Search Results (884)

Imprinted proteins (IPs) are promising materials for producing artificial alternatives to natural recognition systems (antibodies, aptamers, etc.) due to their high sorption properties and specificity. However, contemporary understanding of the imprinting process at the atomic level is rather limited, which hinders the rational design of more efficient IPs. In this paper, we use computational modeling to provide a description of fundamental principles of protein imprinting at the atomic level. We have modeled several potential associates between the protein matrix and template molecules that form during the imprinting process up to the addition of the cross-linking agent. We used bovine serum albumin (BSA) as the protein matrix and 4-hydroxycoumarin (4–HC) as a molecular template. In combination with computational modeling, extensive experimental analyses including isothermal titration calorimetry (ITC) and NMR spectroscopic methods (¹H NMR and diffusion-ordered NMR spectroscopy (DOSY)) were used to evaluate the potential efficiency of imprinted BSA. This study represents a step toward the future rational in silico design of IPs. Full article

Activation of signal transducer and activator of transcription 3 (STAT3) is implicated in tumor progression and correlates with poor prognosis and reduced survival. In colorectal cancer (CRC), STAT3 activation serves as a key indicator of unfavorable outcomes. However, the scarcity of clinically available STAT3 inhibitors hinders the development of personalized treatment strategies targeting STAT3. Therefore, we aimed to develop a novel STAT3 inhibitor based on the molecular structure of STAT3 and our previously reported STAT3 inhibitor LY17 to inhibit the progression of CRC. The binding of the novel STAT3 inhibitor DB-2B to STAT3 was confirmed by computational docking, surface plasmon resonance, isothermal titration calorimetry, and cellular thermal shift assays. Western blotting and immunofluorescent staining demonstrated that DB-2B specifically inhibited STAT3 activation and nuclear translocation. In vitro studies revealed that DB-2B significantly suppressed proliferation, induced apoptosis, arrested cell cycle progression, and attenuated stemness by inhibiting STAT3 activation and its downstream signaling pathways. In vivo, DB-2B exhibited favorable oral bioavailability and safety, while significantly inhibiting the progression of CRC. Collectively, this study presents DB-2B as a promising small-molecule STAT3 inhibitor for the targeted treatment of CRC. Full article

Background/Objectives: Gold(I) complexes are promising bioactive agents with anticancer and anti-inflammatory potential. This study evaluated cytochrome P450 (CYP) interactions and in vitro pharmacokinetic properties of two Au(I)–triphenylphosphine complexes bearing 6-alkoxy-9-deazapurine ligands. Methods: Complexes [Au(HL_1,2)(PPh₃)] (HL₁ = 6-isopropyloxy-9-deazapurine, complex 1; HL₂ = 6-benzyloxy-9-deazapurine, complex 2) were investigated. Inhibition of nine human CYP isoforms was assessed in liver microsomes, and kinetics were analyzed using Dixon and Lineweaver–Burk plots. CYP binding was evaluated by UV–Vis difference spectroscopy. ADME properties (chemical/plasma stability, microsomal stability, plasma protein binding, and PAMPA permeability) were determined. Binding thermodynamics were analyzed by ITC. Results: Both complexes weakly inhibited most CYP isoforms, with stronger effects on CYP2C9 and CYP3A4/5. A non-competitive inhibition mechanism was observed, which may be related to the binding of the complexes to the substrate channels of CYP2C9 and CYP3A4, thereby limiting the active site’s accessibility to the substrate, as supported by molecular docking studies. UV–Vis spectra showed type I binding with Kd values of 9.32 µM (1) and 12.64 µM (2). Both compounds showed high chemical and plasma stability (>90%), moderate microsomal stability (~60% after 60 min), high plasma protein binding (~80%), and low passive permeability. Conclusions: Au(I)–triphenylphosphine complexes with 6-alkoxy-9-deazapurine ligands exhibit moderate CYP affinity and defined pharmacokinetic profiles, supporting further preclinical evaluation. Full article

Glyphosate is a highly polar herbicide, the reliable molecular recognition of which is complicated by co-occurring structural analogues, metabolites, and derivatives in real-world samples. Rather than reporting new aptamer discovery, this study establishes a standardized, solution-phase isothermal titration calorimetry (ITC) workflow to thermodynamically reassess two literature-reported glyphosate DNA aptamers, Seq03 and Seq05, under matched buffer composition and instrument settings. After verification of baseline stability and evaluation of heat-of-dilution contributions, ligand-to-aptamer titrations yielded apparent dissociation constants of approximately 8.14 μM for Seq03 and 40.2 μM for Seq05, enabling affinity-based prioritization of these reported candidates within the tested concentration window. To define an application-relevant selectivity boundary, we further constructed a counter-screen panel restricted to glyphosate-related chemicals, including structural analogues, metabolites, and derivatives, and evaluated all candidates using an identical ITC protocol with explicit background handling. None of the counter-screen compounds produced binding-consistent, saturable isotherms after integration and control-based interpretation; instead, their responses remained close to background heat and were therefore operationally classified as having no detectable binding under the tested conditions, including a reverse-titration format check with Glufosinate-N-acetyl. Collectively, these results position ITC as a label-free, platform-independent validation step for small-molecule aptamer benchmarking prior to analytical translation, while also highlighting that the present conclusions are bounded by the tested PBS-based conditions and the sensitivity window of the current ITC configuration. Full article

Ultra-high-performance concrete (UHPC) matrix faces critical challenges of high carbon footprint and significant autogenous shrinkage. Supersulfated cement (SSC), a potentially lower-carbon binder comprising ground granulated blast-furnace slag and gypsum, offers a promising alternative. This study systematically investigated the effect of gypsum type—phosphogypsum (PG), dihydrate gypsum (DH), and anhydrite (AH)—on the early hydration and shrinkage behavior of UHPC matrix incorporating 30% SSC as Portland cement replacement. A multi-technique approach, including mechanical testing, isothermal calorimetry, XRD, TG-DSC, SEM, LF-NMR, and autogenous shrinkage measurements, was employed. Results demonstrate that gypsum type critically governs sulfate dissolution kinetics, thereby dictating phase assemblage and microstructural evolution. DH provides relatively rapid sulfate dissolution, promoting earlier AFt and gel formation, which is associated with the highest early strengths and a marked reduction in autogenous shrinkage. AH shows a slower but sustained sulfate supply, resulting in comparable 28-day strength with moderate shrinkage reduction. PG yielded the lowest autogenous shrinkage (374 μm/m at 7 d), but it also suffered from severe early-age retardation due to soluble phosphate impurities, as evidenced by the delayed hydration peak and lowest 3 d strength. This behavior is mainly related to strong early-age retardation, delayed hydration, delayed setting, and a prolonged low-stiffness state. These findings suggest that appropriate gypsum selection in SSC enables tailored early-age performance and improved volume stability in the UHPC matrix, offering guidance for utilizing industrial by-products such as phosphogypsum in sustainable high-performance concrete design. Full article

Bongkrekic acid is a lethal mitochondrial toxin produced by Burkholderia gladioli pathovar cocovenenans, posing severe threats to food safety due to their high stability and the lack of effective antidotes. Developing specific, high-affinity recognition elements is crucial to overcoming the limitations of current BA detection methods in food matrices, and thereby safeguarding food safety and public health. In this study, we report for the first time the selection and remodelling of a DNA aptamer with high affinity for BA, which could be used as a promising recognition tool for sensitive BA detection in food. Integrating isothermal titration calorimetry, molecular docking, and molecular dynamics simulations revealed that the binding of BA to F3-1 follows an induced-fit mechanism. This study is the first to report a DNA aptamer with nanomolar affinity for BA, clarify its underlying binding mechanism, and provide a reliable recognition element for sensitive and specific BA detection in food samples. Full article

This review synthesizes recent advances in the characterization of eco-friendly cement composites, focusing on hydration kinetics, microstructural evolution, and mechanical durability. Advanced techniques—from isothermal calorimetry to nanoindentation—enable decoding of reaction pathways, mix optimization, and long-term performance prediction. The analysis covers supplementary cementitious materials (fly ash, slag, silica fume), geopolymers, bio-based additives (SNSs, biochar, CNCs, lignosulfonates), and microbially induced calcite precipitation (MICP). For each category, key mechanisms are identified, property effects quantified, and microstructural correlations established. SCMs achieve pore refinement and enhanced durability through long-term pozzolanic reactions. Geopolymers exhibit exceptional thermal stability (800–1000 °C) and acid resistance. Fly ash-based geopolymers exhibit chloride diffusion coefficients 1–2 orders of magnitude lower than ordinary Portland cement (OPC), though slag-based systems show more moderate improvements due to their different pore structure and higher calcium content. Bio-based additives enable accelerated hydration (SNSs), internal curing and CO₂ sequestration (biochar), pore refinement (CNCs), workability enhancement (lignosulfonates), and autonomous crack healing (MICP). Multi-scale characterization is essential for establishing robust structure–property relationships. The review concludes that properly optimized eco-friendly cement composites offer viable pathways toward sustainable construction with reduced carbon footprint, enhanced durability, and extended service life. This review is novel in its systematic comparison of hydration kinetics, microstructural evolution, and mechanical performance across three distinct classes of eco-friendly additives (SCMs, geopolymers, and bio-based materials), with particular emphasis on the complementarity of advanced characterization techniques—an aspect that has received limited attention in previous reviews. Full article

Achieving low hydration heat without sacrificing strength is essential for early-age temperature-crack control in concrete. This study designed a low-heat Portland cement (LHPC)–fly ash (FA)–ground-granulated blast-furnace slag (GGBS)–silica fume (SF) binder system with LHPC fixed at 80 wt.% and total supplementary cementitious materials (SCMs) fixed at 20 wt.%. Compressive strength at 3, 7, and 28 d, 7 d isothermal calorimetry combined with Krstulović–Dabić (K–D) modeling, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) were used to identify a low-heat/high-strength pathway. The mixture containing 20 wt.% FA (F20) reduced the 7 d cumulative heat to 194.060 J·g⁻¹ but lowered the 28 d compressive strength to 44.2 MPa. Replacing FA with GGBS under the same replacement level restored the strength baseline, and the mixture containing 20 wt.% GGBS (G20) reached 56.7 MPa. Introducing SF created an optimum compositional window, and the mixture containing 10 wt.% FA, 3 wt.% GGBS, and 7 wt.% SF (F10G3S7) achieved the highest 28 d strength of 58.2 MPa. Notably, the mixture containing 10 wt.% FA, 9 wt.% GGBS, and 1 wt.% SF (F10G9S1) combined relatively low 7 d heat (203.545 J·g⁻¹) with high 28 d strength (54.2 MPa). K–D fitting showed that FA lowered the heat potential (Qmax = 217.98 J·g⁻¹) relative to LHPC (236.19 J·g⁻¹), whereas GGBS/SF blends increased Qmax to 268.77–271.55 J·g⁻¹, indicating composition-dependent hydration efficiency. TGA revealed higher bound water per unit LHPC at 28 d (21.46–22.97%) than in LHPC alone (17.17%), and bound water correlated more strongly with compressive strength (R² = 0.75–0.78) than calcium hydroxide (CH) content (R² = 0.66–0.67). SEM confirmed a more continuous gel-rich matrix in F10G9S1, suggesting that the low-heat/high-strength route is governed by efficient heat-to-hydrate conversion and microstructural densification rather than heat output alone. These findings provide both mechanistic insight and practical guidance for proportioning low-heat, high-strength binders for concrete applications requiring early-age temperature-crack control. Full article

Mechanically activated pyrite plays an important role in gold extraction and coal utilization, but its reactivity may change markedly during storage. This study investigates how air deactivation during storage affects the crystal structure and subsequent thermal decomposition behavior of mechanically activated pyrite. Pyrite was mechanically activated and then stored in air for 0, 7 and 180 days. X-ray diffraction (XRD) combined with Rietveld refinement was used to characterize variations in lattice parameters and unit-cell-related structural features, while non-isothermal thermogravimetric–differential scanning calorimetry (TG-DSC) under an argon atmosphere, together with the Flynn–Wall–Ozawa (FWO) method, was applied to evaluate the decomposition kinetics. Air deactivation induced a non-monotonic evolution of lattice parameters and unit-cell volume, which is attributed to combined effects of residual stress relaxation and air-induced surface-related modification during storage. All samples exhibited two mass-loss stages during heating, reflecting stepwise thermal decomposition, and their decomposition behavior varied systematically with deactivation time. The apparent activation energy depended on both conversion fraction and deactivation degree, and nucleation-and-growth-type mechanisms were found to dominate the decomposition process, with their relative contributions evolving with storage time. These results clarify how prior air-deactivation history influences the structural evolution and subsequent thermal decomposition behavior of mechanically activated pyrite and provide useful insight for its storage and utilization in related processes. Full article

This study used calcium hydroxide (CH) to simulate the alkaline environment of cement and to activate lithium slag (LS), aiming to reveal the mechanism of LS in cement. The early-age hydration of LS blended with 10 wt.% CH was monitored via isothermal calorimetry (ICC) at ambient temperature, followed by a comparative analysis of phase assemblage, microstructure, and macroscopic properties under standard and steam curing conditions. The results show that LS exhibits superior early reactivity within the first 9 h, which is attributed to abundant ettringite formation. Two distinct exothermic peaks were identified during LS-CH hydration, corresponding to (i) ettringite formation accompanied by LS dissolution and C–S–H precipitation, and (ii) CaCO₃ crystallization and renewed ettringite formation. The hydrated paste consists of abundant AFt, CaCO₃ polymorphs, unreacted LS particles, and a small amount of C–S–H gel with a low Ca/Si ratio and incorporating Al and S. This unique phase assemblage results in a coarser pore structure and lower specific surface area compared with conventional cement paste. Nevertheless, the system achieves a relatively high 28-day compressive strength, highlighting the promise of LS-CH blends as sustainable cementitious materials. Full article

Background/Objectives: PDE4 is a key regulator of cAMP signaling and a clinically validated anti-inflammatory target; however, the use of PDE4 inhibitors is often limited by adverse effects such as nausea, vomiting, and diarrhea. The natural compound braylin was previously identified as a novel PDE4 inhibitor scaffold, exhibiting an IC₅₀ of 0.96 µM. Using the PDE4–braylin co-crystal structure, we conducted structure-based design and optimization to enhance its potency. Methods: A series of novel braylin derivatives was synthesized and characterized. Their inhibitory activities against PDE4D were evaluated via enzymatic assays, and binding thermodynamics were analyzed by isothermal titration calorimetry (ITC). Molecular modeling was used to predict binding modes, and anti-inflammatory effects were assessed in LPS-stimulated macrophages. Results: Structure-guided optimization yielded lead compound L27, which showed significantly improved PDE4D inhibition (IC₅₀ = 67 nM) and high-affinity binding (K_d = 45 nM) as confirmed by ITC. L27 also exhibited remarkable selectivity against PDE isoforms. Molecular simulations highlighted key interactions with Gln369 and hydrophobic residues in the PDE4 active site. In cellular assays, L27 dose-dependently suppressed LPS-induced inflammation in macrophages at non-cytotoxic concentrations with efficacy comparable to roflumilast. Conclusions: We developed L27, a potent and selective PDE4 inhibitor derived from natural braylin. It demonstrated promising in vitro anti-inflammatory activity and represents a valuable lead for further therapeutic development. Full article

In liquid composite moulding processes, the curing behaviour of thermoset matrices plays a decisive role in determining manufacturing quality and cycle time. Premature demoulding may lead to insufficiently cured components, whereas excessively long curing times reduce production efficiency. Reliable monitoring and modelling of the curing process are therefore essential for process optimisation. In this study, the cure kinetics of a fast-curing epoxy resin system are modelled using the Grindling kinetic model, which accounts for diffusion-controlled reaction behaviour and vitrification effects. Model parameters are identified using both dynamic and isothermal differential scanning calorimetry (DSC) measurements. In addition, the glass transition temperature is described as a function of the degree of cure using the DiBenedetto relationship. To demonstrate the applicability of the model for process monitoring, an experimental mould equipped with temperature sensors was developed to simulate real-time estimation of the degree of cure during isothermal processing. The predicted degree of cure is validated by post-process DSC analysis of the manufactured samples. Initial comparisons reveal systematic deviations caused by temperature measurement uncertainties. After implementing a temperature correction based on experimentally determined sensor deviations, the predicted degree of cure shows significantly improved agreement with DSC measurements. The results demonstrate that combining kinetic modelling with temperature monitoring enables reliable real-time estimation of the curing state for fast-curing epoxy systems. The study also highlights the critical importance of accurate temperature measurement for curing monitoring and provides insights into the practical implementation of sensor-based monitoring strategies in liquid composite moulding processes. Full article

To overcome polymer-based plugging materials’ disadvantage of being prone to degradation and failure under hydrothermal conditions, an epoxy resin plugging particle with a high-pressure-bearing capacity under high temperatures was prepared by optimizing the curing process. Bisphenol A Epoxy Resin E51 and Diethyltoluenediamine (DETDA) were selected as raw materials for sample preparation. Due to the high viscosity of the system, 1,2-cyclohexanediol diglycidyl ether was introduced as a diluent, and an optimal concentration of 20% was determined through experimental optimization. Non-isothermal differential scanning calorimetry, bottle testing, and infrared spectroscopy were employed to investigate the variation laws of curing temperature, curing time and curing degree during the epoxy resin curing process via one-step and multi-step methods. The compressive strength of the epoxy resin prepared using the two processes was evaluated. After comprehensively comparing the preparation time, process complexity, and compressive strength of the final samples of the one-step and two-step curing methods, the one-step process (90 °C/5 h) was determined to be superior. In addition, the results of the fracture plugging experiment showed that after the bulk epoxy resin prepared using the optimized process was made into particles through a mechanical method and treated under hydrothermal conditions at 120 °C, the maximum breakthrough pressure reached 4.2 MPa, which was 950% and 135.96% higher than that of Particle 1 (Poly(2-acrylamido-2-methylpropanesulfonic acid)/acrylamide (PAMPS/AM) gel) and Particle 2 (PAMPS/AM gel treated with Polyethylene glycol (PEG)), respectively, which were used as control groups. This result indicates that epoxy resin can be used as a high-temperature-resistant plugging material and should be further researched. Full article

This study investigates the residual stresses developed during the curing process of polymer fiber-reinforced composites and their influence on fracture behavior, particularly the initiation and propagation of interlaminar cracks. The main objective is to quantify how different curing histories, including incomplete cure, alter the spatial distribution of residual stresses and, in turn, affect the mode-I fracture response of carbon-fiber/epoxy laminates. A transient thermal–structural finite element framework incorporating an autocatalytic cure kinetics model was used to simulate the curing process and predict residual stress development in a unidirectional carbon-fiber/epoxy laminate with an edge crack, considering thermal, chemical, and geometric effects. The cure model was calibrated using isothermal differential scanning calorimetry data to determine the degree of cure under different thermal conditions. The key novelty of this work is the integration of a validated cure-kinetics-based curing simulation with fracture analysis, enabling direct correlation of thermal history and degree of cure with spatially varying residual stresses at the crack front and their effect on fracture toughness. Numerical load–displacement predictions were compared with double cantilever beam experimental results and showed good agreement for the curing profiles examined. The results demonstrate that residual stresses generated by different cure cycles, including hold conditions and incomplete curing, significantly influence fracture toughness. In particular, the incomplete-cure profile produced an approximately 40% reduction in toughness compared with profiles that achieved complete cure, highlighting the importance of cure history in determining final structural performance. Full article

Heat is a crucial factor in all biological processes; therefore, measuring heat change can be a powerful tool for monitoring bioprocesses and metabolism, analyzing biomolecular interactions, and studying cells. The insights gained from thermal measurements can also aid healthcare applications, such as drug susceptibility testing and disease diagnosis. Calorimetry, the science of measuring heat, has seen many advances. However, the pressing need for miniaturization, combined with breakthroughs in micro- and nanofabrication, has led to the development of chip calorimeters and accelerated their innovation. In this comprehensive review, we discuss significant advances in chip calorimetry, including figures of merit, various applications, and key challenges. The review offers an overview of the current state of the art, highlighting prospects and opportunities. Full article