Phospholipase A2 receptor (PLA2R), located at the membrane of glomerular podocyte, is the major autoantigen of idiopathic membranous nephropathy (IMN), and its antibodies with a predominant IgG4 subclass lead to pathological lesions. Further studies could be performed to validate the clinical values of PLA2R-IgG, PLA2R-IgG4, and PLA2R-IgG4-to-IgG ratios, as ultrasensitive and quantitative immunoassays for PLA2R antibodies have been well established in our previous work.  A cohort of 58 IMN patients, 30 of whom were followed from 3 to 42 months, was assessed for serum PLA2R-IgG and -IgG4 levels, and the ratio of PLA2R-IgG4/-IgG combined with relative clinicopathological indicators.  Serum PLA2R-IgG4 level was significantly correlated with glomerular PLA2R staining. In addition, it was strongly correlated with PLA2R-IgG and its ratio. PLA2R-IgG and -IgG4 levels were both correlated with high-density lipoprotein and erythrocyte sedimentation rates. The ratio at the first diagnosis can predict the remission, and its efficacy overmatched PLA2R-IgG4. In the survival curves, negative results for the ratio or PLA2R-IgG4 at the first diagnosis demonstrated higher remission rates.  Serum PLA2R-IgG4 concentration may replace renal PLA2R immunohistochemistry in IMN diagnosis. We propose that the PLA2R-IgG4-to-IgG ratio and PLA2R-IgG4 could be novel indicators for remission prediction in clinical practice. Membranous nephropathy (MN) is an autoimmune kidney disease that is a common cause of nephrotic syndrome in adults, and its incidence has increased gradually in children over the past decades –4. It isThe major antigen in IMN is the M-type phospholipase A2 receptor (PLA2R), a transmembrane protein present in human podocytes . PLA2R iThis study assessed serum PLA2R-IgG, PLA2R-IgG4, and their ratio using quantitative immunoassays with other pathological and clinical indicators for IMN before and after treatment. We evaluated their clinical usefulness and prognostic value in patients with IMN at a local center.A total of 58 IMN patients proved by renal biopsy were enrolled in this study in the Affiliated Wuxi People's Hospital of Nanjing Medical University. Among all, 30 patients were followed up for at least 3 months. This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Affiliated Wuxi People's Hospital of Nanjing Medical University (KYL2016001). The patients had signed informed consent.Specimens and basic data from 58 patients were collected prior to treatment, of which 30 patients received immunosuppressive therapy and continued sampling during follow-up. The basic features presented including gender, age, and with or without a history of hypertension. The pathological indicators included the total score of renal tubular and interstitium examined by light microscopy, immunofluorescence (IF), and electron microscopy, MN stage classified according to Ehrenreich and Churg standards, and IF PLA2R considered positive or negative according to glomerular staining of PLA2R protein . LaboratμL for hematuria, 0-0.3 g/24 h for proteinuria, 8.6-17.4 g/L for serum IgG, 40-55 g/L for ALB, 0-1.7 mmol/L for TG, 0-5.18 mmol/L for TC, 0-3.37 mmol/L for LDL, and 0-15 mm/H for ESR. The cut-off ranges for PLA2R-IgG, PLA2R-IgG4, and PLA2R-IgG4/-IgG ratio were 0-1990 ng/mL, 0-161.2 ng/mL, and 0-8%, respectively.Hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or with antihypertensive drugs. Treatment efficacy was classified as complete remission (CR), partial remission (PR), and no remission (NR). CR was determined when urinary protein was <0.3 g/d with stable eGFR. PR was achieved when proteinuria was 50% reduced to a level < 3.5 g/d. While NR was considered when proteinuria did not arrive at the guideline for PR. The reference ranges in the manufacturer's manuals were 0-25/μL of PLA2R-IgG standard or serum sample (diluted 1 : 200 in assay buffer) was pipetted into each well of a microtiter plate coated with the recombinant PLA2R antigen. After 1 h of incubation at 25° C, the plate was washed three times and then added with 100 μL of diluted Europium-labeled goat anti-human IgG antibody in the assay buffer. After another 1 h of incubation at 25° C, the plate was rinsed six times and pipetted with 100 μL of enhancement solution. The plate was agitated for five minutes and read using an autoDELFIA1235, a time-resolved fluoroimmunoassay instrument. The fluorescence intensity was recorded and the PLA2R-IgG concentration of each sample was calculated by the instrument system. The PLA2R-IgG4 determination was the same as the above protocol but pipetted with the sample diluted 1 : 20 and Europium-labeled mouse anti-human IgG antibody in the first and second incubation, respectively.The PLA2R-IgG and PLA2R-IgG4 assays were described as follows , 14. A 1T tests. If not, they were presented as the median, 25th and 75th percentile, and two-group differences using the Mann–Whitney U test. Enumeration data were analyzed by the Chi-square test. The Spearman correlation coefficient was used to calculate correlations between the variables. The linear correlation was analyzed by the Pearson's test. The 1-survival curves were plotted for the remission and analyzed by the Kaplan-Meier method and the Breslow-Wilcoxon test. A two-tailed P value < 0.05 was considered significant statistically.Statistical analyses were performing with SPSS 22.0  and Prism 8.0 . The measurement data were judged on the basis of whether they obeyed a normal distribution using the Shapiro-Wilk test. If they were, they were expressed as mean ± standard deviation, and differences between the two groups were compared using the independent samples P > 0.05). The serum C3 and IgG levels tended to decrease in the PLA2R-positive group. The median of serum PLA2R-IgG4 was 9.0 and 1016.2 ng/mL in the PLA2R-negative and PLA2R-positive groups, respectively  and the PLA2R-IgG4/-IgG ratio (P < 0.05) compared to serum PLA2R-IgG (P = 0.11) in IMN patients. Serum levels of PLA2R-IgG and PLA2R-IgG4 tended to increase with ESR and decrease with HDL levels. Moreover, PLA2R-IgG4 was strongly correlated with PLA2R-IgG and PLA2R-IgG4/IgG ratio. A linear correlation was significant between PLA2R-IgG4 and PLA2R-IgG with R = 0.70 and P < 0.01. The linear regression equation was y = 1312.3 + 1.9x.Clinicopathological parameters were compared by the Spearman correlation test with IF PLA2R antigen, the PLA2R-IgG and PLA2R-IgG4 levels, and the PLA2R-IgG4/-IgG ratio. As listed in Among the 58 patients enrolled in the study, 30 received treatment and were followed up. After a follow-up period of 3 to 42 months, 9 subjects had NR and 21 subjects achieved PR or CR according to the Kidney Disease Improving Global Outcomes guideline [r = −0.91, P < 0.01; r = 0.77, P < 0.01). Compared with the PLA2R-IgG, the PLA2R-IgG4/-IgG ratios at baseline and endpoint were negatively related to remission (P < 0.05). PLA2R-IgG4 levels after treatment were also negatively related to outcome (P < 0.05). However, there was no correlation or significant difference between the nonremission and remission groups with other common clinical indicators.Twenty patients in remission, including PR and CR, were diagnosed according to proteinuria levels. P < 0.05), indicating that a low serum PLA2R-IgG4 would have a large effect on remission in early treatment.In this study, we described some of our main findings. Compared with anti-PLA2R IgG, the serum level of IgG4 subclass was significantly increased and correlated with renal PLA2R antigen-positive IMN patients. This relationship was also evident between PLA2R-IgG4/-IgG ratio and PLA2R antigen. In addition, PLA2R-IgG4 was strongly associated with PLA2R-IgG and PLA2R-IgG4/-IgG. Anti-PLA2R IgG and IgG4 subclass were both positively related to ESR and negatively relevant to HDL. In follow-up studies, remission patients exhibited lower PLA2R-IgG4 and PLA2R-IgG4/-IgG levels at the baseline, and significantly higher ALB and lower proteinuria, PLA2R-IgG4 and PLA2R-IgG4/-IgG after treatment. The PLA2R-IgG4-to-IgG ratio was negatively related to PR or CR and more sensitive than PLA2R-IgG4. Furthermore, consistently PLA2R-IgG4-negative patients achieved remission relatively quickly at the initial follow-up.Since Dahnrich et al. first developed enzyme-linked immunoassays for the determination of PLA2R-IgG and IgG4 subclasses , severalHuman IgG can be divided into IgG1, IgG2, IgG3, and IgG4 subclasses, wherein IgG4 corresponds to anaphylactogen as the least abundant in plasma. However, anti-PLA2R IgG4 is predominant, followed by IgG1, IgG3, and IgG2, in IMN , 19. Witr = 0.7, P < 0.05), which was similar to the results of a previous study. These findings indicate that the detection of serum PLA2R-IgG4, but not PLA2R-IgG, could reduce the rate of renal biopsies.In our study, the PLA2R-IgG4 and PLA2R-IgG4/-IgG levels, but not PLA2R-IgG levels, were positively associated with glomeruli PLA2R-positive patients, implying that the IgG4 subclass mainly participated in the complex formation of the glomerular basement membrane in IMN, as IgG4 can be found in immune deposits with PLA2R antigen on renal tissue , 22. ThiFrom this cohort, we found that HDL was negatively associated with PLA2R-IgG4 and PLA2R-IgG. This might explain why lipid and lipid-related proteins play a major role in modulating podocyte function. Glomerular disease is associated with an APOL1 sequence variant, which encodes apolipoprotein L1, expressed in podocytes, and an important component of HDL. Fetal HDL does not have antioxidative functions without apolipoprotein L1 . MoreoveESR provides adjective information for the clinical observation of a patient's changes in clinical condition, disease progression, and treatment effect. In renal diseases, it was observed that a high ESR was correlated significantly with persistent proteinuria, tubulointerstitial injury scores, poor long-term outcomes, and urine IgG levels –29. We cThe present study has some limitations. We conducted a single-center study with an insufficient sample size, which may have affected the significance of the tests. Furthermore, each patient would be followed up every 3 months and well documented in future studies. A prospective study with a larger sample size would be required to promote the better understanding of the PLA2R-IgG4/-IgG ratio in the diagnosis and surveillance in the treatment of MN.In conclusion, serum PLA2R-IgG4 and PLA2R-IgG4/-IgG ratio were more strongly correlated with glomerular PLA2R antigen than serum PLA2R-IgG in IMN patients, and the PLA2R-IgG4-to-IgG ratio was significantly and negatively associated with partial or complete remission. Patients with negative PLA2R-IgG4 levels may have higher remission rates during the first 12-month treatment. Therefore, PLA2R-IgG4 could be a noninvasive marker for confirmation and therapy of IMN, and the importance of the PLA2R-IgG4/-IgG ratio and PLA2R-IgG4 level should be considered in predicting the clinical outcome of IMN treatment.


Toxoplasma gondii is one of the most common protozoan parasites and is widely present in all warm-blooded animals. Although clinical disease is uncommon, some species, including ring-tailed lemurs (Lemur catta), have been found to develop acute and lethal toxoplasmosis. The aim of this study was to describe the pathologic, immunohistochemical, serological, and molecular findings of an outbreak of fatal toxoplasmosis in three captive ring-tailed lemurs in Central Italy in 2009. The animals died acutely within few days. The necropsy was immediately performed; necrotic lesions in the spleen, liver, and kidney, as well as interstitial pneumonia, were found histologically. All animals had high titers of anti–T. gondii-specific antibodies (1:1280 IgM and 1:640 IgG) according to a modified agglutination test (MAT) and immunohistochemistry showed scattered tachyzoites in the target organs. Diagnosis was confirmed by PCR and clonal type II was identified. In addition, the seven co-habiting lemurs were seronegative. This paper reports the first outbreak of acute disseminated toxoplasmosis in captive ring-tailed lemurs in Italy. These findings confirm the high susceptibility of this endangered species to toxoplasma infection, which may be considered a further threat to captive population viability. Toxoplasma gondii is a coccidian parasite, member of the phylum Apicomplexa. Apparently, it can be considered the world’s most successful parasite: nearly all warm-blooded vertebrate species worldwide can be infected, including humans [g humans ,2.T. gondii through carnivorism, fecal–oral, transplacental, and other secondary routes, such as lactogenic and venereal, is one factor contributing to its global diffusion [T. gondii oocysts [The transmission of iffusion . Only do oocysts .Although infection may be common in many mammalian and avian species, clinical disease is rare ,5. NonetLemur catta) are primates belonging to the suborder Strepsirrhini. Like other Lemur spp., they are endemic to Madagascar, where they are the only native primate species present [Ring-tailed lemurs  for the breeding of threatened species and shelters over 500 animals belonging to endangered species.In Central Italy, a captive population of ring-tailed lemurs is housed in the Giardino Zoologico di Pistoia (GZP), located in Pistoia, Tuscany. This 75.000 mThe aim of the study was to describe the pathologic, immunohistochemical, serological, and molecular findings of an outbreak of acute, fatal toxoplasmosis in three captive ring-tailed lemurs in Central Italy.The results of serological, molecular, and pathological studies for each lemur included in the present study are summarized in The three lemurs died acutely within a few days of each other. They showed non-specific clinical signs such as anorexia, dehydration, lethargy, and debilitation. Treatment of the animals with dexamethasone , enrofloxacin , NaCl 0.9%, and glucose 5%  was unsuccessful. Their deaths occurred within three days of the treatment beginning. During the postmortem examination, a slight enlargement of the liver, spleen, and kidney due to passive congestion was observed. Small, scattered necrotic foci were detected in the liver and spleen, together with a mild generalized acute pneumonia.Microscopical investigations showed the presence of necro-hemorrhagic inflammatory foci in the spleen, kidney, liver, and lungs .Moderate to severe multifocal necro-hemorrhagic splenitis was found in all three deceased lemurs. Moderate multifocal, random, necrotizing hepatitis was present in 2/3 lemurs. The central nervous system and the heart did not show any histological changes, while multifocal to coalescing interstitial pneumonia, hyperemia, and edema were found in the lungs. Lesions involving liver and lung tissue were found only in the two adult females. In the kidney, cortical congestion, hyperemia of the glomerular capillaries, and mild interstitial nephritis were evident in all three subjects.The results of the immunohistochemical studies are presented in Scattered tachyzoites were found in the spleen, liver, lungs, and kidney of adult female #4429, and the spleen, liver, and lungs of adult female #4376. Tachyzoites were also found in the spleen and kidneys of the infant male lemur. No cysts or pseudocysts were observed in the lemurs investigated.All of the deceased lemurs were seropositive with the same high titers (1:1280 IgM and 1:640 IgG), while the sera of the seven live animals housed in the zoo were negative .T. gondii DNA was detected in the spleen tissue of all three subjects and in the livers of the two adults. Subsequent RFLP-PCR analysis showed a type II banding pattern on several loci in all deceased lemurs  were included in the study. Of these, three  who spontaneously deceased in November 2009 were immediately sent to the Department of Veterinary Science, University of Pisa  for necroscopic examination. Blood samples from the cardiac cavities were used for serology, while representative specimens from the lungs, liver, spleen, heart, kidney, brain, and small intestine were fixed in 10% buffered formalin solution (pH 7.4), stored at room temperature, and then routinely processed for histopathological examination. Spleen and liver samples were also placed in sterile 50 mL polypropylene tubes and stored at −20 °C for molecular analysis.Moreover, seven sera from the healthy ring-tailed lemurs housed in the zoo  were added to the research to conduct a serological analysis. Serum samples were collected for routine health monitoring in March 2010 and were employed to evaluate exposure to the parasite.2), and heated indoor halls during the coldest days of the year . Large glass windows in the two indoor facilities allowed the lemurs to follow the natural 24 h daylight cycle. Foods consisting of chopped fresh fruits and vegetables supplemented with monkey pellets , as well as cold tea, were administered two times per day.The lemurs were housed in an outside enclosure with plants and natural soil  [Fixed lung, liver, spleen, heart, kidney, central nervous system, and small intestine tissue specimens were routinely dehydrated and paraffin embedded. Five-micron tissue sections were stained with hematoxylin–eosin (H&E). Other sections were mounted on polarized Menzel–Gläser Superfrost plus slides  for immunohistochemistry (IHC) with a 1:200 diluted rabbit polyclonal anti-CA, USA) . SectionThe sections were subjected to heat-induced epitope retrieval (HIER) in sodium citrate buffer (pH 6) and Peroxidase Blocking Solution . Afterwards, the primary antibody was incubated for 1 h at room temperature, followed by the addition of a secondary biotinylated goat polyvalent antibody . Finally, DAB  was used as indicated by the manufacturer’s instructions. Before any steps, TBS–Tween washing solution was applied to the sections.T. gondii antibodies. A Toxo Screen DA test  with formalin-treated T. gondii tachyzoites as the antigen, was used according to the manufacturer’s instructions. The cut-off was 1:10 and positive sera were end-titrated using 2-fold dilutions [The blood samples were all centrifuged and the serum obtained was subjected to a modified agglutination test (MAT) to quantify anti-ilutions . The scrSpleen and liver tissue samples underwent PCR procedures. DNA was extracted using a Dneasy Blood & Tissue Kit  from about 25 mg of tissues, following the manufacturer’s instructions and stored at −20 °C before being used.T. gondii B1 gene was performed as described by Jones et al. [T. gondii tachyzoites used for culture. The DNA-positive sample  showing the thickest band was selected for genotyping. RFLP-PCR of 12 genetic markers  was conducted as described by Su et al. [Firstly, a Nested-PCR Protocol targeting the s et al. . Positivu et al. .T. gondii clonal type II was identified as the cause of death by serology, immunohistochemistry, and RFLP-PCR. These findings confirm the high susceptibility of this species to the protozoa and the importance of control measures in facilities housing captive animals.This paper reports the first outbreak of diffuse and fatal toxoplasmosis in captive ring-tailed lemurs in Italy.


Conventional antimicrobial susceptibility tests, including phenotypic and genotypic methods, are insufficiently accurate and frequently fail to identify effective antibiotics. These methods predominantly select therapies based on the antibiotic response of only the lead bacterial pathogen within pure bacterial culture. However, this neglects the fact that, in the majority of human infections, the lead bacterial pathogens are present as a part of multispecies communities that modulate the response of these lead pathogens to antibiotics and that multiple pathogens can contribute to the infection simultaneously. This discrepancy is a major cause of the failure of antimicrobial susceptibility tests to detect antibiotics that are effective in vivo. This review article provides a comprehensive overview of the factors that are missed by conventional antimicrobial susceptibility tests and it explains how accounting for these methods can aid the development of novel diagnostic approaches. Despite the availability of numerous antibiotics and many types of antimicrobial susceptibility tests (ASTs), over 5,000,000 people die each year due to bacterial infections . AccordiNumerous studies have demonstrated a lack of a relationship between the results of routine ASTs and responses to selected antibiotics, indicating that these ASTs were unable to predict the clinical response to antibiotics ,5. TheseThis is also clearly reflected in official statistics that show that around 32,000 people die annually in the US because of antibiotic-resistant bacteria . To put In this review, we analyze the reasons why available ASTs directed to select antibiotics against non-blood-borne infections, such as respiratory infections, skin and soft tissue infections, and urinary tract infections, fail to select effective antibiotics. We also analyze emerging methods of antibiotic selection that can fix the fundamental flaws of routine ASTs.Culture-based ASTs are based on the response of the lead bacterial pathogens from biosamples to antibiotic treatment and are considered a primary diagnostic test for antibiotic selection in clinical settings. In accordance with current recommendations, pure culture isolates should first be obtained and used to test antibiotic efficacy . BiosampTherefore, in order to accelerate the growth-dependent AST step, automated tests have been implemented that require the isolation of a pure bacterial culture, thus replacing the need for a second step of long cultivation of primary pathogens in the presence of different antibiotics ,18,19,20In recent years, some emerging AST techniques have been developed that evaluate very early alterations in different parameters of bacterial cells in the presence of antibiotics. These methods study the morphological changes in individual bacterial cells induced by antibiotics and include the analysis of parameters such as reduction of the early speed growth, alterations of metabolic status, nanomotion detection, identification of resistance-associated macromolecules, detection of growth-related molecules, and antibiotic degradation products, frequently combining optical-based ASTs with some novel approaches, such as micro-channel resonators ,23,24,25Microbiological analysis of data from these growth-based AST includes the evaluation of the minimum inhibitory concentrations (MICs) of tested antimicrobials and the categorization of bacteria as “susceptible” or “resistant” by applying accepted breakpoint values and estimated thresholds of the tested antibiotics to these MICs .However, all of these automated applications still require pure bacterial isolates obtained through routine culture and do not change the phenotypic AST principle. Although these novel methods claim to conduct ASTs sometimes within the hour, such statements do not reflect the need for another 24–72 h cultivation to obtain pure bacterial cultures.Since patients with serious bacterial infections require the initiation of antibiotic therapy in less than 8 h, these culture-based ASTs cannot replace empirical antibiotic selection that apparently requires diagnostic guidance since it fails to select effective antibiotics in over 50% of cases ,27. EvenHowever, the slow turnaround of these methods that take days to get results is not the only contributor to bacterial-infection-related mortality, since even after long cultivation, culture-based ASTs frequently fail to select effective antibiotics . One of As stated above, it is critical to treat patients with severe bacterial infections with effective antibiotics as soon as possible. This explains the rapid rise in diagnostics based on the identification of genomic signatures that predict antimicrobial resistance . These mARG detection can be performed using different methods such as PCR, sequencing, and transcriptome analysis to identify the presence of genes conferring antimicrobial resistance or certain mutations . For theThe primary issue with ARG detection methods is that the presence of resistance genes does not always confer phenotypic resistance . FirstlyThe most broadly used PCR-based methods largely fail to account for adaptive antibiotic resistance, such as the work of efflux pumps or porin loss, while requiring trained personnel and expensive equipment ,37.As a result, antibiotics selected with molecular ARG detection tests are frequently ineffective and tend to be unnecessarily broad-spectrum, which is contrary to the concept of antimicrobial stewardship, which aims to diminish unnecessary exposure to broad-spectrum antibiotics ,39.In summary, both conventional culture-based ASTs and methods based on ARG detection frequently fail to select appropriate antimicrobials, and the antibiotics selected by these methods fail to be effective when used in patients.Below, we review the fundamental flaws of routine culture-based and genetic ASTs that result in failure to select effective antibiotics.Routine culture-based ASTs categorize pathogens as “susceptible” or “resistant” by comparing minimal inhibitory concentration (MIC) values that should be below thresholds predetermined for each antibiotic . The accMoreover, since only some of the unbound antimicrobial agents are capable of providing antibacterial effects, the particularities of binding of antibiotics with proteins and other elements or their penetration into cells in different tissues would differ from those in plasma . For exaTherefore, for non-blood-borne infections, determination of antibiotic efficacy using antimicrobial agents at the free and unbound concentrations that can be achieved at the particular side of infection and not the total plasma concentration seems to be more rational .Another issue is that conventional AST methods study the efficacy of antibiotics based on a fixed concentration that remains stable throughout the cultivation period. However, because different antibiotics possess different mechanisms of action, their efficacy depends on more complicated parameters than just the mean plasma concentration. All antibiotics can be divided into three major groups: time-dependent, concentration-dependent, and dependent on total drug exposure with the area under the curve (AUC) ,46.For example, the efficacy of penicillins, cephalosporins, and carbapenems depends on the time during which they contact bacteria with a concentration above the MIC (T > MIC) that is set by the AST in question . HoweverThus, testing antibiotics while considering T > MIC, Cmax/MIC, and AUC/MIC, depending on the class of antibiotics, would provide more accurate results and enable more precise therapy selection.Standard ASTs evaluate antibiotic efficacy either in planktonic growing bacteria or in the form of monobacterial lawns, but not in bacterial biofilms ,52,53. HBacterial biofilms are complex bacterial structures in which cells are covered with a surface bilipid membrane-like structure and embedded in an extracellular polymeric matrix composed of bacterial secreted proteins, extracellular nucleic acids, and polysaccharides ,62,63,64Another notable element of the higher tolerance of bacteria in biofilms is that microorganisms within these microbial communities share multicellular properties ,68,69. Bacteria in biofilms are characterized by the formation of subpopulations with diverse metabolic activities . CertainFinally, especially significant within biofilms is formation of a subpopulation of dormant persister cells that are particularly tolerant to antibiotics . The fraAlong with the inhibition of antibiotic penetration and inactivation, biofilms contribute to other strategies for bacterial survival in the presence of antibiotics. Biofilm-type growth impairs DNA repair and mismatch repair systems, which in turn triggers the mutS, mutL, uvrD, and oxoG resistance component  pathways to react to various antibiotics ,80.One of the elements of multicellularity is realized through a particular intermicrobial communication strategy involving chemical signaling via quorum sensing (QS) . QS bactP. aeruginosa, rendering resistance to aztreonam, gentamicin, tetracycline, quinolones, β-lactams, and tobramycin [Originally, QS was believed to only control bacterial density in biofilms and, along with its increase, trigger biofilm dispersal through the inhibition of matrix compound synthesis, increased production of surfactants, or the degradation of extracellular polymeric substances . Howeverbramycin ,89,90.Escherichia coli [E. coli density, regulates the expression of the AcrAB protein, a component of the multidrug-resistant antibiotic efflux pump AcrAB-TolC [Another example of how QS aids bacteria in withstanding antibiotic assault has been shown in hia coli . For insrAB-TolC ,93,94.In addition to biofilms, microbial communities formed by spore-forming bacteria of polymicrobial communities having “sporobiota” members are also particularly resistant to antimicrobial therapy ,96. SporIn summary, the lack of consideration of biofilm growth by conventional ASTs results in numerous pitfalls of antibiotic selection.Conventional culture-based methods study the antibiotic response of a lead bacterial pathogen in pure bacterial culture, despite the fact that the majority of infections are polymicrobial ,104,105.Therefore, routine ASTs fail to consider interspecies interactions that have a profound effect on the efficacy of selected antibiotics . The resThere are three major ways in which mixed bacterial communities contribute to protection from antibiotic assault, although they are frequently not mutually exclusive and can also be realized through the formation of microbial biofilms and QS .E. coli trigger extracellular β-lactam degradation, protecting Salmonella spp. and enabling them to survive at antibiotic concentrations above the MIC observed in a pure culture of Salmonella spp. [M. catarrhalis hydrolyze β-lactam antibiotics and protect cohabitant Streptococcus spp. and Haemophilus influenzae within mixed biofilms [Stenotrophomonas maltophilia infection, in which MVs packed with β-lactamases are secreted within a multispecies community, protecting β-lactam-sensitive Pseudomonas aeruginosa and Burkholderia cenocepacia by dramatically increasing their MICs for imipenem and ticarcillin [The first is collective antibiotic resistance, when antibiotic resistance factors released by one type of bacteria are shared across different species, protecting and increasing the MIC of the entire community ,110,111.lla spp. . Anotherlla spp. . MVs arebiofilms ,115. Anoarcillin . Finallyarcillin . This ocarcillin . Notablyarcillin .The second way in which mixed microbial communities protect against assault by antibiotics is by collective tolerance to antibiotics, which occurs when certain bacteria slow down their metabolism, resulting in a slower rate of bacterial death . The thiS. aureus coexistence with P. aeruginosa resulted in the upregulation of several antibiotic pumps belonging to the Nor family, leading to an increase in S. aureus resistance to ciprofloxacin and tetracycline [S. aureus is increased because exposure to P. aeruginosa exoproducts enhances the intracellular accumulation of norfloxacin by S. aureus [Moreover, along with the protection of sensitive cohabitants by the inactivation or binding of antibiotics, there is an increasing body of evidence that, within polymicrobial communities, different bacterial species modulate the expression of antibiotic resistance genes ,124,125.acycline . HoweverP. aeruginosa and S. aureus in a multispecies population [S. aureus and P. aeruginosa increased the frequency of colistin-resistant P. aeruginosa isolate formation, triggering the formation of single nucleotide polymorphisms in genes involved in lipopolysaccharide or pilin biosynthesis, thereby creating a form of heritable resistance against this antibiotic.The third way for the unique profile of antibiotic resistance in microbial communities was shown in a recent study that examined the effects of the species-specific antibiotics colistin and fusidic acid on pulation . The respulation . Genome E. coli was sensitive to ampicillin, while single-species Bacillus subtilis was tolerant to ampicillin. However, when the two organisms coexisted in coculture, E. coli could grow in the presence of the antibiotic, while B. subtilis could not.Along with multiple ways of collective protection of different species within polymicrobial communities against antibiotics, Galera-Laporta et al. showed in a recent study that the population response to some antibiotics in multispecies communities can be opposite to that of each bacterium when cultured as a pure bacterial culture . Single-The lack of recapturing of multispecies communities by conventional ASTs that rely on antibiotic selection in monopathogen settings also results in pitfalls of antibiotic selection due to a lack of consideration of mutualistic interactions. Indeed, within mixed biofilms, different bacteria support each other, minimizing energy loss by sharing different nutritional factors produced by other microorganisms . TherefoIn summary, traditional ASTs are based on unimicrobial bacterial cultures that do not take into account complicated interbacterial interactions arising from polymicrobial growth and the presence of cohabiting species that confer collective protection of the microbial community, resulting in both false-positive and false-negative therapy selection .A novel universal signaling and regulatory receptor system was recently discovered that involves reverse transcriptases, integrases, and previously unknown DNA- and RNA-based receptors located outside the cell membrane called Teazeled receptors (TezRs) ,129. ThiTezRs are classified based on the structural features of their DNA- or RNA-containing domains as well as based on their association with the membrane. Primary TezRs are those that are more tightly bound to the cell membrane, while secondary TezRs can be easily washed out along with the culture medium or matrix. Since both primary and secondary TezRs are localized extracellularly and are DNA- and RNA-based, they could potentially be overlooked within the whole set of the effects of extracellular nucleic acid destruction in microbial communities on antibiotic susceptibility. Indeed, it is a well-documented observation that extracellular nucleic acids in bacterial biofilms contribute to antibiotic resistance and their destruction by nucleases, including those produced by different bacteria at the site of infection, can increase the efficacy of antibiotics against microbial biofilms ,131,132.Destruction of TezRs following treatment with nucleases triggers profound transcriptome alterations in bacteria. Since many bacteria produce extracellular nucleases during real-life infection within polymicrobial communities, the resulting destruction of TezRs might either upregulate or downregulate antibiotic resistance genes ,135. MorTherefore, the lack of consideration of polymicrobial-type bacterial growth by routine ASTs ignores the receptive and regulatory roles of TezRs in antibiotic resistance, resulting in both false-positive and false-negative antibiotic selection.Aeromonas spp., Prevotella spp., and Herbaspirillum spp., have recently been shown to be pathogenic and to contribute to the development of different human infections, including lung and urinary tract infections [ASTs assay antibiotic efficacy against only well-recognized lead pathogens. However, not all bacterial pathogens have yet been identified. Currently, over 90% of bacterial species are still unculturable, meaning that the current understanding of the entire list of pathogenic bacteria is incomplete ,139. Recfections ,146. OveA summary of the reasons for the failure of ASTs to select effective antibiotics is presented in There is an unmet need for the development of novel culture-based methods for antibiotic selection that would take into consideration complicated interbacterial interactions within microbial biofilms and maximally closely recapture the real-life interactions of antibiotics with the mixed biofilm at the site of infection. The development of more effective ASTs should consider the fundamental flaws described above for conventional ASTs. Therefore, the main desirable characteristics of emerging tests for antibiotic selection are as follows: (1) culture-based; (2) rapid and provide results within 8 h from the collection of biosamples; (3) take polymicrobial biofilms into consideration; (4) study the effects of antibiotics on previously unknown pathogens; (5) analyze antibiotic efficacy based on tissue and not plasma concentrations of antibiotics; and (6) take into consideration the type of tested antibiotics—time-dependent, concentration-dependent, or dependent on total drug exposure with the AUC mechanism of antibiotic action.A comparison between the available AST and “ideal” that would correct the fundamental flaws of conventional tests is shown in Recently, novel methods for antibiotic selection that consider all of these characteristics have been developed. AtbFinder is a rapid, culture-based test based on a proprietary pure-culture-free methodology . This isAtbFinder is a 48-well plate filled with novel TGV agar. Unlike conventional AST methods that utilize MIC and susceptibility breakpoints to evaluate antibiotic efficacy, AtbFinder determines antibiotic efficacy based on quantifying antibiotic penetration into different tissues . MoreoveThe workflow of AtbFinder is presented in AtbFinder has been broadly studied for antibiotic selection in both mono- and multi-species bacterial cultures. A critical parameter for any AST is accuracy with a minimal number of false-positive or false-negative results. The accuracy of AtbFinder’s performance was determined for random selection of 10 different antibiotics at 4 h and 24 h timepoints of bacterial cultivation. The correct antibiotic selection for AtbFinder was achieved after 4 h at 98.9%, and the sensitivity, specificity, positive predictive value, and negative predictive value were 99.6%, 98.1%, 98.5%, and 99.4%, respectively. Next, the same parameters were re-analyzed at 24 h to see whether a decrease in cultivation time to 4 h could contribute to error. After 24 h, the specificity, positive predictive value, and negative predictive value were 99.6%, 98.5%, 98.8%, and 99.4%, respectively. These data prove that even within 4 h of cultivation time AtbFinder was able to provide highly accurate antibiotic selection. Category agreement was also high at both 4 and 24 h. Even after 4 h, the overall category agreement for all tested antibiotics was 98.9%, the rate of very major errors was only 1.5%, and the rate of major errors was 0.6%. These values were only nominally higher if the cultivation was extended up to 24 h, with the overall category agreement for all antibiotics tested (99.1%) and the rates of very major errors (1.2%) and major errors (0.6%) .In the same study, AtbFinder performance to select antibiotics against the lead bacterial pathogen directly from polymicrobial biosamples was compared to standard microbroth dilution ASTs that use pure-bacterial cultures isolated form the same polymicrobial biosamples. In 11% of cases, when antibiotics were ineffective with AtbFinder but were shown to be effective with the microbroth dilution method, the follow-up sub-cultivation of pathogens from the TGV agar showed that the lead bacterial pathogen remained and was not eliminated by the tested antibiotic. Therefore, this 11% represents an enormously high rate of false-positive results obtained by conventional ASTs, which causes the selection of ineffective antibiotics. These results are a notable demonstration of how failure to account for biofilm formation and complicated interbacterial interactions in multispecies microbial communities results in the failure of routine ASTs to select effective antibiotics.P. aeruginosa in 81% of cases. Along with P. aeruginosa, other respiratory pathogens, such as S. aureus, Achromobacter xylosoxidans, and S. maltophila, including strains exhibiting multidrug resistance, were eradicated in subjects with cystic fibrosis after antibiotic therapy was switched to drugs selected with AtbFinder.Recently, AtbFinder was used in a pilot study to formulate an antibiotic regimen for patients with cystic fibrosis . The resIt also completely arrested hospitalizations due to pulmonary exacerbations, even among patients who had up to three episodes of pulmonary exacerbations per year. As a result of infection reduction, the use of antibiotic selection using AtbFinder improved lung function (FEV1%) in patients with cystic fibrosis that would normally be treated with antibiotics selected with standard ASTs, is known to be constantly declining due to the progression of the infection. Importantly, following the switch of antibiotics to those selected with AtbFinder, the total number of systemic antibiotic courses was reduced by twofold with a trend of reducing the use of broad-spectrum antibiotics. This means that the improvement of subjects was due to the fact that AtbFinder selected more effective antibiotics, and not because more antibiotics or broad-spectrum antibiotic courses were used.AtbFinder can be customized for various sites of infection, based on the antibiotics and their concentrations that are included in the panel. Recently AtbFinder with the panel of antibiotics used for the treatment of urinary tract infections (UTI) added to TGV agar at concentrations that can be achieved in urea, was successfully used to identify effective antibiotics against recurrent infection . In the In summary, studies using AtbFinder show how novel tests that fix different flaws of conventional ASTs can improve the efficacy of antibiotic therapy.The lack of effective strategies to combat bacterial infections is alarming in both developed and developing countries. With only a few novel antibiotics being registered during the last two decades and the global spread of antibiotic resistance, the failure of conventional ASTs to select effective antibiotics is particularly concerning. Many underlying causes contribute to the lack of novel antibiotics and ARG spread, and it would take decades to solve these problems. However, finding more effective strategies for antibiotic selection can be regarded as a new holy grail for assessing antibiotic resistance that can shortly become available. This is particularly important for lung, skin, soft tissue, and urinary tract infections because conventional ASTs select antibiotics without taking into account the particularities of antibiotic penetration in non-blood tissues.Today, standard culture-based ASTs are the gold standard for antibiotic selection, but along with a lack of accuracy to predict the in vivo success or failure of antibiotic therapy, they take too long to deliver results . A numbeNovel methods that account for the typical shortcomings of current ASTs are urgently required. These novel tests have the potential to unlock the untapped potential of already available antibiotics, bringing the treatment of deadly infections to a new level of efficacy.


The article also describes the GFRC application fields and emphasizes the possibility of the creation of not only structural elements mainly intended for load transferring but also elements accompanying the building process, as well as elements of small architecture that make public spaces more attractive, durable, and safer. Owing to greater design and shaping freedom, GFRC can also better fulfill the needs of habitants of Smart City.The article highlights that glass fiber reinforced concretes (GFRC) can meet the requirements of Smart City better than ordinary concretes. The comprehensive discussion on GFRC composition is presented together with the review of glass fibers’ influence on various concrete properties. First of all, because of their bridging abilities, they can limit the width, length, and total area of cracks. Additionally, GFRC are characterized by enhanced tensile, flexural, and splitting strength; impact, abrasion, spalling, fire, and freeze-thaw resistance as well as ductility, toughness, and permeability. All of this positively influences the mechanical behavior, durability, and corrosion resistance of concrete elements. Moreover, decreased thermal conductivity allows for better energy performance from the building’s point of view. This results in cheaper structures both in manufacturing and maintaining even though GFRC are more expensive materials. However, mechanical properties enhance as long as sufficient workability and uniform fiber distribution are assured. From the environmental point of view, GFRC are eco-friendlier materials than ordinary concretes since their application can decrease the emission of CO Currently, there is a tendency to divide smart cities into three generations which quite well reflects how the approach to cities and urban technologies has changed in the past few decades. The first-generation Smart City 1.0 focuses on new technologies and business makers who encourage cities to adapt their solutions to be more efficient in the management of urban organisms. It must be mentioned that very often city administration units are not prepared to use these advanced technologies. In Smart City 2.0, municipal authorities play a major role and they initiate changes and choose technologies and solutions to increase the inhabitants’ life quality. The most current generation Smart City 3.0, which has been functioning for a relatively short time, since approximately 2015, puts in the center the residents of the city. They co-create their cities, which means that implemented solutions should respond to the problems of inhabitants and be consulted with them. In this last model, more and more emphasis is placed on smart manufacturing, smart buildings, and smart environment. The smart idea should not only be implemented in the utility sphere, but also it should be present in the execution stage. Additionally, the idea of sustainable development is strictly connected with the suggestions of Smart City. One of the current most important global goals is to fulfill sustainability requirements in the concrete industry since it is responsible for 8–9% of total C0fl), diameter (fd), and slenderness (f/dfl). It must be mentioned that the fiber type and geometry have an influence on the mechanical and cracking resistance as well as durability and pore structure of concrete [3. They are characterized by high tensile strength (ftf), from 1200 to even 4800 MPa. Furthermore, GF have a much greater modulus of elasticity than synthetic fibers; however, smaller than steel and carbon fibers. They are resistant to high temperatures and begin to soften at approx. 700–900 °C [Glass fibers (GF) began to be used around 1931 as a reinforcement of mortars and concretes . They arconcrete . Dependi0–900 °C . The dis0–900 °C . As a refV) between 4 and 6% and require careful expertise, special equipment, and experienced workers. Then vibration casting is carried out, which is a much simpler method, in which the GFRC premix is vibrated in the mold until it achieves consolidation. However, water-tight molds are required, and rock molds do not work well in this method. Finally, the sprayed premix method does not need so rigorous quality control as hand spray-up and strengths higher than those obtained in vibration casting can be achieved [Regarding the production process of GFRC, there are three techniques to cast concrete elements reinforced with GF. The first possibility is called the hand spray-up method and this is how most of the ornamental precast elements and precast architectural cladding panels from GFRC are produced. Those mixes have usually higher fiber content  was used, for example, according to Eurocode standards: CEM I 42.5N, CEM I 42.5R, and following Bureau of Indian Standards: OPC 43 and OPC 53, sometimes Portland Slag Cement (PSC) and Portland Pozzolana Cement (PPC). However, to decrease the contribution of cement in concrete composition, different types of replacements were proposed and studied i.e., silica fume (SF), nano-silica (NS), fly ash (FLA), blast furnace slag (BFS), and metakaolin (MK). According to maDx) equaled to 40 mm [fV = 3%. It is a result of further problems with workability, fluidity, and uniform distribution of fibers. On the other hand, in the case of spray-up mixtures, fV was usually higher and in [By its analysis, it can be concluded that the water to binder ratio (w/b) usually varied between 0.35 and 0.55. However, in [to 40 mm , nonetheto 40 mm ,20,27,31to 40 mm ,26,34 weto 40 mm ,30,46,47to 40 mm ,38. GF hr and in  it was er and in , 4 to 5%r and in ,30,32,35fV = 0.05% [fV = 0.04% [fV = 0.07% when GF reinforced mortar mixtures were used [fV in comparison to PC [ = 0.05% , 24% for = 0.04% , and 32%ere used . For SCCon to PC . Additioon to PC ,61,62,63on to PC ,65,66 thfV was increasing. Additionally, a comprehensive study on fiber influence was performed by Mirza and Soroushian [fV = 2.0%) followed the trend that higher GF dosage led to smaller crack width. It was explained by the greater ability of crack bridging since there were more fibers. As it was mentioned before also the number of cracks increased for GFRC from one to a maximum of six cracks, changing the destruction manner. The plastic shrinkage test results performed in [2 for GFRC, so by 57%. It was also observed that PC was characterized by a denser crack pattern while GFRC had multiple subparallel cracks. Considering different types of mixtures, GFRC results were worse than those for steel fiber reinforced concretes (SFRC) but better from polypropylene fiber reinforced concretes (PPFRC). Another research done by Barluenga and Hernández-Olivares [3 of GF to standard concrete type I reduced the crack area by around 60–70% depending on the type of fiber. It must be noted that according to them further increase in fiber dosage did not significantly influence this efficiency. Considering the standard concrete type II enhancements were in the range of 55 to 95%. Additionally, the crack lengths were reduced by more than 90% independently of fiber type and dosage. Considering SCC, the GF incorporation caused a 70–80% decrease in the cracked area for all the mixes. Only the batch with 0.9 kg/m3 of Cem-fil Anticrack HD type was characterized by less significant improvement. Similar to standard concrete, maximum crack lengths were measured for SCC and it occurred that they equaled 35–65% of maximum crack lengths for SCC without fibers. Messan et al. [3 was able to delay the time of crack occurring from 3.5 days for PC to 4.5 days for GFRC. Additionally, the crack width decreased from 1.44 for the control sample to 0.42 mm for the specimen with GF. In summary, the addition of GF has a favorable influence on the limitation of cracks’ widths and their total area. Furthermore, the different types of shrinkages are effectively restrained by the presence of GF. It also must be mentioned that plenty of research was performed to investigate the positive influence of fibers on crack limitation and shrinkage. However, there is a limited number of works that focus on GF and not on SF, PPF, and basalt fibers (BF).Abilities of crack bridging and shrinkage restraining are one of the most important features of fiber reinforced concretes (FRC). In , Patil aroushian . Accordiormed in  revealedOlivares  stated tn et al.  also resn et al.  it was cn et al.  studied n et al. , it was n et al. , even a cmE up to fV = 1.5%, then there was no significant change in the modulus. Based on these findings, it can be indicated that the presence of fibers positively influenced the stiffness of concrete, since microfibers delayed the propagation of microcracks. However, when their amount in the mix was too high, it caused the deterioration of packing and bonding properties between aggregates, fibers, and matrix. Finally, it was concluded that the optimization process is necessary to ensure proper fiber distribution. Regarding smaller fiber dosages in mortars like in [fV was in the range 0.02–0.07%, the effect of fibers was insignificant, namely, cmE increased by up to 2% for the highest fiber dosage. Kizilkanat et al. [cmE following ASTM C469 [cmE slightly reduced when fiber dosage increased. Namely for PC, cmE was equal to 44,305 MPa and for concrete with GF and BF in the range of 41,237–42,831 MPa and 41,860–44,415, respectively depending on fV. The maximum drop of 7% was noted for the GFRC mix with 0.25% of fibers. Additionally, it was observed that when GF were incorporated, cmE was slightly lower than that for BF, which can be a result of a smaller modulus of elasticity of GF compared with BF. On the contrary, in [cmE was seen when 2.5% of GF (f/dfl = 6 + 18 mm/13μm) were added to the batch. cmE was measured following standard ASTM C469 [cmE was noted, up to 6% when 1.0 and 2.0% of GF were incorporated. On the other hand, when only sand was used without any coarse fraction, for fV = 2%, the maximum reduction equaled to 14%. Tassew and Lubell [cmE on 100 mm diameter × 200 mm height cylindrical specimens. Based on the presented research, it was concluded that the effect of GF on cmE is ambiguous. Namely, they may increase the stiffness of concrete when uniform fiber distribution is provided, however, their negative effect on cmE is also recognized in the literature.Mohammed et al.  research like in , where Vt et al.  measuredSTM C469  on cylinrary, in  13% growSTM C469 , 150 mm STM C469 , for thed Lubell  also used Lubell  to test cf change was prepared  instead of one was highlighted [Based on the findings reported in prepared . It can  like in , where tmely, in  the comp studies ,50,51. A studies  stated ttars, in  the earlhlighted ,26.tf) results directly from the data received during the experiment. However, UTT is a very demanding test and has to be performed on the ideal sample under well-controlled conditions that eliminate any eccentricities. For these reasons, UTT is seldomly used in research practice [flf). This test is used willingly because it is easier to execute and less time-consuming. Nonetheless, a significant amount of elastic energy stored in the prism specimen should not be neglected. Additionally, it must be mentioned that through this method only the indirect determination of tensile strength is possible. To reduce even more the complexity of the tensile characterization, STT was developed. Namely, the samples are smaller, hence easier to transport and the test is more stable. The splitting tensile strength (splf) received from STT also requires some additional calculations because it is an indirect method of tensile strength characterization.When designing concrete elements, knowledge about the tensile behavior of the material is required. In the uniaxial tensile test (UTT), the tensile strength  or four types of GF (f/dfl = 3 + 6 + 12 + 20 mm/14 μm) were mixed. It occurred that a combination of more than one fiber type can significantly overcome results for a mono mix for the same amounts of fibers. For example, for f/dfl = 3 + 6 mm/14 μm of GF (fV = 0.06 + 0.24%), tf increased by 41%, while for f/dfl = 3 mm/14 μm of GF (fV = 0.30%) and f/dfl = 6 mm/14 μm of GF (fV = 0.30%), tf was only 19 and 14% higher than that for PC, respectively. The best results from the campaign were noticed for mixture with f/dfl = 3 + 6 + 12 + 20 mm/14 μm of GF because the tensile strength improved 1.5 times compared to concrete without fibers.Regarding UTT, the clear influence of GF inclusion was visible in . Namely,ectively . The higectively . The maxi et al.  also higflf and splf, in the majority of cases presented in fV twice led to flf change from 6.92 to only 6.98 MPa. Furthermore, based on the findings reported in flf were achieved for GF which were 30 mm long than for those which were just 10 mm long. Furthermore, in [flf by not 257, 429, and 481% but by 362, 462, and 514% when 1.0, 1.5, and 2.0% of GF were added, respectively. Similar conclusions about the positive influence of longer fibers were revealed in [flf and splf for greater fV is observed due to problems with workability and uniform distribution of fibers. In conclusion, the optimization of the concrete mix is a key process that allows finding the compromise between the requirements that the individual mix should fulfill and its costs. Ruben et al. [f/dfl = 12 mm/14 μm of 1.0–3.0% with a step of 0.50% of cement weight of GF to the concrete mixture. The enhancement in flf was respectively 19, 23, 37, 22, and 19%, while in splf 22, 26, 39, 41, and 8%. For example, in [flf increased 1.3 and 1.1 times when only 1.3 kg/m3 of GF were included, respectively. In [fV increase was acknowledged since, after the addition of 0.50%, 1.00%, and 1.50% of GF, flf rose from 6.09 MPa to 6.26, 6.57, and 7.10 MPa, respectively. Nevertheless, in some works, even higher increases in strength when adding GF were seen; in [flf was almost four times greater than that for concrete without fibers; in [flf changed from 7.31 for the plain mixture to 8.21 MPa for mixture with GF, and from 7.26 to 8.02 MPa for w/b = 0.34 and w/b = 0.40, respectively. In [splf when fV = 0.75% and 32% for flf when fV = 0.50% of GF were added. However, beyond fV = 0.75% the dominant improvement for basalt fiber reinforced concretes (BFRC) was concluded which could have been attributed to the difficulties in GF dispersion in the concrete matrix. In the end, the comparison of enhancements after GF addition in FTT and STT is shown in fV and in fV. It was concluded that usually, the percentage change of flf and splf was quite similar [Regarding more, in  it was cn et al.  incorpormple, in  for mixtseen; in , ffl wasbers; in ,51 the mbers; in  the failbers; in , more thvely. In , it was vely. In  the bene similar ,34,36,53 similar .fG), which is the energy required to break the sample, and fracture toughness (ICK) which is defined as the ability of the specimen to resist brittle failure or crack extension [5I, 10I, and 20I also rose . It is noteworthy, that higher enhancements were visible for a smaller concrete grade, however, values of impact energies were greater for concrete with higher compressive strength. Finally, in [fV = 0.00, 0.15, 0.20, 0.25, and 0.30% of GF was equal to 3950, 4409, 4688, 4948, and 5426 J, subsequently. On the other hand, the failure impact energy was 3990, 4489, 4828, 5127, 5626 J. The impact energy calculations required knowledge about the mass and the fall height of the hammer and the number of blows. The test was performed in accordance with [3 (fV = 0.1%) the impact resistance can be remarkably strengthened. Furthermore, the hybrid FRC combining SF and GF significantly outperformed the behavior of mixtures with only one type of fiber. It must be mentioned that in the presented research, the hybrid blend with steel and glass fibers was usually more effective than the one with steel and polypropylene fibers. The beneficial aspect of hybridization was macro SF arrested macrocracks while micro GF and PPF bridged microcracks.The impact resistance of GFRC is significantly improved compared to PC. Mastali et al. in  tested the study  are presesult in  also supesult in . Both imally, in  the inflnce with . Similarnce with , for GFRflf of samples with GF after exposure to high temperature decreased, however, these reductions were smaller than the ones for PC. The effectiveness of GFRC in enhancing the spalling resistance is also explained by GFs’ ability of crack arresting: limiting their number, width, but also changing the form of failure from one macrocrack to multiply microcracks. The effect of high temperatures  on cf losses was also investigated by Wang et al. in [cf, flf, and splf increased up to 300 °C and then started to reduce. Additionally, after reaching 500 °C the degradation changes were more visible in the case of concrete without fibers compared with FRC. Finally, it was stated that the mixture with optimized performance regarding compressive, flexural, and splitting characterization subjected to normal and high temperatures was a hybrid mixture of 2% of SF + 1% of GF. This again claimed the advantageous side of hybrid concretes. The results presented in [cf increased by 9–27% and 0.06–18.40% for SFRC and GFRC respectively; the splf increased by 7.96–197.74% and 19.22–213.53% for SFRC and GFRC respectively compared to PC. It was noted that GF were more effective in tensile tests than SF, in contrast to the compression test. Additionally, the weight loss of samples exposed to elevated temperatures was smaller for FRC than for PC. In the end, it is noteworthy to mention that GFRC permanent formworks can upgrade fire protection. Namely, in [In the concrete matrix, water can be found in the form of free water and bound water. When hardened concrete is subjected to high temperatures, the water inside the concrete evaporates and generates internal tensile pressure if entrapped vapor does not have the path to escape. The spalling of concrete occurs due to this phenomenon. In GFRC, the capacity to resist extreme temperatures is increased because the tensile strength is improved. This is in agreement with the findings of Mirza and Soroushian described in , where ft al. in  and the t al. in  where fiented in  also supfV = 2.0% (f/dfl = 10 mm/12 μm) the loss in weight for the sand blasting process was almost 5% smaller compared with PC , while 2.86, 2.85, and 2.97 W/mK when 35.0, 27.5, and 20 kg/m3 of SF were incorporated. Additionally, for PC the thermal conductivity had the value of 2.83 W/mK which was still higher than the value for concrete with GF. Moreover, increasing the amount of GF from 0.4 to 1.2% reduced the thermal conductivity by around 15% in [3 K while for PC it was equal to 1.98 MJ/m3K. The positive behavior of GF on the thermal conductivity of GFRC under high temperatures was also discussed in [fV = 1.5% subjected to 440 °C, respectively. It must be mentioned, that even higher enhancements were concluded, for example for 500 and 580 °C. Second, with the increase of fV, the thermal conductivity decreased. Finally, greater improvements and smaller thermal conductivities for all temperatures were noted for longer fibers. However, for higher temperatures, the difference between short and long GF was getting less significant. All of this led to the conclusion that the addition of GF and applying GFRC instead of concrete with steel fibers can reduce the house heating energy demand which is in agreement with the concept of smart manufacturing and smart building. To sum up, GFRC are characterized by better performance from the building’s point of view.Concrete with the addition of GF have lower thermal conductivity than SFRC  and carbd 15% in . A comprd 15% in . The lowussed in . Herein,fV up to a certain value. The property was equal to 4.85, 3.66, 3.24, 2.69, 2.10, and 2.74% for GFRC with 0.0, 1.0, 1.5, 2.0, 2.5, and 3.0% of GF, subsequently. Based on this data, it was calculated that the water absorption compared with PC was reduced by 24.5, 33.2, 44.5, 56.7, and 43.5%, respectively. The positive effect of fibers on water absorption could be attributed to the good bonding between the matrix and the fibers as well as the smaller permeability of concrete. This feature is also connected with concrete porosity, which in [f/dfl = 25 mm/15 μm) corresponded to 91, 83, and 93% compared with concrete without fibers. Furthermore, the volume of pores was smaller for GFRC than for PC. Within the porosity test, the samples were dried at 100 °C for 2 days. Afterward, the volume of the pores was estimated based on the difference between the sample’s weight before and after putting it in the hot oven. However, it cannot be said that fibers always have a positive influence on concrete permeability since in [fV meant greater values of these concrete properties. The concrete porosity was tested according to ASTM C642 [fV = 1.2% of recycled and virgin GF, with the lengths 21.7, 17.2, 21.2, 19.5, and 25.4 mm, the air content rose by 50, 12, 4, 12, and 65%, respectively. It is noteworthy, that the virgin GF had the highest air content, which showed that using recycled fibers can be a beneficial and reasonable option not only regarding sustainable development [The absorption, porosity, and permeability of concrete indicate the possibilities of water ingress into the concrete. Additionally, water can transport harmful agents—different types of salts which can negatively influence the durability and service life of the concrete elements. In , the watwhich in  for GFRCsince in , the porSTM C642  and sorpSTM C642 . AuthorsSTM C642 . DehghanSTM C642  in theirelopment . The sorICK for FRC surpassed the ICK for PC under normal conditions. Additionally, as a result of 50 freeze-thaw cycles, where temperature changed from +20 to +100 °C, the behavior of concrete with GF was better than the one without fibers  to long (19 mm) fibers mass ratios equaled to 0:0, 0:1, 3:7, 5:5, 7:3, and 1:0 for which cf of concrete decreased by around 22, 9, 11, 7.5, 12, 16.5%, subsequently. Taking into consideration that all samples were frozen for 4 h at −20 °C and then melted for 4 h at +20 °C for 50 salt-solution freeze-thaw cycles, it was concluded that GF enhanced the resistance and durability of concrete. Additionally, within this study, the synergistic influence of PPF and GF on salt-solution freeze-thaw resistance was proven. Regarding the chloride freeze-thaw cycles, Yin et al. [The freeze-thaw resistance can be significantly improved by the addition of fibers e.g., in face slab concrete . Reis ant fibers . This iscles. In , the comcles. In  incorporn et al.  claimed fV = 1.5%, the chloride migration depth for GFRC, PPFRC, and HFRC was 22.7, 19.8, and 19.5 mm subsequently, while for PC around 24.1 mm. As a result, the property reduced by 10.9, 21.7, and 23.3% compared with concrete without fibers. Considering the classifications of chloride penetration resistance, FRC mixtures belonged to the high or very high class. This improved behavior of concretes with fibers was related to the ability of shrinkage crack limitation and porosity reduction. Similar conclusions were obtained in the rapid chloride penetration test. The highest influence of fibers addition was observed for fV = 1.5%. Namely, the charges passed of concretes with GF, PPF, and GF + PPF were reduced by 6.77, 11.3, and 20.15% compared with PC. This meant that the results for PC, GFRC, PPFRC, and HFRC equaled 3626, 3381, 3217, and 2896 C respectively. Ratha et al. [fV = 0.1% of GF (f/dfl = 12 mm/14 μm). For that reason, the electrical resistivity increased 1.40 times when compared with PC which meant good resistance against corrosion. Another important study done by Atewi et al. [One of the parameters that characterizes concrete corrosion durability is electrical resistance. The resistivity of concrete describes sample water saturation degree, chloride penetration resistance, or the corrosion rate. It is one of the criteria for judging the risk of corrosion, namely, higher concrete resistivity means lower corrosion danger. Moghadam et al. concluded in their research  that thea et al.  added toi et al.  showed ti et al.  revealedi et al.  which isYin et al.  concludeThe concept of a Smart City is strongly connected with the idea of sustainable development. As a result, the eco-friendly and economic background of GFRC should be also taken into consideration like it was done for other FRC, for instance, PPFRC in . It has 3 of GFRC with 0.5 and 1.0% fibers equaled 96 and 107.2 USD/m3, respectively, while the price of concrete without fibers was 81.4 USD/m3. However, it must be mentioned that cost of GF was almost 7 and 17% smaller than the price of SF and PPF, respectively. Nevertheless, since GF are lighter than SF but heavier than PPF, the total USD/m3 of GFRC exceeded the cost of PPFRC, although was smaller than the cost of SFRC. For instance, fV = 1.0% for SFRC required 78 kg/m3 of SF, GFRC required 26 kg/m3 of GF, and PPFRC required only 9 kg/m3 of PPF. On the other hand, when taking into consideration the enhanced mechanical properties of GFRC, it was possible to decrease the thickness of the designed concrete pavement. Due to this, the slab depth could have been around 55 and 65 mm smaller for GFRC with fV = 0.5 and 1.0% of GF than the one made from PC. It must be mentioned that the thickness reduction was comparable with the reduction for SFRC and greater than that for PPFRC. In consequence, the overall cost of GFRC pavement (USD/m2) was smaller than that of PC and equaled 5–10% less depending on the GF dosage. Regarding carbon emission, when comparing the production of CO2 kg/m3 the values for GFRC would have been greater than PC. They increased from 356 kg/m3 to 382 and 408 kg/m3 of CO2 emission, so by 7 and 15% for 0.5 and 1.0% of GF addition, respectively. Nevertheless, when analyzing the carbon footprint and CO2 production per m2 the conclusions were different. It occurred that GFRC were composites eco-friendlier by around 17% than concrete without fibers. This is in agreement with the findings of Hussain et al. [3 was higher when compared with PC, namely, 1.31 and 1.14 times for normal and high strength GFRC. Nevertheless, while studying costs per m2 it appeared that normal strength PC cost 15.06 USD/m2 and GFRC 14.91 USD/m2; high strength PC cost 15.54 USD/m2 and GFRC 14.38 USD/m2.The environmental and economic characteristic of GFRC was discussed in , where in et al. , where in et al. , the oveGFRC is an increasingly popular material and is more and more widely used. Nowadays, not only structural elements are made with the use of GF but also elements accompanying the building process, as well as elements of small architecture to create more attractive, durable, and safer public spaces.GFRC is used for the creation of prefabricated façades panels of residential and cultural buildings, airports, stadiums, museums, and galleries . They haThe next field of GFRC application are domes which can occur in palaces, shopping centers, universities, theaters, stadiums, and others . There aConsidering the soundproofing properties of concrete with glass fibers, GFRC acoustic panels are widely used in places when road, train, or intersection noises are bothersome a. The reFurthermore, GFRC are also an incredibly valued material in infrastructure. Primarily due to their high strength, durability, low weight, ease, and speed in handling and assembling. Second, advantages deriving from its fire, corrosion resistance, and other high tolerances on unfavorable environmental conditions make GFRC a suitable material for bridges, viaducts, tunnels, retaining walls, and protective channels for electric cables and pipes . AdditioConcrete with GF is also used to create permanent formworks . These aIt is noteworthy that owing to the high plasticity, high strength, and low weight of GFRC, decreased thickness as well as freedom of shaping an original and unique elements can be created, both large and small. Namely, GFRC applies also to small aesthetic elements like sculptures , corniceNowadays, one of the main streams of GFRC application is landscaping and the creation of natural-looking waterfalls, fountains, rocks, and cliffs . This idThe places of the GFRC application mentioned so far were related to the construction of new elements. However, it must be mentioned that concrete with GF is also used for the reconstruction of damaged elements of monuments and architectural details. Considering wide possibilities in shape formation and coloring to reproduce the original look, it is a suitable material for this purpose.2 in the atmosphere, has to face this challenge and adjust to manufacturing more durable building materials, slenderer concrete elements with extended service life. GFRC can meet these requirements better than ordinary concrete. As a result, it is essential to research both its reasonable structural use, as well as its physical and mechanical advantages. In Smart City 3.0, more and more emphasis is placed on smart manufacturing, smart buildings, and smart environment. Due to this, the idea of sustainable development is one of the most important current global concerns. The concrete industry, as responsible for 8–9% of total C02 by 17%. The article also emphasizes on the possibility of creating not only GFRC structural elements mainly intended for load transferring but also elements accompanying the building process, as well as elements of small architecture that make public spaces more attractive, durable, and safer. It is an interesting point of view since until now only its structural nature was highlighted. Owing to greater design and shaping freedom, GFRC can also better fulfill the needs of the habitants of Smart City. GFRC may be used to manufacture:Pavements;Façades panels of residential and cultural buildings, airports, stadiums, museums, galleries, and others;Domes of palaces, shopping centers, universities, theaters, stadiums, and others;External and internal acoustic panels;Panels of tunnels, bridges, viaducts, and retaining walls;Protective channels for electric cables and pipes;Elements of melioration and drainage systems, ducts, and municipal sewage systems;Permanent formworks;Sculptures, cornices, entryways, bas-reliefs, window surrounds, capitols;Functional components such as tables, benches, fences, flower pots, gazebos, and pergolas;Waterfalls, fountains, rocks, and cliffs in the process of landscaping and creation of natural-looking elements;Repairing works, reconstructions.In


The increased antibiotic consumption and their improper management led to serious antibiotic pollution and its exposure to the environment develops multidrug resistance in microbes against antibiotics. The entry rate of antibiotics to the environment is much higher than its exclusion; therefore, efficient removal is a high priority to reduce the harmful impact of antibiotics on human health and the environment. Recent developments in cost-effective and efficient biochar preparation are noticeable for their effective removal. Moreover, biochar engineering advancements enhanced biochar remediation performance several folds more than in its pristine forms. Biochar engineering provides several new interactions and bonding abilities with antibiotic pollutants to increase remediation efficiency. Especially heteroatoms-doping significantly increased catalysis of biochar. The main focus of this review is to underline the crucial role of biochar in the abatement of emerging antibiotic pollutants. A detailed analysis of both native and engineered biochar is provided in this article for antibiotic remediation. There has also been discussion of how biochar properties relate to feedstock, production conditions and manufacturing technologies, and engineering techniques. It is possible to produce biochar with different surface functionalities by varying the feedstock or by modifying the pristine biochar with different chemicals and preparing composites. Subsequently, the interaction of biochar with antibiotic pollutants was compared and reviewed. Depending on the surface functionalities of biochar, they offer different types of interactions e.g., π-π stacking, electrostatic, and H-bonding to adsorb on the biochar surface. This review demonstrates how biochar and related composites have optimized for maximum removal performance by regulating key parameters. Furthermore, future research directions and opportunities for biochar research are discussed.  Pharmaceutical products are greatly used for medicine and their residues are disposed of the environment. In research articles, the overall expenditure of antibiotics in livestock has been estimated at 63,151 tons in 2010 with the prediction of an increasing rate by 67% by 2030. On the basis of the global consumption of antibiotics 40.2 , billion defined daily doses population per day in 2018 with an increased rate of 46% ; therefoe.g., high porosity, aromaticity, multiple anionic functional groups, and large surface area [−1 for the removal of many antibiotics  from aqueous solutions under pH range between 5 to 11 [Biochar is basically a carbon-rich material produced during pyrolysis that is produced by thermochemically decomposing biomass at a range of temperature of about 300–900°C without oxygen. The physicochemical removal/degradation of a specific group of antibiotics by biochar was often studied, these studies were more focused on their removal efficiency but less emphasized the detailed mechanism such as adsorption, hydrolysis, volatilization, biodegradation, etc. Biochar derived from plant biomass has been considered an effective carbonaceous sorbent for organic and inorganic contaminants (including antibiotics) based on its attractive characteristics ace area . Reducedace area . Moreoveace area . The detace area . Biocharace area . These b 5 to 11 . DependiBiochar received enormous research focus because of its cost-effectiveness and it is more attractive due to its excellent adsorption capacities for organic pollutants from aqueous solutions ,23. Large,g., physical, chemicals, or biological) their surface functionalities  and biodegradation ability are improved which applies to better remediation performance. Overall, this review is to discuss the cause and impacts of antibiotics on the environment. It also provides an overview of the performance of biochar and biochars plausibility for removal of antibiotic pollutants with major emphasis on regulating parameters besides the modification approaches. Furthermore, future research directions and opportunities for biochar research are discussed.This article discusses detailed research updates on the production and engineering of various biochar for the removal or degradation of antibiotic pollutants. Moreover, various antibiotic remediation mechanisms and remediation efficiencies have been summarized based on their physicochemical characteristics. It has also been discussed how biochar properties relate to feedstock, production conditions, technologies, and engineering methods and play role in antibiotic remediation. By varying the feedstock or modifying it with different methods . Three product ratios are varied depending on biomass type and production condition and biochar is likely to be obtained more in a lower temperature range [Biomass feedstock can be any type of residue from a crop, forest, seaweed, manure, etc. that can be used for biochar preparation as an alternative solution . Worldwire range ,37,38. Ere range . The abore range ,41. The re range ,17. The re range .The effective removal of antibiotics is accomplished by native biochar mainly produced at a middle-temperature range of 450–650°C ; 45, 46.3.3PO4 modified two biochar derived from manure and rice straw. Both biochars have shown removal efficiencies ranging from 141 to 154 mg/g at pH 5 mainly involving chemisorptions including H-bonding and π-π electron donor–acceptor interactions. Moreover, these adsorption efficiencies were significantly strengthened by electrostatic attraction between biochars and tetracycline  when solution pH is reduced to 3.3, zwitterionic (TCH2), or partly anionic  at pH 3.3 to 9.7, and fully anionic (TC2−) at pH over 9.7. Moreover, the solution pH also affects the biochar surface charge [pzc) was announced. The pHpzc of biochar and BCFe/S-4 were 8.53 and 5.16 respectively. Therefore, according to the pH value, electrostatic attraction or repulsion works hence the removal efficiency greatly fluctuates along with the pH range [In other previous studies on adsorption including biochar with antibiotics especially TC has several ionizable groups that enable it to be cationic  showed promising adsorption, with a maximum removal efficiency of 100% . The obsThe effective removal of SMX and SPY antibiotics are attained by anaerobically digested bagasse-derived biochar produced at 600°C in which pH was the most regulating factor in achieving maximum removal efficiency . The remThe effect of pyrolysis temperature is well understood on the resulting biochar surface properties. Low pyrolysis temperature results in less removal of biomass elements to form fewer pores, and more surface functional groups for ionic or polar interactions, however, porosity increases with increasing pyrolysis temperature and the resulting biochar are more aromatic and hydrophobic for non-polar interactions . High po4.Pyrolytic production and modification strategies of biochar is a remarkable substance as having the best adsorption qualities, biochar has compliance to adapt modification and during the modification procedure, it improves with one or more aspects such as surface area, pore-volume, aromaticity, more O-containing functional groups, ion-exchange property etc . These mThe physical method  mainly improves the physicochemical properties of biochar, for example, surface area, pore-volume, pH, polarity, aromaticity, ash content, etc., ,79. SpecThe chemical-based modification methods are carried out uniquely or in combination with the physical methods. It may apply acid, metal salts and oxides, and alkali in the majority of studies . The aci4.Biochar is a promising antibiotic adsorbent not only in an aqueous environment for treating wastewater but also found effective for treating antibiotic polluted soil ,97,98. FHerbaspirillum huttiense to bind copper and zinc before degrading both antibiotics enrofloxacin (ENR) and oxytetracycline (OTC). In the study, otcome showed that the combined material could immobilize Cu and Zn well , and remove OTC 41.9% and ENR 40.7% [For soil amelioration, pyrolyzed biochar can bind and degrade antibiotic pollutants in moist environments and also holds the moisture and nutrients that help to increase the crop yield ,99. SeveNR 40.7% .Brassica chinensis L [Moreover, by developing antibiotic resistance genes (ARGs), microbes are becoming super antibiotic-resistant. It was reported last year that the persistence and dissemination of ARGs in soil bacteria posed one of the great threats to food security and public health ,103. Patnensis L . The bionensis L ,107 affiRhodanobacter, Brevundimonas, and Proteobacteria were the hosts of ARGs [It was found that wheat straw biochar enhanced the relative abundance of tet and sul genes in the rhizosphere . This su of ARGs . One of  of ARGs .Biochar also works as a redox agent due to abundant bioavailable electrons in it and once it interacts with microbes can carry out biotic and abiotic transformations . Microbi5.Herbaspirillum huttiense (Gram-negative bacteria) immobilized biochar exhibited maximum degradation efficiency of ENR with 3 wt% biochar application at 35°C [To improve the antibiotic remediation efficiency further, some studies also applied microbial treatment on biochar surfaces ,111. Mic at 35°C . Coloniz at 35°C . Degrada at 35°C . For antRhodanobacter, Brevundimonas, and Proteobacteria were the hosts of ARGs [Proteobacteria, Rhodanobacter, and Brevundimonas as potential hosts of ARGs altered due to biochar presence. Total phosphorus and pH were the factors driving the veterinary antibiotic degrading microorganisms and potential hosts of ARGs. It has also been demonstrated that bacteria have tolerance for antibiotics, as well as co-tolerance for heavy metals such as Cu, demonstrating the emerging potential of bacteria to utilize such compounds for ultimate antibiotic degradation [Raoultella sp. and Pandoraea sp. was capable of degrading 81.72% TC within 12 days of treatment [Bacteroidetes, Acidobacteria, Proteobacteria, and Chloroflexi [Moreover, biochar was also effective in ARGs transmission reduction.  of ARGs . Total P of ARGs . The aburadation ,115. A rreatment . The micoroflexi .Klebsiella sp. are proposed: 1. reduction of an -OH group on C-3 then subsequent dehydration at C-12-a and C-6; 2. demethylation on C-4; 3. oxidation on C-5 and removal of -C = O on C-1 [Klebsiella sp. (strain SQY5) biodegrades TC by removing the -CH3 functional group. Once the TC hydrolysis opened the ring, the -C = O group was removed, and later on removing the -NH2 group which led to the subsequent removal of two-CH3 and three-OH groups. A new putative degradation mechanism was proposed based on the authors’ identification of nine degradation products [Stenotrophomonas maltophilia DT1 demethylates TC at C-4, successively -C = O and -NH2 group removal. During TC degradation, when six biotransformation products were identified. There is a general consensus among the studies that TC biodegradation removes -CH3, -C = O, and -NH2 groups from the parent compound [Biodegradation pathways have been described by several studies recently on TC. Based on eight metabolites, three putative TC degradation pathways by O on C-1 . Other rproducts . Accordicompound .Biodegradation of antibiotics is reported to be more effective in the aqueous phase than that of sludge. AD is normally processed in a sludge dominating system in which the absolute quantity of antibiotic pollutants is more likely to be greater than the aqueous phase ,121. In 6.To optimize the reaction conditions for effective TC biodegradation by various bacteria, researchers have regulated pH, Initial TC concentration, growth, and metabolic parameters. Some parameters are very crucial and affect the microbial degradation performance greatly. The pH is one of the most influencing factors for microbial degradation. A previous study focused on Stenotrophomonas maltophilia DT1 performance for TC biodegradation at different pH conditions . With thThe initial concentration of antibiotics is also affecting the biodegradation rate significantly. TC antibiotics are susceptible to biodegradation based on their initial concentration, which determines the rate of biodegradation by microbes. During tests from 10 to 100 mg/L, Klebsiella sp. SQY5 degradation ratio tended to increase. The maximum degradation ratio reached 89.66% at 80 mg/L of initial TC concentration. However, the degradation ratio decreased later, it is motivating that strain SQY5 could use TC as an energy and carbon source, thus allowing it to survive a selection pressure of 100 mg/L of TC with a lesser degradation ratio . The bacThe effect of temperature on microbial degradation of antibiotics is inadequately reported. As per one previous report, the TC degradation rate was obtained at maximum in swine manure when the system temperature was 55 oC . The stu7.From several recent studies, the majority of them mentioned their wider applications in bioremediation however limited studies have covered their negative and uneconomical perspectives. The researcher’s concerns should also be discussed clearly about their adverse effects on the environment. If any substance has certain toxic content and if it has not been disposed of appropriately. It may reach the surrounding with their potentially harmful effects, especially when used in higher quantities such as for soil amelioration. Biochar also has some harmful effects and it may be intensified when prepared at extremely higher pyrolysis temperature . Such bie.g., oxidative stress, cytotoxicity, and proteins inactivation [Several ways of resource recovery have been developed and reviewed in the past years to improve the recovery of the materials or energy from the solid waste while reusing, reducing, and recycling , and biotivation . Furthertivation . The re-tivation ; howevertivation . Before,Feasibility in biochar costing may depend on biochar availability, which greatly depends on the usage of cheaper raw materials such as solid waste or agricultural, and forestry wastes, and cheaper production processes. To achieve the desirable well-carbonized biochar, it must be produced under controlled pyrolysis conditions and a consistent heating rate ensuring the right temperature range depending on the required surface property for specified applications. In addition, during the pyrolysis process, bio-oil and biogas are also produced, while the preparation or ongoing production of biochar, which is supportive for further energy recovery and offsetting production cost . The disAntibiotics are among the refractory pollutants that accumulate in pharmaceutical wastewater; their concentration in wastewater treatment plants that treat antibiotic production wastewater has also remained high . In the Further studies on catalysis potential determination of biochar (native and engineered) directly on antibiotic degradation as well as an indirect role in the reduction of direct stress on microbial performance are required. Such studies will be pioneering to design effective remediation methods for antibiotic polluted environments in the near future with designer biochar.For engineering of biochar, researchers must focus on improving the biochar ability to activate peroxymonosulfate (PMS) and sodium percarbonate. They act as activators of redox reaction to efficiently exchange required electron for antibiotic biodegradation process.Biochar’s role is becoming pioneering to reduce the direct stress of antibiotics on microorganisms which helps directly and indirectly for antibiotic pollution removal ,123. Bio8.Biochar-based antibiotic remediation is emerging as the most promising method due to its cost-effectiveness, and efficiency. As a result of different pyrolysis conditions, biochar produced at different temperatures has different interactions and removal efficiencies. There are different types of interactions depending on the biochar surface functionalities such as ion exchange, partitioning, π-π stacking, electrostatic attraction, H-bonding, etc. However, beyond their intrinsic ability to remediate antibiotic pollutants, important factors such as pH, temperature, biochar dosing, and initial pollutant concentration play an important role. Among them, pH was found to be the most important governing factor enabling biochar two- to three-fold more removal capacity than that of unoptimized pH removal. Physico-chemical and biological modification enhances native biochar properties significantly to have better removal efficiency for antibiotic pollutants, which was ranging 13–552 mg/g by dosing rate of 1–10 g/L. From the review analysis, biochar obtained from agri- and forestry biomass wastes at 500–700 pyrolysis temperature range was the best performing (274–552 mg/g), and the basis of adsorption involved mainly π-π electron donor––acceptor interaction, H-bonding, and electrostatic attractions. Based on the review analysis, it is important to get more insights into biochar kinetics studies for a multifactorial role in antibiotic removal mechanisms. Moreover, for the eventual disposition of various toxic antibiotic pollutants, it is important to degrade them effectively rather than remove them. Very limited studies have been carried out to establish the biochar-microbial role and their efficiency as compared to biochar alone. More studies must be carried out to compile the advantages of biochar’s role in improved microbial degradation for various antibiotics.