Research on the applications of new techniques such as machine learning is advancing rapidly. Machine learning methods are being employed to predict the characteristics of various kinds of concrete such as conventional concrete, recycled aggregate concrete, geopolymer concrete, fiber-reinforced concrete, etc. In this study, a scientometric-based review on machine learning applications for concrete was performed in order to evaluate the crucial characteristics of the literature. Typical review studies are limited in their capacity to link divergent portions of the literature systematically and precisely. Knowledge mapping, co-citation, and co-occurrence are among the most challenging aspects of innovative studies. The Scopus database was chosen for searching for and retrieving the data required to achieve the study’s aims. During the data analysis, the relevant sources of publications, relevant keywords, productive writers based on publications and citations, top articles based on citations received, and regions actively engaged in research into machine learning applications for concrete were identified. The citation, bibliographic, abstract, keyword, funding, and other data from 1367 relevant documents were retrieved and analyzed using the VOSviewer software tool. The application of machine learning in the construction sector will be advantageous in terms of economy, time-saving, and reduced requirement for effort. This study can aid researchers in building joint endeavors and exchanging innovative ideas and methods, due to the statistical and graphical portrayal of participating authors and countries. The fast global growth of data estimation techniques and analytical methods currently plays a key role in nearly every field of study ,2. TheseGenerally, ML focuses on developing a computer’s or a model’s learning abilities through interpretations, prior practices, and training data samples ,22,23. IIn general, ML is grouped into three classes : reinforAs research on the use of ML to forecast concrete properties increases in response to advancing computational technologies, scientists are confronted with information restrictions that may stifle innovative research and academic collaboration. Consequently, it is crucial to develop and implement a system that helps academics to acquire essential knowledge from the most highly credible sources possible. Using a software program, a scientometric technique may help overcome this deficiency. In this study, we aim to perform a scientometric study of bibliographic records published on ML for concrete between 2001 and May of 2022. A scientometric assessment can achieve a quantifiable assessment of enormous amounts of bibliographic data by utilizing an appropriate software application. Conventional review studies lack the capacity to link disparate portions of the literature accurately and comprehensively. Scientific visualization, co-citations, and co-occurrence are among the highly complicated aspects of contemporary research ,76,77,78In this study, we conducted a scientometric analysis of bibliographic data ,80,81 inThis assessment was performed using the Scopus analyzer to identify the most pertinent study fields. As seen in Construction and Building Materials (CONBUILDMAT)”, “Materials”, and “Engineering Structures” were found to be the top publication journals with 94, 52, and 48 papers, respectively. Furthermore, the same three sources obtained the greatest number of citations between 2001 and May 2022, with “CONBUILDMAT” obtaining 1677, “Engineering Structures” receiving 602, and “Materials” receiving 441 citations. This examination could provide the groundwork for forthcoming scientometric evaluations in ML research for concrete. Additionally, previous conventional review studies were unable to produce systematic graphs. CONBUILDMAT” has a larger frame than the others, indicating that it is a journal of great significance in the present research field. Four clusters were formed, characterized by a distinct color on the map . Clusters were developed based on the extent of the research outlet or the frequency with which they were co-cited in comparable articles [CONBUIDMAT” correlates more strongly with “Materials” than with “Computer-Aided Engineering”.An evaluation of publication outlets  was performed on the data using VOSviewer. A minimum of 15 papers per source was stipulated, and 13 of the 541 publication sources satisfied this requirement. articles . The VOSKeywords are significant in research since they distinguish and emphasize the basic subjects of the study domain . The minCitations indicate a scientist’s impact in a particular field of research . The thrThe number of citations a document obtains signifies its influence in a certain research domain. In their respective study domains, the papers with the most citations are regarded as pioneering. The least number of citations for a document was set at 30, and 125 out of 1367 papers met this threshold. In Numerous countries have presented more documents in the present research area than others, and they plan to continue their contributions. The systematic map was constructed so that readers may examine the regions performing ML applications research for predicting concrete properties. The minimum number of documents a country could possess in order to be included was set at 10, and 31 countries satisfied this threshold. The countries included in This systematic review performed statistical analysis and mapping of the bibliographic data available on the applications of ML for predicting concrete properties. Previous manual review studies lacked the capacity to link disparate areas of the literature completely and precisely. This analysis identified the sources of publications  that published the most documents, the keywords most often used in publications, the documents and researchers with the highest numbers of citations, and the countries that are vigorously engaged in ML applications for concrete research. According to the keyword analysis, ML has been utilized mostly to forecast concrete properties, particularly compressive strength. In addition, the literature and the linkages based on citations were used to identify the highly committed and participating countries, based on publication count. The graphical representation and quantitative analysis of the participating countries and researchers will help young scientists form scientific partnerships, establish joint ventures, and share advanced methods and concepts. Scholars from countries concerned with expanding the research on the applications of ML for concrete can collaborate with other professionals in the discipline and benefit from their expertise.We are on the verge of a fourth industrial revolution, in which data-driven smart approaches, robotics, additive manufacturing, cloud computing, the Internet of Things, and other developing tools will merge the physical, biological, and digital realms. The building industry is lagging behind in seizing the openings presented by the world’s fast transformation. The engineering properties of building materials and structures predicted by ML have applications in propagative smart design. Several knowledge gaps exist that must be filled before structural engineers can imitate procedures employed in mechatronics, robotics, and other sophisticated domains. CONBUILDMAT”, “Materials”, and “Engineering Structures” were the top three sources, with 94, 52, and 48 publications, respectively. In terms of total citations, the top three publishing sources were “CONBULDMAT” with 1677, “Engineering Structures” with 602, and “Materials” with 441.An assessment of publication journals including articles on ML for concrete research revealed that “A keyword analysis of the topic research field revealed that machine learning, learning systems, forecasting, concretes, and compressive strength were the five terms occurring most often. The keyword analysis found that machine learning had mostly been used to forecast concrete properties, particularly compressive strength.The author analysis found that just 53 authors had published at least 7 articles on ML for concrete research. The leading authors were categorized according to their document count, overall citations, and average citations. With 25 publications, Aslam F. was the most prolific author, followed by Wang Y. with 22 and Nehdi M.L. with 19 papers. In terms of total citations, Mangalathu S. had the highest number, with 385, followed by Wang Y. with 351 and Nehdi M.L. with 327 total citations. Moreover, when comparing the average number of citations, the following writers stood out: Mangalathu S. with roughly 48 citations, Alyousef R. with nearly 24, and Liu J., Li S., and Feng D.-C., each with an average number of citations of about 48.An evaluation of articles offering data on ML applications for concrete revealed that the study by Prasanna P.  on “AutoBased on their engagement in ML concrete research, the main countries were identified, and it was found that only 31 countries had produced at least 10 publications. The United States, China, and India produced 298, 289, and 110 papers, respectively. In addition, the papers from the United States received 4260 citations, those from China received 2732 citations, and those from Vietnam received 1633 citations.These revolutionary techniques will aid the building sector by enabling the creation of efficient and economical methods for evaluating the properties of materials. In addition, the adoption and application of a material in the building sector will be expedited by encouraging computational methods.The prevalence of ML applications is forecast to increase as the Internet of Things, big data, and automated systems continue to dominate the industrial sector in the next decades.To improve the performance of ML models, it is recommended that a greater number of input factors should be employed, such as the chemical composition of raw components and the environmental conditions (humidity and temperature). In addition, increasing the number of data samples through additional experimental testing may improve the performance of ML models in terms of real and precise predictions.The purpose of this study was to undertake a scientometric assessment of the available literature on machine learning (ML) applications for concrete, in order to evaluate various metrics. The database Scopus was searched, 1367 related articles were found, and the data were evaluated using the VOSviewer application. The following conclusions were obtained from this investigation:


At present, low tensile mechanical properties and a high carbon footprint are considered the chief drawbacks of plain cement concrete (PCC). At the same time, the combination of supplementary cementitious material (SCM) and reinforcement of fiber filaments is an innovative and eco-friendly approach to overcome the tensile and environmental drawbacks of plain cement concrete (PCC). The combined and individual effect of fly ash (FA) and Alkali resistance glass fiber (ARGF) with several contents on the mechanical characteristics of M20 grade plain cement concrete was investigated in this study. A total of 20 concrete mix proportions were prepared with numerous contents of FA  and ARGF . The curing of these concrete specimens was carried out for 7 and 28 days. For the analysis of concrete mechanical characteristics, the following flexural, split tensile, and compressive strength tests were applied to these casted specimens. The outcomes reveal that the mechanical properties increase with the addition of fibers and decrease at 30 and 40% replacement of cement with fly ash. Replacement of cement at higher percentages  negatively affects the mechanical properties of concrete. On the other hand, the addition of fibers positively enhanced the flexural and tensile strength of concrete mixes with and without FA in contrast to compressive strength. In the end, it was concluded that the combined addition of these two materials enhances the strength and toughness of plain cement concrete, supportive of the application of an eco-friendly circular economy. The relationship among the mechanical properties of fiber-reinforced concrete was successfully generated at each percentage of fly ash. The R-square for general relationships varied from (0.48–0.90) to (0.68–0.96) for each percentage of FA fiber reinforced concrete. Additionally, the accumulation of fibers effectively boosts the mechanical properties of all concrete mixes. In the construction industry, cement has been recognized as the utmost energy-intensive material after steel and aluminum . For theOne of the most reliable techniques to lessen the environmental influence of cement is to replace it with some valuable waste supplementary cementitious material (SCM) such as fly ash (FA). The utilization of SCM not only lessens the energy consumption and resource depleting procedure but is helpful for the eco-friendly utilization of hazardous solid waste . The intThe low tensile properties are a drawback of conventional concrete because it limits its structural applications in the construction industry. Generally, the tensile strength of conventional concrete is 12–15-times lower than its compressive strength ,30,31. M2 emissions embedded in products, mitigating emissions at lower costs than other strategies, and helping countries in their Paris and SDGs commitments” [The utilization of waste materials follows the circular economy model pattern which covers the concept that waste from one source is a product of another source. The complete cycle of the circular economy model has been described by United Nations Conference on Trade and Development (UNCTAD) as shown in itments” .This CE models follow the utilization of waste material for a connection-based relation for eco-friendly infrastructure improvement and economic development.The prime objective of this study is to analyze the mechanical properties of eco-friendly composite material based on the utilization of FA and ARGF. For this aspect, following laboratory tests, compressive, split tensile, and flexural strength tests were applied. After testing, all results of specimens were compared to conventional concrete graphically, analytically, statistically, and theoretically. This study will follow the eco-friendly development of infrastructures through economical resource utilization.The current study involved the following material binders: , sand, coarse aggregates, AR-glass fiber, and water for the development of AR-glass fiber fly ash concrete. The proportions of these materials are designed according to M20 grade concrete. Maple Leaf brand cement with grade 53 of type-1 was utilized as a cementitious material as per ASTM C-150 . AccordiAfter the description of cementitious materials, the next one is fine and coarse aggregates. Locally available well-graded fine aggregates with a maximum size of 4.75 mm were used in this study. The maximum and minimum size of well-graded coarse aggregates is 12.5 mm and 4.75 mm, respectively, and originated from Sargodha, Pakistan. The physical characteristics of these aggregates are listed in Countless kinds of fibers are available on the market; glass fiber is favored due to its higher ratio of surface area to weight. For this research, alkali resistance glass fiber (AR-GF) was used for the preparation of fibrous concrete, as this type of fiber is not affected by the alkaline condition of the cement . The phyIn this study, the utilization of AR glass fiber has been carried out at four distinct percentages  by the volume of concrete. Similarly, fly ash has been added as a replacement for cement at various percentages  by the volume of cement. M20 grade concrete has been used in this investigation at the w/c ratio of 0.60. The binder , and coarse and fine aggregates were put into a mechanical concrete mixture for 4 min. After the required amount of water was added into a concrete mixer, the machine again ran for 2 min. In the end, the required quantity of fibers was added to this wet-concrete blend and the mixer ran for 5 min only. For the homogeneous mixing of all ingredients, special attention was applied during mixing. Before the concrete mix was put into molds, Abram’s slump-cone test was performed for the measurement of workability of concrete as per ASTM C-143 . The worIn this study, the MATEST brand machine with a maximum loading capacity of 2000 kN shown in After the testing of specimens, the separate effect of fly ash and AR glass fiber on the strength of 7D and 28D concrete is illustrated in The outcomes presented in In terms of discussion, the outcomes proved that the low-level integration of FA  successfully participates in the pozzolanic reaction of the binder matrix, as verified by Boga et al. . Due to This section discusses and explains the performance of FA and ARGF on the split tensile properties of each concrete mix ID. Firstly, the individual performance of FA and ARGF at 7D and 28D curing is demonstrated in A brief explanation of each mix ID with or without the mutual effect of FA and ARGF is illustrated in With the varying amount of fly ash, the split strength of ARGF concrete changes simultaneously. Akhtar et al.  stated tThis section explains the flexural strength behavior of each concrete mix at the age of 7D and 28D curing. Moreover, the strength outcomes of ARGF concrete mixes are shown in The combined effect of these two materials, i.e., FA and ARGF, is briefly demonstrated in r) for all types of concrete mixes was also investigated. Moreover, the statistical relationship which includes the percentage of fiber (Pf), fc’, fsp, and fr helpful for the prediction of mechanical properties of fly ash fiber reinforced concrete. f). Results show that the general relation is comparatively weaker than the relationship generated by the addition of fibers. This confirms the positive effect of fibers on the split tensile properties compared to compressive strength properties. A similar relationship can be developed among fc’and fr demonstrated in r in contrast to the relation that originated by the addition of fibers. In the end, the relationship demonstrated in r for all concrete mixes.This section illustrates the statistical relationship between the mechanical properties of concrete. The general relationship among compressive strength (fc’), split tensile strength (fsp), and flexural strength (fIn this study, the consequence of FA and ARGF on the mechanical properties of concrete were successfully investigated. The result includes that the addition of fibers enhances the mechanical properties of concrete. However, the replacement of cement with FA declined the mechanical properties of concrete at 30, and 40% content. The mutual incorporation of these two materials seriously affects the mechanical properties of all concrete mixtures. The 28D highest compressive strength was obtained at a concrete mix containing 10 and 20% FA and 1% ARGF compared to the reference mix. However, the 28D strength of the reference concrete mix and the concrete mix containing 30% FA and 1% ARGF are almost the same which is considered beneficial for the successful utilization of supplementary cementitious materials in fiber concrete mixes. The concrete mix ID contains 10% FA and 1% ARGF, illustrating maximum 28D split tensile strength in contrast to all concrete mix IDs. In the flexural strength scenario, the optimal strength was obtained at the FA10ARGF1.5 concrete mix. However, the 28D flexural strength of the reference concrete mix and the concrete mix containing 40% FA and 1.5% ARGF were almost the same. The general relationship of mechanical properties for all concrete mixes was not strong compared to the relationship developed by the addition of fibers. The statistical analysis of fiber reinforced concrete verified the positive impact of ARGF on the mechanical properties of concrete. However, the higher level of FA lessens the mechanical properties of fiber-reinforced concrete, i.e., 30 and 40% . While a


This study aims to find discontinuous and continuous approaches to reducing the size of planar truss structures with a specified shape and topology. The member's section area has assumed to be a decision variable, and the objective function is to minimize their weight. The member stresses and node displacements are the constraints that must maintain within the allowed limits for each condition. Chaos game optimization (CGO) and social network search (SNS) algorithms were used to optimize four well-known planar truss structures. In discontinuous-size cases, the results of the social network search (SNS) algorithm are the most cost-effective. However, the results of the chaos game optimization (CGO) algorithm are the most cost-effective in continuous-size cases. Discontinuous optimization is an optimization problem considering discontinuous variables in which an object, such as an integer, must be found from a countable set.A continuous optimization problem is one in which an optimal value must obtain from a continuous function. It might be limited or multimodal.Developing a material structure that bears loads optimally is defined as structural optimization . In engiIn recent decades, the ubiquity of trusses as structural systems has made their optimization an important engineering endeavor. Design ideas due sustainable, reliable, and cost-effective for the structure have been the impetus for the many developments of optimization procedures. Therefore, a trustworthy optimization strategy is always needed to tackle a structural optimization issue. Metaheuristic approaches are generic optimization tools that do not need a continuous objective function(s) or gradient information to direct the search process in this respect. Because of this positive quality, researchers in several sectors of science and engineering employ these approaches extensively –9. MetahA hybridized CSS and a sizable bang-huge crunch (CSS-BBBC) were introduced by Kaveh and Zolghadr . The adaThis paper aims to determine the optimal discontinuous and continuous sizes for planar trusses of a certain design and topology so they may be constructed. It is necessary to conduct some case studies, both discontinuous and continuous in truss size, to assess the efficacy of each technique. For this aim, the very recent CGO and SNS algorithms are used in this paper. The CGO and SNS algorithms will each be broken down and examined in further detail in the following sections. Finally, following the introduction of the trusses and the creation of the truss design optimization model, the outcomes of the two approaches are exhibited and compared with the previous study's conclusions. The following is how the remainder of the paper is organized: in The objective of truss size optimization is to lower the structure's weight while adhering to stress and deflection restrictions. As design variables, cross-sectional areas are chosen from a list of the allowable sections. The problem can be formulated as follows:X, are taken into account (design variables), ρi is the material density, W({X}), and Li and Xi are the weight of the truss, the length of members, and the cross-sectional area, respectively. z is the number of members, and n is the number of nodes. The bottom displacement limit is denoted by δmin, the upper displacement limit is represented by δmax, and the displacement of node j is represented by δj. Furthermore, the bottom limit of stress is represented by σmin, the upper limit stress is represented by σmax, and the stress of member p is represented by σp. Xp is the cross-sectional area of the member p that is considered from the allowable section. The components in the allowable section list are ordered in ascending order.Subjected to:P is the unconstrained objective function, and ξ1 and ξ2 are the penalty function coefficients. In this study, ξ1 and ξ2 are both set to 1. K is the number of constraints, and Φj is the number of constraints connected to jth constraint:For unconstrained optimization problems, CGO and SNS are presented. A penalty function method is used to deal with restrictions. In this method, the value of the objective function is determined by the sum of the constraint violation in this technique, and the constrained optimization problem is transformed into an unconstrained one using the following formula:jth constraint are cminj and cmaxj, respectively, and the value of the jth constraint is cj.The lower and upper boundaries of the Xi) , and R is a random integer between 1 and d. Four possible formulations for αi, which regulate the mobility limits of the seeds, are offered to control and adapt the exploration and exploitation pace of the CGO algorithm:A different procedure is used to create the fourth seed to execute the mutation phase in the position updates of the eligible seeds in the search space. The seed's location is updated depending on specific random changes in the selected decision factors. The fourth seed can represent as follows:δ and ε are random integers between 0 and 1. The CGO algorithm's step-by-step approach is listed below, and the algorithm's pseudocode is shown in Rand is a uniformly distributed random number between 0 and 1, while The SNS method was proposed by Bayzidi et al. . This alUsers may follow each other on social media, and when one publishes a new post, their followers will be notified about the shared subject. Networks have become vital instruments for sharing information and ideas due to this property (propagation of views). Users of social media networks can keep track of their loved ones and celebrities. They will be aware of other people's responses if they follow the news. They will attempt to start a debate about the new event by imitating the viewpoint of another person if the new occurrence involves complex thoughts. This sentiment may be mathematically stated as follows :(10)XineUsers of social networks may electronically connect and discuss various topics. Individuals learn from one another and expand their understanding of events during the Talk, which takes the shape of private conversation. Users in conversation have a new perspective on events by hearing other people's perspectives. Lastly, because of the variations in ideas, they may construct a different picture of the problem, according to the following equation :(11)XineUsers discuss and defend their opinions on current events to others when in a disputation mood. This work is done on social media sites, such as in the comments and groups. Users may see various points of view from others in the comment area, which may be impacted by the stated reasons. Furthermore, users may form friendly relationships with one another, so they form a virtual group to share their viewpoints on a specific topic. A random group of persons is identified as a commentator or a member of a group to model this attitude, and the new affected perspective in the argument is as follows  50]:, which the ith user desires to change due to a new thought nnewd. Finally, as xinewd, a new viewpoint of the dt h dimension will be formed. The dimension x(xinewd) will be formed as an interpolation dimension (xinewd) is a dialogue between the new notion (nnewd) and the current (xjd). Changing one dimension, xinewd creates a broad shift in the underlying notion and may be considered a new communication point of view. The following model may be used to represent this process:Users' ideas and experiences are sometimes reflected in what they post. To put it another way, when a person considers a situation, he or she may be able to see it in a new light and get a better understanding of the problem's nature or gain a whole new perspective on it. A topic might have a variety of characteristics, each of which impacts the problem's comprehension. Consequently, modifying one of their ideas will affect the whole notion of the issue, resulting in a unique viewpoint. This notion is used to generate a new viewpoint via the innovation mood:The SNS algorithm's step-by-step method is presented in The CGO and SNS are used in this part to solve discontinuous and continuous optimization benchmark problems using two well-known truss designs. Four well-known planar truss structures were tested to ensure that the findings were accurate and that the suggested algorithms were successful. To do the structural analysis, get the members' forces and node displacements, and optimize by using the CGO and SNS techniques, a program was built in the MATLAB software  programmIn this study, the best configuration of a 10-bar planar truss is investigated, as shown in p1 and p2 are 100 (kips) and zero (kips), respectively, and the sections used to create this truss are as follows:Loads of The best designs presented so far are listed in In the discontinuous size situation, the outputs of the SNS algorithm are more cost-effective than the CGO algorithm, as shown in p1 and p2 are 100 (“kips”) and zero (“kips”), respectively, and the structure's members are chosen from the series' (X) interval as follows:Loads of The study's conclusions are shown along with a summary of the best designs that have been made so far in The outputs of the CGO algorithm are more cost-effective than the SNS method in the continuous-size situation, as shown in p1 and p2 are 100 (“kips”) and 50 (“kips”), respectively, and the structure's members are chosen from the series' (X) interval as follows:Loads of The outputs of the CGO algorithm are more cost-effective than the SNS method in the continuous-size situation, as shown in X) for the design of the eight-node planar truss as follows:The second example of size optimization is a truss system with 15-bar, which is shown in A maximum number of 1000 iterations were set for comparison with other algorithms in the same circumstance. As shown in The optimal design of a 17-bar planar truss is explored, as illustrated in The cross-sectional areas of components are regarded as 17 sizing design factors, with the following minimum permissible values:As shown in The optimal design of a 45-bar planar truss, as illustrated in For design reasons, the structure's components are divided into 23 groups according to As shown in To present a better comparison of the CGO and SNS algorithms, The solved cases demonstrate that the chaos game optimization algorithm and the social network search algorithm can solve the continuous and discontinuous size optimization problems and that these algorithms can find the best structural configuration faster than other methods. Other advantages of using the chaos game optimization algorithm with the social network search technique to solve structural optimization problems include a faster convergence rate, a better solution, and low computational effort.In discontinuous sizes, the designs generated by the social network search algorithm are much more cost-effective than other designs, whereas, in continuous-size instances, the designs generated by the chaos game optimization technique are far more cost-effective.According to a study of convergence rate diagrams in terms of CPU time and function evaluations, the chaos game optimization technique approaches the optimal solution faster than the social network search method.The chaos game optimization approach and the social network search algorithm were used to analyze the continuous and discontinuous size optimization of planar trusses in this research. The findings of a computer analysis of four distinct kinds of planar trusses  that were evaluated under various degrees of discontinuous and continuous size and loading are presented in this study.


PIK3CD-S splice variant is overexpressed in aggressive African American prostate cancer, and its resulting PI3Kδ-S isoform is resistant to PI3Kδ inhibitors, such as Idelalisib and Seletalisib. Molecular modeling and functional validations implicate that a structural change due to exon 20 skipping greatly reduces the affinity between drugs and PI3Kδ-S isoform. Further targeting alternative splicing mechanism drastically sensitizes Idelalisib/Seletalisib-resistant prostate cancers to PI3Kδ inhibitors. These results have highlighted the therapeutic potential of modulating RNA splicing mechanism to overcome drug resistance in aggressive cancers.Higher incidence and mortality rates were observed in African American vs. European American prostate cancers. Alternative mRNA splicing has been suggested as an oncogenic driver in aggressive cancers as well as cancer disparities. Herein, we show that aberrant PIK3CD-S, conferring Idelalisib resistance in African American (AA) prostate cancer (PCa). In the current study, we employed a comprehensive analysis combining molecular biology, biochemistry, histology, in silico simulation, and in vitro functional assays to investigate the PIK3CD-S expression profiles in PCa samples and to elucidate the drug resistance mechanism mediated by PI3Kδ-S (encoded by PIK3CD-S). The immunohistochemistry, RT-PCR, and Western blot assays first confirmed that PI3Kδ-S is highly expressed in AA PCa. Compared with PCa expressing the full-length PI3Kδ-L, PCa expressing PI3Kδ-S exhibits enhanced drug resistance properties, including a higher cell viability, more antiapoptotic and invasive capacities, and constitutively activated PI3K/AKT signaling, in the presence of PI3Kδ/PI3K inhibitors . Molecular docking, ATP-competitive assays, and PI3 kinase assays have further indicated a drastically reduced affinity of PI3Kδ inhibitors with PI3Kδ-S vs. PI3Kδ-L, attributed to the lack of core binding residues in the PI3Kδ-S catalytic domain. Additionally, SRSF2 has been identified as a critical splicing factor mediating exon 20 skipping in PIK3CD pre-mRNA. The inhibition of the SRSF2 activity by SRPIN340 successfully sensitizes AA PCa cells to PI3Kδ inhibitors, suggesting a novel therapeutic option for Idelalisib-resistant tumors.Targeting PI3Kδ has emerged as a promising therapy for hematologic and non-hematologic malignancies. Previously, we identified an oncogenic splice variant,  Prostate cancer (PCa) is the most frequently diagnosed and second leading cause of cancer death among American men. Particularly, African American (AA) men demonstrate a 1.7-fold higher incidence rate and a 2.3-fold higher mortality rate compared to the European American (EA) counterparts  and micrPIK3CD, FGFR3, TSC2, ITGA4, MET, NF1, BAK1, and RASGRP2, were identified and verified with DS events occurring between AA and EA PCa [PIK3CD-S (where exon 20 is skipped) and FGFR3-S (where exon 14 is skipped) have been implicated as critical oncogenic elements to promote AA PCa aggressiveness and drug resistance [Deep sequencing studies have suggested that more than 95% of human genes have undergone alternative splicing at the pre-mRNA level ,16, ofted EA PCa . Notablysistance .PIK3CD (that encodes PI3Kδ splice isoform) is one of the driving mechanisms conferring resistance to Idelalisib therapy. A panel of comprehensive analyses combining immunohistochemistry, biochemistry, molecular biology, in silico molecular modeling, and in vitro functional assays has been applied to validate our hypothesis. Specifically, IHC assays and a Western blot and RT-PCR analysis were performed to examine the expression levels of PI3Kδ-L and PI3K-S isoforms (at the protein and RNA levels) in PCa specimens and cell lines derived from AA and EA patients. Secondly, four small-molecule inhibitors  were used to test the drug efficacies against the PCa cells expressing PIK3CD-L (encoding full-length PI3Kδ) and the PIK3CD-S splice variant. Similar to Idelalisib, Seletalisib is a quinolone-based, orally available small-molecule inhibitor with selective inhibitory activity against PI3Kδ [PIK3CD-S synthesis and functional link with the PI3Kδ-S-mediated drug resistance in AA PCa. To date, this is the first attempt to decipher the molecular mechanism underlying the resistance to PI3Kδ and pan-PI3K inhibitors in PCa. This study aims to provide molecular insights into the interactions/competitions of the inhibitors and ATP with PI3Kδ-L and PI3Kδ-S, facilitating our understanding of the molecular mechanisms underlying Idelalisib resistance and further developing a novel therapeutic strategy for treating resistant AA PCa or PI3Kδ-S overexpressing tumors with hematologic and non-hematologic origins.PI3Kδ is frequently upregulated in B-cell malignancies, such as in chronic lymphocytic leukemia (CLL), multiple myeloma (MM), lymphoma, non-Hodgkin’s lymphoma (NHL), acute myeloid leukemia (AML), and acute promyelocytic leukemia (APL) . Accumulst PI3Kδ . Wortmanst PI3Kδ . Dactolist PI3Kδ . Thirdly2 incubator.PCa cell lines 22Rv1, LNCaP, PC-3, RC77 T/E, and MDA PCa 2b were used in this study. 22Rv1 represents a castration-resistant EA PCa cell line, while LNCaP and PC-3 were derived from EA PCa patients with lymph node and bone metastases, respectively. RC77 T/E is a primary PCa cell line derived from AA patient , while MDA PCa 2b is a cell line derived from bone metastasis of an AA PCa patient. Except RC77 T/E, all the PCa cell lines were purchased from American Type Culture Collection . The EA PCa cell lines LNCaP and 22Rv1 were cultured in RPMI with 10% fetal bovine serum (FBS), while PC-3 was cultured in DMEM with 10% FBS. AA PCa cell lines RC77 T/E and MDA PCa 2b were grown in Keratinocyte SFM with human recombinant EGF1-53 and BPE, and BRFF-HPC1 with 20% FBS, respectively. All the cell lines were maintained at 37 °C in a 5% COPIK3CD-L and PIK3CD-S expression levels, and EIF1AX was used as an endogenous control. The primers for PCR reactions are listed on Total RNA samples were purified from the PCa cells using miRNeasy mini kit  according to the manufacturer’s protocol. Purified RNA samples were reversely transcribed to cDNA using iScript reverse transcription supermix . Briefly, 1 μg of RNA was mixed with 4 μL of iScript RT supermix and RNase-free water to total volume of 20 µL. The reverse transcription reactions were performed at follows: 25 °C for 5 min, 46 °C for 50 min, then 95 °C for 1 min. The resulting cDNA samples were used for PCR reactions to examine Tissue microarrays (TMAs) containing prostate tissues from 3 healthy AAs and 3 healthy EAs, PCa samples, and adjacent normal tissues derived from 40–50 AA PCa and EA PC patients were used for the IHC staining of PI3Kδ-S and SRSF2 expression levels. IHC assays were performed using the standard protocol established in our lab ,30. Brie3 cells/well in 96-well plates and grown for 24 h. The EA PCa LNCaP cells transfected with PIK3CD-L or PIK3CD-S, and AA PCa MDA PCa 2b stably expressing PIK3CD-L or PIK3CD-S were also seeded at density 5 × 103 cells/well in 96-well plates. Then, the cell cultures were replaced with fresh media, and the PCa cells were treated with four small-molecule inhibitors  at concentrations ranging from 0 to 100 μM. MTT assays were then conducted to examine cell viabilities of the tested PCa cells after drug treatment for 48 h. Specifically, MTT assay reagent was added to the cells at a final concentration of 0.5 mg/mL in phenol-free media and incubated for 3 h in a 5% CO2 incubator at 37 °C. Then, the samples were detected by the Mutiskan FC microplate photometer  at the wavelength of 570 nm, then the data were analyzed using the GraphPad Prism 9 program  for graphing and statistical analysis.For the measurement of cell viability, 22Rv1, LNCaP, PC-3, RC77 T/E, and MDA PCa 2b cells were seeded at density 5 × 10PIK3CD-L or PIK3CD-S were subjected to apoptosis assays for evaluating the apoptosis capacities upon different drug treatments. The PCa cells were seeded in 96-well plates at initial cell density of (5 × 103 cells/well) and were grown for 24 h, then were treated with four small-molecule inhibitors  at concentrations of 0, 1, 10, and 25 μM. After drug treatment for 48 h, the PCa cells were harvested for the apoptosis assays using Apo-ONE Caspase-3/7 Assay Kit  according to the protocol described by the manufacturer. The apoptosis activities were measured by detecting fluorescence signals at wavelengths of 498 nm and 521 nm  using Biotek Synergy HT Microplate Reader .LNCaP and MDA PCa 2b cells overexpressing PIK3CD-L- and PIK3CD-S-expressing LNCaP and MDA PCa 2b cells were evaluated using Corning Matrigel Invasion Chamber 8.0 Micron , according to manufacturer’s protocol. Specifically, 2 × 104 cells in serum-reduced medium were seeded in the upper chamber with four small-molecule inhibitors and were cultured overnight in a 5% CO2 at 37 °C. After growing for 24 h, the PCa cells were subjected to invasion assays. The non-invading cells were wiped off from the top membrane of the invasion chamber using cotton swabs, and the cells invading through the bottom membrane were fixed and stained with Wright-Giemsa quick stain , washed with water, and allowed to dry for counting the number of invading cells to determine the invasive capacities of PCa cells in different drug treatment groups.The effects of Idelalisib, Seletalisib, Wortmannin, and Dactolisib at different concentrations  on inhibiting invasion abilities of PIK3CD-L and PIK3CD-S were grown and treated with four small-molecule inhibitors  for 48 h, then the cells were harvested and subjected to Western blot analysis. The Western blot assays were performed using standardized protocol in our lab as previously described [Wild-type 22Rv1, LNCaP, PC-3, RC77 T/E, and MDA PCa 2b without drug treatments were grown and harvested for Western blot analysis. Moreover, MDA PCa 2b cells stably overexpressing escribed ,30. Briehttps://vina.scripps.edu/, accessed since 1 September 2021) and the predicted protein/drug complexes were visualized with the PyMOL software . The three-dimensional (3D) structures of Idelalisib, Seletalisib, Wortmannin, and Dactolisib were drawn by ChemDraw 20.1.1, and then the structures were optimized and used as input structures for docking modeling. The amino acid sequences reflecting the kinase domain of full-length PI3Kδ (PI3Kδ-L) and PI3Kδ-S splice isoform are listed in http://www.expasy.org/swissmod/SWISS-MODEL.html, accessed since 1 September 2021) for homology crystal structure models. A binding pocket was selected by the active site residues involved in the binding of the ATP with PI3Kδ and a grid-based method was used for energy calculation of the flexible ligand with the target protein. RMSD measurements were calculated by finding the square root of the mean square error using Autodock vina and the top energy models were analyzed/visualized by PyMOL.Molecular modeling for interactions of the small-molecule inhibitors with PI3Kδ-L or PI3Kδ-S splice isoform were performed using the AutoDock vina  and incubated in a 5% CO2, at 37 °C. After 16 h, cells were harvested and total proteins were extracted using M-PER reagent with protease and phosphatase inhibitor cocktail, and the His-tagged PI3Kδ-L and PI3Kδ-S isoforms were purified using 1-mL His Gravi Trap column . The purified proteins were then further dialyzed with 10 mM Tris/HCL (pH7.4) at 4 °C, and stored at −80 °C. The purified proteins were confirmed by Coomassie blue staining and Western blots with anti-Histidine and anti-PI3Kδ antibodies from Cell Signaling Technology . For each ATP assay, 10 mM of purified His-tagged PI3Kδ-L or PI3Kδ-S was first bounded to the His Trap column, then the small-molecule inhibitor (10 mM) and ATP (1 mM) were incubated with the nickel column-bound PI3Kδ-L or PI3Kδ-S. The reaction mixtures were spun down, washed, and eluted using 250 mM of imidazole. Finally, the fluorescence signals of the eluted samples were detected at the wavelengths at 535 nm (for excitation) and 587 nm (for emission) using BioTek Synergy HT microplate reader .For understand the competition of small-molecule inhibitors with ATP to specifically bind to PI3Kδ-L or PI3Kδ-S splice isoform, we first prepared purified recombinant protein of PI3Kδ-L and PI3Kδ-S for the ATP-competitive binding assays. To validate the molecular docking results, drug/ATP-competitive assays were conducted. Specifically, purified PI3Kδ-L or PI3Kδ-S isoform was incubated with small-molecule inhibitor and ATP, and the ATP intensity in the final eluted sample  was measured using ATP Colorimetric/Fluorometric Assay Kit . pcDNA3.1-PIK3CD-L-V5-HIS or pcDNA3.1-PIK3CD-S-V5-HIS plasmid were harvested for purification of PI3Kδ-L and PI3Kδ-S isoforms. The His-tagged PI3Kδ-L and PI3Kδ-S were purified using HisPur Ni-NTA spin columns . The Ni-NTA column-bound PI3Kδ-L-6 × His and PI3Kδ-S-6 × His were washed with 1 × PBS twice, then were eluted using the elution buffer . The flow-through, wash, and elute samples were collected for Western blot analysis to evaluate the purification efficiencies  transfected with pcDNA3.1-ciencies . The HisPIK3CD pre-mRNA was labeled with biotin using Pierce’s RNA 3′ end biotinylation kit  according to the manufacturer’s protocol. A total of 50 μL of streptavidin magnet beads was incubated with 50 pmol of biotin-labeled RNA sample in a total volume of 100 μL of 1 × RNA capture buffer. After incubation for 30 min at room temperature with agitation, the biotin-labeled RNA/streptavidin magnetic beads were washed twice with 20 mM Tris (pH7.5) and resuspended in 100 μL of 1 × protein-RNA-binding buffer. A total of 100 μL of PCa lysate-containing RNA-binding buffer was added and incubated overnight at 4 °C with rotation. The RNA-binding protein complexes were then washed twice with 1 × wash buffer and eluted with 50 μL of elution buffer. The eluted RNA-protein complex samples were then subjected to Western blot analysis using anti-SRSF2  or anti-HNRNPF antibody .The negative control RNA and RNA containing SFSR2 and HRNPF putative motifs in upstream flanking intron (intron 19) of Synthesized RNA fragment containing putative SRSF2 and binding motifs of intron 19 was used as RNA template for RIP and RNA pulldown assays. Nuclear protein extract was prepared using the subcellular protein fractionation kit . The RIP assays were performed using Magna RIP RNA-binding protein precipitation kit according to the protocol described by the manufacturer . Briefly, nuclear protein extracts from MDA PCa 2b were incubated with the synthesized RNA fragment containing putative SRSF2-binding motifs. After incubation at room temperature for 30 min, 5 µg of IgG or SRSF2 antibody was added to the RNA/nuclear protein mixture and incubated with rotation at room temperature for 1 h. A total of 50 µL of magnet beads was added to each of the RNA/nuclear protein/antibody mixture for incubation at 4 °C overnight. The immunoprecipitated protein/RNA complexes were then washed with RIP wash buffer five times, then resuspended in 100 μL of RIP buffer. The suspension was subjected to proteinase K/10%SDS digestion in total volume of 150 μL, and RNA was then purified for RT-PCR assays. The primer sequences used for the PCR reactions were listed in PIK3CD were differentially expressed between AA PCa and EA PCa patient specimens [PIK3CD-L (encoding full-length PI3Kδ) and PIK3CD-S , a TMA containing AA and EA PCa specimens and a panel of AA and EA PCa cell lines were subjected to IHC and Western blot assays. Specifically, an antibody specifically designed for detecting the PI3Kδ-S isoform was used in the IHC staining procedure. The TMA used for the IHC contains tumor and adjacent normal tissues derived from 40–50 EA and AA PCa patients and normal tissues derived from 3 EA and 3 AA healthy individuals. The IHC staining results have shown that AA PCa expressed a significantly higher PI3Kδ-S level than EA PCa. Moreover, the PI3Kδ-S is upregulated in AA PCa vs. AA adjacent normal  expressed the highest level of the PIK3CD-S splice transcript compared to all other PCa cell lines. In contrast, the EA PCa cell line LNCaP (an androgen-dependent PCa derived from lymph node metastasis) predominately expressed the PIK3CD-L transcript. The other two androgen-independent EA PCa cell lines, 22Rv1 and PC-3, expressed both PIK3CD-L and PIK3CD-S. The AA PCa cell line RC77 T/E (derived from a primary tumor) expressed very low levels of the PIK3CD-L and PIK3CD-S transcripts. The PIK3CD-S/PIK3CD-L ratios (S/L ratios) of the 22Rv1, LNCaP, PC-3, RC77 T/E, and MDA PCa 2b were 1.03, 0.16, 0.82, 0.57, and 3.28, respectively  vs. metastatic EA PCa  and AA primary PCa RC77 T/E  with high selectivity and potency, Wortmannin is a pan-PI3K inhibitor that targets PI3Kα, β, δ, and γ, while Dactolisib is a dual inhibitor simultaneously targeting PI3K and mTOR [Our previous study suggested that the PI3Kδ-S isoform may have more oncogenic properties than the full-length PI3Kδ-L . To asseand mTOR ,27,28,2950 values of Idelalisib, Seletalisib, Wortmannin, and Dactolisib were 1.1 μM, 15.7 μM, 36.2 μM, and 9.2 μM for 22Rv1; 8.2 μM, 3.7 μM, 0.4 μM, and 0.2 μM for LNCaP; 80.2 μM, 85.5 μM, 46.5 μM, and 0.2 μM for PC-3; 17.2 μM 176.7 μM, 121.3 μM, and 16.4 μM for RC77 T/E; and 123.2 μM, 53.1 μM, 1.4 μM, and 35.9 μM for MDA PCa 2b, respectively  than the EA PCa cell lines.We first observed that the drugs Idelalisib, Seletalisib, Wortmannin, and Dactolisib potently impaired the viability of the 22Rv1, LNCaP, and PC-3 (EA PCa) cells lines and the RC77 T/E and MDA PCa 2b (AA PCa) cell lines in a dose-dependent manner A. The ICectively . OverallPIK3CD-S, which is highly expressed in MDA PCa 2b, may represent a more oncogenic/drug-resistant splice variant compared to the PIK3CD-L. To further verify this hypothesis, the LNCaP and MDA PCa 2b cells expressing the differential PIK3CD-L or PIK3CD-S were treated with pan-PI3K and PI3Kδ-specific drugs to examine the drug efficacies against these PCa cells with distinct PIK3CD-L and PIK3CD-S expression profiles. Specifically, the LNCaP cells were first transfected with pcDNA3.1-PIK3CD-L-V5-HIS or pcDNA3.1-PIK3CD-S-V5-HIS plasmid for 16 h, and then the cells were treated with four small-molecule inhibitors  for an additional 48 h. The MDA PCa 2b cells stably expressing PIK3CD-L or PIK3CD-S .Based on the MTT results from PIK3CD-S  were grockground B. The ICPIK3CD-L- vs. PIK3CD-S-expressing PCa cells. As shown in PIK3CD-L-expressing LNCaP and MDA PCa 2b cells have exhibited an overall significantly higher cell apoptosis activity in response to the inhibitors, when compared to the PIK3CD-S-expressing LNCaP  and MDA PCa 2b cells   A. Moreovectively A. These PI3KCD-L and PI3KCD-S affect the cell invasiveness in PCa. First, the PIK3CD-L- and PIK3CD-S-expressing LNCaP and MDA PCa 2b were treated with the same four drugs, followed by matrigel invasion assays. As anticipated, the four drugs exerted intermediate (35–55%) and potent (>80%) inhibitory effects on the PIK3CD-L-expressing LNCaP cells at 1 µM and 25 µM, respectively. In contrast, the four drugs exerted slight/intermediate (10–35%) and intermediate (20–45%) inhibitory effects on the PIK3CD-S-expressing LNCaP cells at 1 µM and 25 µM, respectively  by Wortmannin and Dactolisib at 1 µM (PIK3CD-L-expressing MDA PCa 2b cells were moderately to significantly inhibited (20–90%) by all the drugs at 25 µM  the MDA PCa 2b cells (endogenously expressing a higher PIK3CD-S level) have shown a generally higher resistance to the drug-mediated invasiveness inhibition, compared to the LNCaP cells . Taken all together, the cell apoptosis and invasion assay results have strongly suggested that the overexpression of the PIK3CD-S splice variant results in more oncogenic activities with enhanced antiapoptotic and invasive capacities.Next, we performed cell invasion assays to assess how PIK3CD-L and PIK3CD-S were grown and treated with four drugs  at 0, 1, 10, and 25 µM. After the drug treatments for 48 h, the cells were harvested for the cell lysate preparation and then subjected to a Western blot analysis. First, the PI3Kδ-L and PI3K-S expression levels in the WT, PIK3CD-L-, and PIK3CD-S-expressing cells are shown in PIK3CD-L- and PIK3CD-S-expressing cells, while significantly higher than the WT cells. Second, a generalized reduction in the pAKT, pmTOR, and pS6  was observed in the PIK3CD-L-expressing cells (but not in the PIK3CD-S-expressing cells) under the Idelalisib and Seletalisib treatments  MDA PCa 2b and the MDA PCa 2b cells stably expressing eatments A,B. In ttrations C. As antng cells D. These Previous studies have shown that PI3Kδ is highly sensitive in responding to Idelalisib, Seletalisib, Wortmannin, and Dactolisib ,27,28,29To further investigate the binding affinities of small-molecule inhibitors with the PI3Kδ-L or PI3Kδ-S, molecular docking modeling was performed using Autodock 4.2.6 . First, PIK3CD-L- and PIK3CD-S-expressing plasmids, and the His-tagged PI3Kδ-L and His-tagged PI3Kδ-S proteins were purified by using Ni-NTA spin columns  were found upregulated in AA PCa vs. EA PCa  were upregulated in the AA vs. EA PCa specimens  by using the SFmap program [PIK3CD-S. To validate this hypothesis, we conducted RNA pulldown and RIP/RT-PCR assays. First, an RNA fragment containing two SRSF2 and one HNRNPF-binding motifs in intron 19  for 48 h, followed by an MTT assay to evaluate the cell viabilities. The MTT assay results have shown that the drug inhibits (from neglected to 30% for the four drugs) the cell viability in a dose-dependent manner. SRPIN340, as a single agent, exerts a moderate inhibitory capacity (~20% decrease in cell viability). However, combining the PI3K/PI3Kδ inhibitor with SRPIN340 resulted in an additive inhibitory effect with a significantly enhanced cytotoxicity (40–50% decrease in cell viability) in the PIK3CD-S-expressing MDA PCa 2b cells  and non-genetic  mechanisms, the aberrant splicing of PIK3CD likely functions as another genetic driver for developing Idelalisib resistance. In cancers, accumulating evidence has highlighted aberrant mRNA splicing as a critical mechanism driving drug resistance. For instance, the aberrant mRNA splicing of BCR-ABL, BIM, IKZF1, BRCA1, TP53, BRAF V600E, CD19, ERG, ERα, and AR pre-mRNAs leads to the resistance of imatinib, the tyrosine kinase inhibitor (TKI), imatinib, the PARP inhibitor, cisplatin, vemurafenib, CART-19, taxanes, tamoxifen, and enzalutamide, respectively [PIK3CD may represent a novel genetic mechanism driving the resistance to Idelalisib. Aberrant mRNA splicing within the PIK3CD pre-mRNA results in a short splice variant, PIK3CD-S, in which the exon 20 is skipped. This PIK3CD-S splice variant encodes PI3Kδ-S, an in-frame 104 kDa protein isoform lacking the hinge and the majority of the hydrophobic region in its catalytic domain. Our in silico molecular docking modeling has shown that the PI3Kδ-selective and pan-PI3K inhibitors perfectly dock in the ATP-binding pocket of the PI3Kδ-L catalytic domain, and the predicted drug-binding modes are consistent with the previous crystallization and molecular docking studies [PIK3CD-S and PIK3CD-L expression profiles in CLL and NHL patients may facilitate our understanding of the mechanisms conferring Idelalisib resistance (other than the IGF1R- and MAP2K1 mutation-mediated MAPK/ERK activation).Besides the genetic  interact with PI3Kδ through contacting a core set of six active site residues  in the ATP-binding pocket. The co-crystallization of PI3Kδ and Idelalisib/IC87114/PIK-39 demonstrated that the inhibitor binding induces an opening of a hydrophobic pocket in the PI3Kδ catalytic domain with high affinity ,50. NotaPIK3CD pre-mRNA. Targeting SRSF2, theoretically, could reverse the aberrant splicing and suppress the synthesis of PIK3CD-S. Indeed, a combination of the inhibition of SRSF2 by SRPIN340 sensitizes the resistant PCa cells to PI3Kδ and PI3K inhibitors (PIK3CD-S variant, which encodes a splice isoform conferring drug resistance.Targeting splicing machinery has been proposed as a promising approach in treating cancers with aberrant splice variants. SRPIN340 and SRPIN-1 have been shown to effectively target SRPK1/2, which leads to inhibiting the phosphorylation of SR proteins ,20,51. Ihibitors D. This nPIK3CD-S/PIK3CD-L profiles in a panel of PCa patients and cell lines, evaluate the functional impacts of PIK3CD-L and PIK3CD-S in PCa invasiveness/apoptosis, perform the molecular docking of drugs with PI3Kδ-L and PI3Kδ-S, validate the physical interaction of the ATP/drug with PI3Kδ-L and PI3Kδ-S, identify the SRSF2-mediated splicing mechanism for PIK3CD-S synthesis, and develop a novel synergistic drug therapy to overcome the Idelalisib resistance in AA PCa.To date, this is the first comprehensive study to validate the PIK3CD-S.In conclusion, a deep understanding of splicing-driven drug resistance mechanisms, a novel synergistic strategy combining PI3K and SRPK1/2 inhibitors, and further screening/designing novel compounds targeting PI3Kδ-S may pave a new path for precision medicine for resistant AA PCa and other hematologic/non-hematologic tumors overexpressing


Procalcitonin increases in bacterial infections, which are often suspected (though rarely confirmed) in paediatric influenza. We retrospectively verified procalcitonin’s usefulness in antibiotic guidance in children hospitalized due to laboratory-confirmed influenza. The ROC curve analysis evaluated procalcitonin’s performance in terms of antibiotic implementation or continuation in patients who were naive or had been receiving antibiotic treatment prior to hospital admission. We also assessed the procalcitonin’s usefulness to predict lower-respiratory-tract infections (LRTI), the presence of radiologically confirmed pneumonia, an intensive care unit transfer and a fatal outcome. Multiple regression models were built to verify the previously reported procalcitonin cut-off values. The study enrolled 371 children (median age 33 months). The AUC (area under the curve) for antibiotic implementation reached 0.66 (95%CI: 0.58–0.73) and 0.713 (95%CI: 0.6–0.83) for antibiotic continuation; optimal cut-offs  resulted in a negative predictive value (NPV) of 79.7% (95%CI: 76.2–82.9%) and 54.6% (95%CI: 45.8–63%), respectively. The use of 0.25 ng/mL as a reference decreased the odds of antibiotic treatment by 67% (95%CI: 43–81%) and 91% (95%CI: 56–98%), respectively. Procalcitonin showed lower AUC for the prediction of LRTI and pneumonia , with a moderately high NPV in the latter case . Procalcitonin use may decrease the antibiotic frequency in hospitalized influenza cases both in terms of antibiotic administration and continuation. Procalcitonin concentrations may suggest bacterial suprainfections at lower concentrations than in adults, and a focus on its rule-out value is of special interest.  Influenza is highly contagious disease, and the estimates of influenza attack rate in children vary between 8.7%  and 15.2The true frequency of bacterial coinfections remains unknown; a confirmation of bacterial presence (with a culture or a molecular assay) in a sample from a sterile site lacks sensitivity, while other diagnostic methods  lack specificity . The useProcalcitonin (PCT) is a precursor of calcitonin, and its concentrations increase mainly in bacterial infections, when cytokines mediate an inflammatory response ,13. At tThe study had a retrospective design and included patients hospitalized at the Department of Paediatrics, Bielanski Hospital, Warsaw, Poland, in the period between January 2013 and December 2019 (7 consecutive years). Due to its retrospective character, the patients’, as well as the parents’/tutors’, consent was waived.Electronical medical charts of hospitalized patients were retrospectively reviewed, and patients diagnosed with influenza were eligible for the study. The inclusion criteria consisted of the ICD-10  codes of J10 (+extensions)—influenza due to an identified virus, and in the case of all patients diagnosed with ICD-10 code J11 (+extensions), influenza due to an unidentified virus. The medical charts were revised in search of an existing influenza confirmation, as a bias related to the ICD coding might have taken place.We enrolled only laboratory-confirmed cases of influenza, and the presence of an aetiological factor was proved either with the use of a rapid influenza diagnostic test (RIDT) or a reverse transcription–polymerase chain reaction (RT-PCR), with the latter being the reference method. Both RIDT and RT-PCR were performed on nasopharyngeal swabs taken immediately at hospital admission; in order to exclude a nosocomial origin of the infection, a time limit for the first signs/symptoms’ presentation was set as within the first 48 hours after admission. We did not include children younger than 30 days. Patients were excluded if they had immune deficiency , diabetes, proliferative disease or a history of a proliferative disease, cystic fibrosis, haemodynamically significant heart disease, burn or a history of a recent burn ; the exclusion criteria also contained a lack of full knowledge on the disease course .Demographical, laboratory and clinical characteristics were collected, including age and gender; duration of signs/symptoms prior to hospitalization, duration of fever prior to hospitalization and antibacterial therapy prior to hospitalization; breath rate and heart rate at hospital admission; C-reactive protein (CRP), procalcitonin, white blood cell count (WBC) and absolute neutrophil count (ANC) at admission and blood cultures taken ; length of hospital stay (LOS), data on rehospitalization or a consultation in the emergency department of the Bielanski Hospital within a month after the discharge (including the treatment performed), need for intensive care unit (ICU) transfer and a fatal outcome.Blood analysis was performed immediately after hospital admission, and only patients who had their procalcitonin level measured were included in the study. Procalcitonin concentrations were measured with the use of the Cobas e411 (until 4 August 2016), and the Cobas 6000 (from 5 August 2016) analysers . All procedures were performed according to the manufacturer’s instructions.Based on a history of their recent antibacterial therapy, patients were assigned into two groups: children who had not received antibacterial therapy within 14 days prior to hospital admission created the No-PAT (no prior antibiotic therapy) group, while children who had had a recent history or were on ongoing antibacterial therapy were assigned to the PAT (prior antibiotic therapy) group.The study endpoints included the following: 1. the use of antibacterials, 2. positive blood culture, 3. ICU transfer, 4. fatal outcome, 5. lower-respiratory-tract involvement and 6. radiologically confirmed pneumonia.In the No-PAT group, the patients were divided into two subgroups based on the treatment they received during the hospitalization (antibiotic versus no antibiotic group). In the PAT group, we compared patients who had antibiotic continued (or another antibiotic was implemented) against those who had the antibiotic discontinued.a. If a child did not receive antibiotics during the hospitalization, an improvement was observed, the patient was discharged and was not readmitted within a month due to influenza complications that would require antibiotic treatment, the treatment was considered successful, and the diagnosis of a sole influenza was a correct one. In theory, although with low probability, a minor bacterial coinfection without clinical effects could have taken place.b. If a patient received antibiotics during the hospitalization, irrespectively of the indications , the benefits of antibacterial therapy could not be excluded. No analysis on particular indications for antibiotic treatment was performed.All children who had not received antibiotics during hospitalization but were later rehospitalized or consulted at the emergency department of the Bielanski Hospital, at which time an antibiotic treatment was implemented, were considered to have received unsuccessful treatment and were assigned to the group who might have benefited from antibiotic therapy during the initial hospitalization.With regard to the rest of the endpoints , the analysis was performed in the whole study group, and no protective effect of prior antibiotic therapy was assumed. Lower-respiratory-tract involvement was defined upon a final diagnosis according to the ICD-10 codes: J10.0 for influenza and pneumonia, J12 to J18 (+extensions) for pneumonia, J20 (+extensions) for bronchitis, J21 (+extensions) for bronchiolitis and J22 for unspecified lower-respiratory-tract infection; the diagnosis was made by a treating physician.Radiologically confirmed pneumonia was defined as the presence of radiological abnormalities consistent with pneumonia .t test) or non-parametric test (Mann–Whitney U test) was used to compare the groups, and Fisher’s exact test was used for frequency comparison. A receiver-operating curve (ROC) analysis was performed for calculations of the optimal procalcitonin cut-off value, for which sensitivity, specificity and positive and negative predictive value  were established. A multiple regression model was created in order to estimate the odds ratios (ORs) with 95% confidence intervals (95%CI) for categorical variables. The LOS was transformed from a continuous into a categorical variable upon the median value. A decrease in antibiotic treatment odds in children with procalcitonin lower than the cut-off values was calculated by subtracting 1 from the odds ratio of receiving antibiotic (No-PAT group) or from the odds ratio of antibiotic continuation (PAT group). Since different optimal cut-off values might have been expected in the ROC analysis, in order to facilitate comparisons, we verified the decrease in the odds of antibiotic treatment only for the previously assumed (based on the literature search) cut-off values of 0.25, 0.5 and 1 ng/mL. The p values under 0.05 were considered to present a statistical significance. The analysis was performed with Statistica 13.1 software . Confidence intervals for sensitivity, specificity, PPV and NPV were calculated with the use of a diagnostic test evaluation calculator available at https://www.medcalc.org/calc/diagnostic_test.php (10 February 2021).The Kolmogorov–Smirnov test was employed to assess the data distribution, and continuous data were presented as a mean and a standard deviation or a median and an interquartile range, according to the distribution. A corresponding parametric .In total, 415 children were hospitalized due to LCI in the period of 2013–2019, and PCT levels were measured in 383 (92.3%) children, including 12 newborns. The final study group consisted of 371 patients, including 291 patients (median age 33 months) without previous antibacterial therapy (No-PAT group) and 80 children (median age 34 months) on an ongoing (71 patients) antibiotic therapy or with a recent history (9 patients) of antibiotic therapy (PAT group) . There wStaphylococcus hominis, and single cases of Staphylococcus epidermidis, Streptococcus mitis/oralis, Micrococcus luteus, and Micrococcus sp. A final diagnosis of a generalized bacterial infection was made only in one patient (where St. hominis was found in the blood), while the other cases were verified and identifies as a sample contamination, including two cases (St. hominis and Micrococcus sp.) where a generalized infection was judged to be extremely unlikely, and antibiotics were not started after the initial alert information on a positive blood culture from the microbiological laboratory. One patient (0.3%) required an ICU transfer because of respiratory failure. There were no fatal cases.Blood cultures were taken in 320 patients (86.3%) and showed a bacterial growth in seven cases (2.2%), with three cases of p < 0.01), including a longer period of fever , and required longer LOS . Antibiotics during hospitalization were administered more frequently in the PAT group  than in the No-PAT group , and the difference was statistically significant (Fisher’s exact test p < 0.05). In the whole study group, the antibiotic therapy frequency reached 35.9% (133 out of 371). No other significant differences between the PAT and the No-PAT groups, including the PCT concentrations, were observed  had been presenting signs/symptoms for a longer period of time  and had a higher breath rate and heart rate at admission , but did not differ with regards to the duration of signs/symptoms or fever. They also required longer LOS  and had higher PCT levels , as well as higher CRP  and WBC   .p < 0.01) with a negative predictive value of NPV = 79.73% (95%CI: 76.18% to 82.87%). An optimal cut-off was calculated at 0.4 ng/mL and showed a sensitivity of 46.43% (95%CI: 35.47% to 57.65%), and a specificity of 85.51% (95%CI: 79.96% to 90.00%), with a PPV = 56.52% (95%CI: 46.49% to 66.04%). At the three other cut-offs reported most commonly in other studies on PCT , the NPV reached 80.23% (95%CI: 75.61% to 84.15%), 77.54% (95%CI: 74.43% to 80.38%) and 76.15% (95%CI: 73.70% to 78.45%), respectively , with a sensitivity of 54.55% (95%CI: 38.85% to 69.61%), specificity of 88.89% (95%CI: 70.84% to 97.65%), PPV 88.89% (95%CI: 72.69% to 96.01%) and an NPV of 54.55% (95%CI: 45.82% to 63.00%) at the optimal cut-off value established at 0.23 ng/mL. The NPV reached 53.33% (95%CI: 44.94% to 61.55%), 44.83% (95%CI: 40.06% to 49.70%) and 42.86% (95%CI: 39.48% to 46.30%) at 0.25, 0.5 and 1 ng/mL, respectively.In children who had previously received antibiotics (PAT group), the AUC for antibiotic continuation was 0.713  in those who had PCT lower than 0.25 ng/mL, while in children with an ongoing antibiotic therapy , lower PCT values were related to a 91% decrease in the odds of antibiotic continuation . A verification of other PCT cut-off values revealed a 78% and 88% decrease in the odds of antibiotic therapy in the No-PAT group . In the PAT group, there was an 88% decrease in the odds of antibiotic treatment at 0.5 ng/mL, while all patients with PCT 1 ng/mL received antibacterial treatment , and the cut-off concentration 0.27 ng/mL had a sensitivity of 49.21% (95%CI: 40.19% to 58.26%), a specificity of 72.24% (95%CI: 66.19% to 77.76%), PPV 47.69% (95%CI: 41.07% to 54.40%) and the NPV of 73.44% (95%CI: 69.61% to 76.96%). For radiologically confirmed pneumonia, the AUC was 0.626 , and a cut-off 0.27 ng/mL showed a sensitivity of 55.43% (95%CI: 44.70% to 65.81%), a specificity of 71.68% (95%CI: 66.01% to 76.89%), PPV 39.23% (95%CI: 33.20% to 45.61%) and NPV 82.99% (95%CI: 79.33% to 86.11%) (The area under the curve (AUC) for the prediction of LRTI was 0.6  .Our study shows that procalcitonin might be helpful in guiding antibiotic therapy in children with influenza, and special interest should be on the rule-out performance of procalcitonin levels. Attention might be focused on PCT as a predictor both of antibiotic implementation and of antibiotic withdrawal in children who were previously receiving antibacterial therapy.n = 84) was compared against a bacterial pneumonia group ; after excluding hospital-acquired cases and immunodeficient patients, and the PCT’s NPV was 0.822 (at a cut-off of 0.5 ng/mL), which is closer to our outcomes.The negative predictive value (NPV) of PCT regarding antibiotic implementation that was observed in our study is promising and reveals comparable, although slightly lower values than those reported in the previous studies . The study by Li and colleagues included 3180 children under five years of age, and PCT showed an NPV of 0.852  regarding a proven bacterial coinfection . Li et aThe AUC observed in our trial was lower  than the ones shown above; however, we can compare our results only to the studies that sought to confirm, not exclude, a bacterial infection. This may be related to the risk of unnecessary treatment in patients without a (proven) bacterial coinfection in our group of patients; on the other hand, a study protocol that focuses on confirmed bacterial infections only, may easily miss non-septic patients who need antibiotic treatment. Thus, we chose a negative predictive value model, following the one used by Stockmann and colleagues for antibiotic guidance in children with pneumonia, a disease that meets a similar problem with its aetiology confirmation . In pneuIn the aforementioned study by Li, a bacterial coinfection was found in 7.1% of hospitalized cases , while ap < 0.01). Adult studies revealed an even stronger diversity , but this might be attributable to the factors mentioned above, mainly concerning the group selection [It needs to be emphasized that there are many potential factors affecting comparisons between the studies, including various study settings or age groups. Nevertheless, procalcitonin levels differ between the coinfected and sole influenza cases. The study by Li et al. showed that PCT was significantly higher in children with a proven bacterial coinfection (1.46 versus 0.21 ng/mL) , while telection ,18,19,20n = 23) had a higher median value of PCT than did other viral pneumonia patients  [There are discrepancies regarding the cut-off values of PCT also. In our study, the cut-off for antibiotic implementation set at 0.4 ng/mL proved to best fit the model (according to the Youden index) and is lower than the cut-off in the study by Li (cut-off = 0.52 ng/mL), but different study protocols were used here. Higher cut-offs, which varied between 0.8  to 1.5 n13–2.51) . Moreove13–2.51) .Obviously, PCT is not a golden standard for the purpose of aetiology identification, since, even in the course of influenza, its increase does not need to be unequivocally related to a bacterial coinfection—it may also be related to other conditions, such as renal insufficiency . A viralPCT’s ability to distinguish patients with lower-respiratory-tract involvement was lower (AUC = 0.6) with a moderate NPV (=0.73), yet it is in line with the research by Leng, who included 551 adults with a bloodstream infection and found no differences in PCT concentrations the between upper- and lower-respiratory-tract involvement . SlightlThere are some limitations to this study that need to be addressed. Firstly, this study has a retrospective design, and no PCT-based protocol was used, but in this respect, any prospective experimental trials need to be based on solid foundations from observational studies. Due to the retrospective character, the study itself did not influence the clinical decisions, which were made at the physicians’ discretion only. Secondly, we performed a single-centre study, and multicentre large analyses are necessary, as the group size in our research opens the possibility for more detailed research. Thirdly, we confirmed only one particular bacterial suprainfection, probably mainly due to the low sensitivity of the methods that are currently available; however, a group selection bias cannot be excluded, although we focused on hospitalized patients only. Last but not least, because of practical implications, we deliberately treated influenza as a homogenous disease, which is an obvious simplification. There are (mainly minor) differences not only between the types but also within the subtypes or lineages; however, this was not the focus of the study, since diagnostic methods that can facilitate a determination of the influenza subtypes/lineages are not routinely available to the vast majority of physicians, even in hospital settings.To conclude, we found procalcitonin to be a useful tool in antibiotic guidance, although, it should be mainly considered as a rule-out, but not a rule-in, test. It should also be emphasized that, in children, procalcitonin may be suggestive of a bacterial suprainfection at lower values than in adults. The implementation of PCT-based protocols might substantially decrease the use of antibiotics in children with influenza.


Taiwan has used technology in reservoir sediments and industrial waste to produce high-performance lightweight aggregate (LWA). LWA can be used to manufacture lightweight aggregate concrete (LWAC) with structural strength ratings. At present, Taiwan’s offshore wind turbines are gradually developing and are moving from coastal areas to deep-sea areas. With this in mind, this study aimed to investigate the feasibility of applying LWAC with synthetic LWA from reservoir sediments to floating offshore wind turbine foundations. LWAC and normal-weight concretes (NWC) of different strengths were prepared, and their fresh, hardened, and durability properties were tested. In addition, reinforced concrete and steel sheets were immersed in a tank of high salinity seawater to examine their resistance to seawater-accelerated corrosion. The test results showed that the total passing charge of the two groups of concrete within six hours was less than 1000 coulombs. Both groups of concrete were classified as having “Very Low” chloride permeability. The average corrosion potential of most reinforced concrete specimens was found to be greater than −200 mV, which means that the corrosion probability of the steel bars was less than 10%. Furthermore, the use of coatings for seawater corrosion protection on steel sheets was not found to be as effective as reinforced concrete. This shows that the use of LWAC with synthetic LWA from reservoir sediments for the floating foundations of offshore wind turbines is feasible and has design flexibility. In the past twenty years, the development of renewable energy and green energy has become an international focus and trend . Offshor−, SO42−, and Mg2+, which can cause the corrosion of concrete structures [− and SO42− have the most serious influences on reinforced concrete. For reinforced concrete structures completely immersed in seawater, the corrosion of sea salt to concrete is mainly a chemical reaction that dissolves calcium hydroxide in the concrete and forms expansive ettringite. This leads to deterioration phenomena such as the swelling, cracking, and spalling of the structure. In addition, the sea level changes with the tide and the alternation of wet and dry periods caused by the change in the sea level will significantly accelerate the deterioration of concrete structures. This behavior is a combination of physical erosion and chemical corrosion. For example, tidal actions can produce waves of different wavelengths and wave heights, which can cause physical impact erosion damage to concrete structures. As for chemical corrosion damage, after salt penetrates the concrete, the crystallization pressure caused by the dry–wet cycle causes the concrete to crack [General floating offshore wind turbine foundations are mostly designed with reinforced concrete . Howeverructures . Among tto crack . This leSeawater salinity is generally defined as the salt concentration  in seawater . It is m−, SO42−, Mg2+) on the tensile and compressive strength values of concrete. The quantitative results showed that, during the 600-day corrosion process, the addition of Cl− could weaken the corrosive effect of SO42− by about 20%, while the addition of Mg2+ or Mg2+ and Cl− could strengthen it by 10–20%.Poupard et al.  conducteThe pH of seawater varies between 7.4 and 8.4 . In the The unit weight of lightweight aggregate concrete (LWAC) prepared by utilizing the low-density characteristics of lightweight aggregate (LWA) is lower than that of general concrete. In the early days, LWAC was only used for non-structural applications due to its low compressive strength. However, with the improvement of the properties of artificial LWAs, the compressive strength of LWAC has been significantly improved, and it has been widely used in structural applications. For example, many large marine structures have gradually used reinforced lightweight aggregate concrete. Under the special conditions of seawater corrosion, the use of reinforced lightweight concrete not only reduces the overall weight of the structure but also effectively reduces the permeability of chloride ions and improves the durability of the structure. Thomas and Bremner  reportedFor nearly two decades, Taiwan has developed techniques to use reservoir sediments and industrial waste to manufacture LWAs with excellent performance ,31,32,33In this study, two groups of concrete were prepared, with lightweight aggregate concrete (LWAC) as the experimental group and normal-weight aggregate concrete (NWC) as the control group. The experimental program used for the two groups of concrete is shown in 2 content was between 86% and 92%. The superplasticizer met the ASTM C494-81 Type F requirements and was a product of Taiwan Sika Corporation (R-550). The fine aggregate was natural sand with a specific gravity of 2.65 and a fineness modulus of 2.8. The coarse aggregate was natural crushed stone with a particle size of about 5 to 10 mm and a specific gravity of 2.65. The lightweight aggregate was an artificial lightweight aggregate, as shown in The materials used in this study included cement, ground-granulated blast-furnace slag, silica fume, water, superplasticizer, fine aggregate, coarse aggregate, lightweight aggregate, rebar, and steel sheets. The cement was Portland Type I ordinary cement produced by Taiwan Cement, and its specific gravity was 3.15. The slag was purchased from Jinyu Enterprise, and its specific gravity was 2.8. The specific gravity of the silica fume was 2.2, and its SiOIn the concrete mix design, the experimental group and the control group were each formulated with three different compressive strength grades to explore their resistance to seawater corrosion. In order to increase the compactness of the two groups of concrete, part of the cement was replaced with silica fume and slag in each concrete mixture, and the replacement amounts were 8% and 15% of the cement weight, respectively. At the same compressive strength, because the strength of the LWA was lower than that of the natural aggregate, the water–binder ratio of the experimental group was lower than that of the control group. Based on the above scheme, the concrete mix proportions of the experimental group and the control group are shown in Due to the high-water absorption of LWAs, pre-wetting was performed one day before mixing. The prewetted LWAs were taken out and drained two hours before mixing to allow them to reach a saturated surface-dry condition. The natural fine aggregates and coarse aggregates were wetted by sprinkling water and mixed evenly until a saturated surface-dry condition was attained. During the mixing operation, cement, slag, silica fume, and natural sand were first put into a forced single-shaft mixer and mixed for 30 s to achieve uniform mixing. Next, the water (evenly mixed with the superplasticizer) was poured into the mixing cylinder and mixed for 60 to 90 s to make a uniform cement mortar. Then, the light aggregate or coarse aggregate was poured into the mixing cylinder and mixed for about 90 to 120 s to produce uniform fresh concrete. After the mixing had been completed, part of the concrete slurry was taken and used for the slump, chloride ion content, air content, and other tests, and the rest of the concrete slurry was used to cast the specimens for various tests. The size and quantity of the specimens are shown in A cylindrical specimen with a diameter of 10 cm and a height of 20 cm was cast in two layers, while a cylindrical specimen with a diameter of 15 cm and a height of 30 cm was divided into three layers. Each layer was tamped with a tamper and tapped with a rubber mallet to fully compact the specimens. For the specimen used in the steel corrosion potential test, the rebar was fixed in the center of the cylindrical specimen mold with iron wire, 4 cm away from the bottom of the mold, as shown in After the specimens in each group had completed 28 days of curing, mechanical, durability, and seawater accelerated corrosion tests were carried out. The methods used for each test are described below.Twenty-four hours before the planned compressive test duration, the specimens were taken out of the curing tank or the seawater test tank. In order to reduce the test error, the compression surface of the specimens was ground to a flat surface with a concrete grinder. After grinding, the specimen was allowed to stand for 24 h to allow it to reach an air-dry state. In accordance with the ASTM C39 specification , the cylIn accordance with the ASTM C469 specification , the cylSpecimens that were about to reach the 28-day curing age were taken out of the curing water tank 24 h in advance. Both sides of the cylindrical specimen were ground to a flat surface with a concrete grinder. The purpose of this was to ensure that the contact surface between the ultrasonic tester and the concrete specimen was tightly connected, thereby reducing errors. After grinding, the specimens were allowed to stand for 24 h to reach an air-dry state. The instrument wave velocity was calibrated with a calibration rod according to the ASTM C597 specification . During The chloride ion penetration test was performed in accordance with the ASTM C1543 . After 2The electrical indication of concrete’s ability to resist the chloride ion penetration test was carried out in accordance with the ASTM C1202-19 specification . After 2Generally, the normal range of seawater salinity is from 33‰ to 37‰. In order to carry out an effective test in a short period of time, it is often used to increase the concentration of the solution to accelerate the corrosion. In this study, a high-salinity seawater solution with a temperature of 60 degrees Celsius was designed. This makes various compounds in the high-concentration seawater fully soluble to ensure that the seawater has a high content of water-soluble chloride ions. In accordance with the ASTM D1141-98 specification [After 28 days of curing, the specimens were immersed in a seawater tank with 10 times the salinity of seawater. After being immersed for the planned durations , the specimens were taken out for various tests. The compression test on the cylindrical specimens after immersion in the seawater tank was carried out according to the ASTM C39 specification . There wThe test method used to assess the corrosion potential of uncoated reinforced steel in concrete was performed in accordance with ASTM C876 . After t3. In terms of the unit weight, the difference between the two groups of concretes could be clearly seen. The fresh unit weights of the L1, L2, and L3 mixtures were 1998, 2007, and 2122 kg/m3, respectively, while those of the N1, N2, and N3 mixtures were 2391, 2397, and 2402 kg/cm3, respectively. The average fresh unit weight of the experimental group was 15% lower than that of the control group. This shows that the lightweight aggregates used could effectively reduce the unit weight of concrete.The compressive strength, elastic modulus, and air-dry unit weight of the two groups of concrete are shown in The ultrasonic pulse velocity test was carried out on the cylindrical specimens that had been cured for 28 days. Two specimens were taken from each concrete mixture for measurement. The test results are shown in Because the LWA had a higher porosity compared with the natural aggregates, the pulse velocity of the experimental group was lower than that of the control group. In addition, with an increase in the amount of the LWA, the pulse speed of the experimental group decreased. This is consistent with the findings of Satpathy et al. . The ultThe test results of the acid-soluble chloride ion concentration in the two groups of concrete samples are shown in 3) at the depth of 7.5 mm of the specimen, it was significantly reduced to 0.28 kg/m3 at the depth of 22.5 mm, and it dropped to 0.11 kg/m3 at depths of both 37.5 mm and 52.5 mm, as shown in With the change in the sampling depth, the changing trends in the chloride ion content of each concrete mixture were roughly the same. The chloride ion concentration measured at 22.5 mm for all specimens was significantly reduced compared to that at 7.5 mm. The trace chloride ions measured at 37.5 mm and 52.5 mm could be regarded as chloride ions contained in the concrete itself. Taking the L1 mixture as an example, the chloride ion content was the highest  and pore structure were observed by scanning electron microscopy. Because the 28-day compressive strengths of the L3 and N2 mixtures were similar , samples were taken from the compressive test pieces after the seawater corrosion of these two mixtures for SEM observation. Compared with the control group, the water in the LWA in the concrete of the experimental group contributed to internal curing, resulting in a higher degree of cement hydration ,49. In pAn SEM photo of the sample magnified 20,000 times is shown in The average steel corrosion potentials of the specimens in each group after being immersed in the seawater tank for different durations are shown in The corrosion potentials of the two groups of specimens showed a downward trend with an increase in the water–binder ratio. Overall, the corrosion potential of a given specimen did not change significantly after different immersion durations, as shown in The coating film thickness of the steel sheet used in the accelerated corrosion test is shown in On the 11th day of the test, the surface layer of the uncoated steel sheet was found to have obvious rust, peeling, and damage, as shown in On the 40th day, granular protrusions were found on the surface of the fluorocarbon-baked steel sheet, as shown in Overall, the use of coatings for seawater corrosion protection on steel is not as effective as using reinforced concrete. Taking electro-galvanizing as an example, not only is the coating damaged, but the internal steel is also corroded, and the corrosion spreads. Taking hot-dip galvanizing as an example, although only the surface of the steel is damaged, the large amount of zinc oxide powder produced may have an impact on the environment. Furthermore, the appearance is relatively unsightly. In contrast, using concrete as the protective layer of steel means that there is no need to worry about seawater corrosion and other related issues.The corrosion potential of steel bars and the accelerated corrosion test results of steel sheets show that reinforced concrete provides better protection against the seawater corrosion of steel than the steel anti-corrosion coating treatments used in this study. For example, after the 180-day seawater accelerated corrosion test for each concrete mixture, the steel bars of all reinforced concrete specimens were not corroded. However, all steels with anti-corrosion coating were damaged after 90 days of accelerated corrosion testing. In particular, the steel sheet treated by electro-galvanizing had not only a destroyed coating but also inner steel corrosion. While the hot-dip galvanized steel sheet did not show corrosion of its internal steel, the coating produced a large amount of zinc oxide powder. If this material is used in marine structures, it may have a certain impact on the environment. In contrast, if reinforced concrete is used, this problem is insignificant.In marine structures, the differences between the use of lightweight aggregates and natural aggregates for reinforced concrete can be divided into physical properties and durability. The main physical properties are the concrete’s compressive strength and unit weight, because different designs have different target strengths. In the concrete mix design used in this study, although the compressive strength of the experimental group was lower than that of the control group, the strength of the L3 mixture reached 76.6 MPa. With a target strength of 70 MPa, using the L3 mixture and the N1 mixture, the compressive strength values reached 76.6 MPa and 70.2 MPa, respectively, meeting the requirements for use. In particular, the unit weight of the experimental group was reduced by 10% compared with that of the control group. In other words, for a given volume, foundations designed with LWAC have a greater buoyancy. In terms of durability, according to the chloride ion penetration test results, the salt crystals were only able to penetrate about 22.5 mm. The results of the rapid chloride permeability test show that, under the condition of a similar water–binder ratio, the ability of LWAC to resist charge intrusion was better than that of NWC. In the seawater accelerated corrosion test, when the compressive strength after 28 days of curing was used as the benchmark, the L1 mixture was the best after 180 days of accelerated corrosion, and the compressive strength ratio after 180 days of accelerated corrosion was 76%. The worst results were produced for the N3 mixture, which had a compressive strength ratio of 61%. In view of the above results, for a given compressive strength of concrete, the use of LWA can effectively reduce the unit weight. In terms of durability, the results of the experimental group were no worse, or were better, than those of the control group. Therefore, the use of LWAC for the floating foundations of offshore wind turbines is feasible and has design flexibility.This study explored the feasibility of applying LWAC with synthetic LWA from reservoir sediments to the foundations of floating offshore wind turbines. According to the above test results and analysis, the following conclusions were obtained.The ultrasonic velocity of the experimental group was between 4294 and 4550 m/s, and this value increased with a decrease in the water–binder ratio. The L1 and L2 mixtures were rated as being of “good” quality, and the L3 mixture was rated as being of “excellent” quality.The chloride ion concentration measured at 22.5 mm for all specimens was significantly reduced compared with that at 7.5 mm. Chloride ions at depths of greater than 22.5 mm were almost impermeable, which shows their excellent resistance to chloride ion penetration.The total charge passing through the two groups of concrete within six hours was less than 1000 coulombs. Both groups of concrete were classified as having “Very Low” chloride permeability.Compared with the accelerated corrosion test age of 28 days, the compressive strength of the accelerated corrosion test age of 90 days had a huge decrease of about 29–43%. However, the compressive strength of the specimens did not change significantly after being immersed in seawater for 180 days.The water in the LWA in the concrete of the experimental group contributed to the internal curing, resulting in a higher degree of cement hydration. The cement paste was firmly bonded to the porous LWA surface, and a portion of the hydration product filled the pores of the outer layer.The average corrosion potential of the L1 mixture immersed for 90 days was −237 mV, and the corresponding corrosion probability was between 10% and 90%. The average corrosion potential of the rest of the specimens was greater than −200 mV, and the corrosion probability was less than 10%. In addition, there was no sign of corrosion in its steel bars.The use of coatings for seawater corrosion protection on steel sheets is not as effective as the use of reinforced concrete. The use of LWAC for the floating foundations of offshore wind turbines is feasible and has design flexibility.