Search Results (14,859)

Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article

Pelvic organ prolapse (POP) is a prevalent condition, affecting women all over the world, and is commonly treated through surgical interventions that present limitations such as recurrence or complications associated with synthetic meshes. In this study, biodegradable poly($ϵ$-caprolactone) (PCL) cog threads are proposed as a minimally invasive alternative for vaginal wall reinforcement. A custom cutting tool was developed to fabricate threads with varying barb angles (90°, 75°, 60°, and 45°), which were produced via Melt Electrowriting. Their mechanical behavior was assessed through uniaxial tensile tests and validated using finite element simulations. The results showed that barb orientation had minimal influence on tensile performance. In simulations of anterior vaginal wall deformation under cough pressure, all cog thread configurations significantly reduced displacement in the damaged tissue model, achieving values comparable to or even lower than those of healthy tissue. A ball burst simulation using an anatomically accurate model further demonstrated a 13% increase in reaction force with cog thread reinforcement. Despite fabrication limitations, this study supports the biomechanical potential of 3D-printed PCL cog threads for POP treatment, and lays the groundwork for future in vivo validation. Full article

Global warming and anthropogenic climate change are projected to expand the geographic distribution and population abundance of ectothermic species and exacerbate the biological invasion of exotic species. DNA methylation, as a reversible epigenetic modification, could provide a putative link between the phenotypic plasticity of invasive species and environmental temperature variations. We assessed and interpreted the epigenetic mechanisms of invasive and indigenous species’ differential tolerance to thermal stress through the invasive species Bemisia tabaci Mediterranean (MED) and the indigenous species Bemisia tabaci AsiaII3. We examine their thermal tolerance following exposure to heat and cold stress. We found that MED exhibits higher thermal resistance than AsiaII3 under heat stress. The fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) results proved that the increased thermal tolerance in MED is closely related to DNA methylation changes, other than genetic variation. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis of DNA methyltransferases (Dnmts) suggested that increased expression of Dnmt3 regulates the higher thermal tolerance of female MED adults. A mechanism is revealed whereby DNA methylation enhances thermal tolerance in invasive species. Our results show that the Dnmt-mediated regulation mechanism is particularly significant for understanding invasive species’ successful invasion and rapid adaptation under global warming, providing new potential targets for controlling invasive species worldwide. Full article

Background/Objectives: Most snakebite incidents in Latin America are caused by species of the Bothrops genus. Their venom induces severe local effects, against which antivenom therapy has limited efficacy. Metabolites derived from Coffea arabica have demonstrated anti-inflammatory and anticoagulant properties, suggesting their potential as therapeutic agents to inhibit the local effects induced by B. asper venom. Methods: Three enzymatic assays were performed: inhibition of the procoagulant and amidolytic activities of snake venom serine proteinases (SVSPs); inhibition of the proteolytic activity of snake venom metalloproteinases (SVMPs); and inhibition of the catalytic activity of snake venom phospholipases A₂ (PLA_2s). Additionally, molecular docking studies were conducted to propose potential inhibitory mechanisms of the metabolites chlorogenic acid, caffeine, and caffeic acid. Results: Green and roasted coffee extracts partially inhibited the enzymatic activity of SVSPs and SVMPs. Notably, the green coffee extract, at a 1:20 ratio, effectively inhibited PLA₂ activity. Among the individual metabolites tested, partial inhibition of SVSP and PLA₂ activities was observed, whereas no significant inhibition of SVMP proteolytic activity was detected. Chlorogenic acid was the most effective metabolite, significantly prolonging plasma coagulation time and achieving up to 82% inhibition at a concentration of 62.5 μM. Molecular docking analysis revealed interactions between chlorogenic acid and key active site residues of SVSP and PLA₂ enzymes from B. asper venom. Conclusions: The roasted coffee extract demonstrated the highest inhibitory effect on venom toxins, potentially due to the formation of bioactive compounds during the Maillard reaction. Molecular modeling suggests that the tested inhibitors may bind to and occupy the substrate-binding clefts of the target enzymes. These findings support further in vivo research to explore the use of plant-derived polyphenols as adjuvant therapies in the treatment of snakebite envenoming. Full article

The usage of fossil fuels has resulted in increasingly severe environmental problems, such as climate change, air pollution, water pollution, etc. Hydrogen energy is considered one of the most promising clean energies to replace fossil fuels due to its pollution-free and high-heat properties. However, the oxygen evolution reaction (OER) remains a critical challenge due to its high overpotential and slow kinetics during water electrolysis for hydrogen production. Electrocatalysts play an important role in lowering the overpotential of OER and promoting the kinetics. Co₃O₄-based electrocatalysts have emerged as promising candidates for the oxygen evolution reaction (OER) due to their favorable catalytic activity and good compatibility compared with precious metal-based electrocatalysts. This review presents a summary of the recent developments in the synthesis strategies and mechanisms of Co₃O₄-based electrocatalysts for the OER. Various synthesis strategies have been explored to control the size, morphology, and composition of Co₃O₄ nanoparticles. These strategies enable the fabrication of well-defined nanostructures with enhanced catalytic performance. Additionally, the mechanisms of OER catalysis on Co₃O₄-based electrocatalysts have been elucidated. Coordinatively unsaturated sites, synergistic effects with other elements, surface restructuring, and pH dependency have been identified as crucial factors influencing the catalytic activity. The understanding of these mechanisms provides insights into the design and optimization of Co₃O₄-based electrocatalysts for efficient OER applications. The recent advancements discussed in this review offer valuable perspectives for researchers working on the development of electrocatalysts for the OER, with the goal of achieving sustainable and efficient energy conversion and storage systems. Full article

This study investigates the feasibility of using volcanic lapillus as a supplementary cementitious material (SCM) in mortar production to improve the sustainability of the cement industry. Cement production is one of the main sources of CO₂ emissions, mainly due to clinker production. Replacing clinker with SCMs, such as volcanic lapillus, can reduce the environmental impact while maintaining adequate mechanical properties. Experiments were conducted to replace up to 20 wt% of limestone Portland cement with volcanic lapillus. Workability, compressive strength, microstructure, resistance to alkali-silica reaction (ASR), sulfate, and chloride penetration were analyzed. The results showed that up to 10% replacement had a minimal effect on mechanical properties, while higher percentages resulted in reduced strength but still improved some durability features. The control sample cured 28 days showed a compressive strength of 43.05 MPa compared with 36.89 MPa for the sample containing 10% lapillus. After 90 days the respective values for the above samples were 44.76 MPa and 44.57 MPa. Scanning electron microscopy (SEM) revealed good gel–aggregate adhesion, and thermogravimetric analysis (TGA) confirmed reduced calcium hydroxide content, indicating pozzolanic activity. Overall, volcanic lapillus shows promise as a sustainable SCM, offering CO₂ reduction and durability benefits, although higher replacement rates require further optimization. Full article

Maximizing the efficient utilization of critical apatite resources through flotation necessitates the exploration of effective and innovative collectors. This study investigates the potential of a fatty acid mixture (FAM) synthesized from saturated palmitic and stearic acids, monounsaturated oleic and palmitoleic acids, and polyunsaturated linoleic acid. The saponified collector FAM and the depressant sodium alginate (NaAl) achieved a direct flotation of apatite from calcite and quartz (97% apatite, 10% calcite, and 7% quartz). The flotation performance with the tested combination exhibited a highly effective enrichment of apatite, mainly from calcite, which aligns with the surface chemistry assessments. Adsorption tests and zeta potential measurements confirmed the micro-flotation results. They provided compelling evidence of a chemisorption interaction between Ca²⁺ sites on calcite and the carboxyl and hydroxyl groups of NaAl. FTIR analyses suggested a reaction between the apatite surface and the carboxyl groups of saturated and unsaturated acid groups in FAM, even those conditioned with NaAl before, facilitating the complex formation. Remarkably, the synergistic effect of the functional groups demonstrates dual functionality, serving as both a hydrophilic entity for calcite and a hydrophobic entity for apatite flotation. The universal mechanism unveils substantial potential for the extensive application of FAM within apatite flotation. Full article

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

A facile way to prepare Cu(OH)₂ inorganic nanofiltration membranes with neatly arranged multilayers has been developed based on the reaction of a sodium hydroxide solution and a copper ammonia solution at the liquid–liquid interfaces. The effects of the concentration, temperature, and time of the liquid–liquid reaction on membrane structure and pore sizes were studied by SEM, TEM, and X-ray diffraction. The growth mechanism of the membrane was discussed and the formation process model was proposed. It was found that the reaction temperature was a key factor in obtaining a Cu(OH)₂ monolayer, and this could be used to adjust the thickness and pore size of the monolayer. The as-prepared Cu(OH)₂ membranes exhibited excellent filtration performance with the pure water fluxes of 156.2 L·m⁻² h⁻¹ bar⁻¹ and retention rates of 100% for methylene blue (50 ppm) at a pressure of 0.1 MPa. This successfully opens up a new method of synthesizing multilayer nanoarrays’ Cu(OH)₂ structure for nanofiltration. Full article

Biocatalysis is one of the oldest fields that has been used in industrial applications, with one of the earliest purposeful examples being the mass production of acetic acid from an immobilized Acinetobacter strain in the year 1815. Efficiency, specificity, reduced reaction times, lower overall costs, and environmental friendliness are some advantages biocatalysis has over conventional chemical synthesis, which has made biocatalysis increasingly used in industry. We highlight three necessary fields that are fundamental to advancing industrial biocatalysis, including biocatalyst engineering, solvent engineering, and mechanistic engineering. However, the fundamental mechanism of enzyme function is often overlooked or given less attention, which can limit the engineering process. In this review, we describe how mechanistic enzymology benefits industrial biocatalysis by elucidating key fundamental principles, including the k_cat and k_cat/K_m parameters. Mechanistic enzymology presents a unique field that provides in-depth insights into the molecular mechanisms of enzyme activity and includes areas such as reaction kinetics, catalytic mechanisms, structural analysis, substrate specificity, and protein dynamics. In line with the objective of protein engineering to optimize enzyme activity, we summarize a range of strategies reported in the literature aimed at improving the product release rate, the chemical step of catalysis, and the overall catalytic efficiency of enzymes. Further into this review, we delineate kinetic solvent viscosity effects (KSVEs) as a very efficient, cost-effective, and easy-to-perform method to probe different aspects of enzyme reaction mechanisms, including diffusion-dependent kinetic steps and rate-limiting steps. KSVEs are cost-effective because simple kinetic enzyme assays, such as the Michaelis–Menten kinetic approach, can be combined with them without the need for specialized and costly equipment. Other techniques in protein engineering and genetic engineering are also covered in this review. Additionally, we provide information on solvent systems in enzymatic reactions, details on immobilized biocatalysts, and common misconceptions that misguide enzyme design and optimization processes. Full article

The aim of our work is to theoretically model the conversion of C6 and C5 carbohydrates derived from lignocellulosic biomass waste into C1–C5 carboxylic acids such as levulinic, oxalic, lactic, and formic acids. Understanding the mechanism of these processes will provide the necessary knowledge to better plan the structure of zeolite. In this article, we focus on the theoretical modeling of two carbohydrates, representing C5 and C6, namely xylose and fructose, into levulinic acid (LE) and formic acid (FA). The modeling was carried out with the participation of Na-BEA zeolite in a hierarchical form, due to the large size of the carbohydrates. The density functional theory (DFT) method (StoBe program) was used, employing non-local generalized gradient-corrected functions according to Perdew, Burke, and Ernzerhof (RPBE) to account for electron exchange and correlation and using the nudged elastic band (NEB) method to determine the structure and energy of the transition state. The modeling was performed using cluster representations of hierarchical Na-Al₂Si₁₂O₃₉H₂₃ and ideal Al₂Si₂₂O₆₄H₃₄ beta zeolite. However, to accommodate the size of the carbohydrate molecules in reaction paths, only hierarchical Na-Al₂Si₁₂O₃₉H₂₃ was used. Sodium ions were positioned above the aluminum centers within the zeolite framework. Full article

Fused and spiro nitrogen-containing heterocycles play an important role as structural motifs in numerous biologically active natural products and pharmaceuticals. The review summarizes various approaches to the synthesis of three-, four-, five-, and six-membered fused and spiro heterocycles with one or two nitrogen atoms. The assembling of the titled compounds via cycloaddition, oxidative cyclization, intramolecular ring closure, and insertion of sextet intermediates—carbenes and nitrenes—is examined on a vast number of examples. Many of the reactions proceed with high regio-, stereo-, or diastereoselectivity and in excellent, up to quantitative, yield, which is of principal importance for the synthesis of chiral drug-like compounds. For most unusual and hardly predictable transformations, the mechanisms are given or referred to. 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

The aim of this study was to analyze how recombinant rabbit NGF (Nerve Growth Factor) encapsulated in chitosan (rrβNGFch) affects sperm viability, motility, capacitation, acrosome reaction (AR), kinetic traits, and apoptosis after 30 min and 2 h of storage. Specific intracellular signaling pathways associated with either cell survival, such as protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2), or programmed cell death, such as c-Jun N-terminal kinase (JNK), were also analyzed. The results confirmed the effect of rrβNGFch on capacitation and AR, whereas a longer storage time (2 h) decreased all qualitative sperm traits. AKT and JNK did not show treatment-dependent activation and lacked a correlation with functional traits, as shown by ERK1/2. These findings suggest that rrβNGFch may promote the functional activation of sperm cells, particularly during early incubation. The increase in capacitation and AR was not linked to significant changes in pathways related to cell survival or death, indicating a specific action of the treatment. In contrast, prolonged storage negatively affected all sperm parameters. ERK1/2 activation correlated with capacitation, AR, and apoptosis, supporting its role as an NGF downstream mediator. Further studies should analyze other molecular mechanisms of sperm and the potential applications of NGF in assisted reproduction. Full article