Proteomics analysis revealed PFN1 involvment in microvesicles (MVs) secretion. In vitro experiments confirmed that PFN1 overexpression increased secretion of MVs. MVs are important mediators of metastasis. Here, we show an increased abundance of MVs in the sera of patients with metastatic NSCLC compared to that in the sera of patients with non-metastatic NSCLC. Both in vitro and in vivo experiments revealed that PFN1 could increase MV secretion, and MVs derived from PFN1-overexpressing cells markedly promoted NSCLC metastasis. We then elucidated the mechanisms underlying PFN1-mediated regulation of MVs and found that PFN1 could interact with ROCK1 and enhance its kinase activity to promote myosin light chain (MLC) phosphorylation for MV secretion. Inhibition of ROCK1 decreased MV secretion and partially reversed the PFN1-induced promotion of NSCLC metastasis. Collectively, these findings show that PFN1 regulates MV secretion to promote NSCLC metastasis. PFN1 and MVs represent potential predictors or therapeutic targets for NSCLC metastasis.Profilin 1 (PFN1), an actin-binding protein, plays contrasting roles in the metastasis of several cancers; however, its role in non-small cell lung cancer (NSCLC) metastasis remains unclear. Here, PFN1 expression was upregulated in metastatic NSCLC tissues. PFN1 overexpression significantly promotes NSCLC metastasis  Non-small cell lung cancer (NSCLC) accounts for ∼85% of all lung cancer cases and has a poor 5-year survival rate of ∼15% . DespiteProfilin 1 (PFN1) is a 135-amino acid, 15 kDa conservative actin-binding protein. PFN1 is expressed at every stage of embryonic development and is ubiquitously expressed by all cell types and nearly all tissues . NumerouExtracellular vesicles are a heterogeneous group of nano-scale lipid-bilayered structures secreted by all cell types, including cancer cells. They are classified by size as exosomes (40–120 nm), microvesicles , or apoptotic bodies   and playin vitro and in vivo. Mechanistically, we demonstrated that PFN1 interacted with ROCK1, followed by its activation, and thus promoted phosphorylation of MLC, which in turn increased the secretion of MVs.In this study, we systematically explored the roles of PFN1 in tumor metastasis and MV secretion in NSCLC, and confirmed that PFN1 promoted NSCLC metastasis by promoting the secretion of MVs Forty-five patients with lung adenocarcinoma admitted to our hospital were divided into metastatic and non-metastatic groups, according to the 2019 Chinese Society of Clinical Oncology guidelines . PatientTissue chips were purchased from Shanghai Outdo Biotech  . For aniTissues were fixed with 4% paraformaldehyde and permeabilized with 0.2% Triton X-100. After blocking with 3% bovine serum albumin , the slides were incubated with primary antibodies overnight at 4°C. Primary antibody concentrations were as follows: anti-PFN1, 1:100 (Abcam), anti-Napsin A, 1:100 (Abcam), anti-ROCK1, 1:100, , anti-ROCK2, 1:100 (ImmunoWay) and anti-annexin A1, 1:100 (Servicebio). Next, the slides were incubated with fluorophore-conjugated secondary antibodies  at room temperature. DAPI (Servicebio) was used to stain the nuclei. The samples were then visualized using a fluorescence microscope .2.H1299 and A549 cell lines were kindly provided by Stem Cell Bank, Chinese Academy of Sciences . HEK-293T cells were kindly provided by Professor Chun Fang Zhang . Cells were cultured in RPMI 1640 medium  or Dulbecco’s modified Eagle medium (Gibco) (HEK-293T cells only) supplemented with 10% fetal bovine serum (Gibco), 100 U/mL penicillin, and 100 μg/ml streptomycin (Gibco) and incubated at 37°C and 5% COEscherichia coli, plasmids were extracted using the FastPure Plasmid Mini Kit (Vazyme). The plasmids were then selected according to sequence screening. All genes were transfected into cells using lentivirus infection. pLVX-EF1α-IRES-puro, pLVX-EF1α-IRES-puro-PFN1-Flag, pLVX-EF1α-IRES-puro-PFN1-R88L-Flag, pLVX-EF1α-IRES-puro-PFN1-H119E-Flag, pLVX-EF1α-IRES-puro-PFN1-H133S-Flag, and pLVX-EF1α-IRES-puro-ROCK2-myc were purchased from General Biology Company . ROCK1 pcDNA3.1-HA-C was purchased from You Bao Biology . PFN1 siRNA and control scramble siRNA were synthesized by Guangzhou RiboBio Co. , and the sequences are listed in The human PFN1-coding sequence was amplified from human cDNA using 2× Phanta Master Mix  and cloned into a pLVX-IRES-ZsGreen1 and pEGFP-C3 vector using the ClonExpress II One Step Cloning Kit (Vazyme). The primers were synthesized by TsingKe Biology Company  and are listed in 5 cells/well). The supernatants were collected from cultured cells transfected with the empty vector (EV) and those overexpressing PFN1. Pipette tips were used to make a straight scratch in each well; we ensured that the width of each scratch was similar. Images were captured under microscopy (Nikon) every 12 h until the wound was healed. Data were obtained from at least three independent experiments.Cells in the logarithmic growth phase were seeded onto six-well plates (3 × 104) suspended in 200 µl serum-free medium were seeded in the upper chamber. The lower chamber was filled with 800 µl complete medium. After incubation at 37°C for 24 h, the cells were fixed in 4% paraformaldehyde for 20 min. After being washed thrice with PBS, the cells were stained using 1% crystal violet  for 10 min. Cells that transmigrated to the lower chamber were counted. Data were obtained from at least three independent experiments.Cell migration was assessed using 24-well Transwell culture chambers . Cells  were isolated using continuous differential centrifugation as described previously . BrieflyMVs were fixed in 2.5% glutaraldehyde. Electron microscopy was conducted at the Department of Pathology of Xiangya Hospital, Central South University .The amount of MVs was analyzed using a three-laser Cytek Northern Lights SpectralFlow Cytometry instrument , according to the manufacturer’s instructions. Standard microbeads (ranging from 100 nm to 1 µm) were used for size calibration. Microparticles ranging from 100 nm to 1 µm were counted. The counting endpoint was set at 25 s for all eligible granules.MVs stained with PKH67  were added to H1299 cells. After incubation for 24 h, cells were fixed and stained with DAPI. Then, fluorescence microscopy (Nikon) was used to detect MS uptake.Total RNA was extracted from cells at the logarithmic phase using TRIzol reagent . Reverse transcription was conducted using the PrimeScript RT Reagent Kit (Takara). RT-qPCR was conducted on a 96-well Automation Compatible Polypropylene PCR Microplate  using the TB Green Premix qPCR Mix (Takara) per manufacturer’s instructions. Primer sequences are listed in Whole-cell lysates were prepared using RIPA Lysis Buffer  containing a protease inhibitor cocktail  and phosphatase inhibitor . The protein concentration was quantified using a BCA Kit (Beyotime). An equal amount of protein (25 µg) was used for electrophoresis. Proteins were separated using 10/12% SDS PAGE and then transferred onto polyvinylidene difluoride membranes . The membranes were then blocked with a solution of 3% BSA (Solarbio) in TBS with Tween 20 (Solarbio) at room temperature for 1 h. The membranes were next incubated with primary antibodies (dilution ratio listed in ROCK1/2 or PFN1 overexpression/mutant plasmids using Pierce™ Protein A/G Magnetic Beads (Thermo Fischer Scientific) per manufacturer’s instruction. The ROCK Kinase assay (Abcam) was used to evaluate the effect of PFN1 or its mutants on ROCK1/2 activity per the manufacturer’s instructions. Data were obtained from at least three independent experiments.Purified ROCK1/2, PFN1, and PFN1 mutants were isolated from HEK-293T cells transfected with 5 H1299 cells/mouse, suspended in PBS, were injected immediately. MVs (tatol MVs collected from 3 × 106 H1299 EV cells or PFN1 OE cells for each mouse) were injected together with cells. When significant weight loss was observed, the mice were sacrificed for subsequent analyses. All animal experimental procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals of Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal University and approved by the Institutional Animal Ethics Committee. All animal experiments complied with the ARRIVE guidelines.Nude mice  were purchased from Hunan SJA Laboratory Animal Co., Ltd. . The mice were nurtured in individual ventilated caging systems under a specific pathogen-free environment. A metastasis model was constructed via intracardiac injection of H1299 cells. Briefly, after being anesthetized by injecting 2% sodium pentobarbital (40 mg/kg) intraperitoneally, the mice’s skin was cut along the left parasternal line to locate the second intercostal space. Needles were inserted into the second intercostal space along the left margin of the sternum. Pulsating arterial blood indicated the correct location in the left ventricle. A total of 8 × 10H1299 EV and PFN1 OE cells were harvested at logarithmic growth period and each cell type was collected in biological triplicate. Total cellular protein extracted by RIPA lysis buffer and concentration of proteins were determined by bicinchoninic acid (BCA) protein assay kit (Beyotime) according to manufacturer instructions. A total of 100ug proteins of each sample were then precipitated by acetone at −20°C overnight. Dissolve protein precipitation by water bath ultrasound for 3 min after adding 100 µl protein resolve buffer. Dithiothreitol (DTT) (Sigma-Aldrich) was used to reduced disulfide bond. Then reduced disulfide bonds were Alkylated by iodoacetamide (IAA) (Sigma-Aldrich). Thoroughly mixed trypsin with the samples in the ratio of trypsin: protein = 1:50 and incubate overnight at 37°C 1,000 rpm to digest proteins. Peptides were labeled by TMT Isobaric Label Reagent Set  according to manufacturer instructions. After SDS cleanup, peptide desalting and gigh-pH pre-fractionation, peptides were freeze at 80°C after vacuum drying and ready for later nanoLC-MS/MS analysis.µ ID ×15 cm, Reprosil-Pur 120 C18-AQ, 1.9 µ, Dr. Maisch). Mobile phases were H2O with 0.1% FA, 2% ACN (phase A) and 80% ACN, 0.1% FA (phase B). Separation of sample was executed with a 90 min gradient at 300 nl/min flow rate. Gradient B: 2–5% for 2 min, 5–22% for 68 min, 22–45% for 16 min, 45–95% for 2 min, 95% for 2 min.For each sample, 2 ug of total peptides were separated and analyzed with a nano-UPLC (EASY-nLC1200) coupled to a Q Exactive HFX Orbitrap instrument (Thermo Fisher Scientific) with a nano-electrospray ion source. Separation was performed by using a reversed-phase column (100 Data dependent acquisition (DDA) was performed in profile and positive mode with Orbitrap analyzer at a resolution of 120,000 (@200 m/z) and m/z range of 350–1,600 for MS1. For MS2, the resolution was set to 15k with a fixed first mass of 110 m/z. The automatic gain control (AGC) target for MS1 was set to 3E6 with max IT 30 ms, and 1E5 for MS2 with max IT 96 ms. The top 20 most intense ions were fragmented by HCD with normalized collision energy (NCE) of 32%, and isolation window of 0.7 m/z. The dynamic exclusion time window was 45 s, single charged peaks and peaks with charge exceeding 6 were excluded from the DDA procedure.Raw MS files were processed using Proteome Discoverer (PD) software  and the built-in Sequest HT search engine . MS spectra lists were searched against their species-level UniProt FASTA databases (uniprot-Homo sapiens-2021-8.fasta), with Carbamidomethyl [C], TMT 6 plex(K) and TMT 6 plex (N-term) as a fixed modification and Oxi- dation (M) and Acetyl (Protein N-term) as variable modifications. The protease was trypsin. A maximum of two missed cleavage(s) was allowed. The false discovery rate (FDR) was set at 0.01 for both PSM and peptide levels. Peptide identification was performed with an initial precursor mass deviation of up to 10 ppm and a fragment mass deviation of 0.02 Da. Unique peptide and Razor peptide were used for protein quantification and total peptide amount for normalization. All the other parameters were reserved as default. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE  partner https://www.r-project.org/) or SIMCA . Differential expressed proteins (DEPs) were defined as student’s t-test p-value < 0.05 and fold change ≤ 0.83 or fold change ≥ 1.2. DEPs were visualized in the form of volcano plot. Hierarchical clustering for representing the DEPs was conducted by R Package pheatmap. The eukaryotic clusters of orthologous groups (KOG) database (http://www.ncbi.nlm.nih.gov/COG/) of protein database was carried out for functional classification of DEPs. Gene ontology (GO) database (http://geneontology.org/) was used to classify and annotate the functions of differentially expressed proteins. All enrichment analyses were based on the Fisher’s exact test with Benjamini−Hochberg correction (p < 0.05).After pretreatment, 5,438 detected proteins were retained. Data were processed with Proteome Discoverer software . Principal component analysis (PCA) was performed using the R package.  data were obtained from TCGA LUAD dataset. The clinical information and expression matrix were obtained from csc.edu/ . The medt-test was used to compare differences between two experimental groups. For comparison of overall differences between three or more groups, one-way analysis of variance was used. Spearman correlation analysis was performed to reveal relationships between PFN1 and p-MLC. All analyses were carried out using SPSS 21.0 ; p < 0.05 was considered statistically significant.All data are presented as mean ± standard deviation. Student’s To investigate the roles of PFN1 in NSCLC, we first conducted IHC to detect the expression of PFN1 in NSCLC tissues. Results showed that PFN1 was highly expressed in NSCLC tissues compared with adjacent non-tumor tissues . We thenTo further investigate the impact of PFN1 on NSCLC cell lines, we constructed stable PFN1-OE and PFN1-KD H1299 and A549 cell lines. The effect of overexpression and knockdown was determined using RT-qPCR  and westp-value < 0.05 and fold change ≤ 0.83 or fold change ≥ 1.2. We identified 581 proteins with significant differences in abundance, as shown in the volcanic plot . Differently expressed proteins (DEPs) were defined as nic plot . Comparenic plot . We nextnic plot . Among tnic plot . Via proPFN1-overexpressing cell supernatants. Transmission electron microscopy, western blotting, and flow cytometry were used for qualitative and quantitative analysis of the MVs  from sera of clinical samples. PFN1 existed in MVs but not in exosomes or free in sera, which indicate PFN1 was correlated with MVs . Then we the MVs . ResultsTo further investigate the relationship between PFN1 and MVs secretion, we analyzed the expression of PFN1 and the MV marker annexin A1  in NSCLCn = 25) and non-metastatic (n = 20) lung cancer and extracted MVs. Flow cytometry  and western blotting (ARF6 used as MV biomarker)   results omarker) . To deternatants . To visu99 cells . We thenn assays . Hence, PFN1-overexpressing cell-treated group was higher than in the EV-expressing cell-treated group   and plasSignaling pathways regulated by the small Ras-related GTPases (ARF6 and Rho family) are thought to govern the formation and release of tumor-derived MVs. All these molecules ultimately regulate the shedding of MVs through the phosphorylation and activation of MLC . The eloIn conclusion, our findings suggest that PFN1, a critical actin-regulating protein, promotes MV release through the ROCK/p-MLC pathway, thereby promoting NSCLC metastasis. Thus, PFN1 may represent a potential therapeutic target for NSCLC metastasis. By reducing the release of MVs, it may be possible to partially reverse PFN1 overexpression-induced NSCLC cell migration. This study provides a potential new approach for the treatment of NSCLC by targeting metastasis that warrants further investigation.


Nutrient requirements of poultry, 1994, National Academy Press) recommendations) levels were fed to 180 breeder ducks  in a completely randomized design for 49 days. Laying performance and reproductive traits were evaluated; additionally, uric acid, total protein total, triglycerides, total cholesterol, low‐density lipoprotein, high‐density lipoprotein, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed. The Lys‐Met above 100% NRC  recommendations with or without L‐carnitine improved feed utilization (p < .05). Furthermore, Lys‐Met above 100% recommendations without L‐carnitine improved egg fertility and hatchability. Fertility and hatchability improved in breeders fed on L‐carnitine with 120% Lys‐Met (p < .05). Serum glucose increased and total cholesterol reduced on 100% Ly‐Met without L‐carnitine or 110% Ly‐Met with 150 mg L‐carnitine (p < .05). Glucose was reduced, while total cholesterol increased on 75 mg L‐carnitine and 100% Lys‐Met (p < .05). Increasing Lys‐Met without L‐carnitine reduced serum protein (p < .05). Albumin and ALT increased on 75 mg L‐carnitine–100% Lys‐Met and reduced on 150 mg L‐carnitine–120% Lys‐Met (p < .05). There were no interaction effects on globulin, uric acid and AST (p > .05). Thus, based on findings, breeder ducks responded to dietary Lys‐Met more efficiently than L‐carnitine; however, more research is needed to evaluate also economic aspects related to L‐carnitine dietary supplementation.The present study aimed to evaluate the influence of dietary supplementation of different levels of L‐carnitine and/or lysine–methionine (Lys‐Met) on reproductive performance of breeder ducks. Three L‐carnitine  and three lysine–methionine (100%, 110% and 120% above the NRC ( A total of 180 (144 ♀ and 36 ♂) native breeder Guilan ducks were weighed individually  and divided into 36 groups of five birds (four ♀ and one ♂). Ducks were fed an isocaloric and isonitrogenous basal diet (Table L‐carnitine (0 mg/kg) and Lys‐Met  and Lys‐Met  and Lys‐Met  and Lys‐Met  and Lys‐Met  and Lys‐Met  and Lys‐Met  and Lys‐Met  and Lys‐Met . All eggs produced were weighed using a digital portable scale  sensitive to ±0.1 g, and the mean egg weight was recorded per pen. Feed conversion ratio (FCR) was calculated as g feed consumed to g egg produced.Eggs collected were labelled per replicate and stored at 17°C and 74% relative humidity for 1 week. Eggs (68.7 ± 1.8 g) were candled and fertile ones incubated in the setter at 37.5°C and 60% humidity with regular turning for the first 25 days. On Day 25, eggs were transferred to the hatcher operated at 37°C and 71% relative humidity. At the end of 28 days of incubation, ducklings were removed and counted. Fertility and hatchability parameters were calculated as:2.3On Day 49 of the trial, three representative birds per replicate were selected and blood samples (1 ml/bird) collected, from the wing vein, for biochemical analysis according to Jahanpour et al. . Blood s2.4ijkY = μ + iA + jB + ijAB + ijke, where μ = the common mean, iA = the effects of the L‐carnitine, jB = the effect of the Lys‐Met, ABij = the effect of the ith A with the jth B, and ijke = the random error. Before performing the statistical analysis, all data were tested by the normality test and transformed, if necessary.Data were analysed using the GLM procedure of SAS software SAS, . The mod33.1p > .05). Dietary Lys‐Met above 100% of NRC (p < .05). In the main effects, neither L‐carnitine nor Lys‐Met level affected the performance parameters observed (p > .05).The results of laying performance and reproductive traits of the ducks Table  showed n% of NRC  recommenp < .05). Feeding of Lys‐Met above 100% of NRC recommendations without L‐carnitine improved egg fertility and hatchability, but the addition of L‐carnitine (75 or 150 mg) improved fertility and hatchability only when Lys‐Met was increased to 120% of the NRC recommendations (p < .05). Based on the main effects, L‐carnitine addition did not affect the reproductive parameters (p > .05), but these were improved with increasing Lys‐Met above 100% of NRC recommendations (p < .05).Egg fertility and hatchability indexes were significantly influenced by Lys‐Met and Lys‐Met interaction (3.2p < .05). Feeding of diet with 75 mg L‐carnitine and 100% Lys‐Met reduced glucose and increased cholesterol (p <.05). There was no interaction effect on other energy blood metabolism parameters studied (p >.05). In the main effects, L‐carnitine did not affect any of the energy metabolism parameters (p > .05), but Lys‐Met level affected serum LDL content (p < .05). Increasing Lys‐Met level from 100% to 110% reduced LDL (p < .05), but by a further increase in Lys‐Met level to 120%, the decrease in LDL was not differed significantly compared with Lys‐Met level at 100% (p > .05). L‐carnitine or Lys‐Met had no effects on other energy metabolism parameters assessed (p > .05). Increasing Lys‐Met without L‐carnitine reduced serum total protein (p < .05), but this was restored with L‐carnitine addition. Higher serum albumin and ALT levels were found on ducks fed 75 mg L‐carnitine with 100% Lys‐Met and lower values on 150 mg L‐carnitine with 120% Lys‐Met (p < .05). There were no interaction effects on serum globulin, uric acid and AST (p > .05).The results of blood energy and protein metabolism parameters are presented in Tables 44.1The effects of dietary supplemental L‐carnitine, Lys and Met on poultry performance have been inconsistent. In fact, while some studies have reported improved performance, others found no significant effect. In the present study, increasing Lys‐Met above NRC recommendations with or without L‐carnitine improved feed efficiency, but L‐carnitine or Lys‐Met alone had no effects on feed utilization and egg production. These results partially agreed with those obtained by El‐kelawy, Improving egg fertility and hatchability can be achieved by increasing Lys‐Met alone above 100% of NRC recommendations or by the addition of L‐carnitine. This pattern further confirms the sparing effect of these amino acids from endogenous biosynthesis of carnitine. The beneficial effects of L‐carnitine on poultry fertility are documented. L‐carnitine increases sperm quantity and quality by protecting sperm against per‐oxidative damage and dysfunction (Alvarez & Storey, 4.2We could not explain the pattern of energy and protein metabolism in this study, but a possible increase in fatty acid oxidation and the subsequently reduced oxidation of gluconeogenic precursors (Greenwood et al., 5It appears from the obtained findings that breeding ducks respond to Lys‐Met more efficiently than L‐carnitine. Increasing dietary Lys‐Met above NRC recommendations has no effect on egg production but improved feed utilization, egg fertility and hatchability. The pattern of the hens’ response in terms of serum metabolites is not consistent, and this needs further investigations. Because carnitine is biosynthesized endogenously from Lys‐Met, the supply of L‐carnitine in the diet will spare these essential amino acids. However, L‐carnitine is still a relatively expensive additive in many countries and there is a need to validate the cost‐effectiveness of its dietary inclusion. However, their availability, ease of use and their positive impact on ducks may make their use in duck feeds justified.None of the authors have any conflict of interest to declare.Maryam Mirzaei, Mehrdad Bouyeh, Afshin Zahedi and Alireza Seidavi conceptualized the study, contributed to methodology, validation and investigation, performed formal analysis and wrote the original draft. Alireza Seidavi, Rifat Ullah Khan, Vincenzo Tufarelli, Mohamed E. Abd El‐Hack, Ayman E. Taha and Ayman A Swelum performed investigation and data curation. Alireza Seidavi, Vincenzo Tufarelli, Marco Ragni, Vito Laudadio and Ayman A Swelum provided resources, performed funding acquisition and supervision, and wrote, reviewed and edited the manuscript.


In order to explore the occurrence area of pervious concrete freeze-thaw deterioration, the mass loss, strength deterioration, ultrasonic longitudinal wave velocity and dynamic elastic modulus attenuation of pervious concrete under freeze-thaw cycles were measured, and a prediction model of freeze-thaw damage was established. The mechanical properties of hardened cement pastes with the same W/C ratio under freeze-thaw cycles were also measured. Mercury intrusion porosimetry (MIP) was used to measure the pore structure characteristic parameters and pore size distribution changes of cement paste under freeze-thaw cycle, and the microstructure evolution of interfacial transition zone (ITZ) of paste and aggregate was observed by SEM scanning electron microscopy. Finally, a pervious concrete model was established by DEM to analyze the relationship between the number of freeze-thaw cycles and the mesoscopic parameters. The results indicated that the quality, strength and dynamic elastic modulus of pervious concrete deteriorate to different degrees under the conditions of water freezing and salt freezing. The damage sensitivity and strength loss of freeze-thaw damage is greater than the dynamic elastic modulus loss, which is greater than mass loss. In the pervious concrete paste which underwent 100 freeze-thaw cycles, the pore structure and macro strength had no obvious change, and hardened paste and the aggregate-interface-generated defects increased with the increase in freezing and thawing times, indicating that the deterioration of pervious concrete performance under freeze-thaw cycles was closely related to the deterioration of the interface strength of the aggregate and hardened paste. The pervious concrete model established by DEM can accurately simulate the change of the compressive modulus and the strength of pervious concrete during freeze-thaw cycles. Pervious concrete is a porous and lightweight concrete made of aggregate, cement, reinforcer, mineral admixture and water. As the surface of the coarse aggregate is covered with thin layers of cement paste and it bonds to itself, a honeycomb structure is formed with evenly distributed pores; this gives pervious concrete the characteristics of air permeability, water permeability and light weight, and is widely used in the engineering field ,2,3. How2) did significant damage to the mass loss and stiffness reduction of concrete [The frost resistance of pervious concrete increased with the decrease in aggregate particle size, increased with the increase in paste to aggregate mass ratio, and decreased significantly with the increase in water–cement ratio ,8. For tconcrete . The thrconcrete . Andersoconcrete . Hassan concrete .Some researchers have improved the freeze-thaw resistance of pervious concrete under extreme cold conditions. Mehmet Gesoğlu et al. found that rubber was an effective solution to the freeze-thaw durability problem of pervious concrete. After 300 freeze-thaw cycles, rubber utilization significantly improved their results. The performance of small size rubber particles was better than that of large size rubber particles . D. TaraHowever, compared with ordinary concrete, whether improving cement-based materials was the most effective way to improve frost resistance required further research on the freeze-thaw failure mechanism of pervious concrete. The mechanical behavior and failure mechanism of cement-based materials under freeze-thaw cycles has been studied by many scholars ,33,34. TIn recent years, many researchers have studied the freeze-thaw deterioration process of concrete through numerical simulations, such as the finite element method (FEM) and discrete element method (DEM), to deepen the understanding of this process ,39,40,41Based on the above introduction, this paper deeply explored the freeze-thaw cycle deterioration area of permeable concrete through a combination of macroscopic and microscopic tests. The strength loss, mass loss and relative dynamic elastic modulus change of pervious concrete under freeze-thaw cycles were measured macroscopically, and the strength loss, mass loss and morphology change of hardened cement paste under the same W/C ratio were compared. Microscopically, the morphology evolution of the aggregate–cement interface was explored by a scanning electron microscopy (SEM) test, and the pore structure change of the hardened cement slurry was obtained by a mercury intrusion porosimetry (MIP) test. Therefore, the damage degradation a model undergoing freeze-thaw cycles was proposed. On the basis of the test, a discrete element model of pervious concrete’s freeze-thaw damage was established, which effectively indicated the relationship between the number of freeze-thaw cycles and the bond strength between particles. The research results can enrich the theoretical system of damage mechanisms of pervious concrete under freeze-thaw cycles, and provide theoretical support for pervious concrete construction under freeze-thaw scenarios.All mixtures were made of ordinary Portland cement with a strength grade of 42.5. Coarse aggregate was limestone with a particle size of 2.5~10.0 mm, and a particle size of 2.5~5.0 mm accounted for 25% of the limestone. In order to make the pervious concrete in this test similar to the actual pervious pavement material, an SR-5 commercial additive produced by Nanjing Jiuherun Engineering Technology Company was used as the admixture. The recommended additive amount was 3~6% of the cement quality; the additive amount in this test was 4% of the cement quality. According to the supplier′s product introduction, the reinforcer mechanism of the strengthening agent is to participate in the cement hydration reaction to form a high-molecular polymer structure, which can significantly improve the compressive strength and bonding strength of the hydration production. The chemical composition of the additive is shown in According to the Chinese standard CJJ/T 135-2009 , the fil(1) Pervious concrete sampleThe size of the permeable concrete sample was a 150 mm cube, and the molding adopted a combination of ramming and vibration. The mixture was assembled into the mold three times, and then it was vibrated on a vibrating table for 15 s, and the mold was removed after 24 h. The samples were covered with geotextiles and watered for 28 days.(2) Hardened cement slurry sampleThe ratio of the prepared cement stone material was the same as that of the permeable concrete cementitious material. The sample size was a cylinder with a diameter of 20 mm and a height of 20 mm. The preparation process was that the cementitious material was put into the vessel and fully stirred, and then the slurry was loaded into the mold and then vibrated on a vibrating table for 30 s and placed in the mold for curing. The sample was demolded after 24 h, and the curing was the same as that of the pervious concrete. The above concrete and paste experiments were carried out in a laboratory with a room temperature of 20 °C and humidity of 70%.P can be obtained by using the difference between actual and theoretical buoyancy. The specimen size was a 150 mm cube and the average value of the three samples was obtained. The calculation formula of porosity P was as follows:P is the effective porosity (%); m1 is the floating weight of the sample (g); m2 is the drying quality of the sample (g); V is the sample volume (cm3).The pore structure of the pervious concrete was composed of connected pores, semi-connected pores and closed pores, among which connected pores and semi-connected pores belonged to effective pores . VolumetUltrasonic wave velocity was an important parameter in ultrasonic testing of concrete, which was related to the number and complexity of pores in the internal structure of concrete. If there were defects  inside the concrete, the ultrasonic waves will be refracted and diffracted there, resulting in a lower ultrasonic wave velocity. The ultrasonic wave velocity was related to the material components, and the W/C ratio and aggregate content all affected the ultrasonic wave velocity of concrete ,50. In aThe transmitting and receiving transducers were placed in the center of two opposite surfaces of the pervious concrete. In order to reduce the influence of the gap between the transducer and the concrete surface on the ultrasonic test results, Vaseline was applied as a coupling agent at the contact position between the transducer and the pervious concrete. The ultrasonic detection frequency was set to 28.2 kHz, and the sampling was started after the relevant test parameters were set. When the ultrasonic wave speed and waveform were stable, the sampling was stopped and the data were saved to record the ultrasonic wave speed. The specimen size was a 150 mm cube and the test results were taken as the average value of the three samples.According to the Chinese standard GB/T50081-2002 , the 150P is the compressive strength, MPa; F is the peak pressure of specimen failure, kN; A is the compressive surface area of the sample, mm2.The calculation formula for the peak compressive strength of pervious concrete is shown in Equation (2):A strain gauge was applied to the hardened cement paste sample to measure the transverse and longitudinal strain under compression. The strain gauge was connected with the strain gauge, and the upper and lower surfaces of the cement stone sample were coated with butter and placed on the bottom support of the electronic universal testing machine. The test control mode was set as displacement control, and the displacement control speed was set as 0.1 mm/min. The peak load was recorded, and the average strength of three cement blocks was obtained.The freeze-thaw cycle test of pervious concrete conforms to the Chinese standard GBT 50082-2009 . There wThe freeze-thaw test block was immersed in the test tank for two days. After it was removed, the test block was wrapped and sealed with plastic wrap until there was no water dripping from the bottom of the test block. Then it was quickly put into the freezer. The freeze-thaw test was started with a freezing temperature of −25 °C and a freezing time for each cycle of 10 h. Then, the test block was put into a water tank (20 °C) to thaw for 4 h.The specimens were dried after curing for 28 days, and the initial mass of group A was weighed. When group A reached the number of freeze-thaw cycles, the samples were thawed, cleaned with water, and weighed after drying for 24 h, and then their ultrasonic speeds were measured. When the number of freeze-thaw cycles was reached, three samples outside group A were selected for a compressive strength test. After curing for 25 days, the sample was immersed in a 3% sodium chloride solution for three days. After soaking, the sample was removed from the sodium chloride solution, covered with plastic film and left to stand for 10 min to drain the water. The pervious concrete test block was sealed with plastic wrap to prevent evaporation of water during the freeze-thaw cycle. The number of test blocks, method steps, sizes and testing methods of freezing and thawing deterioration in the salt freezing test was consistent with that in the water freezing test. The sample size of the clean cement slurry was a cylindrical sample with a diameter of 20 mm and a height of 20 mm. There were 8 groups of samples with 3 pieces in each group. Three groups were tested for mass loss (25 measurements per freeze-thaw cycle) and compressive strength (50 measurements per freeze-thaw cycle). The other 5 groups were subjected to a mercury injection test (25 measurements per freeze-thaw cycle). The freeze-thaw cycle of the cement slurry was consistent with that of pervious concrete.Mercury injection (MIP) of cement paste specimens was measured by an AutoPore IV 9500 automatic porometer in the pressure range of 0.10 to 61,000.00 Psia, and the contact angle between the mercury and the pore surface was θ = 130°. The sample size of the cement paste prepared in this test was 20 mm in diameter and 20 mm in height, which can be directly used for the mercury injection test. Prior to mercury injection testing, MIP specimens were placed in anhydrous ethanol for at least 24 h to dehydrate and terminate hydration. Then, the sample was put into the oven at 45 °C to dry for 24 h until it reached a constant mass so that free water and alcohol evaporation was achieved.2 was knocked off at the aggregate interface. The samples were soaked with anhydrous ethanol to stop hydration. Before the experiment, the samples were taken out and dried to a constant weight at 60 °C for testing.The scanning electron microscopy  was used to observe the microstructure of the interface zone between the aggregate and the hardened paste and the paste zone. After the freeze-thaw test was repeated 50 and 100 times, a thin fragment of 5 mmThe calculation principle of PFC3D discrete element software was mainly based on the force-displacement law and Newton′s second law. It adopted the explicit finite difference method for the cyclic iteration solution and interacted with the internal force and torque. There is bonding strength between particles, and the bond is broken when the force acting on the cohesive bond due to external loads exceeded the strength of the bond itself . In thisAggregate is constructed through six discrete particle units embedded with each other, as shown in The structure of the dropped aggregate slurry was observed in The strength changes of the pervious concrete during freeze-thaw under water freezing and salt freezing are shown in It can be seen from The changes in pervious concrete quality during freeze-thaw cycles in both water and salt freezing environments are shown in However, it was also found that the fluctuation of the effective pore variation of water freezing in the sample did not seem to come from a measurement error, which may be caused by the coupling agent in the ultrasonic test. The coupling agent Vaseline can fill the surface of pervious concrete and reduce the number of connected pores. The effect of water freezing and salt freezing denudation on effective pores was greater than that of coupling agent filling. Salt freezing was more serious because of mass loss, so this effect was not obvious.mL, strength loss σL and dynamic elastic modulus loss EL are calculated according to Equations (3)–(5) below:m0, σc,0 and E0 are the initial mass, compressive strength, and dynamic elastic modulus, respectively, and dm, c,dσ and dE are the mass, compressive strength, and dynamic elastic modulus after reaching the specified number of freeze-thaw cycles, respectively.In order to evaluate the deterioration degree of freeze-thaw damage, the quality loss rate, strength loss rate and freeze-thaw damage model based on ultrasonic wave velocity attenuation were used as evaluation indexes, where the mass loss rate Ψ, the ratio of the effective load area before and after the damage) was used to describe the damage state of the material, and the damage variable D (1 − Ψ) corresponding to the continuum was introduced. The principle of strain equivalence was proposed, and the damage degree can be expressed by the change of elastic modulus:E is the elastic modulus of the material before damage, Gpa; Freezing-thawing cycles can cause irreversible damage to pervious concrete, such as cracks, aggregate spalling and fractures, which makes it difficult to guarantee the mechanical properties and service functions of pervious concrete. In damage mechanics, it was generally considered that material damage was irreversible and was a process of energy dissipation. It was believed that the damage to materials was caused by the microscopic defects of materials, resulting in the reduction of the effective bearing area (A) of materials. This microscopic defect process was difficult to measure and needed to be linked to specific measurable macro variables. The continuum (ED = (aeN/b)(− + c)/100, where ED freeze-thaw damage characterization, N was the number of freeze-thaw cycles, a, b and c were undetermined parameters, and the model was as follows:The degree of damage can be expressed by elastic modulus. Therefore, the freeze-thaw damage model of the water-frozen pervious concrete is represented by Equation (7), and the freeze-thaw damage model of the salt-frozen pervious concrete is represented by Equation (8).mD = (aeN/b)(− + c)/100, where mD is the quality damage characterization, N is the number of freeze-thaw cycles, a, b and c are undetermined parameters, and the model is as follows: Based on the data of 100 freeze-thaw tests, a prediction model of the freeze-thaw quality loss of pervious concrete was established by using the first-order decay exponential function (ExpDec1), namely Equation (9) is the quality loss prediction model of the water-frozen pervious concrete, and Equation (10) is the quality loss prediction model of the salt-frozen pervious concrete. The fitting curve of mass loss of permeable concrete under freeze-thaw cycles is shown in σD = aN2 + kN), where σD is the strength damage characterization and a and k are undetermined coefficients. The model is as follows:Due to the dispersion of the 25 freeze-thaw data in the water freezing test, the strength loss model only considered the salt freezing condition. The strength loss model of the pervious concrete is constructed by using the quadratic function (Equation (11) was the strength loss prediction model of the salt-frozen pervious concrete. The fitting curve of strength loss of the permeable concrete undergoing freeze-thaw cycles is shown in The variations of various parameters of the cement pore structure with different freeze-thaw cycles are shown in The paste accumulative quantity of different freeze-thaw cycles was shown in However, it was also noted that the initial curve also increased greatly at 69 nm, but the final cumulative volume of mercury was about twice that after a freeze-thaw cycle. The paste with a water–cement ratio of 0.31 became denser through the hydration reaction at 5–69 nm during the freeze-thaw cycle. Mehta′s tests showed that pores smaller than 132 nm had no effect on the strength of concrete . This maThe pore size distribution of the cement paste with a 0.31 water–cement ratio under different freeze-thaw times was plotted, as shown in Microcapillary pores of 5~100 nm will exhibit the capillary condensation phenomenon, increasing the hygroscopicity of the pores . The higThe components of the aggregate paste structure can be determined by EDS analysis. The interface area of aggregate and cement paste showed great differences under different freeze-thaw cycles. With the increase in freeze-thaw times, the two-phase contact area of aggregate and hardened paste deteriorated obviously. In the unfreeze-thawing of the concrete sample, the interface between aggregate and cement paste was smooth. It can be seen by comparing The failure process of pervious concrete under freeze-thaw cycles is essentially the process of internal deterioration of the material. Microdefects in the pervious concrete can be regarded as a damage field continuously distributed within the material. In the freeze-thaw cycle, freeze-thaw damage is constantly generated and expanded, which reduces the strength, stiffness, service function and residual life of the pervious concrete material . TherefoThe DEM simulated the macroscopic mechanical response of concrete by means of the law of bond contact at the particle scale, so the macroscopic material parameters obtained through experiments cannot be directly applied to the numerical model. The DEM simulated the macroscopic mechanical response of concrete by means of regular bond contact at the particle scale, so the macroscopic material parameters obtained through experiments cannot be directly applied to the numerical model .tE is as follows:Etis the compression–elastic modulus, Gpa; cσ is the peak stress; cε is the peak stress corresponding strain.The compressive elastic modulus and peak compressive strength of the parallel bond model materials were affected by the effective modulus of the parallel bond, normal bond strength and tangential bond strength ,71. The Et is the compression–elastic modulus, Gpa; * is the effective modulus of parallel bonding, Gpa; cσ is the peak stress (compressive strength), MPa; In this model, the bond strength ratio of normal shear was set as 1:1, and the two were collectively referred to as bond strength. Both effective modulus and compressive strength tests were performed to obtain the relation between the effective modulus and compressive modulus, as shown in Et, the peak stress σc and the number of freeze-thaw cycles should be established first. Since only the initial peak strain was measured in this study, so the relationship between the relative peak strain of concrete and the number of freeze-thaw cycles and the cube′s compressive strength (peak stress) is shown as follows [c,Dε is the compressive peak strain of concrete after freeze-thaw; cε,0 is the compressive peak strain of unfreeze-thawed concrete; cσ,0 is the compressive strength of unfreeze-thawed concrete; N is the number of freeze-thaw cycles.It can be seen from Equation (13) that in order to establish the relationship between the number of freeze-thaw cycles and the meso-parameters of the model, the relationship between the compressive elastic modulus  follows :(14)εc,Dcσ and the number of freeze-thaw cycles can be obtained according to the previous strength loss model Equation (11), the following Equation (15) can be obtained:The relationship between the peak stress −3. The compressive stress and strain of the concrete undergoing freeze-thaw cycles in a salt freezing environment are shown in According to Equations (14) and (15) and the initial compressive strength of freeze-thaw 23.13 MPa, the measured peak strain was 2.78 × 10Equations (12)–(15) were combined to obtain the relationship between the number of freeze-thaw cycles N and the microscopic parameters of the discrete element model, as shown below:N of 0, 25, 50, 75 and 100 into Equation (16) to obtain the model′s microscopic parameters under different freeze-thaw times, as shown in We substitute the freeze-thaw times It can be seen from In this study, through freeze-thaw cycle tests  on pervious concrete and paste with the same W/C ratio, the mass loss, dynamic elastic modulus and compressive strength attenuation laws were investigated, and the freeze-thaw damage prediction model of pervious concrete was established. The relationship between the freeze-thaw damage of a hardened cement paste and the freeze-thaw damage of pervious concrete was studied. At the micro-scale, the evolution of porosity, characteristic pore size and pore size distribution of frozen and thawed paste (at the same W/C ratio as pervious concrete) was studied by the mercury intrusion porosimetry (MIP) method. The damage process and mechanism of the freeze-thaw cycle  on the microstructure of pervious concrete were analyzed by scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). The relationship between the mesoscopic parameters and the macroscopic properties of the pervious concrete specimens was analyzed by the discrete element method (DEM) in combination with the experimental mixed-ratio parameters. The conclusions of this paper were as follows:After 100 cycles of freezing and thawing, the mass loss of the pervious concrete was 0.47% and 0.82%, the strength loss was 16% and 23% and the dynamic elastic modulus loss was 7.9% and 11.4%, respectively. The water–cement ratio did not change the strength significantly. Considering the interfacial crack propagation observed by electron microscopy, it can be concluded that the freeze-thaw deterioration of the pervious concrete mainly came from the interfacial zone.The pore size of the cement paste with a water–cement ratio of 0.31 was concentrated at 5–69 nm, and the change of pore size distribution below 200 nm did not affect the macro-strength of the cement paste. There is almost no aggregate cement interface zone in pervious concrete at a water–cement ratio of 0.31.The DEM model can better simulate strength changes of pervious concrete undergoing freeze-thaw cycles, and its macroscopic strength changes were consistent with the microscopic bond strength changes between particles in the DEM model, indicating that the strength deterioration of pervious concrete was caused by the reduction of the bond strength between the aggregate particles. However, due to the limitation of the assumptions of the model, this model was only applicable to the study of strength loss, and it had limitations in the study of other freeze-thaw deterioration indexes or the change of failure forms of pervious concrete. Therefore, the model can be further improved in the future, and more mesoscopic parameter changes need to be considered and calibrated with physical tests in terms of failure modes.


Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action.To review AMR in Kuwait and initiatives underway addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rise in AMR within Kuwait and to improve patient outcomes.Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used locally for specific CA-RTIs  were also reviewed, plus local antibiotic availability. Insights from a clinician in Kuwait were sought to contextualize this information.National initiatives to address AMR, antibiotic use and prescribing, and availability of susceptibility data, particularly for the key community-acquired respiratory tract infection (CA-RTI) pathogens In Kuwait there have been some initiatives addressing AMR such as annual campaigns for proper use of antibiotics. Antibiotic use is high but there appears to be a low understanding in the general public about their appropriate use. However, there is legislation in place prohibiting over-the-counter purchase of antibiotics. Only international guidelines for CA-RTIs are used. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data of isolates from community-acquired infections in Kuwait, could make management guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve clinical patient outcomes. Even if new medicines are developed, without behaviour change, antibiotic resistance will remain a major threat’.3 The first paper in this Supplement included details about the multiple factors which can drive a rise in AMR along with the global initiatives that are in place to address this threat.2 Each country and/or region must also play their part through local initiatives.Antimicrobial resistance (AMR) is one of the biggest threats to public health throughout the worldStreptococcus pneumoniae and Haemophilus influenzae. National and international antibiotic prescribing guidelines for CA-RTIs, specifically community-acquired pneumonia (CAP), acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS), commonly used by healthcare professionals in Kuwait were also reviewed, along with how these link to local antibiotic availability. Insights from a clinician in Kuwait were sought to contextualize this information. In addition, we aimed to identify areas where more information is required and present a call to action to improve clinical outcome for patients and to minimize further rises in AMR within Kuwait.In order to identify how AMR can be addressed in Kuwait in the future, it is necessary to review what is happening now. In this paper, we present the current situation in Kuwait, determined by using published information  to ascertain any national initiatives to address AMR, antibiotic use and prescribing, and availability of susceptibility data, in particular for the key community-acquired respiratory tract infection (CA-RTI) pathogens 4 many countries began to develop their own National Action Plan (NAP) and in 2018, the WHO reported good progress in the Eastern Mediterranean region in the development of NAPs on AMR. Ten countries had submitted or completed plans and a further seven were in the process of producing plans, including Kuwait,5 although the current NAP status, as reported by the WHO for 2020–21, shows that Kuwait had yet to finalize an AMR NAP.6Following the formulation by the World Health Assembly in 2015 of a Global Action Plan (GAP) for AMR7 the number of antimicrobial stewardship programmes is low in Kuwait.8–10In Kuwait and the Gulf Cooperation Council countries, inappropriate prescribing of antibiotics and self-medication are widespread risk factors for increasing antibiotic resistance. A lack of policies available for limiting inappropriate antibiotic use contributes to the increase in AMR in the region. Although progress is being made,11 Another study on resistance trends in S. pneumoniae in a tertiary hospital in Kuwait during 1997–2007, clearly demonstrated an increase in the prevalence of AMR and drug resistant S. pneumoniae.12A study exploring the patterns of antibiotic resistance found that Kuwait had a growth rate of resistance of 17% for several common pathogens between 1999 and 2003.13The use of antibiotics in treating upper respiratory tract infections (URTIs) was evaluated in primary healthcare centres in Kuwait and the extent to which antibiotic use followed international guidelines was assessed. Half of all URTIs were treated with antibiotics, but of these, 94% (127/135 prescriptions) could not be justified when applying the UK National Institute for Health and Care Excellence (NICE) guidelines that were current at the time of the study. This overuse of antibiotics was linked primarily to the lack of evidence-based practice in Kuwait.14 73% of the respondents had been prescribed an antibiotic in the last 12 months and, of these, 36% failed to finish the course, mainly because they felt better. Antibiotics were used without a medical consultation by 27.5% of participants (187), primarily to treat the common cold, sore throat or cough. There was confusion about whether antibiotics were effective against bacteria or viruses, and almost 47% had little knowledge about the action of, safety and resistance to antibiotics.14Knowledge, attitudes and practices regarding antibiotic use amongst the public was investigated in a study of 770 randomly selected Kuwaiti individuals.15Further work is needed to build awareness of the appropriate use of antibiotics by the public in Kuwait. Studies suggest a multidisciplinary approach must be put in place to: educate the public on appropriate antibiotic use; improve policies regarding the rational prescription of antimicrobials; and increase regulatory control.S. pneumoniae and H. influenzae, which are the most commonly isolated respiratory pathogens in the community.16 Key features of the SOAR study are that it focuses on these pathogens only, and that identification and susceptibility testing are performed in an independent centralized laboratory using standardized methodology (CLSI) allowing for comparisons to be made between countries or regions and for the identification of trends over time. SOAR data is analysed based on three different breakpoints: CLSI, EUCAST dose-specific and PK/PD breakpoints.Several ongoing global surveillance studies provide antibiotic susceptibility data from Kuwait. The Survey of Antibiotic Resistance (SOAR), a multinational antibiotic surveillance study, has been underway in an expanding range of countries since 2002. The study aims to collect and make available in published, peer-reviewed papers, antibiotic susceptibility data, specifically for 17 CLSI and EUCAST define breakpoint values but due to variation in criteria for their definition, there are some differences between CLSI and EUCAST in the clinical breakpoint values for certain bacteria for some antibiotics and this can impact susceptibility interpretation of clinical isolates.18 EUCAST breakpoints are dose-specific and use the EMA-approved doses that are included in the Summary of Product Characteristics of an antibiotic. This means that by application of breakpoints for higher doses, the effect of using a raised dose on the clinical efficacy of a particular antibiotic can be predicted. Currently, clinical microbiology laboratories in Kuwait use CLSI breakpoints, however the international application of the EUCAST breakpoints is expanding,19 so it is possible that dose-specific breakpoints could also be applied in Kuwait in the future. The EUCAST dose-specific breakpoints can also be used retrospectively to calculate the susceptibility of previously collected isolates to show susceptibility levels that would have been achievable with higher doses.Clinical breakpoints are cut-off MIC values used to classify microorganisms into the clinical categories susceptible (S), intermediate (I) and resistant (R) in order to assist in the prediction of the clinical success or failure of a specific antibiotic.S. pneumoniae, the most commonly isolated respiratory pathogen,21 causing conditions such as CAP, AOM, and ABRS, has over time become less susceptible to amoxicillin/clavulanic acid in some countries22 since the MIC of some isolates has increased. When treating infections, it is important to be able to eradicate bacterial pathogens with raised MICs to optimize clinical outcome while at the same time minimizing the risk of selecting variants with even higher MICs. This is possible because β-lactams, unlike many other antibiotics, have time-dependent killing properties. Their efficacy depends on the amount of time the drug concentration is present at the site of action; the use of higher doses and/or more frequent dosing allows for successful eradication of pathogens with higher MICs because the time above the MIC is increased.23Use of the EUCAST dose-specific breakpoints shows the effect of increasing the antibiotic dose on the susceptibility of a pathogen, providing additional information so that the prescriber can decide whether a higher dose would be of benefit. For example, S. pneumoniae isolates (n = 82) to amoxicillin and amoxicillin/clavulanic acid was 86.6% and 87.8%, respectively .16The most recent SOAR results for Kuwait were obtained from a single centre, Kuwait University. Clinical isolates were collected from patients with CA-RTIs. When applying CLSI breakpoints, susceptibility of y Figure . Notably2 the Antimicrobial Testing Leadership and Surveillance (ATLAS) database is fully accessible and searchable and covers susceptibilities of a range of bacterial and fungal pathogens to a bank of antimicrobials.24As outlined in the introductory paper to this Supplement,S. pneumoniae are shown in Figure S. pneumoniae isolates from outpatients in Kuwait with RTIs to amoxicillin/clavulanic acid ranged from 71.4% to 94.0% between 2014 and 2019. Susceptibility to the macrolide erythromycin (which can be used to predict the susceptibility of azithromycin and clarithromycin based on CLSI guidelines), remained low (33.9%–66.0%) over this entire period. A small number of H. influenzae isolates was collected between 2015 and 2017 and showed high susceptibility (88.9%–100%) to the antibiotics tested, including amoxicillin/clavulanic acid (100%), apart from a small reduction in the susceptibility to ampicillin (77.8%–84.6%) . GLASS is a global system which collects national AMR data for selected bacterial pathogens that cause common infections. The aim is to monitor the prevalence of AMR amongst major pathogens in clinical settingsAcinetobacter spp., Escherichia coli, Klebsiella pneumoniae, Neisseria gonorrhoeae, Salmonella spp., Shigella spp., Staphylococcus aureus, and S. pneumoniae. By 2021, the number of countries to have enrolled in GLASS had increased to 107, including Kuwait.27 An important new component in GLASS is the inclusion of antimicrobial consumption (AMC) surveillance at the country, regional and global level and the aim is to provide data on the use of antimicrobials in the population. GLASS data is analysed based on CLSI and EUCAST breakpoints.Pathogens currently included in GLASS-AMR are: Most guidelines suggest a first-line antibiotic or antibiotics along with alternatives and then a second-line antibiotic or antibiotics, also with alternatives. The first-line antibiotic is the recommended initial choice that should be prescribed by the clinician following diagnosis of the infection, supported by the criteria defined by the organization or committee; alternatives may be provided for use in particular circumstances. The second-line antibiotic is for use if the first-line antibiotic does not achieve the anticipated outcome, and again alternatives may be included for specific circumstances.For management of the common RTIs, CAP, AOM and ABRS in Kuwait, clinicians make use of a range of international guidelines, examples of which are shown in Table 31 and the IDSA for adults34 and children.30 For example, a first-line antibiotic treatment recommendation for CAP management from the IDSA 2019 guideline for treating adults with no comorbidities or risk factors for MRSA or Pseudomonas aeruginosa, is amoxicillin or doxycycline or a macrolide  but if the patient has comorbidities, the recommendation is combination therapy with amoxicillin/clavulanic acid or a cephalosporin plus a macrolide or doxycycline, or monotherapy with a respiratory fluoroquinolone. The recommended dosage for adults with comorbidities is amoxicillin/clavulanic acid, 500 mg/125 mg given three times daily, 875 mg/125 mg or 2000 mg/125 mg both given twice daily in combination with a macrolide or doxycycline.34 The BTS also suggests amoxicillin/clavulanic acid, cefaclor, and macrolides as an alternative to first-line amoxicillin in children with low-severity pneumonia.For the management of CAP in adults and paediatrics, the international guidelines referred to by clinicians in Kuwait include those from the British Thoracic Society (BTS)33 In the AAP guidelines, for initial or delayed treatment amoxicillin or amoxicillin/clavulanic acid are recommended. In the case of penicillin allergy, alternatives are cefdinir, cefuroxime, cefpodoxime or ceftriaxone. If there is failure of initial treatment then ceftriaxone or amoxicillin/clavulanic acid is recommended. For the management of ABRS in adults and children the international guidelines used include those from the IDSA,32 which recommend amoxicillin/clavulanic acid rather than amoxicillin alone as initial empirical treatment.For the management of AOM, the international guidelines referred to in Kuwait are principally those from the American Academy of Pediatrics (AAP).Currently there are no local guidelines available or recently published for the management of CAP, AOM and ABRS in Kuwait apart from guidelines published for the management of pneumonia in COVID-19 patients.34 where for outpatients with comorbidities and CAP, the higher dose regimens of amoxicillin/clavulanic acid 875 mg/125 mg or 2000 mg/125 mg both given twice daily are recommended in addition to 500 mg/125 mg three times daily, for use in combination with a macrolide or doxycycline. In children who are outpatients with presumed pneumonia, amoxicillin/clavulanic acid  is recommended by the IDSA as an alternative empirical therapy to first-line amoxicillin treatment for CAP.30In Kuwait, several currently available formulations of amoxicillin/clavulanic acid are mentioned as first- or second-line recommendations by international RTI management guidelines. This includes the IDSA32 recommends either 500 mg/125 mg three times daily or 875 mg/125 mg twice daily as initial first-line therapy. In children with no β-lactam allergy, the IDSA suggests that first-line initial empirical therapy in ABRS is amoxicillin/clavulanic acid 45 mg/kg/day given twice daily. High dose regimens are recommended where there is risk of antibiotic resistance  or for failed initial empirical therapy, the 90 mg/kg/day regimen (based on amoxicillin component) given twice daily is recommended for children and 2 g/day given twice daily for adults.In adults with ABRS, the IDSA guideline 201235Substandard poor-quality or falsified antibiotics promote AMR and the spread of drug-resistant infections. Since poor-quality antibiotics are unlikely to contain the full dose needed to eliminate all infecting pathogens, this encourages resistance to develop and allow resistant strains to survive and be transmitted.35 The GSMS aims to work with WHO member states to improve the quality of reporting of substandard and falsified medical products, and, importantly, to ensure the data collected are analysed and used to influence policies, procedures, and processes to protect public health at all levels. Use of substandard or falsified antibiotics not only compromises clinical outcome but also risks increased AMR. The most recent summary (2013–17) reported substandard and falsified medicines in 46 member states. Antibiotics represented 16.9% of all products reported, second only to malaria drugs (19.6%).The quality of medicines, specifically antibiotics, is an important consideration for countries worldwide. WHO launched a Global Surveillance and Monitoring System (GSMS) for substandard and falsified products.36 This poses an alarming trend and represents a genuine threat to the health of the population and availability of effective antibiotics. Large hospitals in Kuwait publish antibiograms, which outline the resistance pattern of nearly all organisms isolated in that hospital. The microbiology department usually holds a meeting with the department concerned to highlight these resistance patterns and their implications for the proper use of antibiotics in identified infections. However, more effort is needed to make use of these antibiograms and to construct hospital-based antibiotic policies.Kuwait, like many other countries, has a problem of increasing AMR amongst several common bacteria that cause lower RTIs as documented by recent studies.Kuwait, unlike some other countries in The Gulf or Arab region, does not allow over-the-counter (OTC) dispensing of antibiotics, although this does happen to a certain extent. However, there is overuse of antibiotics in public health institutions and more so in private health facilities.37 The infection control directorate also runs an annual campaign for proper use of antibiotics.38 As far as antibiotics policy is concerned there are, unfortunately, no well-publicized or well-used national guidelines/policies. There are some hospital-based policies but often the selection of antibiotics is dictated by physician choice rather than health facility policy. The eight Consensus Principles40 to address increasing antibiotic resistance represent an ideal framework. The challenge for each country is, however, how to implement these principles by using national guidelines that are adhered to, audits, and monitoring of antibiotic usage across all health facilities.There are several attempts and efforts to try to control the problems of infections in general and overuse of antibiotics, in particular. The Kuwait Ministry of Health has a designated Infection Control Directorate which deals mainly with efforts to control health facility-related infections.In an era of rising AMR globally, this paper aims to define areas where action is required to address AMR by analysing and understanding the current situation within a specific country. Information is presented for Kuwait concerning antibiotic use and prescribing, approach to AMR, availability of local susceptibility data, use of international and/or local antibiotic prescribing guidelines and how these link to antibiotic availability. To our knowledge this is the first time this information has been reviewed and presented in detail by country.Whilst the WHO has produced a GAP on AMR, this has yet to be followed up in Kuwait with production of a NAP and, as explained by the clinician from Kuwait in this paper, in terms of national antibiotics policy there are no well-publicized or well-used national guidelines.19 Whilst laws exist prohibiting OTC purchase of antibiotics, the clinician’s comments in this paper indicate that this does still happen. In Kuwait, studies have reported overuse of antibiotics in RTIs and a widespread poor understanding by members of the public of the appropriate use, safety and resistance to antibiotics.Inappropriate antibiotic prescribing in the Gulf Region is widespread and is associated with antibiotic resistance and is leading to multidrug resistance and ultimately an increased mortality rate. The lack of policies available for limiting inappropriate antibiotic use contributes to the increase in antibiotic resistance in the region.In terms of surveillance, the global surveillance studies ATLAS and SOAR include data for Kuwait on the susceptibility of CA-RTI pathogens and reveal a trend towards decreasing susceptibility amongst the common isolates for some antibiotic classes, such as the macrolides. The fluoroquinolone antibiotics have so far retained activity, although guidelines and regulatory bodies urge caution, restricting their use to limited situations due to serious safety concerns.For management of the common RTIs in Kuwait, clinicians make use of international antibiotic prescribing guidelines and for the management of CA-RTIs, amoxicillin/clavulanic acid is a commonly recommended antibiotic, where its choice is substantiated by the available susceptibility data.As mentioned in the clinician’s comments, large hospitals maintain antibiograms of susceptibilities which can be applied to produce an antibiotic policy within that hospital, but an increase in local surveillance studies within the community would lead to the development of regularly updated management guidelines. These, if applied along with updated guidelines relating to the management of COVID-19 patients, would improve clinical outcomes and minimize further rises in AMR.2 This would pave the way for improved adherence and a higher level of appropriate antibiotic prescribing in CA-RTIs which could, in turn, potentially limit AMR development and improve clinical outcomes for patients.While a range of international guidelines is utilized by clinicians in Kuwait, a more standardized inclusive approach is needed to develop local country-specific guidelines These guidelines should be based on up-to-date surveillance data of isolates from community-acquired infections, which would make them more locally relevant for clinicians, reiterating the Consensus Principles as described in the introductory paper to this Supplement.


Utilizing scrap tire rubber by incorporating it into concrete is a valuable option. Many researchers are interested in using rubber tire waste in concrete. The possible uses of rubber tires in concrete, however, are dispersed and unclear. Therefore, a compressive analysis is necessary to identify the benefits and drawbacks of rubber tires for concrete performance. For examination, the important areas of concrete freshness, durability, and strength properties were considered. Additionally, several treatments and a microstructure investigation were included. Although it has much promise, there are certain obstacles that prevent it from being used as an aggregate in large numbers, such as the rubber’s weak structural strength and poor binding performance with the cement matrix. Rubber, however, exhibits mechanical strength comparable to reference concrete up to 20%. The evaluation also emphasizes the need for new research to advance rubberized concrete for future generations. Due to the new infrastructure being built, a significant quantity of waste concrete is generated from destroyed buildings every year. Construction and demolition trash is generated annually in China and the EU at 450 million tons and 200 million tons, respectively. About half of the rubber in a tire is made of natural rubber, butadiene rubber, and styrene-butadiene rubber. The other parts include carbon black, metal, textile, zinc oxide, sulfur, and additives . Tires rIn other words, as seen in Recycling used car tires as substitute aggregates to create new-class concrete is a creative solution with favorable effects on the environment, the economy, and performance. Numerous current findings examine the improvement in the compatibility of crumb rubber particles when utilized as a sand substitute. Shredded and/or crumb rubber particles have been extensively explored as a replacement for concrete aggregate . A studyIn addition to landfilling, there are other options, such as energy recovery, which is often carried out in cement kilns , and pyrWaste tire features that, if managed improperly, might endanger the environment can be utilized to the building industry’s benefit. Numerous research has been done on concrete that substitutes natural aggregate with scrap rubber from old tires in varying percentages . Figure Concrete strength qualities are impacted using scrap rubber tires as aggregates. Some of its qualities, including toughness, impact resistance, energy absorption, and sound and temperature isolation, are improved. However, it lessens various other strength characteristics, including workability, split tensile strength, and compressive strength . It is aIn order to explore sound absorption and the ultrasonic modulus of tire rubber concrete, the research used the ultrasonic echo method to conduct an ultrasonic analysis. The authors came to the conclusion that rubberized concrete is a powerful sound and shaking energy absorber . AccordiAiello and Leuzzi  substituBrief literature shows that several researchers focus to utilized rubber tire waste in concrete. However, the potential application of rubber tires in concrete is scattered and not clear. No one can easily judge the suitability of waste rubber tires in concrete. Therefore, a compressive review is required to summarize the positive and negative impact of rubber tires as aggregate on concrete performance. The important properties of fresh concrete properties , mechanical strength , and durability  were considered for analysis. Furthermore, different treatments, microstructure study (scan electronic microscopy), and application of rubberized concrete were also included. Finally, the review also highlights the future research aspects for future generations to further improvement in rubberized concrete.In addition, mixes created with fine crumb rubber were better to work with than those prepared with coarse tire chips or a combination of tire chips and crumb rubber, according to research. The slump was also shown to diminish as rubber proportion improved . The rubKhatib and Bayomy  claim thThe fresh mix performance was completely different for materials with a higher natural aggregate to rubber replacement ratio. As additional rubber was included, the droop became worse. However, the nonwetting rubber particles improved the flow of newly mixed concrete . The sluConcrete with a larger proportion of rubber particles was less workable. This is mostly because of rubber particles’ greater water absorption rates, which cause the mixture to have less free water overall and, as a consequence, have lower workability. Different sizes of rubber show a decline in flow with a rise in tire particle replacements . According to the experimental findings, rubberized concrete absorbed more water than regular concrete, and the amount of rubber in the concrete enhanced the water absorption. Therefore, water, chloride, and chemical assaults on rubberized concrete are more likely to occur . Due to 3 and the greatest being 2240 kg/m3. This is due to the fact that the tiny rubber filled up any gaps between the small concrete particles and served as a fine aggregate, increasing the density [Air content and fresh concrete density are correlated. Fresh concrete’s density will decline as the amount of air in the mixture rises. Concrete’s properties might alter when different materials are used. It can be noted that the density of various materials differs in the new concrete density test.  density . Accordi density . Gesog L density  found th density  indicate density  replacedHowever, it can be observed that rubber as coarse aggregate increased air content more than the fine aggregate. When crumb rubber was added to the concrete, Kardos et al.  discoverDepending on the dose of rubber-based aggregate, the strength of concrete containing that aggregate was lowered. The lowest compressive and capacity were seen when rubber fine particles replaced fine natural aggregate by 30% . The sciObinna Onuaguluchi et al.  discoverWhen 5% of the concrete was replaced, the presence of crumb rubber caused a 63.64% strength reduction relative to the goal strength. CS decreased by 52.73% when 2% of the material was replaced with rubber . AlthougThe causes of the rubberized concrete’s declining flexural and CS as per past study  are, (a)At a 20% rubber replacement, CS is just 12% less than the benchmark concrete CS. Rubber may be used up to 20% in concrete without having a materially detrimental impact on strength since the CS of concrete with a replacement of rubber is almost equivalent to the CS of reference concrete. However, when the percentages climbed (beyond 20%), a significant decline in CS was seen. Rubber replacement, even at 50%, shows CS 60% lower than reference concrete. Therefore, it is suggested to use rubber up to 20% in concrete. For a higher dose of rubber, treatment of rubber particles should be applied, or it can be used in precast non-load bearing building walls and precast roofs for green buildings. Concrete’s compressive strength (CS) is decreased by 10% to 23% when rubber particles are substituted for 7.5% and 10% of the typical concrete’s aggregate. When rubber is substituted by 7.5% to 10%, the tensile strength (TS) of concrete decreases by 30% to 60% , which iTo investigate the strength and toughness characteristics of rubberized concrete mixes, Eldin and Senouci carried out tests. Their findings showed that when the coarse aggregate was completely replaced with chipped tire rubber, the compressive strength decreased by around 85%, while the splitting TS decreased by about 50% . With a Despite losing some of its CS and TS, Deepak and Naidu  found th2 value greater than 90% seems to be straight. Therefore, the equation shown in The concrete TS shows the same pattern as the concrete CS. Therefore, a substantial link between the TS and CS of concrete. FS was found to improve by 12% when shredded rubber was covered with a NaOH solution that was the opposite of what the authors had previously found . A studyThe findings of compressive and flexural tests showed that substituting coarse aggregate rather than fine aggregate resulted in a greater loss of mechanical characteristics of rubber concrete. By replacing the coarse aggregate with rubber shreds, the post-cracking behavior of rubberized concrete was favorably impacted, displaying excellent energy absorption and ductility indices in the range seen for fibrous concrete . ConcretThe specimens containing tire rubber fibers up to 20% exhibited higher FS than the control specimens . ConcretIn mixes including rubber particles, significant reductions in FS and breaking tensile strength were observed. When the replacement ratio is 50%, the largest strength loss occurs . The invFive indicated rubber contents with volume percentages ranging from 10% to 50% were evaluated by Benazzouk et al. . A rubbe2 value greater than 90% seems to be straight. Therefore, the equation shown in The concrete FS shows the same pattern as the concrete CS. Therefore, a substantial link between the FS and CS of concrete. The concrete cylinder’s failure pattern during a compressive strength test is seen in The rubberized fiber-based concrete cylinders exhibited uneven failure planes because the fiber keeps the aggregate and cement paste together to prevent the fracture, but the control mix and the mixes with simply RCA replacement broke along well-defined failure planes, as seen in The failure pattern of the concrete beam during an FS test is seen in The rubber is cleaned with water to remove additives, organics, contaminants, and dirt that were placed on its surface during manufacture. According to certain studies, rubberized concrete made with rubber that has been cleaned with water is a little bit stronger than the rubberized concrete used as a control. The cement’s compressive strength rose by 15% . When coThe strength of rubberized cement cannot be increased only by water washing. Water cleaning, on the other hand, may effectively remove rubber contaminants that are soluble in water before adding the combination since it is the most cost-effective and ecologically beneficial way. It shows a positive development in the rubber exterior’s hydrophilicity . There i2, and NaOH, followed by UV exposure and partial oxidation. Chemical treatment cleans the oil from the rubber surface, gets rid of the dust and grime, and makes the rubber more hydrophilic and uneven. By modifying the rubber with NaOH liquor, rubberized cement characteristics are most often improved. This is due to the improved wear resistance, fracture energy, and FS shown by rubber that has been treated with NaOH liquid. In addition, the research found [The only chemically altered rubber surface is the latex treatment. This procedure involves soaking rubber in a solution containing CS2, KMnO4, acid, SCA, acetone, Ca(OH)ch found  that theAccording to research , treatinThe density and compressive strength of rubber-modified cement composites were further improved by a cement coating created using a silane coupling agent around rubber particles. The 30% cement coating was more successful in improving density than the 60% cement coating. The compressive capacity of concrete modified with rubber was greatly enhanced when the silane coupling agent was combined with cement coating as opposed to the silane coupling agent alone. At the rubber contents utilized in the investigation, the silane coupling agent surface treatment increased compressive strength by 9% to 24%, but the 30 weight % cement coating increased compressive strength by 27% to 110%. The increase in compressive strength was significantly greater for the 60 weight % cement coatings, ranging from 53% to 168%. The rubber-modified cement composite was able to preserve a considerably greater percentage of the compressive capacity of the reference pastes without rubber, thanks to the rubber’s considerable rise in the compressive capacity as a result of its two-staged surface treatment. For instance, the composite comprising 60% cement-coated rubber could sustain 94% of the strength of the reference paste at a rubber level of 5%. The compressive capacity formed with 60 weight % cement-coated rubber was greater than 50% from the control paste, even at a rubber content of 15%.The hard shell that formed around rubber particles because of cement hydration, as shown in Rubber’s elastic modulus and interfacial transition zone (ITZ) adhesion were both enhanced by the procedure of coating it with cementitious ingredients. As a result, it was very successful in enhancing the strength and durability characteristics of rubberized concrete. Additionally, the basic materials employed in this process have a variety of uses. They thus hold promise for industrial and large manufacture of rubberized cement for structural purposes . Ordinar2-treated concrete is comparable to reference concrete. In concrete mixes, replacing rubber increases the depth of water permeability. In comparison to the second combination, the first mixture exhibits a greater rise in water permeability depth. Mixtures with substitutions of 5% and 7.5% rubber are categorized as having low permeability, while mixtures with replacements of 10% tire rubber are categorized as having medium permeability. In concrete mixes, replacing rubber improved water penetrability depth and enhanced water absorption when coarse aggregate was replaced but decreased water absorption when cement was replaced [replaced .2 treatment of rubber aggregates is the most successful method for lowering the permeability of concrete mixes. Additionally, the highest outcomes were seen during a 72 h therapy period. While the aggregates’ permeability was likewise decreased after being treated with NaOH, the improvement was noticeably less than after being treated with Ca(ClO)2. This decrease is also due to better rubber aggregate/paste bonding, which reduces the ITZ’s porosity [The results indicate that the Ca(ClO)porosity . For theporosity . Additioporosity . The resporosity .The initial combination samples that were examined for water absorption looked to have fractured during oven drying, which led to noticeably higher values. The weaker link between the cement pastes and the bigger rubber particles (as opposed to the powder rubber in the second batch) may be the cause of this breaking. This rise is brought about by the substitution of rubber for sand, which has various forms and structures and develops some porosity, enhancing water absorption. Conversely, improving the quantity of fiber in concrete decreases water absorption .The authors draw the conclusion that the water absorption is higher than it was for the control combination. This is because the connection between the cement pastes and big rubber particles has decreased. In contrast, when the proportion of replacement is raised, the water absorption of the second combination containing powdered tire rubber decreases. It seems that filling cavities with powdered rubber has decreased the porosity of the concrete, which has decreased water absorption in this combination . By prevOne significant unrecognized risk to the safety of buildings is the durability of concrete in the sea environment. The impact of dry-wet alternation substantially speeds up the diffusion of corrosive ions, and the tidal range region develops the maximum severe area for concrete structure corrosion. Among them, chloride ion diffusion is one of the primary causes of the durability of concrete .According to Oikonomou and Mavridou , as the Rubber may prevent concrete fractures from forming and can lower the peak value of steel corrosion, according to research by Jian Liang et al. . Han ZhuAccording to research , replaciIt was nearly impossible to see any difference when samples of rubberized concrete were exposed to temperatures of 150 °C and 200 °C. All samples had an increase in mass loss as the heating temperature rose. The early mass loss was caused by the evaporation of capillary and gel water from the cement matrix, followed by the escape of absorbed and interlayer water, as demonstrated by the thermogravimetric measurement of rubber particles, which displayed that rubber disintegration begins quickly on the attainment of a temperature of 300 °C. The delivery of chemically bonded water, which is a component of cement hydration results and is particularly resistant to evaporation, may be responsible for the mass loss at higher temperatures . The CSHWhen related to the strength characteristics found for materials held at laboratory temperature, a study  found th2 were collected for microstructural investigations are shown in 2 treatment. This is explained by stronger aggregate/matrix bonding brought on by the rough tire surface and decreased porosity brought on by potential Friedel’s salt production. This is consistent with the strength data, which demonstrated that treating aggregates with Ca(ClO)2 for 72 h almost totally neutralized the strength decline shown for rubber particles that were not treated.Scan electronic microscopy (SEM) and digital microscopic pictures of concretes with rubber aggregates treated for 72 h with water, NaOH, and Ca(ClO)According to Pelisser et al. , treatmeWhen rubber is treated with a NaOH solution, the ITZ porosity of rubberized concrete is reduced, and the rubber–cement adhesion is increased, which lowers the mixture’s resistivity . In ordeWhen compared to traditional concrete, rubberized concrete is more resilient to pressure, impact, and temperature. It is also cheaper and more cost-effective. It has been noted that the compressive and tensile strengths of rubber-modified concrete (RMC) are quite low. However, they have increased acid resistance, minimal shrinkage, strong impact resistance, suitable water resistance with low absorption, and great sound and thermal insulation. In comparison to a standard concrete mix, studies reveal that CRC (crumb rubber concrete) specimens stayed intact after failure (did not shatter). For construction that has to have strong impact resistance qualities, this behavior could be advantageous. Concrete samples aggregated with thick rubber were notably noticeable to have rubberized concrete with improved impact resistance.Additionally, the special properties of rubberized concrete will find new applications in building structures for use as earthquake shock-wave absorbers, sound barriers, and highway construction as shock absorbers. It lessens plastic shrinkage, cracking, and concrete’s susceptibility to disastrous collapse.Presently, precast sidewalk panels, non-load-bearing building walls, and precast roofs for green buildings all employ concrete that has had scrap tires added to it . It is oWaste tire-modified concrete mixes might provide a feasible replacement to the standard weight concrete since rubberized concrete can also be utilized in non-load-bearing elements such as lightweight concrete walls, building facades, or other light architectural units . WhereveThe practice of rubber tires in concrete undoubtedly offers advantages, and the building sector as a whole cannot ignore this trend. For instance, rubber tires may be utilized as a substitute for natural aggregates. More than 100 modern and historical pieces of literature were evaluated to study the impact of rubber tires on the strength characteristics, freshness, and durability of rubberized concrete. The following were the key findings.Increase in rubber concentration. Rubberized concrete loses workability. However, it may be enhanced by adding admixtures such as plasticizers or other filler ingredients;The lower specific gravity and tendency to absorb air of rubber, rubberized concrete density reduces significantly when rubber content is increased. Rubberized concrete is hence advantageous for lightweight buildings;Concrete’s mechanical strength may generally be decreased by adding rubber, and this tendency becomes worse as rubber content rises. Due to the poor adherence of rubber with cement paste, a broad and porous weak interfacial transition zone (ITZ) was seen in rubberized concrete. The detrimental effects of rubber on the strength qualities of regular concrete may be lessened if the bond is strengthened at ITZ by any practical and affordable techniques. As a result, the construction industry would be able to employ rubberized concrete efficiently in a variety of concrete buildings;The decline in flexural capacity was lower than the decline in compressive capacity;The majority of studies feel that rubberized concrete with NaOH treatment has improved mechanical qualities. Other studies, however, asserted that the strength characteristics of rubberized concrete that has been treated with NaOH solution remain unchanged or even improve. The inconsistent findings might have been caused by varying rubber particle sizes, rubber suppliers, solution concentrations, and processing times;The silane coating agents (SCA) process transforms the rubber’s hydrophobic surface into a hydrophilic one and creates a chemical link between it and the cement matrix, enhancing the rubberized concrete’s mechanical characteristics and durability.Rubberized concrete performs badly at the moment. Pozzolanic filler additives could make it perform better. However, more detailed research is required before it may be used in a practical setting;The microstructure of rubberized concrete should be properly studied;Steel reinforcing bars’ corrosion behavior in rubberized concrete is recommended to be explored;Rubber surface treatment raises the price of utilizing rubber as a concrete aggregate. The cost of rubber surface modification should be investigated to evaluate its cost-effectiveness and identify the cheapest and most effective approach, which is crucial for more field applications;The thermal properties of rubberized concrete should be explored in more detail;The dry shrinkage and freeze–thaw action of rubberized concrete should be studied in detail.