In this contribution, we reported the synthesis of a novel trifunctional POSS cyclic carbonate [POSS-3(5CC)]. With a difunctional five-member cyclic carbonate and a trifunctional polyetheramine as the precursor, the nanocomposites of polyhydroxyurethane (PHU) with POSS were synthesized. Transmission electron microscopy (TEM) showed that the nanocomposites of PHUs with POSS were microphase-separated; the spherical POSS microdomains via POSS-POSS interactions were generated with the size of 20~40 nm in diameter. After the introduction of POSS microdomains, the nanocomposites displayed improved thermal and mechanical properties. More importantly, the nanocomposites still displayed the reprocessing properties of vitrimers. Polyurethanes (PUs) are a class of important polymers, which have wide applications in various fields such as coatings, adhesives, foams, and textiles ,2. DespiIn the past years, there has been ample literature to report the synthesis and correlation of structure with properties of PHUs ,28,29,303O4 nanoparticles with five-membered cyclic carbonates. The surface-modified nanoparticles were readily incorporated into a PHU of erythritol-based five-membered cyclic carbonate with polyetheramine and the nanocomposites were successfully obtained. It was found that the nanocomposites exhibited excellent reprocessing and laser-induced shape memory properties.The incorporation of inorganics in organic polymers is an important technique to develop materials with excellent comprehensive properties. Recently, organic-inorganic nanocomposites of PHU with various inorganic nanoparticles have been also reported; the nanocomposites possess enhanced thermal, mechanical properties, and other specific properties ,38,39,40Polyhedral oligomeric silsesquioxanes (POSS) are a class of important organic-inorganic building blocks. POSS molecules have cage-like nanostructures; their corner silicon atoms were bonded with organic substituents, one or more of which is reactive or polymerizable. With these functional groups, POSS can be incorporated into organic polymers in the form of pendent groups or main chain structural units. Over the past years, mono-, di-, tetra- and octa-functional POSS macromers have been used to form the organic-inorganic nanocomposites with a variety of polymers ,48,49,50In this contribution, we first reported the synthesis of a novel tri-functional POSS five-membered cyclic carbonate [denoted POSS-3(5CC)]. The POSS macromer had an incompletely condensed and open cage-like nanostructure, which was in marked contrast to the completely condensed POSS cages ,52. Thisn-butylammonium iodide (TBAI), 4-dimethylaminopyridine (DMAP), 1,3-bis(hexafluoro-2-hydroxyisopropyl) benzene (BHFB), chlorodimethylsilane, allyl glycidyl ether, and sodium hydroxide were purchased from Adamas Co, Shanghai, China. Carbon dioxide (CO2) was supplied by Air Liquid (Shanghai) Co., Shanghai, China. Trifunctional polyetheramine under the trade name of Jeffamine-T403 was purchased from Sigma Co, Shanghai China and it had a quoted molecular weight of nM = 443 Da. Diglycidyl ether of bisphenol A (DGEBA)-based five-membered cyclic carbonate (denoted DE5CC) was synthesized following the approach of literature . Compared to the 1H NMR spectrum of POSS-3EP, the signals of resonance at 2.42, 2.58 and 3.01 ppm fully shifted to 4.22, 4.42, and 4.72 ppm as shown in 1H NMR results indicate that POSS-3(5CC) was successfully synthesized.The route of synthesis for trifunctional POSS five-membered cyclic carbonate [denoted POSS-3(5CC)] is shown in arbonate . The 1H 2) with a trifunctional polyetheramine . To ensure sufficient reaction of DE5CC, POSS-3(5CC) with Jeffamine T-403, the crosslinking reactions were started from the mixtures of DE5CC, POSS-3(5CC), Jeffamine T-403 with tetrahydrofuran. The reaction was carried out under the refluxing condition of tetrahydrofuran. Notably, the system was gradually gelled as the reaction proceeded. After the removal of solvent, the gelled products can be further processed (this will be addressed later). The PHU-POSS composites were subjected to Fourier transform infrared (FTIR) spectroscopy as shown in −1, which was attributable to the stretching vibration of the carbonyl group of five-membered cyclic carbonate. In the case of POSS-3(5CC), the stretching vibration band of the carbonyl group slightly shifted to 1803 cm−1. After the crosslinking reaction of DE5CC or/and POSS-3(5CC) with T403, notably, the carbonyl stretching bands fully disappeared; concurrently there appeared the new bands at 1698 cm−1, assignable to the stretching vibration of carbonyl groups in urethane structural units. The FTIR spectroscopy indicates that PHU and/or PHU-POSS networks were successfully obtained.The novel POSS macromer, POSS-3(5CC) was introduced into PHU to obtain the organic-inorganic composites. The control PHU network was obtained via the crosslinking reaction of a difunctional five-member cyclic carbonate which was synthesized from diglycidyl ether of bisphenol A (denoted DE5CC) and carbon dioxide (COTd’s), suggesting that the introduction of POSS cages did not significantly affect the thermal degradation of PHU networks. However, the composites displayed the retarded degradation or decomposition in the range of 600~700 °C. The higher the contents of POSS, the more pronounced the retardance of flame, indicating that the introduction of POSS significantly enhanced the thermal stability of PHU. The improved thermal stability was attributable to the following factors: (i) POSS itself had the higher thermal resistance than PHU; (ii) the introduction of POSS cages in the place of PHU segments restricted the release of gaseous products generated during thermal degradation. For control PHU, notably, the degradation, as well as decomposition, was undergone completion at 800 °C. For the PHU-POSS composites, however, there were still the residues of decomposition, the yield of which increased with increasing the contents of POSS. Assuming that the residues were only the inorganic component , which was rendered from the thermal degradation and oxidation of POSS cages, the yields of the degradation residues can be employed to calculate the contents of POSS cages in the composites with the following equation:POSS(wt%)W is the POSS content in the nanocomposites, POSSM is the molecular weight of POSS, 2SiOM is the molecular weight of SiO2, and 2SiOW is the residue yield at 800 °C. The calculated POSS contents were 3.2, 6.6, 12.1, and 15.3 wt%, respectively, which were slightly lower than the theoretical values.The control PHU and organic-inorganic composites were subjected to thermal gravimetric analysis (TGA). The TGA measurements were carried out with air atmosphere. In all cases, the two-step curves of degradations were displayed See . The firTransmission electron microscopy (TEM) was performed to investigate the morphologies of the PHU-POSS composites; the TEM images are shown in G′ and G″) was frequency-dependent. The values of G′ were higher than that of G″, indicating that the samples displayed the properties of elastic solids due to the generation of crosslinked networks. Notably, the values of G′ increased with increasing the contents of POSS. The increased G’ values are interpreted on the basis of the following aspects. On the one hand, the POSS microdomains have exerted the nanoreinforcement on the PHU matrix, which causes the enhancement of modulus. On the other hand, the POSS-POSS interactions with the POSS microdomains constituted the additional crosslinking, which resulted in the increase in modulus. To demonstrate the nature of physical interactions caused by the POSS microdomains, the rheological measurements with strain amplitude sweep were carried out and the data were presented in The POSS-POSS interactions were further investigated by means of rheological analysis. Tg’s were enhanced; the Tg’s increased with the increasing content of POSS. For the PHU-POSS20 sample, the Tg was increased to 51.1 °C. The increased Tg’s are associated with the following two aspects. On the one hand, the increase in Tg’s are ascribed to the nanoreinforcement of POSS microdomains on PHU matrices. The nanoreinforcement of POSS microdomains restricted the segmental motion responsible for glass transition. On the other hand, the increase in Tg’s is accounted for the generation of additional crosslinking with the POSS microdomains as the crosslinking sites. The additional crosslinking also constituted the restriction on the segmental motion of PHU. It should be noted that only the single Tg’s were detected although the TEM results showed that the PHU-POSS nanocomposites were heterogeneous. A possible explanation is that the Tg’s of POSS microdomains were too high to be tested. The nanoreinforcement of POSS microdomains and the additional crosslinking caused with the POSS microdomains were also evidenced by the fact that the storage moduli (E’) in the glassy and rubbery states were all higher than that of PHU.The thermal properties of PHU and PHU-POSS nanocomposites were studied by dynamic mechanical thermal analysis (DMTA). εb = 370% was exhibited. This observation is attributable to the fact that the PHU had the glass transition temperature  quite close to room temperature . Under this circumstance, there was intense segmental motion, which hindered the occurrence of forced high-elastic deformation. Upon introducing POSS, the segmental motions were restricted. Consequently, forced high-elastic deformation (viz. yield phenomena) occurred; the yield behavior was exhibited for PHU-POSS5, PHU-POSS10, and PHU-POSS15. Notably, the stress at the yield point increased with increasing the contents of POSS. For PHU-POSS20, a brittle fracture occurred due possible to the too strong nanoreinforcement of POSS microdomains. Notably, Young’s modulus and tensile strength increased with increasing the contents of POSS which was a result of the nanoreinforcement of POSS microdomains  by comparing the fracture energy of the samples, which are defined as the integral area below the stress-strain curves  was successfully synthesized. The POSS macromer was successfully introduced into the PHU networks and the organic-inorganic nanocomposites of PHU with POSS were successfully obtained. The nanocomposites had microphase-separated morphologies and the POSS cages were self-organized into the spherical POSS microdomains via POSS-POSS interactions with the size of 20~40 nm in diameter. Compared to control PHU, the PHU-POSS nanocomposites displayed the improved Young’s modulus and tensile strength. Notably, the PHU-POSS nanocomposites still preserved reprocessing properties although the recovery of the mechanical properties was slightly decreased with the introduction of POSS.


The construction industry relies heavily on concrete as a building material. The coarse aggregate makes up a substantial portion of the volume of concrete. However, the continued exploitation of granite rock for coarse aggregate results in an increase in the future generations’ demand for natural resources. In this investigation, coconut shell was used in the place of conventional aggregate to produce coconut shell lightweight concrete. Class F fly ash was used as a partial substitute for cement to reduce the high cement content of lightweight concrete. The impact of steel fiber addition on the compressive strength and flexural features of sustainable concrete was investigated. A 10% weight replacement of class F fly ash was used in the place of cement. Steel fiber was added at 0.25, 0.5, 0.75, and 1.0% of the concrete volume. The results revealed that the addition of steel fibers enhanced the compressive strength by up to 39%. The addition of steel fiber to reinforced coconut shell concrete beams increased the ultimate moment capacity by 5–14%. Flexural toughness was increased by up to 45%. The span/deflection ratio of all fiber-reinforced coconut shell concrete beams met the IS456 and BS 8110 requirements. Branson’s and the finite element models developed in this study agreed well with the experimental results. As a result, coconut shell concrete with steel fiber could be considered as a viable and environmentally-friendly construction material. In the building sector, concrete is the most extensively used construction material. After water, it is the second most-consumed material by humans . The manCoconut shell aggregate from agricultural waste has lately been used in concrete manufacturing ,27,28. C3, putting it in the lightweight concrete category. Reduced dead load, less seismic stresses, simpler formwork, reduced foundation area, enhanced fire resistance, better thermal insulating characteristics, good sound absorption behavior, better frost resistance, enhanced hydration of concrete, and easy transport of concrete are just a few of the benefits of lightweight aggregate concrete (LWAC). It also has a lower stiffness, which results in fewer micro-cracks, and a uniform distribution of cracks at the micro-level, which increases its durability in harsh environments [Furthermore, the challenges of the disposal and recycling of coconut shell trash have been greatly simplified. As a result, it might be an innovative method and a sustainable approach to concrete production for the benefit of the construction industry. Basri et al.  claimed ronments .2 emissions, the production of cement is a significant contributor to global warming [2 emissions. Furthermore, according to the research in this field, cement manufacturing accounts for 85% of the total CO2 emissions during the lifecycle of concrete structures [Due to its enormous CO warming . Concret warming ,36. Cemeructures ,38,39. Iructures ,41,42. Iructures ,46,47,48Because lightweight concrete (LWC) is 20–25% lighter than conventional concrete, its cheaper handling and shipping costs make it an attractive material . LWC hasIncorporating fibers into construction materials, on the other hand, has been practiced in various regions worldwide since ancient times. The necessity to improve the tensile capacity of the materials’ ‘perceived’ brittle properties was the driving force behind this work. This method was used to create fiber reinforced concrete (FRC) in the 20th century, which gained popularity in the building sector because of its increased strength. Steel fiber incorporation in the cement matrix improves the toughness, yield load, first cracking load, moment of resistance, and crack resistance of reinforced concrete beams subjected to transverse loading, according to research on fiber-reinforced concrete ,58,59,60Although there are plenty of previous studies on the mechanical characteristics of fiber-reinforced coconut shell concrete, the research into the flexural characteristics of steel fiber-reinforced coconut shell concrete RC beams through analytical and numerical analysis is rare. Hence, this study explored the influence of steel fibers at 0.25%, 0.5%, 0.75%, and 1.0% with a constant fly ash replacement of 10% on the compressive strength and flexural behavior of coconut shell concrete beams. Additionally, this study investigated the impact of steel fiber addition on the load-carrying capacity, crack resistance, and ductility of the steel fiber-reinforced coconut shell reinforced concrete beams under flexural testing to analyze its feasibility for use as structural concrete. The analytical and numerical analysis was carried out and the results were compared with the experimental results.2/g specific surface area and 3.13 specific gravity as specified by IS:12269-1987 [2/g specific surface area and 2130 kg/m3 density, respectively. As a fine aggregate, river sand confirmed as Zone II was employed. The coconut shell was taken from a local copra processing yard. The coconut shell was then crushed into smaller pieces. Crushed coconut shells with sizes of 12.5–4.75 mm were utilized as the coarse aggregate. Clean water was used to wash the produced coconut shell aggregate, which was then dried in the sun. Coconut shell aggregates require immersion in clean water for 24 h due to their high rate of moisture retention capacity. To attain the saturated surface dry (SSD) state of the coconut shell concrete, the soaked aggregates were then air-dried. The SSD state aggregate will not absorb water further, ensuring that the workability of the final product is unaffected. The binder taken for this investigation was ordinary Portland cement  grade 53 with a 3350 cm269-1987 . As a suIn total, five mixes for the plain coconut shell and steel fiber-reinforced coconut shell concrete beams were cast. The compressive strength test on 100 mm cube specimens was tested as per IS:516-2014. The flexural strength was determined using 100 mm × 150 mm × 1700 mm size reinforced concrete beams. The bottom side of the RCC beams was reinforced with two 10 mm diameter bars. The top side was reinforced with two 8 mm diameter bars. Stirrups of 6mm diameter bars at 90 mm center to center were provided at the supports. The flexural strength test was carried out in a 500 kN loading frame. The experimental setup consisted of four-point loading with pinned supports on both ends of the beam. The pinned supports at a span of 1500 mm were used. The distance between the point loads was 500 mm. The load was applied at a loading rate of 2.3 kN/s until ultimate failure using a load cell connected to the datalogger. The linear variable displacement transducers  were used to determine the deflection at the midspan and one-fourth point of span. The deflection was measured for each load increment. The experimental setup is shown in As is widely-known, steel fiber addition has a stronger influence on the concrete compressive strength than synthetic fibers. Steel fibers have a higher strength, length, and modulus of elasticity than the other fibers. All of the specimens  showed tThe experimental moment capacity values beams are shown in Furthermore, when the fraction of the steel fiber addition was less than 0.50%, the beam generated a small increase in the moment capacity. The increase is expected to be between 8% and 12%. In comparison to a plain coconut shell concrete beam, when the steel fiber addition exceeded 0.5% volume fraction (0.75 and 1%), the beam generated a significant improvement in moment capacity (10–14%). This result indicates that a minimum of 0.5% steel fiber is required to significantly increase the moment capacity of steel fiber-reinforced coconut shell concrete. Because the fibers are randomly dispersed across the cross section of steel fiber-reinforced coconut shell concrete beams (tension and compression zones), the tension and compression toughness is enhanced, resulting in a significant increase in the flexural load capacity.The actual and theoretical moments of a steel fiber reinforced coconut shell concrete beam are compared in The load–deflection behavior of all specimens with and without steel fibers is shown in The ratio between the span and service load deflection should not exceed 250 in order to fulfil the serviceability limit state as defined by IS456 and BS 8110. The aggregate stiffness was influenced by the porous structure and low density of CS. As a result, the modulus of elasticity of concrete produced using the CS aggregate was low. Due to the low modulus of elasticity of the coconut shell concrete, the displacement within the service loads for singly reinforced beams is acceptable since the span–deflection ratios of the mix CS were 555, which is well within the permitted limit set by IS456:2000 and BS 8110. To meet the serviceability standards of the beams, IS 456 and BS 8110 propose a permitted limit of span/250 for the deflection. According to IS456 and BS 8110, the span/deflection ratio of the fiber-reinforced coconut shell concrete such as CSF25, CSF50, CSF75, and CSF100 is likewise within the permitted range.Once the yield stage is reached, the fibers play a critical role in the post-yielding flexural characteristics of the steel fiber-reinforced beams. The difference in deflection at the ultimate and yield stages of the beam can be used to achieve this. Once the bars yielded, the applied load was not only accepted by the reinforcement, but was also transferred from the steel reinforcement to the concrete in order to attain a new equilibrium. The steel fiber led to fiber–matrix interfacial bonding, which enhanced the concrete beam’s load bearing capability over a protracted deflection. In the yielding and final phases, this improves the toughness of the steel fiber-reinforced coconut shell concrete beams.gI represents the gross moment of inertia without reinforcement, while crI represents the cracking moment of inertia. The service moment is aM, and the first cracking moment is crM. Deflection at mid-span for each beam with two symmetrical points load is calculated using Equation (2).aM is the moment acting on the beam; “a” is the distance between the load location and the support; E is the concrete’s elastic modulus; L is the beam’s span; and I is the moment of inertia. Because I is not constant while the concrete beam is loaded, it is substituted by the term eI, which gives the effective value of the moment of inertia of the beam. Deflection can be precisely determined experimentally. When the experimental value is entered into Equation (3), the experimental eI may be calculated as shown in Equation (3).Branson  suggestem) can be written as:From Equation (1), the power value (m) in Branson’s calculation for beams should be about 4.2. The revised Branson’s equation for coconut shell concrete beam is given by Equation (5).Regression analysis for the whole service load was conducted using the experimental moment of inertia obtained. The results suggested that the average power value . The solid can rupture under strain and crush under compression. The element is defined by eight nodes, each of which has three translational degrees of freedom in the The consideration of nonlinear material properties is the most critical part of this element. The concrete can crack , crush, distort plastically, and creep. The reinforcing bar can withstand tension and compression, but not shear. Additionally, they can undergo plastic deformation and creep. BEAM188 is appropriate for assessing thin to moderately stout/thick beam structures. The element is founded on the Timoshenko beam theory, which accounts for the shear–deformation phenomena. The element gives options for unconstrained and constrained cross-section warping.By default, the element incorporates stress stiffness terms in any study with significant deflection. The provided stress–stiffness terms allow for elements to examine the flexural, lateral, and torsional stability issues .TARGE170 is utilized for a variety of 3D ‘target’ surfaces and the accompanying contact elements such as CONTA173, CONTA174, CONTA175, CONTA176, and CONTA177. The contact elements themselves overlay the solid, line elements, or shell, so characterizing the border of a deformable body, and may be in contact with the target surface, as described by TARGE170.Creating a model for concrete behavior is a difficult endeavor. Concrete is quasi-brittle and behaves differently under compression and strain. In this investigation, material nonlinearity was utilized. From the experimental results, the elastic modulus and flexural strength of all the combinations were determined. The FEA comprised the modeling of beams with experimentally-determined sizes and mechanical properties. To generate the FEM in ANSYS, numerous steps must be undertaken for the model to function correctly. Models may be produced using either a graphical user interface or a command prompt.In the first step of the FEA, the beam model is meshed. The beam model is subdivided into numerous smaller pieces during meshing. After applying a load, the stress and strain are determined at the points of integration of smaller parts. Mesh density selection is one of the primary processes in finite element modeling. When a model contains a sufficient number of elements, the convergence of outcomes is achieved. Practically, this is achieved when an increase in mesh density has a negligible impact on the outcomes. In order to determine the optimal mesh density for this finite element modeling, a convergence analysis was conducted. The finite element models duplicated the dimensions of the full-scale beams. With an increasing number of smaller parts, 100 mm × 150 mm × 1700 mm beams with their real material properties were modeled using ANSYS. The response parameters for beams are the deflection of the bottommost fiber at midspan and the compressive stress on the topmost fiber at midspan. The convergence of findings is attained when a sufficient number of smaller model elements are utilized. When the density of the mesh is increased, convergence issues may emerge. The needed mesh density is determined solely from trial solutions. All of the nodes were blended together to create a rigid model.To obtain accurate results from the SOLID65 element, a higher order 3D solid element with 20 nodes and quadratic displacement behavior is employed. With the aid of the meshing tool menu, meshing is performed. The mesh tool menu contains a global set holding the size of the element’s divisions, which determines the element’s size. As the number of elements increases as the size of the element lowers, the findings obtained are accurate. As the number of elements increases, so does the time required to solve the problem under the given load, necessitating an increase in computer memory capacity. Due to the extremely small diameter of reinforcing bars, the above-described process for meshing reinforcing bars necessitates a significant reduction in the bar element size. The meshed model is shown in The finite element models were loaded in the identical places as the actual beams. The model must be constrained by displacement boundaries in order to yield a unique output. To ensure that the model behaves identically to the experimental beam, boundary conditions are implemented at the points of symmetry where the supports and loads exist. The beam was designed with a hinged support at one end and a roller at the opposite end.The model’s FEA was configured to investigate the beam’s various behaviors. Linear analysis was performed to identify the deflection, stress–strain graphs, and experimental values for validation. Newton–Rapshon equilibrium iterations are used in ANSYS software. Newton–Rapshon equilibrium iterations give convergence within tolerance limits at the conclusion of each load phase. To avoid the divergence issue, a force convergence criterion with a tolerance limit of 5% was applied. The number of equilibrium iterations required was increased to 100. The stress contour shown in On observing the strain pattern obtained from the finite element analysis from This research explored the outcomes of the experimental and theoretical analyses of the steel fiber-reinforced sustainable concrete made with coconut shell, an agricultural waste, as coarse aggregate and class F fly ash, an industrial by-product as a partial substitute for cement. The influence of steel fiber at up to 1% volume fraction on the compressive strength and flexural characteristics of fiber-reinforced coconut shell concrete were investigated. The experimental flexural characteristics were compared with the analytical as well as numerical study developed in this investigation. The following conclusions were drawn.-Steel fiber inclusion enhanced the compressive strength of coconut shell concrete from 15% to 39%.-A typical flexural failure was seen in plain coconut shell concrete beams and steel fiber-reinforced coconut shell concrete beams.-Adding steel fibers to coconut shell concrete beams enhanced their ultimate moment capacity by 5–14%. When the steel fiber content was more than 0.5%, the moment capacity and crack resistance of the steel fiber-reinforced coconut shell concrete beam specimens were enhanced significantly.-It was found that when compared to the non-fibrous beams, all fiber-reinforced beams showed a reduction in ductility, which can be attributed to strain localization. The ductility ratio for structural ductility was met by all of the fiber-reinforced coconut shell concrete beams.-The experimental moment capacity of all of the beams was found to be higher than the theoretical moment capacity. Because the equations specified in codes such as IS and BS are not intended for fiber-reinforced concrete components, the observed moment capacity and displacements of the steel fiber-reinforced coconut shell concrete beams either overestimated or underestimated the theoretical values.-The steel fiber addition increased the flexural toughness of the coconut shell concrete beams up to 45%.-According to IS456 and BS 8110, the span/deflection ratio of all of the fiber-reinforced coconut shell concrete beams was found within the permitted range.-For the fiber-reinforced coconut shell concrete beam, Branson’s model was developed, and the findings were in good agreement with the experimental data.-The finite element models were created and analyzed using ANSYS. The findings of all of the finite element beams demonstrated that the ultimate loads were close to the experimental values. The measured deflection agreed reasonably with the deflection derived from the finite element calculations.Coconut shell concrete with the partial replacement of fly ash can be used as an eco-friendly building material because coconut shell is a renewable and naturally available resource while fly ash is a type of industrial waste. The addition of steel fiber further enhanced the mechanical and flexural performance of coconut shell concrete, thereby making it feasible for structural applications. Consequently, the development of steel fiber-reinforced coconut shell concrete with fly ash blends will contribute to the sustainability of the concrete industry.


BLM is sumoylated in response to replication stress. We have studied the role of BLM sumoylation in physiologically normal and replication-stressed conditions by expressing in BLM-deficient cells a BLM with SUMO acceptor-site mutations, which we refer to as SUMO-mutant BLM cells. SUMO-mutant BLM cells exhibited multiple defects in both stressed and unstressed DNA replication conditions, including, in hydroxyurea-treated cells, reduced fork restart and increased fork collapse and, in untreated cells, slower fork velocity and increased fork instability as assayed by track-length asymmetry. We further showed by fluorescence recovery after photobleaching that SUMO-mutant BLM protein was less dynamic than normal BLM and comprised a higher immobile fraction at collapsed replication forks. BLM sumoylation has previously been linked to the recruitment of RAD51 to stressed forks in hydroxyurea-treated cells. An important unresolved question is whether the failure to efficiently recruit RAD51 is the explanation for replication stress in untreated SUMO-mutant BLM cells. DNA replication is a highly coordinated process involving many protein factors. Some factors are stably associated with the replication fork, carrying out functions related to chromosome duplication, whilst other factors associate with the fork when replication is perturbed by DNA damaging agents or inhibitors of polymerases . Some faBlm mouse model  is an inhibitor of ribonucleotide reductase that stalls replication forks by reducing by approximately 50% the levels of dATP and dGTP . BLM aloin vitro, suggesting sumoylation of BLM is required for efficient recruitment and retention of RAD51 to collapsed replication forks mediated by a SUMO interaction motif  was performed as previously described . BrieflyFor assessment of fork restart, cells were pulse-labelled with 100 µM IdU for 40 min. Cells were then treated or not with 2 mM HU for 5 h and subsequently released into fresh medium containing 100 μM CldU for 40 min. Signals corresponding to fork restart , fork collapse and termination (IdU label only), and new origin firing (CldU label only) were scored and expressed as a percentage of total signals. For measurement of fork velocity, fork density, and IdU/CldU ratio, cells were sequentially pulse-labelled with 100 μM of IdU and CldU for 40 min.IdU/CldU ratio were calculated as the ratio of the longest track over the shortest, thus all ratios are ≥ 1 . Fork de1/2. Error bars represent SEM across three independent experiments.BLM+ or SM-BLM cells were treated with 2 mM HU for 24 h and imaged using Leica SP5-II confocal microscope using a 40x/1.25NA PL Apo (oil) lens. Single-foci regions of interest (ROIs) were photobleached using a VIS Ar-488 laser. Recovery was obtained for 1 minute following bleaching at 0.5 s intervals. Time to half of maximum recovery was calculated and represented as TCells were lysed in RIPA buffer supplemented with 5 mM EDTA, 1 mM EGTA, 25 mM sodium fluoride, 1 mM sodium orthovanadate, 1 mM phenylmethane sulfonyl fluoride (PMSF) with 1x EDTA-free protease inhibitor . Protein concentration were measured using Pierce 660 nm Protein Assay. 15 μg of total protein from cell lysates were separated by electrophoresis through Bio-Rad 4%–15% acrylamide mini-PROTEAN TGX gels or Bio-Rad Criterion 10% acrylamide TGX gels, and transferred onto Amersham™ Protran™ 0.45 μm nitrocellulose membranes by semi-dry transfer. To control for protein loading and transfer, prior to blocking, the membranes were stained with Ponceau S (Sigma P7170) for 5–10 min, washed two times with 1% glacial acetic acid in water, and imaged. Membranes were blocked for 1 h in either Tris-buffered saline (TBS) with 5% Bio-Rad Blotting-Grade Blocker, or Prometheus OneBlock Western-CL Blocking Buffer, then incubated with primary antibody in 5% BSA in TBS + 0.1% Tween-20 overnight at 4°C. After washing with TBS-T the membranes were incubated with secondary antibodies ; imaging was done on a Syngene G: Box Chemi gel documentation system. Primary antibodies for immunodetection were obtained as follows: anti-BLM , anti-CHBLM-deficient cells showed a reduced frequency in fork restart, which was associated with increased fork collapse  and SUMO-mediated protein degradation through the ubiquitylation activity of RNF4 keep the steady-state levels of sumoylated protein low. Based on Western blot analysis of cell lysates and immunoprecipitated BLM, under uninduced conditions the steady-state levels of sumoylated BLM are less than 2% of total BLM protein , but witOur data suggested fork stalling is more severe in SM-BLM cells compared to BLM-deficient cells based on the γ-H2AX, RPA, and RAD51 phenotypes and based on our measure of fork instability using the IdU/CldU ratio. However, In genetic terms, the SUMO lysine to arginine substitutions of BLM at amino acids 317 and 331 are separation-of-function mutations. Sumoylation appears to strongly influence BLM’s associations with two central factors in homologous recombination by diminishing its interaction with RAD51 and increasing its interaction with RPA, without affecting its DNA helicase activity yet increasing its affinity for ssDNA . BLM is The most striking of the replication defects in SM-BLM cells related to the reduction in fork velocity, which exhibited a more severe phenotype compared to BLM-deficient cells. The FRAP results showed that SUMO-mutant BLM is less mobile at stalled forks, suggesting that sumoylation regulates protein turnover there and possibly relieves some inhibitory activity of the BLM complex. It may also destabilize interactions with protein factors besides RPA. Recently, it was shown that BLM interacts with MCM6 and disruption of BLM interaction with MCM6 results in increased fork velocity in unperturbed cells . These rWith regards to the mechanism by which BLM sumoylation facilitates the function of the replisome in unperturbed, physiological normal DNA synthesis, we suggest the following model. There is evidence in yeast that SMC5/6 complex is a sensor of fork slowing or pausing . SMC5/6 As noted above, SM-BLM was less mobile at stalled forks, suggesting that one role of sumoylation is to control the turnover of BLM during replication stress. Consequently, we might expect that inhibition of the processing of SUMO-BLM by the STUbL RNF4 by siRNA depletion might produce some similar phenotypes by leaving an excess of immobile, albeit sumoylated, BLM protein at sites of damage. We recently reported that SUMO-BLM is a substrate of RNF4 and RNF4 depletion led to a hyper-accumulation of SUMO-BLM at collapsed forks generated by prolonged HU treatment . ConsequIn a careful examination of other phenotypes, we noted little phenotypic concordance between SM-BLM cells and RNF4-deficient cells. The differences are enumerated as follows : 1) NumbCancer cells are often sensitive to the induction of replication stress. The manifestations described here of replication stress under physiologically normal conditions in cells that express a SUMO-mutant BLM suggest that inhibition of BLM sumoylation could make a useful target for chemotherapeutic development. The technical challenge of achieving specific anti-sumoylation activity with a small molecule might be approached through inhibiting BLM’s interaction with the SUMO E3 ligase NSMCE2. More broadly, the genomic and chromatin-associated characteristics of difficult-to-replicate DNA and of the role of sumoylation and other responders to replication stress in facilitating replication fork translocation across these regions are of fundamental importance to our understanding of the process of faithful chromosome duplication.


This paper investigates the properties of white high-strength concrete (WHSC) prepared with ground limestone powder (GLP). Response surface methodology (RSM) was used to design the proportions of mixes and evaluate the influence of the water–binder ratio (w/b), slurry volume fraction (Vs), and the content of GLP in a binder (Cg) on the slump, whiteness and compressive strength of WHSC via Box–Behnken equations. Results indicate that quadratic polynomial regression equations can be used to predict the performance of WHSC as influenced by combined factors. Both slump and compressive strength of WHSC are found highly influenced by w/b while GLP significantly improves the whiteness of WHSC. An optimal mix proportion of WHSC is provided by the multi-objective optimization with high-accuracy predictions. This paper demonstrates the feasibility of preparing WHSC with GLP and presents the potential of using RSM in the mix proportioning of concrete. White concrete is attracting increasing attention from architects worldwide ,2,3,4. HWith the increasing shortage of river sand, manufactured sand, especially limestone manufactured sand, has been gradually taken as a main fine aggregate for concrete ,9. NormaGrinding has been proven as an effective solution to improve the properties of limestone powder. It is found that ground stone powder can improve the working performance and strength of concrete compared with ordinary stone powder . HoweverHowever, the interactions between multiple parameters and properties make it a challenge to identify the optimal mix proportion from simple orthogonal experiments, as a large number of samples are required. From this viewpoint, numerical methods can be used for analyzing the covered relationship between properties and mix proportions. Response surface methodology (RSM) has been one of the most useful tools to explain and establish the mathematical relation between input variables and the output responses . It invos), and the content of GLP in a binder (Cg) on the workability, whiteness, and compressive strength of WHSCs were analyzed via RSM. In addition, the optimal mix proportion is predicted and validated.Therefore, this paper investigates the potential of GLP as the mineral admixture to prepare white high-strength concrete. The influence of the water–binder ratio (w/b), the slurry volume fraction , with a solid content of 21.3% and a water-reducing rate of 27.5%.3 was used as the fine aggregate. Crushed gneiss with a diameter between 5 mm and 25 mm was used as the coarse aggregate.River sand with a fineness modulus of 2.5 and a density of 2.62 g/cmg, represented by factors A, B, and C, respectively. Factors and factor levels of independent variables are shown in Different model types exist in the RSM analysis package, including Box–Behnken, Central Composite, historical, and so on. In Box–Behnken design, factors are usually taken at three levels and all the design points fall within the safe operating zone. It is considered to be more proficient and powerful than other designs. In addition, it is typical for three input variables, which is the case in the current study. Thus, it is used for experimental design and data analysis. The independent variables used are w/b, Vs, and CThe workability of fresh concrete mixtures was measured via the slump test according to the Chinese national standard GB/T50080-2016 .The compressive strength of hardened concrete mixtures was tested according to the Chinese national standard GB/T50081-2019 .Whiteness was measured according to the Chinese national standard GB/T 5950-2008 . BrieflyThe micro morphology of the hardened mixtures at 3 days and 28 days was observed by a scanning electron microscope  with an accelerated beam current of 80 mA and a voltage of 20 kV.The slump, whiteness, and 28-day compressive strength of the WHSCs formed from the mixing proportions defined in p. The smaller the probability , the more significant the model is. Specifically, p < 0.01, 0.01 < p < 0.05, and p > 0.05 represent very significant, significant, and not significant, respectively. It can be seen from p-values of the quadratic polynomial model are the smallest while the corresponding mismatched p-value, adjusted value of the coefficient of determination (R2), and predicted value of R2 are the largest. Similar results can be found for both whiteness and compressive strength. Therefore, the quadratic polynomial model is used in the modeling.The statistical significance of the hypothesis testing analysis and mismatch test analysis is expressed by 1), whiteness (Y2), and compressive strength (Y3) are shown in Equations (1)–(3), respectively.The response surface Box–Behnken analysis was used to perform a multiple regression fitting of the test data in p-value indicates that the model has a stronger significance and a higher simulation accuracy. The p-value of the mismatch term reflects the significance of the non-correlation between the test data and the model. When p < 0.05, i.e., the 95% confidence interval, the significance is high. p values of the concrete slump (Y1), whiteness (Y2), and compressive strength (Y3) models are 0.0152, 0.0039, and 0.0155, respectively, and the F values are 5.79, 9.22, and 5.76, respectively. Thus, these values are significant, and the whiteness and compressive strength values are very significant. Among the three single factors, w/b (A) and Cg (C) are significant while Vs (B) is not significant. Additionally, the order of influence on the slump is C > A > B. Similarly, it is also found that the whiteness of concrete is significantly influenced by C but not A or B. The order of influence on concrete whiteness is C > B > A. In addition, the compressive strength is significantly influenced by A, but not by B or C. The order of influence on compressive strength is A > C > B.R2 values can be used to verify the fitting degree of a regression equation. In addition, the smaller the value for the coefficient of variation (CV), the higher the reliability and accuracy of a test for the signal-to-noise ratio greater than four. 1, Y2, and Y3, respectively. In addition, the R2 values of predictions for Y1, Y2, and Y3 are 0.8816, 0.9222, and 0.8810, respectively. The adjusted values of R2 are 0.7294, 0.8221, and 0.7280, respectively, while the CVs are 2.54%, 2.44%, and 3.75%, respectively. It is thus inferred from the above data that the developed models have high reliability and accuracy.The closeness of the adjusted and predicted The 3D plots of the slump with variations of various parameters are shown in The 3D plots of concrete whiteness with variations of various parameters are shown in The 3D plots of 28-day compressive strength with variations of various parameters are shown in 3S). This decreases the concentration and directional arrangement of calcium hydroxide crystals at the interface, which increases the content of C-S-H at the interface, thus providing nucleation sites for hydration products [The SEM images of concrete mixtures with GLP are shown in products ,35. As cMixture optimization is performed to determine the optimal mix proportion by maximizing the slump, whiteness, and compressive strength. A target criterion is set up so that all the possible combinations for the variables and responses are captured. The internal optimization program of Design-Expert software is used to optimize the mixing proportion parameters of WHSC. The optimal mixing proportion parameters of WHSC are obtained with a w/b of 0.333, a Vs of 0.326, and a GLP content of 22.4%. Accordingly, a WHSC was prepared with the optimized mix proportion parameters, followed by the measurement of properties with results shown in D is the relative error, E is the experimental value, and p is the predicted value.It is demonstrated that the relative error between the test value and the predicted value is less than 2%, indicating the favorable predicting performance of the developed model. Therefore, WHSC with preferred multi-objective properties is obtained by the multi-objective optimization of RSM.The slump, whiteness, and compressive strength can be well predicted by the Box–Behnken models with high accuracy.g show moderate influence.Both slump and compressive strength of concrete are significantly influenced by w/b while Vs, and Cs.Increased GLP content significantly improves the whiteness of high-strength concrete while this property is negligibly influenced by w/b and Vg of 22.4%.Multi-objective optimization is performed via RSM to provide optimized mix proportion with the maximized slump, whiteness, and compressive strength. The optimal mix proportion is the w/b of 0.333, Vs of 0.326, and CIn this paper, RSM is used to evaluate and predict the properties of WHSC prepared with GLP. The following conclusions can be drawn from the findings.This paper demonstrates the feasibility of preparing WHSC with GLP, meanwhile presenting the potential of using RSM in mix proportioning of concrete.


The construction of subways, hydroelectric stations and water substations is exposed to stray currents, which can accelerate concrete corrosion. The influence of stray currents on reinforced concrete structures is unclear. In this paper, the influence of concrete strength grade, reinforcement diameter and stray current intensity on the extent of reinforcement corrosion and calcium ion dissolution were investigated, and the damage of reinforcement and calcium ion corrosion to concrete strength was investigated by simulating a stray current environment and conducting an electrified acceleration test. The test results show that the higher the strength grade of concrete, the lower the stray current intensity and the smaller the corrosion rate and calcium ion dissolution rate of reinforcement; with the increase in the diameter of reinforcement the corrosion rate decreases, but the calcium ion dissolution rate is not affected by reinforcement diameter. The damage effect of reinforcement corrosion on concrete compressive strength is more obvious than that of calcium ion corrosion. The metros in Chinese cities use direct current traction power supply systems. However, the insulation between the walking track and the metro bed is not completely sealed, and there will be part of the direct current based from the walking track leakage . In the The concrete structures of subways, hydropower stations and water substations often work in water-saturated environments and suffer from the corrosion of stray currents . The con2 of concrete was decomposed under the action of stray currents, which deteriorated the pore structure of concrete. The research of Yang [In recent years, with regard to the research on the durability of reinforced concrete under the action of water-saturated environments and stray currents, some studies have found that when the concrete structures working under water-saturated environments are corroded by stray currents, the reinforcement in the concrete will accelerate corrosion and the concrete itself will undergo electrochemical corrosion ,7. Ekstr of Yang  shows th of Yang  pointed However, in stray current environments, the reinforcement corrosion and calcium ion corrosion of concrete structures in water-saturated environments occur at the same time . Most ofIn this paper, the influence of reinforcement corrosion and calcium ion corrosion on water-saturated concrete strength under stray currents is studied.The cement was P·O 42.5 ordinary Portland cement. Its chemical composition is shown in In order to simplify the later calculation, the cube specimens’ dimensions were 100 mm ×100 mm ×100 mm. They were cured under standard conditions for 28 days. The length of the reinforcement was 80 mm. After derusting and weighing, the external conductor was connected. The erection size was 70.7 mm × 10 mm × 1 mm acrylic plate to ensure that the reinforcement was in the center of the concrete after pouring, as shown in The specific grouping and main parameters are shown in Before the test, the test pieces were immersed in deionized water for 270 h, so that the test pieces were nearly water saturated ,13, and M is the initial mass of CaO contained in a single concrete specimen (mg); m is the mass of CaO dissolved from a single concrete specimen (mg); B is the amount of cement in concrete mix proportion (kg/m3); 62.1% is the mass fraction of CaO in cement clinker; During the electrification test, the corrosion current flowing through the specimen and the development of cracks on the concrete surface were measured. When each group of tests reached the preset test energization time, the power supply was turned off, the test block was taken out of the electrolytic cell, a resistivity test and compressive strength test were conducted on the test block, and the calcium ion dissolution amount in the electrolytic cell was measured. The calcium ion dissolution rate was calculated according to Equations (1) and (2). After the compressive strength test was completed, the reinforcement from the concrete was taken out and the corrosion rate of the reinforcement was calculated according to Equation (3).Through the test of 9 groups of specimens after corrosion, a total of 45 data of rebar corrosion rates and 45 data of calcium ion dissolution rates were obtained, and the change rules of rebar corrosion rate and calcium ion dissolution rate under different strength grades, rebar diameters and energizing voltage with energizing time were obtained . The absWith the same diameter of reinforcement and the same energizing voltage, the smaller the strength grade of concrete, the more serious the corrosion of reinforcement and the smaller the critical corrosion rate at the time of concrete cracking. For example, after 100 h of power on, the corrosion rate of reinforcement in C25 concrete is 2.32%, and the rate in C35 concrete is 1.98%. Compared with the latter, the corrosion rate of reinforcement in the former increases by 17.17%. This is because the corrosion rate of reinforcement is affected by the water–cement ratio of concrete. The water–cement ratio of C25 concrete is 0.52, and the water–cement ratio of C35 concrete is 0.66. The smaller the water–cement ratio, the denser the concrete paste and the greater the concrete resistance, making the current through the reinforcement in the concrete smaller;With the same strength grade and energizing voltage, in the same energizing time, the larger the diameter of the reinforcement in the concrete specimen, the lower the corrosion rate and the later the crack occurs. It can be seen from With the same strength grade and reinforcement diameter, under the same energizing time, the greater the energizing voltage, the more serious the corrosion of reinforcement in the test piece. For example, the final corrosion rate of reinforcement under 40 V corrosion is 2.18 times that of 20 V. It can be seen from From The corrosion degree of low-grade concrete specimens is more serious than that of high-grade concrete specimens. For example, when the reinforcement diameter is 12 mm, the energizing voltage is 40 V and the energizing time is 100 h, the calcium ion content of C25 test piece is 0.561%, the calcium ion content of C30 test piece is 0.464%, and the calcium ion content of C35 test piece is 0.384%. This is because the water–cement ratio of the concrete with small strength grade is large, the porosity in the cement stone matrix is large, and the calcium ion in the concrete is easier to penetrate into the pore solution;At the same strength level and energizing voltage, the different diameters have no obvious effect on the corrosion results. For example, the calcium ion dissolution rates corresponding to the diameters of the three kinds of reinforcement after 100 h of power on are 0.384, 0.387%, and 0.385%, respectively, and the difference from the average is within 0.1%;When the voltage applied to the test piece is different, the dissolution rate of calcium ions is different. In the selected voltage range, the higher the voltage, the higher the dissolution rate of calcium ions. For example, when the voltage is 20 V, the dissolution rate of calcium ions is 0.27%, while the value is 0.374% when the voltage is 30 V, and the corresponding dissolution rate is 0.464% when the voltage is 40 V.From cf is the original compressive strength (MPa); d is the diameter of reinforcement (mm); U is the corrosion voltage (V); t is the power on time (h); γ is the corrosion rate of reinforcement (%); 2 of the model 2 of the model Nonlinear regression fitting was carried out on the 9 groups of data in the above analysis and the regression equations of each parameter on the corrosion rate and calcium ion dissolution rate of reinforcement were obtained, as shown in Equations (4) and (5).The larger the corrosion current flowing through the concrete, the faster the ion migration and the more calcium ions are dissolved . When thIt can be seen from Under the condition of keeping the electrified voltage constant, the corrosion of reinforcement affects the corrosion indirectly by affecting the corrosion current, and with the development of reinforcement corrosion, the dissolution rate of calcium ions gradually decreases. Therefore, it can be predicted that the corrosion behavior of calcium ions in concrete under stray currents will slow down with the increase in corrosion degree of reinforcement.Three groups of concrete specimens, C30-14-20, C30-14-30 and C30-14-40, before and after the electrical test were tested by an RST Electrochemical Workstation, and the AC impedance spectra of the specimens were obtained, as shown in It can be seen from In the AC impedance spectrum, the real resistance corresponding to the smallest imaginary impedance is called the volume resistance and is represented in the diagram as the real resistance at the junction of the high and low frequency regions. The volume resistance is equivalent to the DC resistance of the component under test . AccordirD and calcium ion dissolution rate, as shown in Equation (6). The data of calcium ion dissolution rate and volume resistance loss rate of three groups of concrete specimens are fitted with Exp function to obtain the functional relationship between volume resistance loss rate As far as this experimental device is concerned, the concrete specimen, electrolyte, reinforcement and stainless-steel plate can be regarded as a circuit with series resistance. Although the concrete resistance gradually decreases with the increase in the calcium ion dissolution rate, the corrosion of reinforcement leads to the increase in the interface resistance between reinforcement and concrete. The corrosion current does not increase with the decrease in the concrete resistivity, so it can be seen that the total resistance of the circuit increases during the electrification process, indicating that the decrease in the concrete resistance is smaller than the increase in the reinforcement concrete interface resistance.To sum up, calcium ion corrosion slows down the increase in the total resistance value of the circuit, thus slowing down the decrease in the corrosion current of the reinforcement, and then indirectly affects the corrosion of the reinforcement by affecting the corrosion current.Under the action of stray currents, the corrosion of reinforcement in concrete and the calcium ion corrosion behavior of concrete will damage the compressive strength of concrete. The loss of concrete compressive strength is the result of the joint action of reinforcement corrosion and calcium ion corrosion.It can be seen from the analysis in According to the test data of 13 groups of test pieces, the three-dimensional curved surface relationship between the corrosion rate of reinforcement, calcium ion dissolution rate and concrete damage degree can be drawn, as shown in It can be seen from The higher the strength grade, the lower the corrosion of the internal reinforcement and its electrochemical corrosion. With the increase in reinforcement diameter, the corrosion rate decreases, but the calcium ion dissolution rate is not affected by reinforcement diameter. The greater the stray current intensity, the greater the corrosion rate of reinforcement and the dissolution rate of calcium ions and the smaller the critical corrosion rate of reinforcement when concrete cracks under strong currents;The corrosion behavior of calcium ions in concrete under the stray current will slow down with the increase in the corrosion degree of reinforcement;Through nonlinear regression fitting of the test data, the regression equations of the original compressive strength, reinforcement diameter, corrosion voltage, electrification time and other parameters on the corrosion rate and calcium ion dissolution rate of reinforcement were obtained;The damage degree of concrete is closely related to the corrosion of reinforcement and the dissolution of calcium ions. The damage effect of rebar corrosion and calcium ion dissolution on concrete strength is affected by stray current intensity and rebar diameter. When the rebar corrosion rate and calcium ion dissolution rate are the same, the smaller the rebar diameter or the larger the stray current intensity, the more significant the damage effect is. Moreover, the damage effect of rebar corrosion on concrete compressive strength is more obvious than that of calcium ion dissolution.The influence of reinforcement corrosion and calcium ion corrosion on concrete strength under the action of stray currents was studied by simulating stray current environments and accelerating tests. The following conclusions were reached:


Inappropriate use of antibiotics could have a profound negative impact on individual and community. This study aimed to assess the prevalence of inappropriate use behaviors of antibiotics in Chinese antibiotic users and explored their related factors.https://www.wjx.cn) and was used to collect data from respondents in China on demographic and sociological characteristics, antibiotic use and related knowledge. Main outcomes included self-medication with antibiotics (SMA), self-storage with antibiotics (SSA), and non-adherence to antibiotic treatment (NAAT). Logistic regression was used to identify the related factors of above inappropriate use behaviors of antibiotics.A cross-sectional survey was conducted from July 1, 2018 to September 30, 2018. A structured questionnaire was widely distributed on the online survey platform .Of the 15,526 participants, 37.1% reported SMA in the past 6 months, 67.9% reported SSA in the past 6 months, and 48.3%, 15.2%, 25.5% and 78.0% of respondents said that they had missed antibiotics, increased antibiotic dosage, decreased antibiotic dosage, and discontinued antibiotics once symptoms disappear, respectively. Overall, 53.3% reported NAAT during this period. After adjusting for other variables, multivariate logistic regression analyses showed that those aged 30–44 years old, with higher levels of education, poorer status of self-perceived health, or lower levels of antibiotic knowledge were more likely to have these inappropriate use behaviors of SMA, SSA, and NAAT (The prevalence of SMA, SSA, and NAAT is high in China. Developing a nationwide action plan for the rational use of antibiotics among publics, including national media publicity, online and offline health education, and medication guidance from general practitioners, is urgently needed. Self-medication with antibiotics, self-storage with antibiotics, and non-adherence to antibiotic treatment are important performances of inappropriate use behaviors of antibiotics.The results of this study showed that the prevalence of inappropriate use behaviors of antibiotics among Chinese antibiotic users were between 37.1% and 67.9%.A nationwide action plan for rational use of antibiotics is urgently needed in China. Under the interaction between supply and demand sides, inappropriate use of antibiotics in humans has attracted widespread attention in the field of global medical and health care , 2. AccoThe prevalence of inappropriate use of antibiotics reported by different countries varied widely. A sample survey in Europe found that 19.8% of Romanian had SMA, and 68.0% of them had SSA at home . Two surInappropriate use of antibiotics is serious in China. Although China has issued a series of policies to promote the appropriate use of antibiotics, most of them focused on limiting antibiotic prescribing in medical institutions and regulating antibiotic for sale in retail pharmacies –13. For Therefore, this study aimed to assess the prevalence of inappropriate use behaviors of SMA, SSA, and NAAT among Chinese antibiotic users, and identified their related factors, in order to provide evidence for the development of targeted intervention strategies.This study was approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (Number: 2018IECS175). All participants were informed about the goal of this study and informed consent was obtained from electronic signatures of all participants. Data were collected anonymously. All methods were carried out in accordance with the Declaration of Helsinki.https://www.wjx.cn). Questionnaire Star is a professional service platform for electronic questionnaire design and data collection, which has been widely used by researchers. This study focused on following three aspects of inappropriate use behaviors: SMA, SSA, and NAAT. The NAAT consisted of four types of non-adherence behaviors including missing antibiotics, increasing antibiotic dosage, decreasing antibiotic dosage, and discontinuing antibiotics. To ensure the stability and reliability of the survey results, the sample size should be as large as possible. In our study, the maximum sample size was calculated with the minimum prevalence of these target behaviors. We used the formula:n is the sample size, p is the prevalence of the research target, z is the normal deviation (1.96) and d is the margin of error (d = 0.1p). When determining parameter p, we took the prevalence of target behaviors among publics in the past 6 months as the criterion according to previous studies. Among them, the prevalence of non-adherence behavior with proactively increasing antibiotic dosage was the lowest with 8.3%–22.0% , To reflect the prevalence of inappropriate use behaviors of antibiotics among Chinese antibiotic users, we selected three main outcomes: the percentage of SMA, the percentage of SSA, and the percentage of NAAT. In this study, SMA was defined as answering “yes” to the question: “During the past 6 months, did you self-administer antibiotics without a doctor’s prescription?” SSA was defined as answering “yes” to the question: “During the past 6 months, did you self-storage antibiotics at home for future use?” NAAT was measured according to four types of non-adherence behaviors that were developed from previous studies : (1) DidTo identify the relevant factors of inappropriate use behaviors of SMA, SSA, and NAAT, we also collected the demographic and sociological characteristics, including gender, age, place of residence , educational level (junior high school or below/ high school/junior college or above), self-perceived economic status (good/ average/poor), self-perceived health status (good/ average/poor), and antibiotic knowledge. Antibiotic knowledge is assessed by asking 10 questions in three sections: the knowledge regarding antibiotic role, antibiotic use and antibiotic resistance. These 10 questions are estimated using a scoring scheme, with score of 1 for a correct response and 0 for an incorrect response. The total scores of knowledge range between 0 and 10. We divided the total scores of antibiotic knowledge into three levels as following: (1) high level: 8–10 scores; (2) medium level: 3–7 scores; (3) low level: 0–2 scores. In the questionnaire, Cronbach’s α coefficients of non-adherence behavior scale and antibiotic knowledge scale were 0.71 and 0.84 (> 0.70), respectively. Confirmatory factor analyses showed that the standardized factor loading of each item of non-adherence behavior scale ranged from 0.52 to 0.57 (> 0.40), and these values of the antibiotic knowledge scale were all above 0.70. The results of these tests indicated that the questionnaire had good reliability and validity.We designed a questionnaire and generated a valid QR code of this questionnaire on the online survey platform. Then, we recruited 50 graduate and undergraduate students from the School of Public Health at Huazhong University of Science and Technology as investigators in July 2018. Four of them refused the request to distribute questionnaires, with a participation rate of 92%. After the unified training, the investigators would get the QR code of questionnaire. During the summer vacation, all sent out electronic questionnaires through their personal social software such as “WeChat”. The respondents scanned the QR code on their mobile phones to fill in the questionnaire. The data administrator checked the questionnaire and sorted out the data through the background every week. When each region  reached the minimum required survey sample of 2532, the administrator closed the network link and finished the survey.Before the survey, we conducted a questionnaire pilot test to ensure the smooth implementation of all steps including the respondents’ login on the platform, questionnaire filling and submission. we set the following inclusion criteria that the respondents filling in the questionnaire must meet: (1) adults aged 18 years or above; (2) living in the area for more than 6 months; (3) normal cognitive and understanding abilities; (4) aware of the term “antibiotic” and having used antibiotics. To ensure that only one questionnaire per respondent can be filled out, we limited one IP address per submission on the online survey platform and required to log in with a personal mobile phone number  before filling in the questionnaire. During the survey, to improve the enthusiasm of respondents, we paid 3 Yuan in cash to each person who completed the questionnaire as an economic incentive. To ensure that respondents must read and answer the questionnaire carefully, we set three quality inspection questions at different locations, namely: “Where is the capital of China?”, “What is 7 minus 2?”, and “What is 1 plus 3?” If the answer to any of these three questions was incorrect, the questionnaire would be marked as invalid. After the respondents completed the questionnaires, all the questionnaires were automatically input into a data file, and two researchers independently collated and verified the data to ensure the reliability of the survey data.During the process of the survey, 21,874 respondents visited the questionnaire link, and 17,062 respondents actually completed the questionnaire. Since this was an online survey, the true response rate could not be determined here. Among all the questionnaires, 1280 questionnaires were excluded because of unqualified quality inspection, and 256 questionnaires were also excluded because of respondents under the age of 18. Finally, 15,526 valid questionnaires were obtained.P value < 0.05 was considered to be significant.Descriptive analysis of the demographic and sociological characteristics, antibiotic knowledge, and various inappropriate use behaviors of the participants was conducted. The classified variables were expressed as frequency and percentage, and the continuous variables were expressed as mean and standard deviation (SD). To examine the possible impact of the controversial Q5 and Q9 from the antibiotic knowledge scale Table  on the sOf the 15,526 valid participants, 6222 (40.1%) were male. Their mean age was 34.6 (SD = 11.7) years old. Among all the participants, 70.8% were from urban places of residence, 64.3% had a junior college education or higher, more than 75.0% of participants self-perceived their economic status as average, and nearly half (49.1%) of participants self-perceived their health status as good , ≥ 45 years old , with junior college or above level of education , with average  or poor  status of self-perceived health, with medium  or low  levels of antibiotic knowledge had a higher risk of SMA. Those who were female , aged 30–44 years old , with high school  or junior college or above  levels of education, with average  or poor  status of self-perceived health, with medium  or low  levels of antibiotic knowledge were more likely to have SSA. Respondents aged 30–44 years old , ≥ 45 years old , with high school  or junior college or above  levels of education, with average  or poor  status of self-perceived health, with medium  or low  levels of antibiotic knowledge were more likely to have NAAT   and SerbThis study comprehensively explored the related factors of inappropriate use behaviors of SMA, SSA, and NAAT. The results showed that age, education level, self-perceived health status and antibiotic knowledge level were associated with all three inappropriate use behaviors. The population aged 30–44 years old had the highest risk of SMA and SSA. This may be due to the fact that most aged 30–44 years old are in the ascendance of their careers and the time cost of seeking medical services in hospitals is too high, which may lead them to choose SMA and SSA . It was In this study, the overall level of antibiotic knowledge in Chinese antibiotic users was not high, and the lower the level of antibiotic knowledge, the higher the risk of these inappropriate use behaviors. Many health behavior change theories, such as Health Belief model and Knowledge-Attitude-Practice model, agree that knowledge is the prerequisite and important basis for behavior change and also provides necessary information for individuals to make health decisions , 38. TheGlobal Action Plan on Antimicrobial Resistance to promote the rational use of antibiotics and reduce the AMR [This study was the first to conduct a survey of inappropriate use behaviors of antibiotics in a large sample of antibiotic users in central, eastern and western China. As this survey was conducted online, 74.8% of participants aged 18–44 years old and 64.3% of participants had junior college or above. Combined with the above association between age and education level and inappropriate use behaviors of antibiotics, the lack of elderly and non-educated population might lead to a higher prevalence in this study. On the whole, our population was young and highly educated, but their level of antibiotic knowledge was still low. Therefore, online health education on the rational use of antibiotics should be a priority strategy for young and middle-aged population. In addition, by removing Q5 and Q9, the sensitivity analysis showed that although the proportion of participants with different levels of antibiotic knowledge had changed, the overall level of antibiotic knowledge in Chinese antibiotic users was still not high, and there was still a significant negative association between antibiotic knowledge level and these inappropriate use behaviors. This proved the stability of research results to some extent. At present, AMR has become a global public health problem. WHO is urging all countries to participate in the  the AMR . Our stuHowever, our study had several limitations. Firstly, as with all self-reported questionnaire survey, the results were inevitably subject to recall bias. Secondly, this study adopted the form of online questionnaire to carry out the survey. As young people were more skilled in using mobile phones and social software, the population in this study was young, highly educated and has good self-reported health, which might lead to a certain degree of response bias, namely a higher prevalence. Thirdly, this study was a cross-sectional survey. Therefore, it was difficult to infer causal conclusions, and further prospective studies should be conducted to test the conclusions of this study.Under the characteristics of young and highly educated population, the overall level of antibiotic knowledge in Chinese antibiotic users is still low, and the prevalence of SMA, SSA, and NAAT was at a high level. Those aged 30–44 years old, with higher levels of education, poorer status of self-perceived health, or lower levels of antibiotic knowledge were more likely to have all three inappropriate use behaviors of antibiotics. In the future, it is very necessary for the Chinese government to formulate a nationwide action plan for the rational use of antibiotics, especially for young and middle-aged population, including national media publicity, online and offline health education, and medication guidance from general practitioners, so as to promote the rational use of antibiotics in the daily life of the publics.


Cement-slag concrete has become one of the most widely used building materials considering its economical advantage and satisfying uniaxial compressive strength (UCS). In this study, an AI-based method for cement-slag concrete design was developed based on the balance of economic and mechanical properties. Firstly, the hyperparameters of random forest (RF), decision tree (DT), and support vector machine (SVM) were tuned by the beetle antennae search algorithm (BAS). The results of the model evaluation showed the RF with the best prediction effect on the UCS of concrete was selected as the objective function of UCS optimization. Afterward, the objective function of concrete cost optimization was established according to the linear relationship between concrete cost and each mixture. The obtained results showed that the weighted method can be used to construct the multi-objective optimization function of UCS and cost for cement-slag concrete, which is solved by the multi-objective beetle antennae search (MOBAS) algorithm. An optimal concrete mixture ratio can be obtained by Technique for Order Preference by Similarity to Ideal Solution. Considering the current global environment trend of “Net Carbon Zero”, the multi-objective optimization design should be proposed based on the objectives of economy-carbon emission-mechanical properties for future studies. Concrete is widely used in modern construction projects because of its low price, simple production process, high UCS, good durability, and other characteristics . AlthougTypically, engineers use the laboratory test method to design high-performance concrete to meet the mechanical characteristics of high UCS, large flow performance, good durability, and so on ,28. HoweAlthough the price of concrete is low, with the increasing use of concrete in the construction industry, the cost of concrete is also a significant expense for the construction industry. There is a linear relationship between concrete price and mix ratio, so the optimization of concrete cost can be studied by the formula. However, there are few studies on cost optimization of concrete, and even fewer studies on multi-objective optimization of UCS and cost. To solve the above problems, this paper proposes a multi-objective optimization the beetle antennae search (MOBAS) algorithm to optimize the UCS and cost of the concrete mixture . For theFor the optimization of the cost of concrete, the decision variables, objective functions, and constraint conditions need to be defined first, and then the model is built according to the relationship between cost and admixture. There is a big difference between single-objective optimization and multi-objective optimization. The non-dominant solution that is suitable for single-objective optimization can be applied to multi-objective optimization only under special conditions. Multi-objective optimization usually requires high computing power to obtain the non-dominant solution set and the Pareto frontier. Additionally, the optimization of the concrete mixture will be affected by the curing environment, performance, material type, and so on. To solve the above problems, this study proposed the use of a weighted method to construct the MOBAS algorithm to solve the optimal solution of the multi-objective function value. Finally, Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) was used to determine the final optimal mix ratio of the concrete optimization problem. The framework of the multi-objective optimization model in this study is shown in 3, respectively. From A reliable database is a basis for verifying the accuracy of prediction models for the UCS of concrete. This study collected 102 datasets from previously published articles to form the database . In thisThe BAS algorithm is a new meta-heuristic algorithm that is inspired by beetle search behavior during foraging. The long antennae of beetles usually contain several odor-picking cells that can be used to detect the scent of prey. Beetles wiggle their antennae to locate food while foraging. If the intensity of the smell received by the left tentacle is greater than that received by the right, the beetle will fly to the left, otherwise, it will fly to the right to find food.d is the dimension of the variable. The formula for calculating the spatial coordinates of the left and right antennae of beetles is as follows:t. The position of the beetle is as follows:t, and h and step size h and In the BAS algorithm, the objective function to be optimized is regarded as food, and the variable of the objective function is regarded as the location of the beetles. For unknown areas, the beetles usually use random search to generate random directions. This process is stimulated by the following formula:m. The bootstrap sampling method is used to extract K datasets with size n from the training dataset D, and train K decision tree models, respectively. In the process of spanning the tree, mtry Scope constraintsTo solve the multi-objective optimization problem, after determining the objective function of concrete cost optimization, the next step is to determine the constraint conditions. The constraints are as follows:In the optimization process of the concrete mix ratio, the decision variables need to be constrained according to the range of data in the database, namely:(2)Proportional constraintsIn the optimization process of the concrete mixture problem, several proportions need to be restricted according to the data of the database used in this study including the proportion of water to cementitious material (W/C + SF), the proportion of blast furnace slag to cementitious material (SF/C + SF), the proportion of superplasticizer to cementitious material (SP/C+SF), the proportion of coarse aggregate to aggregate (CA/CA + FA), and the proportion of coarse aggregate to cementitious material (CA/C + SF). The range of proportion relation of each component is shown in (3)Volume constraintTaking the sum of the total volume of each component in concrete as equal to one, set the concrete volume constraint equation as follows:(4)UCS constraintIn this optimization problem, the UCS of concrete must be greater than the design value, so the UCS of concrete is constrained as follows:X is the decision variable, The multi-objective optimization problem is a field of multi-criteria decision making, which refers to the simultaneous optimization of multiple objective functions. Its mathematical expression is as follows:Because the multi-objective optimization problem needs to optimize multiple objective attributes at the same time, it cannot be judged by comparing the size relationship between two individuals like the single-objective optimization problem. Therefore, dominant relations are defined to judge the merits of different goals. In the minimization multi-objective optimization problem, suppose individuals In multi-objective optimization problems, there are conflicting objectives, that is, if the sub-objective of one non-dominant solution is improved, the optimization effect of other sub-objective function values will be reduced. Therefore, the optimal solution obtained by a multi-objective optimization problem is usually not unique, but the optimal solution set is composed of multiple non-dominant solutions, also called Pareto optimal solution set. The solutions in the Pareto solution set are not dominated by other solutions, and relative to other solutions, at least one objective is optimal. The distribution of the Pareto solution, dominant solution, and Pareto solution boundary in the case of two objectives is shown in Shown in kth objective function, which is randomly generated from the uniform distribution, and n beetle populations are initialized first, and then target values of beetles are compared. The best solution can be obtained by generating random weights. After the iteration, n non-dominant solution points can be used to approximate the real Pareto front. In this study, the weighting method is used to combine multiple targets into single targets, and the formula used is as follows:i represents a Pareto solution, n represents the number of objectives, jth ideal solution in the single-objective optimization problem, and TOPSIS is the most commonly used multi-criteria decision analysis method in multi-objective decision analysis. TOPSIS is a method for evaluating relative merits and demerits among a limited number of objects. This method sorts the finite number of evaluation objects according to their proximity to the ideal target. By comparing the alternatives with the positive ideal solution  and the negative ideal solution (the worst solution), the optimal solution closest to the positive ideal solution and furthest from the negative ideal solution is found. Additionally, rank the different solutions according to the proximity coefficient. The positive ideal point BAS is used to tune the hyperparameters of RF, DT, and SVM. The RSME values of RF and SVM converge gradually with the increase in the number of iterations, while the RMSE value of DT does not change with the increase in the number of iterations, demonstrating that BAS has a poor effect on DT hyperparameter tuning, but a better effect on SVM and RF hyperparameter tuning.(2)By comparing the predicted value and actual value of RF, DT, and SVM optimized by BAS, it is found that RF and SVM have a better prediction effect on concrete UCS. However, due to the over-fitting of SVM, the RF model was selected in this study to predict the UCS of concrete considering the R values of the training set and test set of the RF model are 0.9832 and 0.9516, respectively.(3)3.To find the best mixture ratio for the optimization of the UCS and cost of concrete, this paper uses TOPSIS to rank the scores of twenty Pareto front optimal solutions. The MOBAS model proposed based on the weighted method can smoothly find the Pareto optimal solution for the UCS of concrete. The multi-objective optimization model proposed in this paper can effectively reduce the cost of concrete without changing the UCS of concrete and the multi-objective optimization model has a good effect and strong generalization ability. The Pareto front optimal solution with the highest score is 1 and the UCS of the corresponding concrete is 119.48 MPa and the cost is 37.29 USD/mIt is a challenge in civil engineering to improve the performance of concrete by designing the proportion of the concrete mixture. As one of the most widely used building materials, economical advantage and satisfactory UCS were considered in the present study for the concrete design. An AI-based method for cement-slag concrete design based on the balance of economic and mechanical properties was developed and a multi-objective optimization model was proposed to optimize the proportion design of the concrete mixture. Based on the developed machine learning process, the following conclusions can be drawn:This study proposes a new intelligent design method for concrete design based on the consideration of economical and mechanical properties. However, in the current global environment of “Net Carbon Zero”, the design output index of carbon emissions has not been considered. Therefore, in future research, a multi-objective optimization design should be proposed, considering the objectives of economy-carbon emission-mechanical properties to be achieved.