Researchers have been investigating the possibility of replacing cement with industrial waste in concrete production to reduce its environmental impact. Therefore, the focus of this paper is on the effective use of wheat straw ash (WSA) together with silica fume (SF) as a cement substitute to produce high-performance and sustainable concrete. Different binary and ternary mixes containing WSA and SF were investigated for their mechanical and microstructural properties and global warming potential (GWP). The current results indicated that the binary and ternary mixes containing, respectively, 20% WSA (WSA20) and 33% WSA together with 7% SF (WSA33SF7) exhibited higher strengths than that of control mix and other binary and ternary mixes. The comparative lower apparent porosity and water absorption values of WSA20 and WSA33SF7 among all mixes also validated the findings of their higher strength results. Moreover, SEM–EDS and FTIR analyses has revealed the presence of dense and compact microstructure, which are mostly caused by formation of high-density calcium silicate hydrate (C-S-H) and calcium hydroxide (C-H) phases in both blends. FTIR and TGA analyses also revealed a reduction in the portlandite phase in these mixes, causing densification of microstructures and pores. Additionally, N2 adsorption isotherm analysis demonstrates that the pore structure of these mixes has been densified as evidenced by a reduction in intruded volume and a rise in BET surface area. Furthermore, both mixes had lower CO2-eq intensity per MPa as compared to control, which indicates their significant impact on producing green concretes through their reduced GWPs. Thus, this research shows that WSA alone or its blend with SF can be considered as a source of revenue for the concrete industry for developing high-performance and sustainable concretes.Cement and concrete are among the major contributors to CO Worldwide, concrete production has significantly increased due to urbanization and urban development, reaching 25 billion tons per year . SubsequThese issues can be controlled by following the sustainability approach in the construction sector. One such approach is to replace cement with supplementary cementitious materials (SCMs) at the construction site or during cement manufacturing. Another approach is to conserve natural resources by replacing aggregates with alternate ecofriendly materials. Hence, the search for supplementary cementitious materials has resulted in the usage of industrial byproducts such as volcanic ash ,6, silicIn developing countries, agrowaste is one of the significant issues which arise from different food crops such as sugarcane, rice, and wheat. Wheat is one of the most important cereal crops and a major food source for around 2.5 billion people globally . The worBurned wheat straw produces ash, which is pozzolanic in nature. However, the pozzolanic efficiency of the WSA mainly depends on its source; therefore, its composition varies with regions primarily due to soil properties and climatic conditions . In addiResearch studies have highlighted the efficacy of the WSA both as filling and pozzolanic material in concrete and mortar. The addition of WSA in mortar increased the compressive and flexural strength . MoreoveThe binary and ternary blends of various agroindustrial wastes have increased its pozzolanic activity. Among many, SF is widely used component of ternary blends to enhance mechanical as well as durability performance of concrete. Generally, SF is obtained as a byproduct during the production of silicon and ferrosilicon alloys at a very high temperature around 2000 °C in an electric furnace arc . Oxygen 2) adsorption isotherm analysis. At the end, the global warming potential (GWP) of all the concrete mixes was calculated in kg CO2-equivalent per unit concrete and kg CO2-equivalent per unit concrete/MPa by using the green concrete lifecycle assessment (LCA) tool.The purpose of this study is to investigate the novel use of WSA and its blend with SF as a cement substitute to produce environmentally sustainable concrete that does not compromise on its mechanical properties. Therefore, the impact of WSA and its blend with SF, as a high-volume replacement of cement, on the mechanical, durability, and microstructural characteristics of concrete were investigated. Additionally, X-ray fluorescence (XRF) and X-ray diffraction (XRD) methods were used to measure the physical and chemical properties of cement, WSA, and SF. Concrete specimens were prepared, namely, control (100% cement), three binary with only WSA , and three ternary containing WSA along with SF . In ternary mixes, a large amount of cement was substituted (up to 50%). Mechanical properties, such as the compressive and split tensile strengths with aging , and water absorption (WA) and apparent porosity (AP) after aging for 91 days were evaluated for hardened concrete samples. Additionally, the effect of WSA and its blend with SF on the microstructure and pore structure of the cement paste matrix was studied by employing scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM–EDS), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and nitrogen . The specified physical and chemical properties of these materials are listed in Besides binder materials, aggregates from local sources were obtained for using as fillers in concrete. The chemical properties of WSA are largely dependent on the source (wheat straw), the organic composition, and the sintering temperature . FurtherIn addition to CC, three binary and three ternary concrete mixture proportions were designed. The CC having 100% cement, whereas the binary concrete mixtures were designed by partial substitution of cement with 10%, 20%, and 30% WSA, and are respectively identified as WSA10, WSA20, and WSA30. The ternary mixtures incorporating blends of WSA and SF were designed by substituting high amounts of cement ranging from 30% to 50% as 25% WSA + 5% SF (WSA25SF5), 33% WSA + 7% SF (WSA33SF7), and 40% WSA + 10% SF (WSA40SF10). 3), the water content for the concrete mixtures was maintained at 160 kg/m3. Consequently, to achieve the target workability corresponding to slump values of 120 ± 30 mm, additional dosages (wt.%) of the naphthalene-based water-reducing admixture were employed for each concrete mixture, as listed in Adding SF to ternary concrete mixtures was primarily to increase the percent of cement replaced by WSA without compromising the mechanical or durability characteristics. Thus, to improve the mechanical strength of binary concrete as compared to those of CC, SF is added at a rate of 5%, 7%, and 10% to concrete mixtures containing a high percentage of WSA as 25%, 33%, and 40%, respectively. The water-to-binder ratio was maintained at 0.35 for all the concrete mixtures. In accordance with the constant water-to-binder ratio and binder content . The cylindrical molds were covered with plastic sheets after fabrication and kept under standard laboratory temperature of 20 ± 1 °C and relative humidity of 60 ± 5% for 24 h. Concrete specimens were demolded 24 h after casting and moist cured in a curing tub until being tested at 7, 28, and 91 days. The upper and lower surfaces of concrete specimens were leveled by an end-surface grinder after reaching the desired curing period.As per ASTM C39, compression strength tests were conducted on cylindrical specimens using a 200-ton-capacity universal testing machine  assembly at 0.2 MPa/s loading rate. Additionally, the split tensile test was performed in accordance with ASTM C496 by using a 200-ton UTM at a loading rate of 1 MPa/min.In addition to compressive and splitting tensile tests, tests for WA were also performed on hardened concrete samples of all the concrete mixtures according to ASTM C948. To perform WA tests, 100 mm diameter and 50 mm thick concrete samples were cut from 91-day moist-cured concrete specimens. Samples of cut concrete were soaked in water at 21 °C for 24 h and then periodically weighed until the saturated-surface dry weight (SSD) stabilized. If less than 0.5% difference in weight occurred between successive SSD weight measurements, the weight was considered stable. The letter “B” refers to the most recent yielded weight of the samples. Afterward, the mass of the specimens suspended in water was measured to the nearest 0.01 g and labeled as “A”. Concrete samples were oven-dried at 100−110 °C, and their weights were taken every 24 h. Upon achieving a weight loss of <0.5% of the last measured weight, the sample was cooled inside a vacuum desiccator at room temperature and weighed, which is referred to as “C”. To calculate WA and AP, the following equations were used:Paste samples for the control (100% cement) and other mixes with various amounts of WSA (binary) and blends of WSA with SF (ternary), as partial substitutes for cement (weight percentage), were prepared. Using a Hobart mixer , a paste of standard consistency was obtained for all mixes. The freshly mixed cement paste was poured into small plastic containers (20 mm diameter and 50 mm height) immediately after mixing. The plastic containers were subsequently sealed and capped prior to curing. Following 91 days in the cured state, the specimens were dried with a solvent exchange method to inhibit the hydration process. Finally, the flaky slices and powder specimens were then washed with isopropanol for 15 min. In order to remove the isopropanol present in the paste samples, the samples were dried in an oven at 40 °C for 30 min. The samples were then sealed in plastic bags for storage before testing.The SEM–EDS analysis of all concrete mixes was performed on hardened fragments in the form of slices of cement paste using a JSM-IT100 scanning electron microscope. Isopropanol was used to dry the fragments of hardened paste using the solvent exchange method. After that, all specimens were examined for changes in morphology and composition.2 sorptiometry was conducted on all the tested concrete mixes. The surface area and pores of the powdered specimen (weighing approximately 0.3 g) obtained from the 91-day cured hardened paste were measured by N2 sorption analysis  at 273 K. First, the samples were degassed to remove airborne contaminants that had absorbed during curing. Afterward, N2 adsorption was performed at ambient temperatures and controlled pressure on the specimens.In addition to the SEM–EDS study, N−1.All the mixes studied were additionally characterized using FTIR using a PerkinElmer Spectrum Two FTIR spectrometer to determine their individual phases. The powdered samples of all of the studied mixes were dried and examined under an infrared light source, and the IR spectra were taken in the wavenumber range 400 to 4000 cm2 as a medium under static conditions. Moreover, alumina powder was used as a reference for thermal stability at elevated temperatures. Finally, a comparison plot was developed using the built-in software to show the loss of weight of various paste specimens in various temperature ranges.To perform TGA of all the concrete mixes, the powdered specimens obtained from 91-day cured pastes were placed in ceramic vessels fitted with thermogravimetric analyzers. The specimens were heated inside the thermal gravimetric analyzer to a temperature of 20 to 1000 °C at a rate of 10 °C/min, using N2 (CO2-eq) emissions using the green concrete LCA tool. This tool is typically designed to calculate the environmental impact of concrete, its constituent materials , and consumption of fuels and water. The environmental carbon footprint effect of all the seven concrete mixes used in this study was evaluated [In this study, the GWP of all concrete mixes was calculated as equivalent to kg COvaluated . The stuvaluated .A comparison of compressive strength development between CC and those containing WSA alone (binary mixes) and WSA jointly with SF (ternary mixes) is presented in As shown in To achieve high sustainability in terms of lesser GWP, efforts were made to regain the reduction in the compressive strength of binary mixes containing high percentages of WSA by adding different percentages of SF . The test results show significant improvement in strength of ternary mix with an equal percentage of cement substitution (WSA25SF5) to that of the corresponding binary mix having WSA alone (WSA30) at all ages. Owing to addition of 5% SF, the improvement in strength that occurred remained slightly lower than that of CC. However, an encouraging response was noticed for ternary mix (WSA33SF7) containing a slightly high percentages of SF (7%) in presence of high percentage of WSA (33%), where the compressive strength was higher than that of CC at all ages. These results demonstrated fast early-age hydration and better packing and filling abilities due to slightly increased amount of very fine SF along with the later-age pozzolanic reaction of high-volume WSA. With a further increase in cement substitution with 10% SF in presence of 40% WSA (WSA40SF10), a slight reduction in strength was observed as compared to CC at all ages. This is because a high percentage of cement substitution (50%) affected both the early hydration and later-age pozzolanic reaction due to the production of less calcium hydroxide (C-H). However, the strength performance of this ternary mix (WSA40SF10) is commendable, despite of its high cement substitution, as it either shows higher compressive strength than other binary mixes (WSA10 and WSA30) or comparable to ternary mix WSA25SF5, despite of its low cement substitution. These results are, once again, attributed to the addition of a high percentage of very fine SF (10%) due to its better packing and filling abilities at early ages (7 days). Among all the mixes, the highest compressive strength at 7 days was demonstrated by the binary mix WSA20, while at 28 and 91 days by the ternary mix WSA33SF7.In contrast to compressive strength, To summarize, the current findings demonstrated a decrease in compressive strength owing to a low (WSA10) or high (WSA30) cement replacement with WSA. Contrarily, a significant increase in both compressive and splitting tensile strength was obtained for 20% cement replacement with WSA (WSA20). Similar to binary concretes, the compressive strength of ternary concrete mixes decreased owing to a low (WSA25SF5) or high (WSA40SF10) cement replacements. However, a significant increase in both compressive and splitting strengths was observed for ternary concrete blend having 33% WSA jointly with 7% SF (WSA33SF7).The comparison of the other important properties (WA and AP) of the binary and ternary concrete mixtures with that of the CC was also performed in addition to the strength characteristics. This is because the durability of the hardened concretes can be indirectly assessed based on the WA and AP values. The different trends of changes in the WA and AP according to various amounts of cement substitution with WSA alone (binary concretes) and WSA with SF (ternary concretes) are depicted in Regardless of the type of mixture proportions, curing conditions, aging, or binder type and its content, the values of the experimental STS of concrete can be correlated with their corresponding compressive strength, mainly due to the existing consistency between their general trends of development with aging. In addition to the existing codes such as ACI 318 , ACI 363del code , ACI 318del code , and Kimdel code , respectdel code , the effFrom these findings, it is revealed that the correlation between the compressive and splitting tensile strengths of concrete is not significantly influenced by the type of binder and aging. Kim et al.  also notAccording to the findings of past researchers ,62,63, t−1 are associated with vibrations of Si-O bands in C-S-H phase [−1) was detected in WSA20. On the other hand, the ternary concrete samples with different percentages of SF  showed a broader and significant shift (980 cm−1). A shift toward a higher wavenumber in the spectrum of binary and ternary pastes suggests formation of a high amount of C-S-H gels. A large amount of C-S-H gels are produced from the nucleation sites provided by the fine particles of SF, as also observed earlier through SEM–EDS analysis. The development of high compressive strength in these mixes can be linked to the formation of a large amount of C-S-H gels. Moreover, the peaks at 720, 875, and 1415 cm−1 are associated with calcite formed as a result of carbonation [As illustrated in -H phase . The IR bonation .−1 indicates the presence of free OH groups, which suggests the presence of the portlandite phase. The control sample exhibits a wider and more visible peak as compared to all other binary and ternary samples. However, this portlandite peak was reduced in all the binary mixes, which indicates the extent of portlandite consumption caused by the presence of amorphous silica in WSA. Interestingly, in ternary mixes containing WSA and SF, the peak remained very small or almost disappeared, indicating a high pozzolanic reactivity, which consequently results in greater consumption of C-H. This leads to formation of more C-S-H gels in these mixes [In all the paste samples, the peak at 3645 cmse mixes . As disc3/g) was observed for a ternary mix with 40% cement substitution (WSA33SF7) followed by WSA25SF5 (0.045 cm3/g), WSA40SF10 (0.046 cm3/g), WSA10 (0.048 cm3/g), WSA20 (0.049 cm3/g), control (0.050 cm3/g), and WSA30 (0.051 cm3/g). The binary mixes with lower percent of WSA (WSA10 and WSA20) exhibited lesser nitrogen intrusion volume as compared to control, however, the maximum nitrogen intrusion volume was observed for WSA30. This is most obviously due to reduced pozzolanic reactivity when a high percent of cement replaced with WSA, which consequently had led to increased porosity and vascularity in the paste matrix.2/g) as compared to all other mixes. An increased BET surface area of the ternary mix indicates its improved and denser microstructure of C-S-H gels [2/g), which showed a slight reduction that could be due to a high amount of cement substitution leading to a large amount of unreacted WSA in the mixture [2/g) or WSA20 (13.0 m2/g), also showed slightly larger BET surface areas than that of control (12.7 m2/g), which ultimately had led to their improved microstructure of C-S-H gel. However, contrary to this, BET surface area decreased with further increase in percent of WSA (more than 20%) as was observed for WSA30 (12.0 m2/g). This clearly indicates the presence of unreacted WSA that had caused the hydration products to jam the pores and form a porous paste matrix. These results suggest a restricted use of WSA in binary mixes by not more than 20% when used as a sole substitute of cement.A comparison of Brunauer–Emmett–Teller (BET) surface areas between control and other binary and ternary mixes is presented in S-H gels ,69. As d mixture . SimilarThe thermal decomposition of 91-day cured cement paste samples of control, binary, and ternary mixtures was performed by TGA to evaluate the effect of WSA and SF on the amount of C-H (%), which occurred due to the weight loss between 400 and 500 °C ,72. BaseFrom Similar to C-H, it can be further seen from 2-eq per unit volume concrete) between control and other binary as well as ternary concrete mixtures. In this figure, the distribution of CO2-eq for each concrete mixture is illustrated by its ingredients and major production processes. The value of CO2-eq for all concrete mixtures was calculated by using the green LCA tool according to the data listed in 2 emission for all the mixtures. Following cement production, transportation of the raw materials and their products represents the second-highest source of CO2 emissions, which varies between 8.5% and 19.5%. Most importantly, the CO2 emissions associated with noncementitious materials are very low and remained almost same for all concrete mixes. According to the calculations, the SCMs (WSA and SF) constituted only 0.3% to 1.4% of total calculated CO2 emissions. Similarly, concrete batching and mixing account for very small percentages, between 0.4% and 0.5%.It can be seen in 2-eq/m3 among all mixes . As illustrated in 2-eq/m3/MPa for all the mixes were drawn with respect to their compressive strength and aging . The CO2-eq intensity of different mixes is used as a measure to evaluate their important impact on compressive strength of concrete and associated GWP per unit concrete volume and strength [strength .2-eq/m3/MPa trend due to increasing compressive strength with aging. Moreover, it can be further noted that the amount of CO2-eq/m3/MPa decreases with decreasing quantity of cement in all the binary and ternary mixtures. The only exception is the binary mix WSA30, where it slightly increased as compared to WSA20. This is due to drop of strength in WSA30 because of the high amount of cement substitution (30%) in this mix as compared to WSA20. A sharp decrease in CO2-eq/m3/MPa in a binary (WSA20) and ternary mix (WSA33SF7) is due to their high compressive strengths as compared to other mixes.It can be seen in 2-eq intensities by replacing cement with only one type of SCM (WSA) or blends of SCMs (WSA with SF). According to the current findings, the intensities of CO2-eq improved significantly in ternary blends as compared to binary, without compromising any strength potentials. For instance, despite of almost similar compressive strength of binary WSA20 (43.6 MPa) and ternary WSA33SF7 (44.6) mixes at 91 days, CO2-eq intensity decreased to 7.9 kg/m3/MPa in ternary mix (mix #6 having 60% cement) from 10 kg/m3/MPa in binary mix (mix #3 having 80% cement). Furthermore, the addition of higher amounts of WSA (40%) and SF (10%) in ternary mix (mix #7 having 50% cement) causes a further reduction in CO2-eq intensity as 7.8 kg/m3/MPa as compared to 12.5 kg/m3/MPa in binary mix (mix #2 having 90% cement). This might be due to slightly higher 91-day strength of ternary mix (40.2 MPa) as compared to binary mix (38.3 MPa). These findings are equally applicable for these mixes at other ages as well, such as 7 and 28 days. Consequently, these results suggest that the intensities of CO2-eq can be reduced without compromising the strength of concrete by optimizing concrete mixes with appropriate amount of cement replacement and selection of a suitable type of SCMs with their correctly chosen or tested blend percentages.The current results dictate the possibility of lowering CO2 adsorption techniques to scientifically understand the impact of adding WSA and SF on the resulting paste matrix. At the end, GWP as kg CO2-eq per unit volume of concrete and kg CO2-eq per unit volume of concrete/MPa were also calculated using the LCA tool and compared among different mixes used in this study.This study investigated the use of high-volume WSA and its blend with SF as a partial substitute of cement for the development of high-performance and sustainable concrete. Besides control (100% cement), several other concrete mixtures were prepared by partially substituting cement with only WSA as binary system  and WSA together with SF as ternary system . Subsequently, the influence of adding WSA and WSA with SF on the hardened mechanical properties  was assessed and compared to those of CC. Finally, paste samples were prepared for all mixes to examine their microstructures and pore structures using SEM–EDS, FTIR, TGA, and NThe main findings of this study are summarized as follows:The current findings demonstrated a decrease in strength of binary concrete corresponding to their relatively low (WSA10) and high (WSA30) cement substitution rates, while a significant increase in strength was observed for moderate substitution rate of cement (20%) for binary concrete WSA20. In a very similar manner, the ternary mixes also showed a decreasing trend of strengths both at low (WSA25SF5) and high (WSA40SF10) blends of cement substitution, and the significant increase in strength was obtained for the moderate ternary blend of 33% WSA and 7% SF (WSA33SF7). Moreover, these increased strengths of WSA20 and WSA33SF7 were validated by their relatively lower apparent porosity and water absorption values among all mixes.A correlation between experimental compressive and tensile strengths showed close agreement to models proposed by Noguchi–Tomosawa and De Larrard and Malier. Based on the results of current findings, it is recommended to use these models to properly estimate the tensile strength of tested concretes containing WSA alone or WSA jointly with SF, except the CC and WSA33SF7, as the JSCE model demonstrated a close agreement for these two concrete mixes. In addition, the JSCE model safely predicts the tensile strength of other binary and ternary concrete mixes with their slightly underestimated values.Analysis of SEM–EDS data reveals that the incorporation of WSA as 20% replacement of cement (WSA20) leads to the densification of the paste matrix by decreasing the Ca/Si ratio in both the C-S-H and C-H phases. Furthermore, adding a 7% SF jointly with 33% WSA in the ternary mix (WSA33SF7) resulted in the lowest Ca/Si ratio among all the concrete mixtures tested. These findings suggest better refinement of microstructure for these mixes, which ultimately would lead to improvement of their engineering performance.−1) were also significantly smaller in all ternary mixes as compared to binary mixes. This, consequently, suggests an improved pozzolanic reactivity and the formation of more C-S-H gels that ultimately leads to a more refined and denser microstructure.A visible shift in Si-O band was observed through FTIR analysis for almost all the binary and ternary mixes. Comparatively, the shift was more pronounced in all ternary mixes containing WSA together with SF, which clearly demonstrates the presence of high levels of C-S-H gels. Moreover, the portlandite peaks  showed a smaller surface area and more intruded pore volume. This could be possibly due to the presence of unreacted WSA in these mixes that might have caused high porosity and vascularity in their paste matrices.Similar to FTIR analysis, a densification of the paste matrix and refinement of the pore structure also suggested by the results of NAs a matter of further validation of these findings, TGA results also showed a reduction in the portlandite phase of binary and ternary mixes. This occurred especially in those binary mixes that contained high doses of WSA (WSA20 and WSA30), partly because of a lesser amount of cement in these mixes and due to the pozzolanic reactivity of amorphous silica present in WSA. A further reduction in the proportion of portlandite phase occurred in ternary mixes due to very fine and amorphous silica present in both WSA and SF, which would ultimately consume the C-H phase to generate additional C-S-H phases and lead to densification of the paste matrix.2-eq/m3) mixes decreased with decreasing amount of Portland cement simultaneously with an increase in amounts of SCMs. The highest GWP of 533 was generated by the control mixture (100% OPC) while the least GWP, only 313, was produced by the ternary concrete mixture (WSA40SF10) having 40% WSA jointly with 10% SF and only 50% OPC.The GWP per unit volume of concrete . The ternary mixes containing highest percentages of SCMs, at 40% (WSA33SF7) and 50% (WSA40SF10), resulted in lower CO2-eq intensity/MPa as compared to that of CC, regardless of aging. Consequently, it may be safe concluding that the efforts for using larger amounts of regionally available SCMs can have an important positive effect on producing green concretes together with reduced GWP without compromising any strength potentials.Regardless of aging, all the binary and ternary concrete mixes containing SCMs (WSA or WSA with SF) exhibited lower CO


Recognition of antibiotic stewardship programs (ASPs) as essential components of quality health care has dramatically increased in the past decade. The value of ASPs has been further reinforced during the coronavirus disease 2019 (COVID-19) pandemic because these programs were instrumental in monitoring antibiotic use, assessing emerging COVID-19 therapies, and coordinating implementation of monoclonal antibody infusions and vaccinations. ASPs are now required across hospital settings as a condition of participation for the Centers for Medicare and Medicaid Services and for accreditation by The Joint Commission. In the 2019 National Healthcare Safety Network annual survey, almost 89% of hospitals met the Seven Core Elements for ASPs defined by the Centers for Disease Control and Prevention. More than 61% of programs were co-led by physicians and pharmacists, evidence of the leadership role of both groups. ASPs employ many strategies to improve prescribing. Core interventions of preauthorization for targeted antibiotics, prospective audit and feedback, and development of local treatment guidelines have been supplemented with numerous emerging strategies. Diagnostic stewardship, optimizing duration of therapy, promoting appropriate conversion from intravenous to oral therapy, monitoring at transitions of care and hospital discharge, implementing stewardship initiatives in the outpatient setting, and increasing use of telemedicine are approaches being adopted across hospital settings. As a core function for medical facilities, ASP leaders must ensure that antibiotic use and ASP interventions promote optimal and equitable care. The urgency of success becomes progressively greater as complex patterns of antibiotic resistance continue to emerge, exacerbated by unpredictable factors such as a worldwide pandemic. Antibiotic stewardship programs (ASPs) have existed for more than half a century, but their recognition as an essential component of quality health care has dramatically increased in the past decade. To best understand the state of stewardship today, it is important to reflect on the factors that have contributed to that recognition, the current penetration of antibiotic stewardship within health care, innovative approaches gaining traction in the field, and possible future priorities. When the term antibiotic stewardship was coined, it was immediately embraced because it more accurately reflected the central goals of ASPs to support appropriate antibiotic use: the right drug, at the right dose, for the right reason and the right duration.Historically, ASPs have often been viewed as antibiotic restriction programs, measured by the magnitude of cost savings rather than the value of improved patient outcomes, lowered risk of treatment failure, and the potential to ameliorate the emergence of antibiotic resistance. Hospital administrators eliminated programs when they mistakenly believed prescribing improvements would be sustained without further support, only to see a marked rebound in inappropriate prescribing and costs to the hospital. The increasingly urgent crisis of antibiotic resistance, as well as the priority to improve healthcare quality and reduce adverse, highly morbid events such as Clostridioides difficile colitis, have shifted perceptions of ASPs. Notably, in 2014, President Barack Obama issued an executive order to combat antibiotic-resistant bacteria that clearly included antibiotic stewardship as an important strategy. The Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) developed the National Action Plan for Combating Antibiotic-Resistant Bacteria, which called for universal implementation of ASPs in acute-care hospitals.ASPs have been plagued by inadequate resources and limited buy-in from hospital leadership and clinician prescribers. largely structured on the Core Elements for Hospital ASPs defined by the Centers for Disease Control and Prevention (CDC), a leader in combating antibiotic resistance and supporting antibiotic stewardship. In January 2020, the TJC added a requirement for all TJC-accredited ambulatory healthcare organizations to identify an antibiotic stewardship leader and establish an annual goal with evidence-based guidelines, educational resources for clinical staff, and analysis and reporting of data related to that antibiotic stewardship goal. Importantly, the Centers for Medicare and Medicaid Services (CMS) issued a Condition of Participation (CoP) that every participating hospital as of March 30, 2020, including critical-access hospitals, have an active facility-wide ASP to reduce inappropriate antibiotic use and antibiotic resistance with designated leaders to guide and oversee the programs. These are major victories for the advancement of ASPs from being perceived as optional programs at risk of elimination to mandatory programs central to quality care and public health.Advocacy by PACCARB, professional societies, and public health experts have borne fruit. For accreditation, The Joint Commission (TJC) added a new medication management standard for hospitals, including critical-access hospitals, and nursing care centers COVID-19 is a new disease with constantly evolving knowledge and information. Patients presented with severe respiratory disease, and often had leukocytosis and elevated procalcitonin and inflammatory markers. Evaluation and bedside examinations were challenging; radiography and diagnostic procedures were minimized when possible. The default, particularly early in the pandemic, was to treat with broad-spectrum antibiotics for possible secondary bacterial infection. Patients with prolonged hospitalizations continued to have antibiotic exposure. Antibiotic use tracked with the number of COVID-19 patients hospitalized; hospitals in the highest quartiles of COVID-19 cases showed greater increases in antibiotic use. Not surprisingly, increases in antibiotic resistance were also noted. Nosocomial pathogens identified in hospitalized patients demonstrated a 42% increase in methicillin-resistant Staphylococcus aureus and a 134% increase in extended-spectrum β-lactamase–producing gram-negative bacteria.Over the past year, the coronavirus disease 2019 (COVID-19) pandemic has reinforced the importance of ASPs and has broadened the appreciation of the different ways that ASPs are essential to the functioning of healthcare facilities. but inappropriate antibiotic use remained a significant issue at many facilities. Tired and stressed physicians, devastated by the number of deaths and severe, prolonged debilitation of their patients, were less open to stewardship interventions. Difficulty speaking face to face or being present on the wards due to efforts to minimize congestion in work rooms and patient-care areas made communication between antibiotic stewards and treating physicians difficult. ASPs continued to work to improve antibiotic use and to limit overprescribing. ASPs actively monitored those infections, worked to identify emerging outbreaks, and conducted appropriate surveillance to tailor appropriate empiric and definitive antibiotic therapy.As the pandemic progressed, clinicians learned from experience and from numerous studies reporting that coinfection with COVID-19 and bacterial or fungal infection at presentation were relatively infrequent,Beyond the essential role of ASPs during the pandemic to reduce the reactive overuse of antibiotics, members of the ASP were involved with assessing emerging treatment regimens for COVID-19; implementing use of remdesivir, dexamethasone, or interleukin-6 inhibitors; and participating in decisions about implementation of monoclonal antibody infusions and vaccinations. The expertise of ASPs in infectious diseases and pharmacologic agents was indispensable across healthcare facilities.Their new stature as CMS-required programs, with the recent pandemic to reinforce their essential value, affords ASPs an opportunity to examine the current approach to ASP structure and implementation. The 2019 annual survey from the CDC National Healthcare Safety Network (NHSN) provides important data to inform this process. The findings provide a snapshot of the increased uptake of ASPs across the country and provide data on the 7 core elements of ASPs: (1) hospital leadership commitment; (2) facility leader(s) accountable for ASP outcomes; (3) pharmacy expertise; (4) action (implementing interventions); (5) tracking the impact of interventions, antibiotic use, and other outcomes such as C. difficile; (6) reporting of antibiotic use and resistance; and (7) education for stakeholders.The CMS requires hospitals to report their healthcare-associated infections through the NHSN and conduct an annual survey of infection control practices. In 2014, questions about ASPs were included for the first time. In the most recent 2019 survey, data on ASPs were expanded and made more robust. This trend is due in a large part to accreditation and regulatory requirements for an ASP.In 2014, only 40.9% of participating hospitals met all 7 core elements. By 2019, that proportion was 88.9%, and although facility type, bed size, and teaching status varied, ˜80% of critical-access hospitals or hospitals with ≤50 beds met all requirements, an impressive improvement in adoption. Adequate support for the stewardship team is essential and should continue to be a focus of advocacy.Several other findings of interest were identified by this survey. Hospital commitment, as judged by 3 priority commitments , is notably more robust for IT support than for stewardship support. Physician and pharmacist steward commitment, as defined by their contract or job description, is as low as 12.9% and 29.6%, respectively, at critical-access hospitals. General acute-care hospitals met this commitment to physician and pharmacy stewards approximately half the time. A 2018 survey suggested that physician steward support of 0.4–1.0 full-time equivalents (FTEs) and pharmacist steward support of 1.0–3.0 FTEs, depending on hospital size (by number of beds), optimizes ASP effectiveness and outcomes.The NHSN survey shows that physician and pharmacist stewards co-led ASPs and were jointly accountable for outcomes in >61% of hospitals. Co-leadership was lowest in surgical and critical-access hospitals, with 34.2% and 38.7%, respectively, relying on a pharmacist leader. Physicians are not full-time at many hospitals, including community and rural hospitals. They often have privileges at numerous sites which they visit on a rotating basis. The pharmacist is on site, hired by that facility, and can form deeper relationships with other healthcare providers. Access to pharmacy expertise is high across facilities, ˜95% or greater. By providing that expertise as well as leading or co-leading programs, pharmacy stewards have become the dominant force in ASPs. This evolution has many possible factors. or Making a Difference in Infectious Diseases (MAD-ID). It is unclear whether antibiotic expertise has shown similar growth among physicians and medical students. When medical students were surveyed in 2012, their knowledge of antibiotic stewardship was limited and their knowledge of antibiotics suboptimal. Physicians who choose to specialize in infectious diseases (ID) receive education about antibiotics, but it is variable. The support that pharmacists and ID-trained pharmacists provide at academic centers, where most ID fellowships are based, can supplant active learning about antibiotics by ID fellows. In qualitative interviews, ID fellows identified the pharmacist steward, and not ID physician leaders, as their primary resource for antibiotic teaching. Excellent training programs in antibiotic stewardship, developed through the Infectious Diseases Society of America, assume a basic knowledge of antibiotics and focus more on the structure of ASPs, how to conduct interventions in professional and collegial ways, and other aspects of implementation rather than a deep understanding of pharmacology.Infectious diseases expertise in pharmacy has blossomed, with increased numbers of residencies and comprehensive training programs, such as those offered by the Society of Infectious Diseases Pharmacists (SIDP)Beyond foundational training about antibiotics in school, residency and subspecialty training, the professional activities of pharmacists are more in line with what a steward does compared with physicians. Pharmacists are responsible for verifying and dispensing medications. For all medications, they optimize therapy, review appropriate doses and durations, monitor drug interactions, allergies and adverse events. They track antibiotic resistance and work to contain costs. Indeed, the pharmacy professional approach is one of individual chart review and intervention. In contrast, physicians do not routinely review other physician’s patient care to critique and make recommendations. They have no direct responsibility for verification before the drug is dispensed. They put a high priority on peer respect and collegiality.Physician time is more costly for hospitals. When stewardship is part of a physician’s contract or job description, the amount of effort assigned and therefore compensation, is often a small percentage. In addition, physicians are more likely to be expected to do a myriad of other activities because their stewardship role is less well defined than that of pharmacist stewards. Pharmacists are more likely to be given a full- or half-time position that allows them to do more intensive stewardship work, form relationships with providers, and be recognized as the hospital antibiotic steward. A physician who is an ally and active partner was identified as one of the most important components of a successful ASP. Physicians interviewed were similarly supportive of their pharmacist co-lead, and they viewed the co-led team the optimal structure.However, physicians remain essential to successful programs. They have a deep clinical knowledge and are able to put complicated stewardship decisions into context and understand the mindset of the prescriber. They are able to synthesize the clinical data and judge whether de-escalation is safe or escalation is needed. They can use their clinical expertise to prioritize new initiatives and are often in a better position to advocate with hospital leadership for support and resources. They remain an important resource for the pharmacist steward. In interviews with pharmacist antibiotic stewards, although they do almost all of the day-to-day work, they strongly believe that a physician leader is necessary for an effective program.Early in antibiotic stewardship, the programs were frequently, though not exclusively, led by physicians. Now that has changed. Although physician groups should focus on the pivotal primary role that physicians play, they must do so recognizing the reality of ASPs today and the leadership of pharmacy. The model that seems most reasonable is recognition that the physician supports their stewardship program with a population health perspective, advocates for new programs and adequate resources, and is available for regular patient review and consultation as needed, while pharmacists lead and perform day-to-day activities. are less likely to be effective.The NHSN survey also probed interventions to improve antibiotic use. Facility-specific treatment guidelines was a strategy used by >92% of the facilities surveyed while implementation of preauthorization of select antibiotics and prospective audit-and-feedback strategies lagged behind Table . Hospita Implementing new technology can be expensive, but it is worthwhile if it improves evidence-based care. ASP involvement is crucial to guide appropriate use of diagnostic testing and to interpret and apply those tests to optimize antibiotic treatment.Diagnostic stewardship has become a major approach. Strategies range from creating customized microbiology reports to guide prescribing and educate prescribers to implementation of new molecular testing with ASP backup. Antibiotic therapy for community-acquired pneumonia has evolved from 10–14 day courses to courses as short as 3 days. Intra-abdominal infections can be treated for 4 days after source control. Optimizing the duration of therapy is an effective intervention for numerous infections and the shortened exposure to antimicrobials minimizes the selective pressure for antibiotic resistance as well as the risk of C. difficile infection.Each year, more data emerge about the safety of shorter durations of therapy. or bone and joint infections. Emerging data of comparable outcomes with oral agents to complete treatment courses for those deep-seated infections are encouraging and provide patients with options that avoid the risk of indwelling lines, limitations on lifestyle, and other disadvantages of long courses of antibiotics.Initiatives to transition patients from intravenous to oral antibiotics were originally used to optimize use of bioavailable agents, such as fluoroquinolones, to reduce costs, but they now are transforming the dogma mandating weeks of intravenous therapy for bloodstream infections and endocarditis Patients are often discharged on antibiotics that unnecessarily extend durations of treatment. Many patients are also discharged to complete complex antibiotic regimens. ASPs can help coordinate appropriate outpatient monitoring, provide patient education and perform clinical follow-up.Other initiatives include better management at transitions of care. More than 60% of antibiotic expenditures are in outpatient practices, of which ≥ 30% are inappropriate. Also, 44% of outpatient antibiotic prescriptions are for acute respiratory tract infections, of which half are inappropriate, accounting for 34 million excess prescriptions each year. Ambulatory pediatric practices have improved inappropriate prescribing because of robust stewardship efforts, but less progress has been seen in adult medicine.ASPs are also aggressively moving into the ambulatory arena, both because of accreditation and anticipated regulatory requirements and because of the volume of antibiotics in ambulatory care and high rates of unnecessary use. The COVID-19 pandemic has necessitated a major shift to telehealth, largely enabled by an unprecedented acceptance of telehealth by insurers, providers, and patients, and this trend has created an environment that can further promote stewardship via this approach.Antibiotic stewardship via telemedicine is a promising strategy to support healthcare facilities, particularly those without onsite infectious diseases resources such as rural or critical-access hospitals.The increased implementation of other ASP strategies is noteworthy and should be the focus of more detailed survey questions in the coming years. there was strong consensus that stewards should not be ‘antibiotic police.’ Provider engagement strategies are critical to achieve success, and recommendations must be communicated in a collegial manner that does not judge physician competence or autonomy. There must be collaboration, shared decision making, and respect.These stewardship strategies must be optimally implemented to impact patient care. In qualitative interviews with physician and pharmacist stewards in 2 healthcare systems,But a question that is seldom asked is what if the prescribers are wrong? The time spent convincing recalcitrant providers is significant and can be exhausting and frustrating. ASPs want buy-in and do not want to create conflict. There are countless gray areas in antibiotic stewardship that must rely on the judgment of clinicians providing direct patient care. However, a growing number of strongly evidence-based interventions should not be optional, such as β-lactam antibiotics for methicillin-susceptible staphylococcal infections or short courses of treatment for clinically stable patients with community-acquired pneumonia.With TJC and CMS support for ASPs, there is explicit acknowledgment that these programs work and are essential for health care. In addition to continued pressure to provide adequate resources for ASPs, serious consideration should be given to advocate for greater enforcement authority by ASPs when interventions are unambiguously supported by clinical experience, research, and guidelines. Although concerns about reducing the collaborative nature of the ASP are valid, we can look to the evolution of infection control programs. There is acceptance that isolation precautions, for example, are not up to the individual providers because they are based on strong scientific evidence and protect the health of other patients and providers. Hospital epidemiologists and infection preventionists remain respected content experts and maintain excellent relationships with other healthcare professionals. ASPs may weaken their own message if those programs lack the conviction to assert that some interventions are so robustly supported by data that an individual provider cannot overrule it. Thus, optimizing the duration of therapy would have a major impact. This approach could serve as an important step toward accomplishing core goals, asserting the strength of the evidence base and the nonoptional nature of the interventions, simultaneously allowing ASPs to focus on difficult discussions with providers about more challenging stewardship decision making.The next stage in the evolution of ASPs should be the identification of a finite number of stewardship interventions that could be considered mandatory for ASPs and should be set by the CDC as components of its core elements. CMS uses the CDC core elements as the basis of its Conditions of Participation so those interventions would be included in the standards by which the CMS determines whether ASPs are meeting expectations. Such identification would be incorporated into accreditation evaluations. Defined durations of therapy for pneumonia, skin and soft-tissue infections, and urinary tract infections would be logical initial targets for mandatory interventions given the strong evidence base. Those infections are the 3 most common community-onset infections and comprise a significant number of infections treated within health care. Although many of those prescriptions are inappropriate and therefore African-American patients may be receiving better care, it is for inequitable reasons.Stewardship strives to give the most effective drug with the narrowest spectrum as appropriate for the shortest amount of time in a consistent and equitable manner. There are not enough data about antibiotic prescribing and ASP activities through the lens of equity. On the inpatient side, antibiotic stewards struggle with physicians who have trepidation de-escalating or stopping antibiotics for fear that the patient will relapse or worsen, but we do not typically examine all the factors that influence how providers choose the antibiotic or when they choose to accept ASP interventions. In addition, there has been little examination of the role that bias may play in ASP recommendations. On the outpatient side, physicians often prescribe due to perceived patient demand and to improve patient satisfaction. Studies in ambulatory care have demonstrated that white patients are twice as likely to receive a prescription as African-American patients.ASPs should commit to examining equity and implicit bias by evaluating their own data and ensuring that ASP recommendations are based on evidence-based medicine and quality care and not influenced by the patient’s race or ethnicity, sex or gender, or other socioeconomic demographics. Professional infectious diseases societies, public health organizations, and other stakeholders should promote examination of these issues. This examination should include discussion and goals related to equity in white papers and guidelines, support for collaborative research in this area, and advocacy for federal funding to study these crucial issues.In conclusion, antibiotic stewardship has come a long way, but there is a long way to go. With recognition that ASPs are a core function for medical facilities, we can start to reimagine our place in health care. The urgency of success becomes progressively greater as complex patterns of ABR continue to emerge, exacerbated by unpredictable factors such as a worldwide pandemic. Although new agents have been developed, they are not keeping pace with ABR. Those of us participating in ASPs, as well as any provider who writes an antibiotic prescription, have a responsibility to patients and the greater community to make this a high priority.


The field of macrocyclic host–guest chemistry was born with the discovery of crown ethers (CEs) by Pederson and has been the catalyst that led to the field of supramolecular chemistry more generally . Apart fAlcázar et al. investigated the impact of CB[7] on the synthetic dyes 7--aza-coumarin derivatives (SACs), which bear two basic sites in their structure  and SAC2 (pKa = 2.35) are more likely to be protonated. However, the protonation of SAC3 could take place both in the heterocyclic nitrogen (pKa = 1.67) and dialkylamino nitrogen (pKa = 1.75) independently. These protomers of the SACs were confirmed by UV-vis absorbance experiments and DFT calculations. Intriguingly, in the presence of CB[7], the heterocyclic nitrogen was favored to be protonated over the dialkylamino nitrogen, which may be due to a change in the protonation preference of SACs induced by CB[7] upon host–guest interaction. Notably, a bathochromic shift of ≈4500 cm−1 (SAC1-3) was observed in the presence of CB[7].The structure of molecules in the solution is determined by the intrinsic properties of the molecules and their interaction with the surrounding solvent. Therefore, the protonation site of a molecule depends on both their intrinsic strengths and different stabilizations by the solvent. The complexation of a guest molecule with multiple basic sites and a macrocyclic host could stabilize, probe, or facilitate the formation of a specific protomer. To verify this, tructure . They fivia the conversion of receptors into optical sensors that can sense binding of different guests. Given the rapid development of supramolecular host–guest chemistry, macrocycle-based FID assays have received considerable attention due to their potential in the area of chemical sensing. Food additives based on phenolic compound play a key role in the food industry on account of their remarkable antibacterial and antioxidant properties. However, the excessive use and accumulation of food additives in the environment is gradually increasing and is responsible for significant environmental concern. In this context, Duan et al. prepared a novel FID assay based on a cationic PA[6] (CP6) for the detection of some vital phenolic food additives, such as p-gallic acid (GA), trans-ferulic acid (FA) and coumaric acid (CA)  was used as the fluorescent indicator in this FID system due to its enhanced emission in non-polar environments. Upon the host-guest complexation of CP6 and TNS, the fluorescence of TNS was switched on. However, in the presence of GA, FA and CA, the fluorescence was turned off due to the guest’s displacement from the cavity of CP6. As a result, the host–guest chemistry-based FID system can be used as a sensor towards these phenolic food additives.Fluorescent indicator displacement (FID) assays are an excellent method to probe analytes cid (CA) . The 6-pDuan et al. further summarized recent progresses on FID assays based on macrocyclic arenes  emulsions can be obtained by using CaCO3 NPs and a surfactant (SDS) of different concentrations  formed by surfactants in water are usually driven by hydrophobic interactions. In this Research Topic, trations . Once thIn conclusion, this Research Topic collects some new advances in macrocycle-based host–guest chemistry covering a broad range of supramolecular chemistry research. As the field further develops, we believe host–guest chemistry will continue to be a source of intrigue for basic science and gradually, with investment and critical thinking provide real-world applications across health, environmental and materials science.


Urocortin-3 (UCN3) is a glucoregulatory peptide produced in the gut and pancreatic islets. The aim of this study was to clarify the acute effects of UCN3 on glucose regulation following an oral glucose challenge and to investigate the mechanisms involved.We studied the effect of UCN3 on blood glucose, gastric emptying, glucose absorption and secretion of gut and pancreatic hormones in male rats. To supplement these physiological studies, we mapped the expression of UCN3 and the UCN3-sensitive receptor, type 2 corticotropin-releasing factor receptor (CRHR2), by means of fluorescence in situ hybridisation and by gene expression analysis.Crhr2. Conversely, acute antagonism of CRHR2 signalling increased insulin secretion by reducing SST signalling. Consistent with these observations, acute drug-induced inhibition of CRHR2 signalling improved glucose tolerance in rats to a similar degree as administration of glucagon-like peptide-1. UCN3 also powerfully inhibited glucagon secretion from isolated perfused rat pancreas (perfused with 3.5 mmol/l glucose) in a SST-dependent manner, suggesting that UCN3 may be involved in glucose-induced inhibition of glucagon secretion.In rats, s.c. administration of UCN3 strongly inhibited gastric emptying and glucose absorption after oral administration of glucose. Direct inhibition of gastrointestinal motility may be responsible because UCN3’s cognate receptor, CRHR2, was detected in gastric submucosal plexus and in interstitial cells of Cajal. Despite inhibited glucose absorption, post-challenge blood glucose levels matched those of rats given vehicle in the low-dose UCN3 group, because UCN3 concomitantly inhibited insulin secretion. Higher UCN3 doses did not further inhibit gastric emptying, but the insulin inhibition progressed resulting in elevated post-challenge glucose and lipolysis. Incretin hormones and somatostatin (SST) secretion from isolated perfused rat small intestine was unaffected by UCN3 infusion; however, UCN3 infusion stimulated secretion of somatostatin from delta cells in the isolated perfused rat pancreas which, unlike alpha cells and beta cells, expressed Our combined data indicate that UCN3 is an important glucoregulatory hormone that acts through regulation of gastrointestinal and pancreatic functions.The online version contains supplementary material available at 10.1007/s00125-022-05675-9. Urocortin-3 (UCN3), a 38-amino-acid peptide from the corticotropin-releasing factor family , 2, is eMale rats were purchased from Janvier . Experiments were approved by the Danish Animal Experiments Inspectorate (2018-15-0201-01397 and 2020-15-0201-00756). For further details, see electronic supplementary material (ESM) g, 4°C, 10 min) within 30 min and plasma was stored at −20°C. At the end of the experiments, rats were returned to their housing location and were observed daily for a week. No signs of failure to thrive were observed. Weight did not differ between experimental groups .Rats fasted for 8–12 h were used. Blood was sampled from conscious rats by sublingual puncture (200 μl/sample) into EDTA-coated tubes, which were immediately placed on ice. After collection of baseline samples , rats received glucose by oral gavage  at time 0 min together with a subcutaneous injection (200 μl) of one of the following compounds prepared in isotonic saline (154 mmol/l NaCl) with 0.1% HSA: isotonic saline (vehicle); UCN3 (30 nmol/kg); glucagon-like peptide-1 ; or the corticotropin-releasing hormone receptor 2 (CRHR2) antagonists, antisauvagine-30 or K41498 (100 μg/kg). Plasma exposure data later showed that the UNC3 group had ~¼ of the concentration observed in the 30 nmol/kg group in the second in vivo study (where concentrations after formulation was verified). Concentration is thus presented as an adjusted dose of 7.5 nmol/kg. Blood was collected at time points 5, 10, 15, 30 and 45 min by the procedure described above. Samples were centrifuged (16502 overdose). UCN3 was formulated in 50 mmol/l HEPES, 180 mmol/l glycerol and 0.007% polysorbate 20, pH 8. Weight did not differ between experimental groups .The study design was as for study 1 but with following exceptions: 250 μl blood was withdrawn at each time point; time points were −30, −15 (baseline), 5, 10, 15, 30, 45 and 90 min; UCN3 challenge at time 0 min was with 2, 7.5 or 30 nmol/kg; and rats were euthanised at the end of the study . Two days after transfection, cells were incubated either with synthetic mouse UCN3 at a concentration range of 1×10−12 to 1×10−7 mol/l or with one of the following CRHR2 antagonists: antisauvagine-30; or K41498. Changes in receptor activity were quantified by use of in vitro HitHunter cAMP assay. For further details, see ESM COS-7 cells were modified for either mouse or rat CRHR2 expression using a transient calcium phosphate precipitation transfection procedure  with pCMProtein concentrations were quantified in gastrointestinal and pancreas tissue biopsies (~1–1.5 cm/piece) by Pierce BCA Protein Assay Kit  and extracts were purified using tc18 cartridges . See ESM Ucn3 and Crhr2 expression by standard procedures, using antibodies listed in ESM Table Rat  pancreas, gastric ventricle, jejunum, distal ileum and mid-colon were investigated for Ucn3 and Crhr2 was compared with expression of the well-known genes Gcg, Glp-1r , Ins-1  and Ins-2  in rat islets. The expression of UCN3 and CRHR2 was compared with expression of GCG, UCN1, UCN2 and GLP1R in human islet alpha, beta and delta cells. Further information can be found in ESM Expression of genes encoding UCN3 and CRHR2 was investigated in rat islets by qPCR and in human islets by re-analysing publicly available human islet single-cell sequencing data. The qPCR used primers listed in ESM Table O-methyl-d-glucose (3-OMG) concentrations, we developed a sensitive and low volume LC/MS-based quantification . Graphs were constructed in GraphPad Prism and edited in Adobe Illustrator . p<0.05 was considered significant. No animals/samples were excluded from the presented data set.Data are expressed as means ± SEM. For perfusion data, averaged basal and response outputs were calculated by averaging output values over the entire stimulation period  and the period leading up to stimulus administration . Output (fmol/min) was the product of peptide concentration (pmol/l) and flow rate (ml/min). Statistical significance was assessed by two-way ANOVA or by one-way ANOVA for repeated measurements (as indicated in figure legends), followed by Tukey’s multiple comparison test. Alternatively, Student’s paired p≥0.80 between groups). Blood glucose profiles in the vehicle- and UCN3-treated groups were similar (n=10) , while GLP-1 injection resulted in an expected pronounced delay in blood glucose rise   . With the low UCN3 dose (2 nmol/kg), blood glucose and paracetamol data matched those in the first in vivo study Fig. . This wale) Fig. . A time The t½ of UCN3 in rodents is unknown, so we determined the t½ of UCN3 after i.v. and s.c. administration in rats. The t½ after i.v. and s.c. administration was 1.9 and 12.2 min (based on first-order kinetics), respectively Fig. . To compn=6). A similar distribution pattern was observed when data were normalised to tissue wet weight (data not shown). Subsequently, we investigated whether intra-arterial UCN3 infusion affected glucose-dependent insulinotropic polypeptide (GIP), GLP-1, neurotensin (NT) or SST secretion from isolated perfused rat small intestine. We found that this was not the case, although taurodeoxycholic acid (positive control) increased their secretion at least twofold  were found in extracts of all investigated segments; concentrations were highest in the proximal jejunum and distal ileum Fig. , n=6. A Crhr2 transcripts were found in cells along the submucosal surface of the circular muscle layer in the pyloric antrum, jejunum and distal ileum, morphologically resembling intestinal cells of Cajal . The expression translated into high concentrations of extractable UCN3, well above the detection limit  whereas the remaining genes were not differentially expressed (p>0.05).To investigate whether these expression patterns translated to human islets, we investigated single-cell expression of ing data  ; glucagon output was subsequently reduced by 80% by SST-14 infusion . In the same experiments, UCN3 increased SST output three- to fourfold . To investigate whether endogenous UCN3 affects insulin or SST secretion, we infused the CRHR2 antagonists antisauvagine-30 and K4148 into the rat pancreas perfused at 10 mmol/l glucose at a concentration that efficiently inhibits UNC3-mediated activation of CRHR2 . This increased insulin secretion approximately twofold . Subsequent change of the glucose in the perfusate from 10 mmol/l to 3.5 mmol/l further decreased insulin secretion by ~66%  or UCN3 subcutaneously were similar, apparently indicating that UCN3 did not affect intestinal glucose entry, absorption, or disposal. However, this was clearly not the case since both gastric emptying and glucose absorption and insulin secretion were reduced by >50%, in agreement with previous findings in mice and rats [Crhr2 in the gastrointestinal arterioles supports this hypothesis, although in our study, glucose absorption after UCN3 was still reduced to one-third as judged by plasma 3-OMG concentrations. Despite its short-lasting effect on gastric emptying, GLP-1’s reduction of glucose absorption was even more pronounced than that of UCN3, possibly because of additional inhibitory effects on intestinal motility [Crhr2 expression in the gastric submucous plexus and in the submucosal surface of the circular smooth muscle layer of the pyloric antrum.The purpose of this study was to clarify the acute effect of UCN3 on glucose tolerance and to investigate the mechanisms involved. In our first and rats , 15. Herand rats , 17. Gluand rats . Our finmotility . Given tmotility , we hypomotility . InsteadUcn3 ablation in mice or antagonism of CRHR2 in rats led to improved glucose tolerance [With regards to UNC3’s effects on blood glucose, previous studies in rats and mice, using 90–100 nmol/kg UCN3, have shown reduced glucose tolerance following an OGTT ; conversolerance , 5. It wolerance , the twoUcn3 was highly abundant in beta cells but not in alpha cells or delta cells, while Crhr2 was exclusively detected in delta cells. These expression patterns are consistent with previous findings [UCN3 was also expressed in alpha cells, consistent with previous reports [Ucn3-null mice was two- to threefold higher than the insulin secretion from wild-type littermates [With regards to the mechanisms underlying UCN3-mediated suppression of insulin secretion, our expression data on rat islets suggested that this may occur indirectly through SST since findings , 22, 23. reports , 23, 24. reports  during htermates , which atermates  but aligtermates .In this study, we did not observe any changes in the plasma concentrations of glucagon in vivo following UCN3 administration, in contrast to previous reports also arising from rat studies . The expOur study highlights UCN3 as being a powerful inhibitor of gastric emptying and shows that it delays glucose absorption by more than 50%. At the same time, UCN3 inhibits glucose-stimulated insulin secretion by paracrine mechanisms that depend on SST secretion. As such, UCN3 may act as a so-called ‘decretin’ , a hormoESM 1(PDF 407 kb)


One of the most science-intensive and developing areas is nano-modified concrete. Its characteristics of high-strength, high density, and improved structure, which is not only important at the stage of monitoring their performance, but also at the manufacturing stage, characterize high-performance concrete. The aim of this study is to obtain new theoretical knowledge and experimental-applied dependencies arising from the “composition–microstructure–properties” ratio of high-strength concretes with a nano-modifying additive of the most effective type. The methods of laser granulometry and electron microscopy are applied. The existing concepts from the point of view of theory and practice about the processes of cement gel formation during the creation of nano-modified high-strength concretes with nano-modifying additives are developed. The most rational mode of the nano-modification of high-strength concretes is substantiated as follows: microsilica ground to nanosilica within 12 h. A complex nano-modifier containing nanosilica, superplasticizer, hyperplasticizer, and sodium sulfate was developed. The most effective combination of the four considered factors are: the content of nanosilica is 4% by weight of cement; the content of the superplasticizer additive is 1.4% by weight of cement; the content of the hyperplasticizer additive is 3% by weight of cement; and the water–cement ratio—0.33. The maximum difference of the strength characteristics in comparison with other combinations ranged from 45% to 57%. Currently, in modern construction, there is a problem associated with the mismatch of existing traditional building materials with the ever-growing high rate of requirements for buildings and structures. There are problems that relate to territory preparation, problems of complex engineering and geological conditions, differences in the density of urban development, and many other complicating factors that ultimately lead to a large overspending of resources, materials, energy, labor, and time during the construction of buildings and structures.One of the most popular materials used in modern construction is concrete. It is used both for traditional reinforced concrete products and structures and various types of monolithic concreting. At the same time, concrete, remaining one of the most popular applied materials, is also the subject of study and research by many scientists involved in developments in the field of construction.Therefore, one of the most promising concrete types is high-strength concretes. These concretes, class B60 and higher in strength, can reach even more significant values when composed correctly and when the correct technological factors are applied in their manufacture. The class of concrete is the value of the cubic compressive strength of concrete in MPa, which is provided with a confidence probability of 0.95, considering the statistical variability of concrete strength. One of the most science-intensive and developing areas is nanomodified concrete. High-strength concretes are characterized not only by high-strength characteristics, but also by high density and improved structure, which is important to ensure not only at the stage of monitoring their performance, but most importantly, at the stage of their manufacture.The prior knowledge required to study building materials, their properties, characterization methods, and standard laboratory test methods is provided in . The useSlag nanomodification of cement composites has already established itself as a promising and effective solution for improving the micro- and macrostructure of various characteristics of concretes, mortars, products, and structures composed of them ,9,10,11.Ash, similar to slag, is also an effective additive in concrete, used as a replacement for a part of cement, or in the form of a nanomodifying additive, improving the compressive and flexural strength, plasticity, and deformation characteristics ,19,20,21A common method for obtaining high-strength concretes is the addition of carbon nanotubes (CNTs) or multilevel carbon nanotubes (MWCNTs) ,24,25,26The modification of the following types of additives proved to be effective in improving the characteristics of cement composites: flask, diatomite , ultrafiThe investigation of calcium silicate hydrate gel, which is the main binder phase in Portland cement, at the micro- and nanoscales allows us to identify and quantify the strength scaling “mechanisms arising from various types of defects, and critically assesses the susceptibility of CSH gel to physical and/or chemical wear, quantifies determining their influence on the structural integrity of the gel, which is subsequently projected as a decrease in the bearing capacity of the material” . The mecModification with microsilica is currently very popular due to its effectiveness in improving the properties of concrete both separately and in combination with other additives ,41,42,43The nano-modification of concrete with nanosilica ,49,50,51Article  describeIn general, in the technology of high-strength concrete, it is important to take into account a number of factors that guarantee the creation of a strong and dense concrete structure with a correspondingly high final strength see .It has been established that the physical and mechanical properties of cement stone and concrete as a whole are affected by the ratio between the crystalline and gel-like phases, as well as the presence of ultrafine filler, including nanoparticles. With the optimal ratio between the gel-like and crystalline components of the composite mass, a denser packing of filler grains is provided .The most promising direction in the creation of nano-modifying additives is the development of complex nano-modifiers, for which new-generation superplasticizers are used in combination with various nanosized active and low-active mineral additives. To control the processes of structure formation of cement systems, it is necessary to synthesize such organomineral substances, which, depending on the structure of the inorganic carrier and the organic component, the degree of modification of the sorbent and the strength of the fixation of organic substances on the surface of the solid phase will be able to split off the organic substance in the required technological period and thereby provide a differential impact on the rheological properties, rate of hydration, and localization of neoplasms .2) and aluminate phases of the hardening cement have a significant effect on hardening, which leads to the formation of easily soluble hydroxides and sparingly soluble calcium salts” [The achievement of the maximum characteristics of high-strength concretes is due to the effectiveness of the superplasticizers used, which ensure the production of workable mixtures at the lowest possible values of the water–cement ratio. In this study, the optimization of the compositions of nano-modifiers was conducted. The “influence of sulfate-containing additives such as sodium sulfate is reduced to accelerating the hydration of the silicate phases of cement by increasing the ionic strength of the solution. In addition, the exchange reactions of the additive anion with the portlandite phase (Ca(OH)m salts” .-Nanosized particles provide an increase in the volume of chemisorption-bound water and a decrease in capillary-bound water; all this together leads to an increase in the packing density of dispersed particles and a general decrease in the porosity of the cement matrix;-The catalytic role of nanosized particles as crystallization centers with the corresponding effect of lowering the energy threshold of this process and accelerating it;-Nanosized particles participate in the chemical processes of the phase formation of hydrated compounds.The influence of nanoscale modifiers on the hardening system of high-strength fine-grained concretes can be explained as a result of the interaction of several mechanisms:Therefore, for example, the implementation of the first mechanism depends directly on the physical characteristics of nano-additives (granulometric composition and specific surface area) and their dosage.The catalytic mechanism is realized at the stages of colloidation, nucleation, and phase formation, when nanosized particles act as crystalline seeds and crystallization centers.A chemical interaction can be performed only under the condition that the composition of the particles substantially corresponds to the products of hydration of cement minerals .Thus, there is a scientific deficit, to which the research will be directed, as well as to the solution of applied problems of modern construction, described above.-Firstly, the study of the process of cement gel formation during the creation of nano-modified high-strength concretes with nano-modifying additives;-Secondly, we choose the most rational way of performing the nano-modification of such concretes through additional research in terms of optimization;-Thirdly, and finally, by linking the well-known combination of “composition–structure–properties” in relation to nano-modified concrete, we show the applied effectiveness of the theoretical knowledge obtained for the structure formation and properties of high-strength concrete using nano-modifiers.Due to the fact that the subject of the study is not only the characteristics of the finished concrete, but also the process of its structure formation, we set the following research objectives:The aim of the study is to obtain new theoretical knowledge and experimental-applied dependencies arising from the “composition–microstructure–properties” ratio of high-strength concretes with a nano-modifying additive of the most effective type.Portland cement grade PC 500 D0 (CEM I 42.5 N) produced by OAO Novoroscement was used as a binder in the experimental studies. The main characteristics and chemical and mineralogical compositions of the cement are presented in Quartz sand produced by OAO Arkhipovsky Quarry  was used as a fine aggregate. Fine aggregate characteristics, according to GOST 8736–2014 “Sand for construction works. Specifications”, are presented in Microsilica grade MK-85 was used as a nano-modifying additive. The chemical composition, granulometric characteristics, and X-ray diffraction analysis of microsilica are presented in ,56,57.To regulate the processes of structure formation of concrete mixtures and the physical and mechanical properties of concrete, various chemical additives were introduced into the composition of the molding mixtures: superplasticizer MELFLUX 1641 F BASF Construction Additives ; hyperplasticizer “MC-PowerFlow”  based on the latest technology of MS polycarboxylate esters; and sodium sulfate MetallEnergoHolding group of companies . The technical characteristics of the additives are presented in The grinding of microsilica MK-85 was performed in a planetary ball mill “Activator-4M”  for 2, 4, 6, 8, 10, 12, and 14 h at a speed of 800 rpm.-Technological equipment—laboratory concrete mixer BL-10 ;-Testing equipment—hydraulic press IP-1000 , R-50 tensile testing machine ;-Measuring instruments ,62,63,64For the manufacturing and further testing of samples in this study, the following equipment was used:The structure of the modified cement stone was studied using a ZEISS CrossBeam 340 double-beam scanning electron/ion microscope equipped with an Oxford Instruments X-Max 80 X-ray microanalyzer (Carl Zeiss Microscopy GmbH (Factory), Jena, Germany)” .The study of the granulometric characteristics was conducted using a CPS Disk Centrifuge DC24000 centrifuge . The CPS centrifuge is a fast and sensitive particle-size analyzer for colloidal solutions. This instrument works with particles ranging in size from 10 nm to 40 µm.3 of concrete mix, and the consumption of fine aggregate was 1175 kg per 1 m3 of concrete mix. The content of the sodium sulfate additive also remained unchanged and amounted to 1.5% by weight of the binder.The amount of binder and sand for the preparation of the experimental compositions of high-strength fine-grained concrete remained unchanged. The consumption of cement was always 760 kg per 1 mTo achieve the maximum effect of modification with a complex additive, the following procedure for preparing a fine-grained concrete mixture was adopted. To a thoroughly mixed mixture of aggregate, Portland cement and sodium sulfate with the addition of the superplasticizer MELFLUX 1641 F, a part of the mixing water  was added. Separately, in the Activator-4M planetary ball mill, a complex nano-modifier was prepared in the form of a suspension, consisting of a mineral additive (nanosilica), the MC-PowerFlow hyperplasticizer, and the rest of the mixing water. Subsequently, the finished nano-modifier in the form of a suspension was added to the concrete mixture and mixed for 5 min. With such a scheme for preparing a concrete mixture, competitive adsorption of two superplasticizers for positively charged active functional groups on the surface of the solid phase was excluded. In this case, the superplasticizer introduced into the mixture of aggregate with Portland cement paste was adsorbed on particles of clinker minerals and hydrate neoformations, dispersing the formed floccules .Ready-mixed concrete was poured into metal molds  and vibrated on a laboratory vibration platform SMZh-539-220A . Then, the molds with the mixture were placed in a normal hardening chamber  and kept there for a day. Subsequently, the samples were removed from the molds and again placed in the hardening chamber, where they were kept for another 27 days. Following 28 days, the samples were subjected to strength tests according to GOST 10180 “Concretes. Methods for strength determination using reference specimens”.The experimental research program is shown in To determine the optimal conditions for the mechanical dispersion of microsilica to a nanoscale state, several experiments were conducted. The grinding of microsilica was performed at a speed of 800 rpm.The size distribution of microsilica particles following grinding is shown in Note that, with an increase in the grinding time, significant changes in the particle-size distribution can be observed. Thus, for silica fume subjected to mechanical activation for 4 h, the maximum peak falls on particles 170 nm in size and amounts to 7.4%; with the increase in the dispersion time reaching 8 h, the maximum peak of the distribution of the particles shifts to the left, which corresponds to particles with a size of 160 nm and is 9.2%. The same is true for particles ground for 10 h; however, here, a sharper jump is observed towards a decrease in particle dispersion. Here, the peak falls on particles 120 nm in size and amounts to 10.3%. When microsilica is activated for 12 h, the peak falls on particles of 80 nm (11.4%); that is, the jump in the decrease in dispersion is comparable to a grinding time of 10 h. However, with an increase in the grinding time to 14 h, the peak, as well as at 12 h, falls on particles with a size of 80 nm and amounts to 11.8%. From all this, we can conclude that the most effective mode of mechanical dispersion of microsilica is its grinding for 12 h at a speed of 800 rpm.The optimization of the composition of the nano-modifier was performed using the Box–Wilson second-order orthogonal compositional planning method.The optimization parameters and values of the variation factors are shown in The results for determining the strength characteristics of fine-grained high-strength concretes modified with a nano-additive are presented in t-test, and the adequacy of the regression equations for the experimental data was checked using the Fisher criterion. Thus, according to the results of the calculations, the following regression Equations (1)–(4) were obtained:The significance of the coefficients of the regression equation was checked using the Student’s It follows from the data in Additionally, the most effective combination of all four studied factors is:-The content of nanosilica—4% by weight of cement;-Content of superplasticizer additive MELFLUX 1641 F—1.4% by weight of cement;-The content of the hyperplasticizer additive “MC-PowerFlow”—3% by weight of cement;-Water–cement ratio—0.33.To illustrate this statement, let us present the influence of each of the factors on the change in the compressive strength of nano-modified high-strength fine-grained concrete .A similar pattern of change is also observed for the axial compressive strength, tensile strength in bending, and axial tensile strength.The introduction of a nano-modifying additive based on silica makes it possible to eliminate the defectiveness of the concrete structure by filling the microcracks and micropores of fine-grained concrete with nanosilica and products of its interaction with cement clinker minerals .The structure formation of a cement composite nano-modified by the developed complex nano-modifier based on nanosilica was studied using photographs of the microstructure, which are shown in In It is clear, according to the test data for a physical experiment, the optimal dosage of nanosilica in high-strength concrete has a parabolic dependence and there are cases of both the undersaturation of concrete with a nano-modifier, which leads to a deterioration in its structure and properties, and possible cases of the oversaturation of concrete with nanosilica, which also reduces its characteristics. and degrades its structure. This can be clearly observed on the microphotographs, in which, at the optimal dosage of nanosilica, the densest structure is observed with the densest packing of particles, the smallest number of microstructural defects, and, in general, the relationship of “the most perfect structure—the best properties” is also clearly observed . In the Having studied the photo of the microstructure of the resulting composite, based on which the nano-modified high-strength concrete on nanosilica is created, we presented a theoretical interpretation and textual description of the obtained photographs of the microstructure. As is known, in traditional concrete without the presence of nano-modifiers, the process of cement hydration is important, and crystallization during concrete-structure formation occurs according to a typical standard scenario with the gradual disappearance of physically bound water from concrete, which accompanies cement hydration and the curing of the concrete during the process. The nano-modifier used by us allowed us to intervene and control the process of the formation of new crystallization centers due to the active interaction between nanosilica particles, provided that these particles were rationally dosed, which allowed new crystallization centers to form in the concrete body and contribute to the formation of a denser packing of particles of an improved structure and, ultimately, greater concrete strength. In this case, we acted not only at the level of physically bound water, but also influenced the process of cement gel formation due to the appearance of new nano-modified crystallization centers.Earlier in the studies , we obtaIn this regard, our current research has led to even better results and made it possible to control the structure and properties of already high-strength concretes, the characteristics of which increase depending on the improvement of the structure due to the method of the nano-modification of high-strength concretes with the addition of nanosilica that we used.The process of the nano-modification of high-strength concretes can be considered in three aspects .E is the energy efficiency of the process of composite-structure formation; τ is the duration of the process of structure formation of the composite; and R is the quality of the resulting composite, namely, its physical and mechanical characteristics.The “Action” aspect can be considered in an effort to perform the “Process” of cement hydration and cement-stone-structure formation to obtain the desired result. Therefore, for example, the effectiveness of the use of complex modifying additives can be assessed according to three criteria: Quantitative and qualitative kinetic changes in the characteristics of the solid–liquid phases and the pore space of hardening cement are the result of the sequential and parallel-sequential flow of the following processes in time: wetting, adsorption, and chemisorption; peptization of cement particles; dissociation of cement clinker minerals and formation of corresponding cations and anions; diffusion of dissociation products from the “surface” to the “intergranular” hydration volume; formation of and changes in the course of diffusion of the concentration gradient of these products in the “surface” and “intergranular” volumes; a gradual increase in the concentration of anions and cations; and the achievement of the state of their saturation and supersaturation in the liquid phase of the “intergranular” volume ,65.τ can be conducted by applying the function of the degree of cement hydration in time h = fV(τ), the rate of hydration h/ddVτ, the activation energy of process Ea in a causal correlation of these indicators with the type of nano-modifier additives and their dosage.Thus, the assessment of the effectiveness of nano-modification according to criteria E and The means of controlling the process of cement hydration should first be considered, such as the change in the conditions of saturation and supersaturation of the “water + cement” system with anions and cations. Changing the conditions of saturation and supersaturation usually depends on the rate of hydration and the rate of the diffusion of cations and anions in relation to the “intergranular” volume.The greater the supersaturation created in the system, the lower the energy threshold for the formation of particles of a new phase. At the same time, the higher the saturation, the smaller the critical size of nascent particles ,66.Ea of the hydration process. Its velocity constant K increases exponentially (according to Arrhenius), according toA is the pre-exponential factor (frequency factor) characterizing the frequency of collisions of reacting molecules; R is the universal gas constant; and T is temperature.The effectiveness of introducing additives of nano-modifiers can, based on the foregoing, be characterized by a measure of lowering the energy threshold for the formation of particles of a new phase and, accordingly, decreasing the activation energy cI introduced during the application of nano-additives on the increase in the hydration rate ν results in an increase in the volume increment of the new phase (an increase in the degree of cement hydration) dV per unit time τ according to the expression [At the same time, the influence of the number of crystallization centers pression ,67.(6)d(1)A mechanism that provides an increase in the packing density of the system for the addition of dispersed particles, a decrease in its total porosity, and a change in the structure of the porosity of the material—the nanosized particles present in the system are able, by increasing the volume of adsorption and chemisorption-bound water, to reduce the volume of capillary-bound and free water—lead to change in the rheological properties of the cement paste and concrete mixture, to increase their viscosity and plastic strength;(2)The mechanism associated with the catalytic role of nanosized particles as crystallization centers with the corresponding effect of lowering the energy threshold of this process and accelerating it;(3)The mechanism of zoning the hardening structure by nanosized particles ;(4)The mechanism associated with the possibility of the direct chemical participation of nanosized particles in the heterogeneous processes of the phase formation of hydrate compounds  .In the general case, the structure-forming participation and modifying effect of nanosized modifiers can be the result of the following interrelated mechanisms ,69:(1)A It is clear that the measure of implementation of these mechanisms of the nano-modification of the structure of the cement stone and their effectiveness was determined by the type, characteristics, dosage, and methods of introducing nanosized particles into the system. The implementation of the first mechanism was determined by the following interrelated factors related to the characteristics of additives: size, morphology, surface area, specific surface energy of nanosized particles, and their dosage. With a decrease in the size of nanosized particles, their surface area and specific surface energy related to the mass of particles increases, which not only fills the micropores, but also significantly reduces the amount of capillary-bound and free water, compacting the system. From this point of view, nano-modifiers of various substantive varieties, having a size of no more than 20 nm, of a spherical or tubular structure, capable of not only adsorption, but also chemisorption-binding water, are the most effective. The catalytic mechanism is realized at the stage of colloidation, nucleation, and phase formation, when nanosized particles act as crystalline seeds and crystallization centers. The most important factors in the implementation of this mechanism, depending on the properties of additives, are the following: the substance of nanosized particles and their size, which determine the duration of the mechanism, as well as the concentration of nanosized particles per unit volume of the hardening system. It should be pointed out that small nanosized particles (less than 10–20 nm) related to the minerals of the cement system in their crystallochemical structure can play the role of crystallization centers only for a very short time. Thus, the studies  found thThe material structure zoning mechanism is mainly determined by the specific surface energy of nanosized particles, which, in turn, is a function of particle size and their specific surface area. According to the calculations, the volume of space that is energetically zoned by one nanoparticle with a size of 5–20 nm is not only comparable to its own volume, but can also exceed it by a factor of 2–3. From this point of view, a decrease in the size of the nanoparticles makes it possible not only to significantly saturate the microvolumes of the material with energy, but also to reduce the dosage of nanosized particles, which favorably affects the economic side of the issue of their use in concrete technology. The chemical mechanism can be realized only under the condition that the composition of particles substantially corresponds to the products of hydration of cement minerals, since this is connected with their direct participation in the chemical reactions of the formation of a new phase. It is on this basis that it is preferable to modify the structure of cement stone with nanosized particles of calcium hydrosilicates, calcium hydrosulfoaluminates, chrysotile, and silica .The existing ideas were developed from the point of view of theory and practice concerning the processes of cement gel formation when creating nano-modified high-strength concretes with nano-modifying additives.The main scientific results of the study are as follows.(1)The most rational method for the nano-modification of high-strength concretes was chosen through additional research in terms of optimization. The effective time of grinding microsilica to nanosilica was 12 h;(2)A complex nano-modifier containing nanosilica, superplasticizer, hyperplasticizer and sodium sulfate was developed;(3)The most significant influence on the strength characteristics of high-strength fine-grained concretes was exerted by the following factors: dosage of nanosilica; dosage of superplasticizer; and water–cement ratio;(4)The most effective combination of the four considered factors was obtained: nanosilica content was 4% by weight of cement; the content of the superplasticizer additive was 1.4% by weight of cement; the content of the hyperplasticizer additive was 3% by weight of cement; and water–cement ratio was 0.33. The maximum difference in strength characteristics, in comparison to other combinations, ranged from 45% to 57%, depending on the type of strength;(5)From the point of view of the structure formation of the cement composites, the developed nano-modifier allowed us to interfere and control the process of formation of new crystallization centers due to the active interaction between nanosilica particles, provided that these particles were rationally dosed, which formed new crystallization centers in the concrete body and contributed to the formation of a denser packing of particles that developed a more advanced structure. The effect was proven not only at the level of physically bound water, but also on the process of cement gel formation due to the appearance of new nano-modified crystallization centers.Comprehensively assessing the achieved effect and taking into account the change in the cost of the material due to its nano-modification, reducing defects, and improving the quality and efficiency of construction as a whole, according to preliminary estimates, the cost of construction for improved concrete will decrease by about 10%.The planned, promising directions for the development of research are the theoretical, experimental, and analytical tests of the effectiveness of the proposed ideas in relation to other nanomodifiers.