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Ulcerative colitis (UC) is a gastrointestinal disease with complex etiology, and the shortage of the treatment further intensifies the need to discover new therapies based on novel mechanisms and strategies. TGR5 and DPP4 are beneficial to treat UC through multiple mechanisms, notably increasing GLP-2 levels by promoting secretion and inhibiting degradation respectively. However, some unwanted systemic effects caused by systemic exposure hinder development, especially the gallbladder-filling effects. Herein, we firstly reported a series of high-potency gut-restricted TGR5-DPP4 bifunctional molecules by gut-restriction and multitarget strategies to utilize the positive impacts of TGR5 and DPP4 on UC and avoid unwanted systemic effects. In particularly, racemic compound 15, a high-potency TGR5-DPP4 bifunctional molecule, showed favorable intestinal distribution, preferable efficacy in mice colitis model and good gallbladder safety. Therefore, the feasibility of gut-restricted TGR5-DPP4 bifunctional molecule was confirmed for the treatment UC, providing a new insight into the development of anti-UC drugs.

The effects of water/binder ratio and temperature on hydration heat and properties of ternary blended cement containing slag and iron tailing powder were investigated. The hydration heat was determined by isothermal calorimeter. The Ca(OH)2 content of ternary hardened paste was obtained based on the thermogravimetric results. The microstructure and compressive strength development were also analyzed. Partial substitution of iron tailing powder by slag reduces the early-stage exothermic rate, but increases the cumulative hydration heat at later-stage hydration. The high temperature dramatically increases exothermic rate and cumulative hydration heat, especially for ternary blended cement with large amount of slag. The addition of high quantity of iron tailing powder negatively affects properties development of blended cement. But partial substitution of iron tailing powder by slag increases bound water content, reduces Ca(OH)2 content, refines pore structure, densifies structure and finally improves compressive strength, especially at low water/binder ratio. The early high temperature curing results in poor properties of blended cement containing high quantity of iron tailing powder, but it is advantageous to the properties development of ternary blended cement containing slag and iron tailing powder.

To improve iron tailings utilization, the properties of precast concrete with iron tailing powder as mineral admixture were investigated by measuring the compressive strength and chloride ion permeability of the precast concrete, and determining the chemically bound water content, pore structure, hydration products and morphology of the hardened paste. The results show that precast concrete with 50% iron tailing powder has low compressive strength, low chemically bound water content, porous structure and low resistance to chloride ion permeability compared with Portland cement concrete. Replacing a portion of iron tailing powder with slag or fly ash can reduce the adverse impact of iron tailing powder on the properties of precast concrete. The addition of iron tailing powder does not change the kinds of hydration products produced in precast concrete. Small iron tailing powder particles are beneficial to the properties of precast concrete, but large iron tailing powder particles weakly bond with surrounding hydrates. The microstructure of hardened paste with iron tailing powder and slag is much denser than that with iron tailing powder and fly ash. Iron tailing powder can be used as mineral admixture to produce precast concrete. The most advantageous properties of precast concrete are obtained when using blended mineral admixture of iron tailing powder and slag.

In the intestine, several phenols and aromatic acids are generated by microbiota and are highly related to the formation of uremic toxins. Herein, we developed a new derivatization reagent, 2-bromo-1-[4-(dimethylamino)phenyl] ethyl ketone (BDAPE), that reacted simultaneously with phenols and aromatic acids. Following a reaction within 2 h at 60 °C in the presence of 200 mM potassium carbonate (K2CO3), the obtained BDAPE derivatives were separated on a reversed-phase C18 column and quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in positive electrospray ionization mode. This method allowed a lower limit of quantification (LLOQ) of 0.090 μΜ for 3-indolepropionic acid (3IPA), indole-3-acetic acid (3IAA), p-cresol (PC), benzoic acid (BA), and phenol (PN); 0.30 μΜ for phenylacetic acid (PAA); 0.45 μΜ for 4-hydroxyphenylacetic acid (4HPAA); and 0.60 μΜ for 3-phenylpropionic acid (PPA). Methodological validation further demonstrated acceptable accuracy (%RE

The properties of 5-year-old concrete containing steel slag powder were investigated by determining the compressive strength, porosity, chloride ion permeability, morphology and composition of hydration products. The results show that compared with Portland cement concrete, the concrete containing steel slag powder with the same water-to-binder ratio still has low compressive strength, high interconnected porosity and low resistance to chloride ion permeability after 5 years. Long-term properties of concrete with steel slag powder are improved at low water-to-binder ratio. The higher compressive strength, lower porosity and very low permeability of concrete with higher content of steel slag powder are obtained at 5 years with constant 28 days' compressive strength. Many steel slag powder particles are still not fully reacted after 5 years. The structure of 5-year-old concrete with steel slag powder is much looser than that of Portland cement concrete. The hydration of RO phase is extremely slow even after 5 years. The poor bond between RO phase and hydration products negatively affects the long-term properties of concrete. The incorporation of steel slag powder decreases the Ca/Si and Ca/(Si + Al) ratios of C-S-H gel, but increases the Al/Si ratio of C-S-H gel.

The properties of high-strength concrete under standard curing condition (20 °C, 95% RH), high-temperature curing condition (50 °C) and temperature match curing condition were comparatively investigated. The cumulative hydration heat of composite binder containing fly ash and silica fume is lower than that of composite binder containing the same amount of slag. Addition of fly ash and silica fume clearly reduces the adiabatic temperature rise of concrete, but adding slag leads to higher adiabatic temperature rise than Portland cement concrete. High-temperature curing condition and temperature match curing condition lead to the sustainable increase in compressive strength of concrete containing mineral admixture, but they hinder the later-age strength development of Portland cement concrete. For cement–slag paste and cement–fly ash–silica fume paste, the non-evaporable water contents increase significantly and the pore structures are much finer under high-temperature curing condition and temperature match curing condition, which negatively affect the pore structure of Portland cement paste. The differences in properties of concrete among three curing conditions become smaller with time. The properties obtained under standard curing condition can approximately reflect the long-term properties of high-strength concrete in the real structure. The concrete prepared with cement–fly ash–silica fume composite binder has the highest compressive strength, finest pore structure and best resistance to chloride permeability under any curing condition. This composite binder is very suitable to prepare the high-strength concrete with large volume.

The hydration heat of composite binder containing up to 70 % blast furnace ferronickel slag (BFFS) was determined at 25°C, 45°C and 60°C. The hydration kinetics process and parameters were simulated and analysed. BFFS shows pozzolanic activity in a strong alkaline solution. Increasing the BFFS content retards hydration and reduces the exothermic rate. The high temperature dramatically promotes hydration, especially for the composite binder containing no more than 30 % BFFS. The hydration kinetics process involves nucleation and crystal growth (NG) → interactions at phase boundaries (I) → diffusion (D) at 25°C and 45°C. However, this process becomes NG → D at 60°C. The addition of BFFS decreases the overall hydration rate. BFFS has a smaller effect on the overall hydration of the composite binder than ground granulated blast furnace slag, but has a greater effect than fly ash.

This study investigated the influence of ultrafine metakaolin replacing cement as a cementitious material on the properties of concrete and mortar. Two substitution levels of ultrafine metakaolin (9% and 15% by mass) were chosen. The reference samples were plain cement concrete sample and silica fume concrete sample with the same metakaolin substitution rates and superplasticizer contents. The results indicate that simultaneously adding ultrafine metakaolin and a certain amount of polycarboxylate superplasticizer can effectively ensure the workability of concrete. Additionally, the effect of adding ultrafine metakaolin on the workability is better than that of adding silica fume. Adding ultrafine metakaolin or silica fume can effectively increase the compressive strength, splitting tensile strength, resistance to chloride ion penetration and freeze–thaw properties of concrete due to improved pore structure. The sulphate attack resistance of mortar can be improved more obviously by simultaneously adding ultrafine metakaolin and prolonging the initial moisture curing time.

The hydration heat evolution rate and cumulative hydration heat of composite binder containing slag, fly ash or quartz powder and the reaction degrees of slag, fly ash and cement were determined to investigate the hydration heat of slag or fly ash in the composite binder at 25 °C, 45 °C and 60 °C. Results show that a certain amount of hydration heat of slag is observed at 25 °C, but the amount of hydration heat of fly ash is very small at 25 °C. Elevated temperature promotes the hydration of composite binder and increases the reaction degrees of slag and fly ash. Much more amount of hydration heat of slag or fly ash is determined at elevated temperature. The elevated temperature has greater promoting effect on the reaction of slag than fly ash. There is a good linear relationship between the reaction degree of slag (or fly ash) and the hydration heat of slag (or fly ash). The total hydration heats of per gram of slag and per gram of fly ash are 530 J and 285 J, respectively. The result is acceptable due to the slight deviation between the calculated value and experimental value of cumulative hydration heat of composite binder.

The early-age hydration characteristics of composite binder containing iron tailing powder were investigated by determining the hydration heat, non-evaporable water content, pore structure, and morphology of hardened paste as well as the compressive strength of mortar. The results show that the reaction degree of iron tailing powder is extremely low at early age. Addition of coarse iron tailing powder negatively affects the properties of composite binder paste and mortar. Compared to samples containing coarse iron tailing powder, the samples containing fine iron tailing powder show a large amount of hydration heat, high non-evaporable water content, fine pore structure of hardened paste and high compressive strength of mortar. The iron tailing powder significantly promotes the hydration of binder at low water-to-binder ratio. The iron tailing powder particles are well graded with cement particles in the paste, but the large iron tailing powder particles bond poorly with the surrounding hydrates. The decreasing ratio of compressive strength of mortar is much lower than the replacement level of iron tailing powder, especially for the mortar containing fine iron tailing powder at low water-to-binder ratio.

The calorimetric data of composite binder containing slag or fly ash at different water-to-binder ratios were measured at 298 and 333 K by an isothermal calorimeter. The influences of water-to-binder ratio on the hydration heat characteristics of composite binder were analyzed. Based on the hydration kinetics model, the controlling processes during hydration, nucleation and crystal growth (NG), interactions at phase boundaries (I) and diffusion (D), were determined, and the kinetics parameters were calculated and discussed. The results show that water-to-binder ratio slightly affects the early-stage hydration heat evolution rate and cumulative hydration heat, but a lower water-to-binder ratio results in a lower hydration heat evolution rate and cumulative hydration heat at later stage. The water-to-binder ratio has a great effect on the hydration of composite binder at elevated temperature. Decreasing water-to-binder ratio does not change the hydration mechanism of composite binder, which is NG → I → D at 298 K and becomes NG → D at 333 K. The decrease in water-to-binder ratio increases the apparent rate constant of composite binder containing slag, but the inverse trend is obtained for composite binder containing fly ash during NG process at 298 K. The lower water-to-binder ratio leads to the lower apparent rate constant for composite binder containing large amount of slag or fly ash during NG process at 333 K. Decreasing water-to-binder ratio decreases the apparent rate constant during D process for all samples. The apparent activation energy of composite binder decreases with decreasing water-to-binder ratio.

The reaction degrees of slag and fly ash in composite binder pastes were comparatively studied by selective dissolution and BSE image analysis. The reaction degree of slag or fly ash determined by selective dissolution is higher than that by image analysis at early age, but the inverse regularity is observed at later age. When the selective dissolution method is used, the reaction degrees of slag and fly ash may be overestimated at early age due to the loss of the superfine particles through the filtration and the partial dissolution of slag or fly ash, and underestimated at later age owing to the presence of cement and hydration products. The narrow reacted slag rims formed at early age cannot be accurately identified during image analysis procedure, which leads to an underestimation of the reaction degree of slag. Due to the destruction of fly ash particles during grinding or polishing process, the reaction degree of fly ash obtained by image analysis is overestimated. At later age, the small particles cannot be fully counted at low magnification and the outer part of particles cannot be calculated at high magnification, and thus high reaction degree may be obtained. BSE image analysis could give more reliable results with acceptable error than selective dissolution.

In this study, thermodynamic and kinetic models are established to describe the early hydration of tricalcium silicate, by means of considering of dissolution and precipitation mechanisms separately. Since both the dissolution of C3S and the precipitation of hydration products are affected by the ions concentrations, these two procedures are coupled via the aqueous properties of the solution. In this model, a critical length of outer-CSH is introduced to modify the boundary nucleation and growth. The influence of hydration temperature and particle size distribution on the early hydration kinetics of C3S are evaluated with the newly developed model. A good simulation is obtained.

The G-protein-coupled bile acid receptor TGR5 agonists were widely developed in type 2 diabetes and gastrointestinal disorders, but were also full of challenges, due to the systemic on-targeted side effects, especially the gallbladder-filling effects. Here, to circumvent these risks, several TGR5 agonists with soft-drug designation had been designed and synthesized with the properties of rapid metabolized after drug effect. Among them, compound 19 showed negligible systemic exposure and favorable gallbladder safety on a 3-day continuous administration, providing a novel strategy for developing TGR5 agonists.

The effect of gypsum on the properties of composite binder containing high-volume slag and iron tailing powder was studied by measuring compressive strength, hydration heat, bound water content, hydration products, pore structure and morphology. The addition of gypsum increases early-age compressive strength and bound water content, but the opposite trend is observed at later ages. A higher quantity of gypsum leads to a higher third exothermic peak and a higher total hydration heat. Although incorporating gypsum promotes early hydration of cement and slag, it limits their further hydration at later ages. Adding gypsum forms a large amount of ettringite and densifies early-age pore structure, but it coarsens later-age pore structure. The addition of gypsum increases Ca/Si and S/Si ratios of C-S-H, but it doesn’t affect Al/Si ratio. The addition of gypsum compensates for the poor early-age properties of composite binder containing high-volume slag and iron tailing powder, and the later-age properties are acceptable.

The mechanical properties, microstructure and permeability of high-volume iron tailing powder (HVITP) concrete and high-volume fly ash (HVFA) concrete were comparatively investigated by measuring the adiabatic temperature rise, rate of temperature rise, compressive strength, splitting tensile strength and chloride permeability grade of concrete and determining the pore structure, bound water content and morphology of paste. The total adiabatic temperature rise of HVITP concrete are lower than that of HVFA concrete. But the early higher rate of temperature rise of HVITP concrete is obtained. The HVITP concrete shows low compressive strength and splitting tensile strength, coarse pore structure, loose microstructure and high chloride permeability compared with HVFA concrete with the same water/binder ratio. The early temperature matching curing (TMC) adversely affects the later-age properties development of HVITP concrete, but it promotes the properties development of HVFA concrete. The decrease in water/binder ratio or the partial replacement of ITP with slag improves the properties of HVITP concrete, especially for the early properties under TMC condition. But these two means still lead to properties difference between HVITP concrete and HVFA concrete due to the low reactivity of ITP.

Hydration heat characteristics of blended cement containing up to 50% steel slag were studied at 25 °C, 45 °C and 60 °C by isothermal calorimeter. Kinetics equations were used to explore kinetics of blended cement. Kinetics parameters, n , K , and E a , were calculated and analyzed. Results indicated that the activity of steel slag was very low. Steel slag accelerated the hydration of aluminates but decelerated the hydration of silicates in cement clinker. Small amount of steel slag affected little the hydration process of cement. Elevated temperature obviously promoted the hydration of blended cement. The hydration of blended cement containing no more than 35% steel slag was controlled by nucleation of hydrates in acceleration period and by diffusion of ions in decay period. The hydration of blended cement containing 50% steel slag was mostly dominated by phase boundary reaction, then directly by diffusion. E a increased with increasing steel slag content.

Hydration heat evolution rate and cumulative hydration heat of cement–slag blends were measured at 298, 318 and 333 K by isothermal calorimeter. Based on hydration kinetics model, three hydration processes of composite binder, namely nucleation and crystal growth (NG), interactions at phase boundaries (I) and diffusion (D), were characterized, and the relationship between hydration rate and hydration degree of binder was discussed in individual periods. The kinetics exponent, n, rate constant, K, and apparent activation energy, E a, of hydration were calculated and analyzed. Results indicated that the kinetics model could simulate the hydration process of composite binder containing no more than 70 % of slag, whose process sequence is NG → I → D at 298 and 318 K, but it becomes NG → D at 333 K. Composite binder containing 90 % of slag cannot use this model due to the variation in mechanism. The simulation error has a certain increase as increasing temperature and slag content. E a increases with an increase in slag content.

The microstructure of cement–slag and cement–fly ash pastes leached by fresh water for 2–3 years was investigated by MIP, XRD, TG and SEM. Results indicated that long-term fresh water leaching caused degradation of the pastes in terms of mass loss, increase in porosity and decrease in Ca(OH) 2 content and Ca/Si ratio of C–S–H gel, but showed no decomposition of hydration products. The pastes containing a small amount of fly ash were not damaged severely, incorporation of 65% of fly ash deteriorated most severely, whereas the cement–slag pastes (⩽70%) showed high long-term fresh water leaching resistance.

The compressive strength of mortar, pore structure, hydration heat, and non-evaporable water content of slag-blended cement used to prepare self-consolidating concrete were investigated. The blended cement pastes were cured at different temperatures to simulate the condition of real concrete structure. The blended cement containing 30% of slag possesses almost same characteristics as pure Portland cement. Incorporation of 70% of slag shows much lower properties than them. The dosage of slag in blended cement should be controlled in a reasonable range. Elevated temperature activates the hydration of binders but shortens the hydration continuing time, which results in a coarse paste microstructure and a low final strength.

Hydration heat evolution rate and quantity of cement–slag binder and cement–fly ash binder were measured at 25 °C, 45 °C and 60 °C by isothermal calorimetry. Composite binder hydrates slower than pure cement at 25 °C. The hydration of composite binder is accelerated by the elevated temperature. The hydration heat of composite binder containing no more than 50% of slag and that of pure cement have little difference in the later period at 45 °C. It becomes the same or even higher at 60 °C. The hydration heat between composite binder containing fly ash and pure cement still has certain gap at 45 °C, but the gap is narrowed obviously at 60 °C. Raising temperature promotes the hydration of composite binder greater than that of pure cement. The hydration of composite binder containing slag is very sensitive to temperature.

The characteristics of C-S-H gel in hardened Portland cement pastes and complex binder pastes with ground granulated blast furnace slag were investigated with nanoindentation. The composition of C-S-H gel was analysed with SEM-EDS. The obtained results showed that the volume fraction of LD C-S-H gradually reduced and the volume fraction of HD C-S-H increased with the prolongation of hydration age. Most of the C-S-H gel produced at later age was HD C-S-H. The volume fraction of HD C-S-H increased as the fraction of slag in complex binder pastes increased, suggesting that HD C-S-H was mainly in the hydration products of slag. The chemichal compositions of the two types of C-S-H gel were simlar, meaning that formation and transformation of the two types of C-S-H gel were not affected by their Ca/Si ratio.