional file 2: Supplemental figure 1. Number of packages and NIHDI expenditure per 1000 inhabitants by month (2019). Supplemental figure 2. Number of packages (A) NIHDI expenditure (B) by region per 1000 inhabitants per year (2010-2019). Supplemental figure 3. Number of packages (A) and NIHDI expenditure (B) by rurality category per 1000 inhabitants per year (2010-2019).


RoKSN, a TFL1 homologue. In this work, we studied the origin, the diversity and the selection of the RoKSN gene. We analyzed 270 accessions, including wild and old cultivated Asian and European roses as well as modern roses. By sequencing the RoKSN gene, we proposed that the allele responsible for continuous-flowering, RoKSNcopia, originated from Chinese wild roses (Indicae section), with a recent insertion of the copia element. Old cultivated Asian roses with the RoKSNcopia allele were introduced in Europe, and the RoKSNcopia allele was progressively selected during the 19th and 20th centuries, leading to continuous-flowering modern roses. Furthermore, we detected a new allele, RoKSNA181, leading to a weak reblooming. This allele encodes a functional floral repressor and is responsible for a moderate accumulation of RoKSN transcripts. A transient selection of this RoKSNA181 allele was observed during the 19th century. Our work highlights the selection of different alleles at the RoKSN locus for recurrent blooming in rose.Blooming seasonality is an important trait in ornamental plants and was selected by humans. Wild roses flower only in spring whereas most cultivated modern roses can flower continuously. This trait is explained by a mutation of a floral repressor gene,  Arabidopsis thaliana1 and progressively in numerous cultivated plants such as rice and cereals2, poplar3, and pea4. Flowering time is an important adaptive trait for plants since the date of flowering is essential for reproductive success, and consequently, for the production of flowers or fruits and the survival of the species. During the processes of natural selection and domestication, flowering has been subjected to major modifications to adapt to different environments and human uses. Evolutionary studies have demonstrated the central role played by flowering genes in these processes. In A. thaliana, in the response to vernalization (cold requirement to accelerate flowering), two loci, FRIGIDA (FRI) and FLOWERING LOCUS C (FLC), were subjected to natural selection. In the last few thousand years, two nonfunctional alleles at the FRI locus were selected, leading to early-flowering ecotypes , probably linked to the weediness of A. thaliana5. At the FLC locus, in the presence of an active FRI allele, local adaptation was demonstrated by a latitudinal distribution of haplotypes6 that mainly presented cis polymorphism, leading to functional differences in the vernalization response during the domestication of rice (Oryza sativa L.). Early-flowering and reduced-photoperiod-sensitive genotypes were selected to permit the extension of cultivation to northern latitudes7. Nonfunctional alleles at the Hd1 (HEADING DATE 1) locus, a CONSTANS homologue, may have been selected to diversify flowering times8. Other loci were also proposed for selection in rice2. In soybean (Glycine max), mutations in a homologue of the floral repressor TFL1 (TERMINAL FLOWER 1) that determines growth habit were selected during domestication9. Similarly, in sunflower (Helianthus annuus), a dominant mutation in a floral activator FT (FLOWERING LOCUS T) homologue was selected during domestication, leading to late flowering cultivars via interaction with another FT paralog10.Flowering is a complex trait under the control of endogenous and environmental factors that allows plants to adapt to different environments and to flower at an appropriate time. Molecular and genetic networks have been deciphered in the model plant Rosa sp.), the processes of natural selection and domestication are poorly understood. Today, rose is the most economically important plant worldwide, with the production of cut, garden and potted roses in the ornamental sector, and the production of essential oils in the perfume sector12. The tremendous success of rose is due to its symbolism and esthetics. Indeed, throughout the centuries, roses have been chosen for their form, their flower shape and especially their scent. In Europe, rose was already used in ancient Rome. Pliny the Elder described more than six cultivated species thought to correspond to cultivated forms of R. alba, R. gallica, R. damascena, and R. moschata13. Rose cultivation continued in the Middle Ages, not only for its ornamental uses but also as a religious symbol and for its medicinal benefits15. In Europe, before the 19th century, cultivated roses were mainly hardy once-flowering (OF) shrubs that flowered in spring or early summer. Only a few roses had the ability to occasionally and weakly rebloom in autumn, including R. moschata and R. dasmascena ‘Quatre saisons’, also known as the Autumn Damask rose16. In Asia, roses were cultivated before the Han Dynasty, more than 2000 years ago, with progressive selection of roses with new traits such as continuous-flowering (CF)17. The CF trait was only found in cultivated roses. In China, CF roses were first described during the 12th century17. At the end of the 18th century, the introduction of Asian roses in Europe caused a revolution in rose breeding with the introduction of new traits such as CF, new scents and new colors19. A clear genetic differentiation was detected between old European and Asian roses20. The 19th century was an intensive period of rose breeding, with crosses between old European and Asian roses21 and with a temporal shift from European to Asian genetic background in the hybrids obtained in Europe at that time20. During this century, CF behavior was highly selected, leading to the production of CF roses, which were key for the tremendous success of modern roses.In rose  element  was detected, and the loss of the gene is due to a large 5-Mbp rearrangement on chromosome 325. Furthermore, in a CF R. rugosa, a seasonal expression of RoKSN was associated with CF behavior26, but the genetic determinism of this CF behavior has not yet been elucidated.CF behavior is controlled by a monogenic recessive locusNWT Fig. . Due to RoKSN gene that controls CF in rose. In Europe, and especially in France, the golden age of rose breeding was the 19th century, so we focused on accessions from this period, which have been preserved by vegetative multiplication in rose gardens.Our objectives were to study the origin, the diversity and the selection of the RoKSN) in rose during the 19th and 20th centuries, we genotyped a large collection of 270 rose accessions for the presence of the copia retrotransposon. This large collection of garden roses represented wild Asian and European roses, old cultivated Asian and European roses (assumed to be the ancestors of modern roses), and modern roses (from the late 19th century to the present)  or for the RoKSNcopia allele , and heterozygous RoKSNcopia/RoKSNLTR , RoKSNcopia/RoKSNWT , and RoKSNcopia/RoKSNLTR/RoKSNWT . All the individuals with the RoKSNLTR allele were climbing mutants, as previously described24. Even if the rose collection presented different ploidy levels, the copy number of each allele  was not determined given that they were scored as co-dominant (presence/absence) because of technical limitations.Five genotypic profiles were observed at the RoKSNWT in the homozygous state for the most part . For the Asian wild roses, one piece of data was missing, and one individual (R. gigantea from the rose garden of Haÿ-les-Roses) was RoKSNWT/RoKSNcopia. Three R. gigantea accessions were present in the studied rose collection, and the other two only had the RoKSNWT allele. The presence of the RoKSNcopia allele in this assumed wild accession may be explained by a misidentification in the rose garden.We studied the frequency of these different genotypic profiles in roses cultivated in Europe during the 19th and 20th centuries  or in the homozygous state (13 accessions with only RoKSNcopia). For European cultivated roses, we observed a gradual decrease of the homozygous genotype profile for the wild allele RoKSNWT until its absence after the 1920s. On the contrary, the RoKSNcopia allele was increasingly present over time, initially in the heterozygous state (RoKSNcopia/RoKSNWT) and then in the homozygous state (RoKSNcopia). Indeed, before the 1800s, all European cultivated roses were homozygous for the wild allele RoKSNWT. Between 1800 and 1860, the wild allele was almost equally present in the homozygous and heterozygous states. Then, up until the 1920s, the homozygous profile for the wild allele RoKSNWT decreased to 15%, whereas the heterozygous profile RoKSNcopia/RoKSNWT increased or remained stable (55–75%). In contrast, the copia allele in the homozygous state (RoKSNcopia) increased to 30% during this period. After the 1920s, European cultivated roses always presented the RoKSNcopia allele, with an increase in the homozygous state until the 1980s (increasing from 30 to 50%). In the last decades, the cultivated varieties were generally heterozygous (65%) for the RoKSNcopia allele. Surprisingly, some of these heterozygous genotypes (RoKSNWT/RoKSNcopia) had the ability to rebloom , then at the homozygous state (1860–1980) and, later, a return to the heterozygous state (1980 to the present).These results show a progressive selection of accessions presenting the 17. The CF behavior is due to an insertion of a copia-like retrotransposon into the floral repressor gene RoKSN. As we previously showed, the RoKSNcopia allele was present in the large majority of old cultivated Asian roses but was absent in European roses cultivated before 1800  retrotransposon, and it was proposed that the insertion time of this retrotransposon type can be estimated by the divergence between the two LTRs at both ends27 because their sequences were identical at the insertion event28. Assuming that two LTRs accumulate point mutations independently, the nucleotide divergence between the two LTRs reflects the time since the insertion event. We sequenced the 5′ and 3′ LTR elements in R. x wichurana. The two LTRs were totally similar  were A292G and T1043C, which were detected in 108 and 117 individuals, respectively, either at the homozygous  or the heterozygous  state.Then, to identify the origin of the RoKSNcopia or heterozygous RoKSNcopia/RoKSNLTR. Among the 181 accessions sequenced for the RoKSN gene, 34 presented one of these two profiles. All of the 34 accessions (except for one with missing data) presented a single haplotype from the 17 identified SNP sites at the RoKSN locus: GACGGCAGCTAACCCGT  were thought to have no effect on the protein structure. The former (A1068T) changed a serine into a cysteine, which is a surface residue, independent of any interaction in the florigen activation complex. Furthermore, this amino acid was not conserved in TFL1 proteins Fig. . The latR. gallica for which no recurrent blooming was ever described18 and some old cultivated European roses that were OF  in 47 accessions Fig. . The samR. fedtschenkoana) or in summer and autumn for ‘Adam Messerich’ and R. moschata  and grouped into the same cluster  and homozygous (7) states Fig. . Among tRoKSNcopia allele  and looked for the presence of the A allele in more recent accessions. We detected 17 accessions with the A allele at the homozygous state and 18 with both alleles, G and A . Both alleles were able to complement the tfl1-11 mutant. The RoKSNG181 allele was already shown to be able to fully complement the tfl1-11 mutant with indeterminate growth and late flowering  and late flowering , and the variation did not significantly modify the activity of the protein. In conclusion, like for the RoKSNG181 allele, the protein encoded by the RoKSNA181 allele is active and is a floral repressor in Arabidopsis.We first tested if the protein encoded by the RoKSNA181 allele was not modified during the reblooming process. We compared the RoKSN transcript accumulation in roses homozygous for the RoKSNA181, RoKSNG181 or RoKSNcopia allele. As previously demonstrated24, roses presenting only the RoKSNcopia allele did not accumulate RoKSN transcripts  still accumulated RoKSN transcripts in comparison with CF roses, but this accumulation was 10–20-fold less than for OF roses 24; the other allele (RoKSNnull) is due to a 5 Mb rearrangement, leading to the loss of several genes, including RoKSN25. Interestingly, many roses have intermediate phenotypes with a weaker ability to rebloom, considering the blooming quantity and period 24.Rose presents different modes of flowering, ranging from roses that flower only in spring (OF) to roses that can flower all the time as long as the growing conditions are favorable (CF)RoKSN locus that might be responsible for recurrent blooming. Using sequencing, we identified 17 SNPs at this locus, with five SNPs leading to protein modifications , we had assumed that the protein activity could be modified. However, on the basis of functional validation in Arabidopsis thaliana (tfl1 mutant complementation), we were unable to detect any changes between the proteins encoded by the G or A allele  that were able to rebloom with different intensities  other alleles can be present at the RoKSN locus which were not considered, as the RoKSNnull allele25, (3) we should consider the dose of the allele in a polyploid context which is known to modify the expression of the phenotype as shown in Brassica for flowering date34, and (4) we cannot exclude that the RoKSNcopia allele can interfere with the RoKSNWT allele by modifying its expression as described for the paramutation where one allele (paramutagenic) can silence the other allele (paramutated) with a high variability in the penetrance and heritability35. Further analyses should be necessary to verify these hypotheses.The genetic determinism of recurrent blooming seems to be more complicated that previously proposed. CF was first described as being controlled by a recessive mutation of a floral repressor in F1 progenies19. Only some species like R. moschata were able to rebloom in the summer or autumn. Nevertheless, blooming for these European roses was lower than for Asian roses with CF. This CF behavior is due to an insertion of a copia-like retrotransposon in the RoKSN floral repressor gene24. Our results obtained for the RoKSN locus suggest the following scenario.Blooming is an important breeding criterion for garden roses. Until the 19th century, European roses were mostly non-recurrent, blooming only in the springcopia element was always associated with a particular haplotype . When a transposable element (such as copia) is inserted, it creates a pair of LTRs with identical sequences at the two breakpoints28. At the RoKSN locus, both LTRs of the copia element are identical  occurred recently. This scenario is strengthened by the presence of only one haplotype associated with the RoKSNcopia allele , which resulted in an increase of the presence of this allele in European cultivated roses, first at the heterozygous state and later at the homozygous state  and occasional-reblooming roses , where breeders would have combined a hypomorphic allele (RoKSNA181) and a recessive allele (RoKSNcopia). It can be suggested that these hybrids (RoKSNcopia/RoKSNA181) were more reblooming than hybrids with the copia allele at the heterozygous state (RoKSNcopia/RoKSNWT). This raises the question of the dose of the different alleles in the polyploid context, which is the case of the rose accessions bred during the 19th century38. As we were unable to quantify the different alleles at the RoKSN locus, it was not possible to test this hypothesis in our study. The origin of the RoKSNA181 allele is not clear since the allele is found in Asian (such as R. rugosa) and European (such as R. moschata) materials.Moreover, our results showed a transient selection of the 39, we hypothesize that R. moschata has a wild ancestor related to R. rugosa ; CF roses ; and occasional-reblooming roses .A large collection of garden roses (270 accessions) was sampled. This collection consisted of wild Asian (18 accessions) and European (13 accessions) roses, old cultivated Asian (36 accessions) and European (108 accessions) roses, and modern roses . The studied roses are detailed in Supplementary Table RoKSN: RoKSNWT, RoKSNcopia and RoKSNLTR, which were identified using two pairs of primers: KSN_F100 x KSN_R6 and KSN_LTR1 x KSN_R6 . Amplifications were carried out using MyCycler thermalcycler . The thermal cycling protocol had an initial denaturation at 94 °C for 2 min, followed by 40 cycles of denaturating at 94 °C for 45 s, annealing at 60 °C for 45 s and extension at 72 °C for 90 s, and ended with a 7-min final extension at 72 °C. The amplified fragments were separated on a 1.7% agarose gel and then stained with ethidium bromide and revealed by ultraviolet light.DNA was extracted using the NucleoSpin Plant II kit  according to the manufacturer’s instructions. The 270 accessions of the rose collection were genotyped for the three known different alleles of _R1 Fig. . PCR reaRoKSN gene was performed for 181 accessions  and fragment B . The PCR conditions used were the same as for the RoKSN gene genotyping. PCR products were sequenced using SANGER technology with the same primer pairs used for the PCR amplification (Supplementary Table Rosa x wichurana (HQ17421124) and the nucleotide polymorphism at this position. For example, SNP A292G means that a SNP was identified at position 292 and that the accessions had either adenine or guanine at this genome position.A partial sequencing of the 40. PCR reactions were performed in a volume of 15 µl with 10 ng genomic DNA, 1 X Green GoTaq® Flexi buffer, 0.125 mM dNTPs, 2 mM MgCl2, 0.2 µM of each primer, and 0.1 U GoTaq® Flexi DNA polymerase , with the following program: 95 °C for 3 min, 40 cycles , and 72 °C for 5 min.Degenerated CAPS (dCAPS) was developed to genotype the G181A SNP detected by sequencing. The primers  according to the manufacturer’s instructions. The digestion led to the production of three DNA fragments for the allele, with a guanine at position 181, RoKSNG181 , and two DNA fragments for the allele with an adenine at the same position, RoKSNA181 (64 and 87 bp). DNA fragments were separated on a Resophor gel (4.5% w/v), stained with ethidium bromide.Amplified PCR fragments were then digested using RoKSNG181 allele was obtained from a construction previously obtained in a p35:KSN:pENTR plasmid31. We used this construction to substitute the G for an A by proceeding to a site-directed mutagenesis using the QuikChange II Site-Directed Mutagenesis Kit , according to the manufacturer’s instructions, with the primers mRmKSN_F2 and mRmKSN-R3  by thermal shock at 42 °C for 1 min.The Arabidopsis thaliana (L.) tfl1-11 mutants (N6235)41 were provided by the Nottingham Arabidopsis Stock Center. The binary vector was introduced by electroporation into Agrobacterium tumefasciens EHA10542 containing the plasmid pbbR. A. thaliana tfl1-11 mutants were transformed using the floral dip method43. Transformed plants were selected on Murashige and Skoog basal medium supplemented with 50 mg l−1 kanamycin. Plants were grown under long day conditions  and were scored for the number of rosette leaves and the presence of terminal flowers.31. cDNAs were obtained by reverse transcription performed on 500 ng of total RNA using Iscript Ready-to-use . The real-time amplification (q-PCR) was performed with SsoADV Univer SYBR Green Supermix  using cDNA as a template, with the following program: 98 °C for 30 s and 40 cycles . Fluorescence detection was performed using a CFX ConnectTM Real-Time System . The amount of cDNA in each sample was normalized using the TCTP gene44, and the relative expression level was calculated according to Pfaffl45 from two biological replicates and three technical repetitions per replicate. Primers for the amplification of RoKSN and TCTP genes are listed in Supplementary Table Young growing shoots after axillary bud outgrowth were harvested in October 2013 and in August 2014 in the “Loubert” Rose Garden . Total RNAs were extracted from axillary buds using the NucleoSpin RNA Plant kit . The absence of genomic DNA contamination was checked by PCRcopia element insertion in the RoKSN locus, we sequenced the two LTR elements from R. x wichurana using SANGER technology with the following primers: KSN_F3 and KSN_InsR3 for the 3′LTR, and KSN_LTR5′F and KSN_R5 for the 5′LTR. Sequences were analyzed using Geneious software v8.1.8 . For a second genotype, R. chinensis ‘Old Blush’, we recovered the LTR sequences from the haploid genome reference46 with the copia element (ms324231_RchiOBHmChr3_RLC_denovoRcHm_v2.0-B-P313.2180-Map5_reversed) inserted into the RoKSN locus (RchiOBHm_Chr3g0473011 and RchiOBHm_Chr3g0473021).To date the R. fendschenkoana, R. moschata, R. x wichurana, ‘Stanwell Perpetual’, ‘Old Blush’, and ‘Tuscany Superb’). The number of flowers at a particular stage  was counted every week for six months (from mid-May to mid-November), and the recurrent blooming was estimated by visual observation  in 2012 and 2013 (‘Adam Messerich’, ‘Belvédère’, ‘Camaieux’, ‘Jean Bach Sisley’, ‘Leda’, ‘Madame Hardy’, ‘Pergolèse’, Supplementary Figure 1Supplementary Figure 2Supplementary Figure 3Supplementary Figure 4Supplementary Table 2Supplementary Table 3Supplementary Table 4Supplementary Table 1


Most commonly used antibiotics have origins in the chemical wars between diverse microbes competing over millennia in crowded environmental niches, like soil. This enduring need to attack their neighbours has made some microbes ruthless killers armed with the ultimate weapon—antibiotics. Antibiotics target biological functions central to the growth or survival of bacteria with an exquisite specificity that has been honed through countless selective iterations over a very long time.However, their touted, known mechanisms of action may not be so simple.The way cells respond to antibiotics are complex and multifactorial, both for the bacterial pathogens and infected hosts. For example, bacteria treated with antibiotics can display a plethora of alterations—physiological, behavioural or regulatory—that are seemingly unrelated to the direct killing mechanisms of the antibiotic. These “off target” secondary impacts of antibiotics can be difficult to explain.Some secondary impacts might reflect alternative biological functions of the molecules, related to the needs of native producing organisms, such as chemical signalling. Alternatively, they may be collateral effects that do not alter the fitness of the antibiotic producers, or poorly defined downstream consequences of the primary antibiotic targeting mechanism. These illicit effects occur for both fully and semi-synthetic antimicrobials.Penesyan et al.), antibiotic-induced mutagenesis, as measured using microscopy (Revitt-Mills and Robinson) and bacterial tolerance of antibiotics (Sulaiman and Lam). The outstanding research papers showcase the broad cellular and regulatory effects that the last-line antibiotic tigecycline has beyond inhibiting translation , how antibiotics can trigger increased gene transfer via quorum sensing , the complex interactions between antimalarials and antibiotics in bacteria , and the impact that antibiotics have on animals with brain ischemia .This Research Topic in Frontiers in Microbiology focuses on these underexplored secondary effects of antibiotics which impact the physiology, behaviour, and evolution of bacterial, host and other co-localised cells. The secondary effects are frequently subtle, lurking beneath the surface of the primary killing/inhibition action, but become apparent through anecdotal observations, or after prolonged antibiotic use. These effects reveal the secret double lives of antibiotics that have sidestepped significant attention, but whose impacts extend to alterations in bacterial virulence, resistance development and treatment efficacy. The papers in this Research Topic describe targeted and cutting-edge investigations into antibiotic secondary effects and their mechanistic bases. The Research Topic comprises of seven papers, including three reviews and four original research articles that discuss the antibiotic secondary effects that are evident throughout all walks of life. The imperative review papers in the collection discuss the secondary effects of antibiotics on microbial biofilms  used transcriptomic approaches to reveal a global network of genes for tigecycline resistance, many of which were out-of-scope for the expected if this antibiotic simply inhibits translation, including changes in toxin-antitoxin systems, peptidoglycan biosynthesis and unrelated antibiotic resistance gene.Insights into the secondary effects of antibiotics can be gleaned through unbiased genome scale analyses, such as transcriptomics. Tigecycline is an important antibiotic in our arsenal, that is saved for the most difficult and deadly infections, like those caused by the notoriously resistant pathogen Shu et al., demonstrate that transfer of vancomycin resistance in Enterococcus faecalis increased dramatically when cells were treated with other antibiotics, namely streptomycin and spectinomycin. The finding that treatment with commonly used antibiotics leads to dissemination of plasmids encoding resistance to different antibiotics is a terrifying and problematic example of the knock-on effects of antibiotic usage.Vancomycin is used as the last line of defence against serious infections caused by a range of Gram-positive bacteria. Vancomycin resistant enterococci are widespread and on the WHO priority list of bacteria for which new antibiotics are urgently needed. Pheromone-induced conjugation facilitates rapid dissemination of antibiotic resistance in enterococci populations. Olateju et al. performed a range of assays to investigate this occurrence between quinoline antimalarials and the beta-lactam antibiotic ampicillin. This research revealed that chloroquine and quinine have limited antibacterial activity alone, but the combination of one of these compound and ampicillin results in at least additive bacterial inhibitory effects. This could be important in the design of treatments for malarial/bacterial co-infections.Microbial co-infections occur relatively frequently, particularly in situations where one pathogen is immunosuppressive, resulting in the need to co-administer different classes of antimicrobials. This raises a very interesting but complicated phenomenon, where the primary or secondary impacts of one antimicrobial may modulate the activity of others. Lee et al.) report that the oral administration of antibiotics may lead to further cognitive impairment in patients with brain ischemia. They demonstrate that oral administration of vancomycin and ampicillin to mice with brain ischemia, may lead to neuroinflammation, via the increased translocation of LPS into the brain caused by changes in their gut microbiome.Antibiotics are recommended to prevent pathogen infection in patients with brain injury, however in addition to reducing infection risk (Overall, these reported effects likely represent only the tip of the iceberg of the known secondary roles that antibiotics play within cellular environments. Antibiotics clearly lead a double life that is only now being revealed; in addition to being ruthless and effective killers of bacteria, antibiotics have multifaceted roles in nature that are often overlooked. Future research, especially those employing global molecular approaches, will allow us to fully comprehend the overall consequences of antibiotic treatment on both bacterial pathogens and host cells. Only then can we begin to understand and comprehend the full cellular effects of these complex killing molecules.All authors contributed to the drafting and editing of this editorial.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.


Iron ore tailings (IOTs) are gradually used as building materials to solve the severe ecological and environmental problems caused by their massive accumulation. However, the bulk density of IOT as aggregate is too large, which seriously affects the concrete properties. Therefore, in this paper, the effect of hydroxypropyl methylcellulose (HPMC) on the workability, mechanical properties, and durability of concrete prepared from IOT recycled aggregate was studied. The action mechanism of HPMC on the workability and the mechanical properties of the IOT concrete was analyzed by mercury intrusion porosimetry (MIP) and scanning electron microscope (SEM). The results show that HPMC can effectively improve the segregation problem caused by the sinking and air entrainment of IOT aggregate and improve the crack resistance of concrete with little effect on its compressive strength and electric flux. These results are due to the air-entraining thickening effect of HPMC, which improves the slurry viscosity, hinders the sinking of aggregate, and improves the workability. At the same time, HPMC film, after concrete hardening, will bridge the slurry and aggregate through physical and chemical effects, hinder the propagation of microcracks, and improve the crack resistance. With the continuous development of the global social economy, the consumption of concrete as a building material is increasing rapidly at the rate of 4.4 billion tons per year . More thIron has always played an essential role in the development of modern human civilization . After tCompared with the natural aggregate, the IOT aggregate in concrete is made from the waste stone stripped from the open-pit mine through crushing and screening . The IOTCellulose ethers (CEs) have been widely used in modern building products due to the function of preventing uncontrolled water loss into porous matrix . HPMC, aUntil now, researchers have studied the mechanism of different kinds of CEs in paste and mortar, but there are few reports of HPMC on concrete, especially the concrete used by IOTs as an aggregate. This paper focuses on the effect of HPMC on the workability of full IOT aggregate concrete. Moreover, the influence mechanism of HPMC on the mechanical properties of IOT concrete was also clarified.Cement (P.O. 42.5) is the main binder produced by Benxi Yuntian Cement Co., Ltd.  according to GB/T 175-2007 . The phyThe coarse and fine aggregates are formed by the IOT waste rock mechanism. The particle size of the coarse aggregate is 5–20 mm, while the fineness modulus of the fine aggregate is 2.2. The gradation compositions of coarse and fine aggregates are presented in The mixture design of IOT concrete in this paper is shown in The SJD60 concrete horizontal-axle mixer was selected for concrete preparation. The cement and fly ash were dry mixed for one minute, the aggregate was added for another minute, and water and SPs were added for another two minutes. Specimens of 100 mm cubes, 150 mm cubes, and 100 × 400 mm prisms were prepared for each concrete mixture. The 100 mm and 150 mm cubes were used to determine the compressive strength and splitting tensile strength tests. The prisms were used to evaluate the flexural strength test. The permeability test took a 50 mm thick round pie sample from a 100 × 200 mm cylinder. The samples were cured under ambient conditions for 1 d, demolded, and further cured in a standard curing tank at a temperature of 20 ± 2 °C and humidity of more than 95% until the aging.The slump, expansion, and entrained air content of the IOT concrete were measured. The slump and expansion tests were conducted by ASTM C143-15a . The entThe mechanical properties of IOT concrete were determined using a universal testing machine with a loading capacity of 2000 kN following the Chinese Standard GB/T50081-2002 . The loaTo determine the chloride ions charge in the concrete specimen, the Chloride penetration tests were conducted according to ASTM C1202 . The cylThe mercury intrusion porosimetry (MIP) testing instrument is AutoPore IV 9500, produced by the Micrometrics Instrument Corporation. The relationship between the applied pressure and the cylindrical pore diameter is described by the Washburn equation . The totThe slices were cut, immersed in isopropanol, and dried in an oven. Then, the slices were immersed in epoxy resin under vacuum for about 30 min and placed for hardening for one day. The hardened sample was first polished on sandpaper (320#) so that the sample surface was completely exposed, and the sample edge could be seen under the irradiation of a fluorescent lamp. Then, the samples were polished to 1 μm until the sample surface was smooth and flat on the polishing machine, using diamond suspension as the polishing solution and gasoline as a lubricant. The sandpaper grades used ranged from 800#, 1000#, 1200#, 1500#, 2000#, 2500#, to 4000#. According to the sample surface conditions and each grinding condition, the grinding time ranged from 20 to 60 s. In order to avoid the influence of residual diamond impurities and improve the efficiency of sample preparation, the samples need to be cleaned with ultrasonic in isopropyl alcohol solution during polishing. The polishing disc needed to be cleaned with a special detergent and brush. After polishing, the samples were stored in a vacuum dryer for 2 days to remove the residual organic solvent and avoid polluting the probe inside the scanning electron microscope (SEM). The samples were sprayed with carbon to form a carbon layer with a thickness of about 10 nm on the surface before the SEM test. The backscattered electron (BSE) images were obtained by FEI FEG quanta 650 field emission environmental scanning electron microscope with an accelerating voltage of 20 kV and a beam spot diameter of 3.0 nm.BSE was used to evaluate the properties of ITZ, and the image analysis was carried out to quantify the microstructure. The ImageJ software was used to remove the aggregate. For image binarization, a 5 μm strip was used. The proportion of the object image was obtained by dividing the number of pixels in the gray range of the object image by the total number of pixels in the strip. The multiples and resolutions of the images used were consistent.The iron ore tailings are generated by the waste rock mechanism stripped from the open-pit mine. Compared with ordinary natural aggregate, the IOT has a larger bulk density due to the iron content inside, leading to the natural sinking and difficulty of mortar binding with the aggregate . When IOThe addition of HPMC improves the fluidity of concrete, which is mainly due to the action of HPMC’s chemical groups to improve the water retention effect of concrete so that more mortar can well wrap the aggregate , Table 6The results of compressive strength tests of IOT concrete with and without HPMC are presented in 2+ and Al3+ to form a viscous gel and fill in the concrete internal void, playing a role of flexible reinforcement, thereby improving the compactness of concrete and increasing the splitting tensile strength. Moreover, smaller IOT powder enhances the bond between the aggregate and the matrix, improving the splitting tensile strength [The splitting tensile strength test was presented in strength .The flexural strength test results of IOT concrete with and without HPMC are displayed in The chloride ion flux results for HPMC0 and HPMC1 are displayed in The differential pore size distribution and cumulative porosity of HPMC0 and HPMC1 are shown in After curing for 28 days, the harmful pores and the total porosity for HPMC0 and HPMC1 have decreased compared to those cured for only three days Due to the iron content in tailings aggregate, the density is relatively large, which leads to the aggregate sink and separation. The surface activation of HPMC can induce air, retain water and thicken to improve the viscosity of mortar and aggregate, prevent tailings aggregate from sinking, and improve the workability of concrete.(2)Although HPMC can improve workability, it is not conducive to the development of compressive and flexural strength. However, it can improve the splitting tensile strength, which shows that the addition of HPMC can improve crack resistance.(3)2+ and Al3+ to form membrane structure, which plays a bridging role, hinders the propagation of microcracks, improves the splitting tensile strength of concrete, and then ameliorates the crack resistance of concrete.When the concrete is hardened, the air entrainment of HPMC will form pores and reduce the compressive strength and flexural strength. At the same time, HPMC reacts with Ca(4)The ITZ of ordinary C30 concrete is the key to affecting the concrete’s strength and its weakest link. The addition of HPMC increases more bubbles in the ITZ and reduces the compactness, which is not conducive to the development of strength. However, the final strength grade is consistent with that without HPMC. The chloride ion flux is about 1800, which does not affect the durability. Therefore, it is an effective measure to improve the workability of IOT concrete by adding HPMC.In this study, the effect of HPMC on the workability of IOT concrete was studied. Moreover, the influence mechanism of HPMC on the mechanical properties of IOT concrete was further clarified. Based on the experimental results, several conclusions can be drawn: