Search Results (534)

Janus kinase is critical for cytokine-mediated signaling, and its hyperactivation due to mutations drives various diseases. The activation of Janus kinase 1 (JAK1) involves a conformational transition from a closed to an open state, but the underlying mechanism remains unclear. This study investigates the roles of two tyrosine residues, Y1034 and Y1035, within the activation loop of the tyrosine kinase domain. Molecular dynamics simulations reveal that phosphorylation, particularly bisphosphorylation at Y1034 and Y1035, promotes the transition to the open conformation, with pY1035 exerting a greater influence than pY1034. Phosphorylation increases the negative charge on the TK domain surface, facilitating its dissociation from the FERM domain, while also weakening TK-FERM interactions. However, the loop between the TK and PK domains formed stable hydrogen bonds with other domains, hindering the full activation process. Using 1 µs molecular dynamics simulations is not sufficient for full activation. These findings elucidate the molecular mechanisms governing the JAK1 initial activation and provide insights for targeting its regulation in disease contexts. Full article

In response to the growing issue of iron and manganese pollution in water bodies, this study systematically investigated the adsorption performance of municipal sludge-derived biochar prepared at pyrolysis temperatures ranging from 300 to 700 °C for the removal of Fe²⁺ and Mn²⁺. Among the series of adsorbents (BC300–BC700), BC600—with its well-developed pore structure and high specific surface area—exhibited the best adsorption performance for both metal ions. Kinetic and isothermal adsorption experiments, in combination with XPS characterization, collectively revealed that (1) the adsorption mechanisms of Fe and Mn differ markedly, with Fe adsorption primarily governed by physical interactions, whereas Mn adsorption is largely controlled by chemical processes; (2) Fe²⁺ adsorption occurs mainly via electrostatic interactions and hydrogen bonding; and (3) Mn²⁺ forms carbonate precipitates with C=O groups during redox reactions. Thermodynamic analysis further indicated that the adsorption process was spontaneous and endothermic. Moreover, BC600 demonstrated excellent reusability for Fe adsorption across different water matrices, maintaining efficiencies above 95% after five cycles, although the adsorption performance for Mn declined. This study provides theoretical support for the application of sludge-derived biochar as a cost-effective and efficient adsorbent for metal ion remediation. Full article

The growing use of composites in automotive and aerospace fields highlights the need for effective joining of dissimilar materials. Adhesive bonding offers significant advantages over traditional methods. Therefore, comprehensively exploring the relationship between multiple design variables and joint strength, and subsequently achieving accurate prediction of joint strength based on this understanding, is essential for enhancing the effectiveness and efficiency of adhesive joint structural optimization. However, the joint—the critical yet weakest part—has strength governed by complex structural variables that are not fully understood, limiting optimization potential. Based on the effectiveness of finite element simulation in tensile fracture mechanics, this study developed a deep neural network (DNN). Combining the DNN model with a genetic algorithm (GA), both single-objective and multi-objective optimization were conducted. The single-objective optimization focused solely on maximizing joint strength, while the multi-objective GA further quantified the Pareto optimal trade-offs between joint strength and bond area, identifying compromise solutions. The effectiveness of the optimized parameters was validated, demonstrating higher efficiency and accuracy compared to traditional optimization methods such as response surface methodology (RSM). This integrated approach provides a robust framework for predicting joint strength and achieving effective optimization of bonded structures. Full article

Agriculture plays a crucial role in discussions about environmental challenges because of its ecological footprint and high vulnerability to environmental shocks. To better understand the social and behavioral dynamics among food producers and their perceptions of climate change-related risks, this paper draws on forty-one in-depth, semi-structured interviews with farmers and ranchers in Colorado (USA). Leveraging the concept of social capital, the paper extends the concept analytically in a direction missed by previous research highlighting network structures, such as by focusing on its bonding, bridging, and linking characteristics. Instead, focus centers on the inclusiveness and diversity of values, beliefs, worldviews, and cultural orientations within those networks, arguing that these elements can be just as influential, if not more so in certain instances, than structural qualities. The concept of social capital heterogeneity is introduced to describe a network’s level of diversity and inclusivity. The findings do not question the importance of studying network structures when trying to understand how food producers respond to threats like climate change; an approach that remains useful for explaining social learning, technology adoption, and behavioral change. However, this method misses elements captured through a subjective, interpretivist perspective. With social capital heterogeneity, we can use social capital to explore why farmers and ranchers hold specific values and risk perceptions, peering deeper “within” networks, while tools like quantitative social network analysis software help map their structures from the “outside.” Additionally, social capital heterogeneity provides valuable insights into questions about “effective” agro-environmental governance. The paper concludes by discussing practical implications of the findings and reviewing the limitations of the research design. Full article

The bond market serves dual roles in fiscal and financial spheres, playing a crucial role in coordinating monetary policy. This paper investigates the impact of quantitative and price-based monetary policies on the liquidity level of China’s bond market. A comprehensive index measuring the liquidity of the local bond market is constructed using a combination weighting method that integrates the entropy method and the coefficient of variation. Employing the time-varying stochastic volatility structure vector autoregression (TVP-SV-SVAR) model on data spanning from 2013 to 2021, this study empirically compares the impulse response of local bond market liquidity to monetary policy shocks. The findings reveal that both types of monetary policy operations exhibit asymmetric, nonlinear, and time-varying impacts on bond market liquidity. Quantitative monetary instruments induce deeper impulse responses, with longer-lasting effects. These conclusions offer insights for monetary policy reforms and bond market development in China. Full article

Solvent-exchange-induced in situ forming gel (ISG) refers to a drug delivery system that transforms from a solution state into a gel or solid matrix upon administration into the body and exposure to physiological aqueous fluid. This study investigates the molecular behavior and phase inversion process of cellulose acetate butyrate (CAB)-based in situ forming gel (ISG) formulations containing moxifloxacin (Mx) or benzydamine HCl (Bz) as model drugs dissolved in N-methyl pyrrolidone (NMP) using molecular dynamics (MD) simulations and density functional theory (DFT) calculations. The simulations reveal a solvent exchange mechanism, where the diffusion of water molecules replaces NMP, driving the formation of the CAB matrix. Bz exhibited faster diffusion and a more uniform distribution compared to Mx, which aggregated into clusters due to its larger molecular size. The analysis of the root mean square deviation (RMSD) and radius of gyration confirmed the faster diffusion of Bz, which adopted a more extended conformation, while Mx remained compact. The phase transformation was driven by the disruption of CAB-NMP hydrogen bonds, while CAB–water interactions remained limited, suggesting that CAB does not dissolve in water, facilitating matrix formation. The molecular configuration revealed that drug–CAB interactions were primarily governed by hydrophobic forces and van der Waals interactions rather than hydrogen bonding, controlling the release mechanism of both compounds. DFT calculations and electrostatic potential (ESP) maps illustrated that the acetyl group of CAB played a key role in drug–polymer interactions and that differences in CAB substitution degrees influenced the stability of drug-CAB complexes. Formation energy calculations indicated that Mx-CAB complexes were more stable than Bz-CAB complexes, resulting in a more prolonged release of Mx compared to Bz. Overall, this study provides valuable insights into the molecular behavior of CAB-based Mx-, Bz-ISG formulations. Full article

The interface between high-performance thermoelectric materials and electrodes critically governs the conversion efficiency and long-term reliability of thermoelectric generators under high-temperature operation. Here, we propose Al_xCoCrFeNi high-entropy alloys (HEA) as barrier layers to bond Cu-W electrodes with p-type skutterudite (p-SKD) thermoelectric materials. The HEA/p-SKD interface exhibited excellent chemical bonding with a stable and controllable reaction layer, forming a dense, defect-free (Fe,Ni,Co,Cr)Sb phase (thickness of ~2.5 μm) at the skutterudites side. The interfacial resistivity achieved a low value of 0.26 μΩ·cm² and remained at 7.15 μΩ·cm² after aging at 773 K for 16 days. Moreover, the interface demonstrated remarkable mechanical stability, with an initial shear strength of 88 MPa. After long-term aging for 16 days at 773 K, the shear strength retained 74 MPa (only 16% degradation), ranking among the highest reported for thermoelectric materials/metal joints. Remarkably, the joint maintained a shear strength of 29 MPa even after 100 continuous thermal cycles (623–773 K), highlighting its outstanding thermo-mechanical stability. These results validate the Al_xCoCrFeNi high-entropy alloys as an ideal interfacial material for thermoelectric generators, enabling simultaneous optimization of electrical and mechanical performance in harsh environments. Full article

This paper presents a theoretical model of a thin, penny-shaped piezoelectric actuator bonded to an isotropic thermo-elastic substrate under coupled electrical-thermal-diffusive loading. The problem is assumed to be axisymmetric, and the peeling stress of the film is neglected in accordance with membrane theory, yielding a simplified equilibrium equation for the piezoelectric film. By employing potential theory and the Hankel transform technique, the surface strain of the substrate is analytically derived. Under the assumption of perfect bonding, a governing integral equation is established in terms of interfacial shear stress. The solution to this integral equation is obtained numerically using orthotropic Chebyshev polynomials. The derived results include the interfacial shear stress, stress intensity factors, as well as the radial and hoop stresses within the system. Finite element analysis is conducted to validate the theoretical predictions. Furthermore, parametric studies elucidate the influence of material mismatch and actuator geometry on the mechanical response. The findings demonstrate that, the performance of the piezoelectric actuator can be optimized through judicious control of the applied electrical-thermal-diffusive loads and careful selection of material and geometric parameters. This work provides valuable insights for the design and optimization of piezoelectric actuator structures in practical engineering applications. Full article

Anthraquinone acid dyes are widely used in dyeing polyamide due to their good exhaustion and brightness. While ionic interactions primarily govern dye–fiber bonding, the molecular weight (Mw) of these dyes can significantly influence migration, apparent color strength, and fastness behavior. This study offers comparative insight into how the Mw of structurally similar anthraquinone acid dyes impacts their diffusion, fixation, and functional outcomes (e.g., UV protection) on polyamide 6 fabric, using Acid Blue 260 (Mw~564) and Acid Blue 127:1 (Mw~845) as representative low- and high-Mw dyes. The effects of dye concentration, pH, and temperature on color strength (K/S) were evaluated, migration index and zeta potential were measured, and UV protection factor (UPF) and FTIR analyses were used to assess fabric functionality. Results showed that the lower-Mw dye exhibited higher migration tendency, particularly at increased dye concentrations, while the higher-Mw dye demonstrated greater color strength and superior wash fastness. Additionally, improved UPF ratings were associated with higher-Mw dye due to enhanced light absorption. These findings offer practical insights for optimizing acid dye selection in polyamide coloration to balance color performance and functional attributes. Full article

This study examines the energy behavior of a strengthening system consisting of a Fiber Reinforced Polymer (FRP) plate bonded to a rigid substrate and subjected to tensile loading, where the adhesive interface is governed by a bilinear bond–slip law with a vertical descending branch. The investigation focuses on the interaction between the elastic energy stored in the FRP and the adhesive interface, as well as the characteristic lengths that control the debonding process. Analytical expressions for the strain energy stored in both the FRP plate and the adhesive interface are derived, enabling the identification and evaluation of two critical characteristic lengths as the bond stress at the loaded end approaches its maximum value $l_c$, at which the elastic energies of the FRP and the adhesive interface converge, signaling energy saturation; and $l_{max}$, where the adhesive interface attains its peak energy absorption. Upon reaching the energy saturation state, the system undergoes failure through the sudden and complete debonding of the FRP from the substrate. The onset of unstable debonding is rigorously analyzed in terms of the first and second derivatives of the total potential energy with respect to the bond length. It is further demonstrated that abrupt debonding may also occur in cases where the length exceeds $l_c$ when the bond stress reaches its maximum, and the bond–slip law is characterized by a vertical branch. The findings provide significant insights into the energy balance and stability criteria governing the debonding failure mode in FRP-strengthened structures, highlighting the pivotal role of characteristic lengths in predicting both structural performance and failure mechanisms. Full article

Carboxypeptidase A4 (CPA4) is an exopeptidase that cleaves peptide bonds at the C-terminal domain within peptides and proteins. It preferentially cleaves peptides with terminal aromatic or branched chain amino acid residues such as phenylalanine, tryptophan, or leucine. CPA4 was first discovered in prostate cancer cells, but it is now known to be expressed in various tissues throughout the body. Its physiologic expression is governed by latexin, a noncompetitive endogenous inhibitor of CPA4. Nevertheless, the overexpression of CPA4 has been associated with the progression and aggressiveness of many malignancies, including prostate, pancreatic, breast and lung cancer, to name a few. CPA4’s role in cancer has been attributed to its disruption of many cellular signaling pathways, e.g., PI3K-AKT-mTOR, STAT3-ERK, AKT-cMyc, GPCR, and estrogen signaling. The dysregulation of these pathways by CPA4 could be responsible for inducing epithelial--mesenchymal transition (EMT), tumor invasion and drug resistance. Although CPA4 has been found to regulate cancer aggressiveness and poor prognosis, no comprehensive review summarizing the role of CPA4 in cancer is available so far. In this review, we provide a brief description of peptidases, their classification, history of CPA4, mechanism of action of CPA4 as a peptidase, its expression in various tissues, including cancers, its role in various tumor types, the associated molecular pathways and cellular processes. We further discuss the limitations of current literature linking CPA4 to cancers and challenges that prevent using CPA4 as a biomarker for cancer aggressiveness and predicting drug response and highlight a number of future strategies that can help to overcome the limitations. Full article

Macrocyclic organic nanostructures have emerged as crucial components of functional supramolecular materials owing to their unique structural and chemical features, such as their distinctive “infinite” cyclic topology and tunable topology-dependent properties, attracting significant recent attention. However, the controlled synthesis of macrocyclic compounds with well-defined compositions and geometries remains a formidable challenge. On-surface synthesis, capable of constructing nanostructures with atomic precision on various substrates, has become a frontier technique for exploring novel macrocyclic architectures. This review summarizes the recent advances in the on-surface synthesis of macrocycles. It focuses on analyzing the synthetic mechanisms and conformational characterization of macrocycles formed through diverse bonding interactions, including both covalent and non-covalent linkages. This review elucidates the intricate interplay between the thermodynamic and kinetic factors governing macrocyclic structure formation across these bonding types and clarifies the critical influence of the reaction temperature and external conditions on the cyclization efficiency. Ultimately, this study offers design strategies for the precise on-surface synthesis of larger and more flexible macrocyclic compounds. Full article

Using density functional theory (M06-2X-D3/def2-TZVP), we investigated the 1,2-addition reactions of NH₃ with a series of heavy imine analogues, G13=P-Rea (where G13 denotes a Group 13 element; Rea = reactant), featuring a mixed G13–P–Ga backbone. Theoretical analyses revealed that the bonding nature of the G13=P moiety in G13=P-Rea molecules varies with the identity of the Group 13 center. For G13=B, Al, Ga, and In, the bonding is best described as a donor–acceptor (singlet–singlet) interaction, whereas for G13=Tl, it is characterized by an electron-sharing (triplet–triplet) interaction. According to our theoretical studies, all G13=P-Rea species—except the Tl=P analogue—undergo 1,2-addition with NH₃ under favorable energetic conditions. Energy decomposition analysis combined with natural orbitals for chemical valence (EDA–NOCV), along with frontier molecular orbital (FMO) theory, reveals that the primary bonding interaction in these reactions originates from electron donation by the lone pair on the nitrogen atom of NH₃ into the vacant p-π* orbital on the G13 center. In contrast, a secondary, weaker interaction involves electron donation from the phosphorus lone pair of the G13=P-Rea species into the empty σ* orbital of the N–H bond in NH₃. The calculated activation barriers are primarily governed by the deformation energy of ammonia. Specifically, as the atomic weight of the G13 element increases, the atomic radius and G13–P bond length also increase, requiring a greater distortion of the H₂N–H bond to reach the transition state. This leads to a higher geometrical deformation energy of NH₃, thereby increasing the activation barrier for the 1,2-addition reaction involving these Lewis base-stabilized, heavy imine-like G13=P-Rea molecules and ammonia. Full article

Emerging markets face growing pressures to integrate sustainable English business practices while maintaining economic growth, particularly in addressing environmental challenges and achieving carbon neutrality goals. English Financial information extraction becomes crucial for supporting green finance initiatives, Environmental, Social, and Governance (ESG) compliance, and sustainable investment decisions in these markets. This paper presents FinATG, an AI-driven autoregressive framework for extracting sustainability-related English financial information from English texts, specifically designed to support emerging markets in their transition toward sustainable development. The framework addresses the complex challenges of processing ESG reports, green bond disclosures, carbon footprint assessments, and sustainable investment documentation prevalent in emerging economies. FinATG introduces a domain-adaptive span representation method fine-tuned on sustainability-focused English financial corpora, implements constrained decoding mechanisms based on green finance regulations, and integrates FinBERT with autoregressive generation for end-to-end extraction of environmental and governance information. While achieving competitive performance on standard benchmarks, FinATG’s primary contribution lies in its architecture, which prioritizes correctness and compliance for the high-stakes financial domain. Experimental validation demonstrates FinATG’s effectiveness with entity F1 scores of 88.5 and REL F1 scores of 80.2 on standard English datasets, while achieving superior performance (85.7–86.0 entity F1, 73.1–74.0 REL+ F1) on sustainability-focused financial datasets. The framework particularly excels in extracting carbon emission data, green investment relationships, and ESG compliance indicators, achieving average AUC and RGR scores of 0.93 and 0.89 respectively. By automating the extraction of sustainability metrics from complex English financial documents, FinATG supports emerging markets in meeting international ESG standards, facilitating green finance flows, and enhancing transparency in sustainable business practices, ultimately contributing to their sustainable development goals and climate action commitments. Full article

Electrostatic adsorption plays a crucial role in nanoparticle-based drug delivery, enabling the targeted and reversible loading of biomolecules onto nanoparticles. This review explores the fundamental mechanisms governing nanoparticle–biomolecule interactions, with a focus on electrostatics, van der Waals forces, hydrogen bonding, and protein corona formation. Various functionalization strategies—including covalent modification, polymer coatings, and layer-by-layer assembly—have been employed to enhance electrostatic binding; however, each presents trade-offs in terms of stability, complexity, and specificity. Emerging irradiation-based techniques offer potential for direct modulation of surface charge without the addition of chemical groups, yet they remain underexplored. Accurate characterization of biomolecule adsorption is equally critical; however, the limitations of individual techniques also pose challenges to this endeavor. Spectroscopic, microscopic, and electrokinetic methods each contribute unique insights but require integration for a comprehensive understanding. Overall, a multimodal approach to both functionalization and characterization is essential for advancing nanoparticle systems toward clinical drug delivery applications. Full article