Hasil untuk "General. Including alchemy"

Dario Vassetti, M. Pagliai, P. Procacci

Molecular dynamics simulations have been performed to compute the solvation free energy and the octanol/water partition coefficients for a challenging set of selected organic molecules, characterized by the simultaneous presence of functional groups coarsely spanning a large portion of the chemical space in druglike compounds and, in many cases, by a complex conformational landscape (2-propoxyethanol, acetylsalicylic acid, cyclohexanamine, dialifor, ketoprofen, nitralin, profluralin, terbacil). OPLS-AA and GAFF2 parametrizations of the organic molecules and of 1-octanol have been done via the Web-based automatic parameter generators, LigParGen [ Dodda et al. Nucl. Acids Res. 2017 , 121 , 3864 ] and PrimaDORAC [ Procacci J. Chem. Inf. Model. 2017 , 57 , 1240 ], respectively. For the water solvent, three popular three-point site models, TIP3P, SPCE, and OPC3, were tested. Solvation free energies in water and 1-octanol are evaluated using a recently developed nonequilibrium alchemical technology [ Procacci et al. J. Chem. Theory Comput. 2014 , 10 , 2813 ]. Extensive and accurate simulations, including all possible combinations of organic molecule, solvent, and solvent model, are allowed to assess the accuracy with regard to solvation free energies of the latest release of two widespread force fields, OPLS and GAFF. The collected data are relevant in the evaluation of the predictive power of these classical force fields (and of the related support software for automated parametrization) with regard to binding free energies in a drug-receptor system for industrial applications.

Moritz Bensberg, Marco Eckhoff, F. E. Thomasen et al.

Binding free energies are key elements in understanding and predicting the strength of protein–drug interactions. While classical free energy simulations yield good results for many purely organic ligands, drugs, including transition metal atoms, often require quantum chemical methods for an accurate description. We propose a general and automated workflow that samples the potential energy surface with hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and trains a machine learning (ML) potential on the QM/MM energies and forces to enable efficient alchemical free energy simulations. To represent systems including many different chemical elements efficiently and to account for the different descriptions of QM and MM atoms, we propose an extension of element-embracing atom-centered symmetry functions for QM/MM data as an ML descriptor. The ML potential approach takes electrostatic embedding and long-range electrostatics into account. We demonstrate the applicability of the workflow on the well-studied protein–ligand complex of myeloid cell leukemia 1 and the inhibitor 19G and on the anticancer drug NKP1339 acting on the glucose-regulated protein 78.

Evangelia Tarazi, Dimitra Statha, Christina Barda et al.

Second-degree burns are common dermal injuries requiring effective interventions to promote timely and complete skin regeneration. This study evaluated the wound-healing efficacy of topical hydrogels containing powdered licorice root (<i>Glycyrrhiza glabra</i> L.) extract at concentrations of 5%, 10%, and 20% <i>w</i>/<i>w</i> in a standardized murine model. Female SKH-hrHR2 hairless mice (<i>n</i> = 8 per group) were subjected to second-degree thermal burns, and treatment hydrogel formulations were applied once daily under occlusive dressings. Wound healing was assessed by planimetric area measurements, transepidermal water loss (TEWL), and histopathology. By Day 19, complete wound closure was achieved in 87.5% of animals in the 5% group, compared with 50.0% in the 10% group, 37.5% in the 20% group, and 25.0% in the sodium alginate control (Fisher’s exact test, <i>p</i> = 0.008). TEWL remained unchanged in the 5% group (baseline vs. Day 19: 8.4 ± 1.2 vs. 8.6 ± 1.3 g/m²/h; <i>p</i> > 0.05) but increased significantly in all other groups (e.g., sodium alginate: 8.2 ± 1.1 to 13.5 ± 2.0 g/m²/h; <i>p</i> = 0.0001). Histologically, the 5% formulation showed near-normal epidermal architecture and minimal inflammation (mean total score 2.0) compared with higher concentrations (6.0 for 10% and 7.3 for 20%) and sodium alginate (8.3). These findings demonstrate that a 5% <i>Glycyrrhiza glabra</i> hydrogel provides, among the concentrations studied here, the most favorable balance of wound closure, barrier restoration, and histological recovery, supporting its further development as a topical therapy for second-degree burns.

Alexander Bäumchen, Johnn Majd Balsters, Beate-Sophie Nenninger et al.

Alginate hydrogels are integral to many cell-based models in tissue engineering and regenerative medicine. As a natural biomaterial, the properties of alginates can vary and be widely adjusted through the gelation process, making them versatile additives or bulk materials for scaffolds, microcarriers or encapsulation matrices in tissue engineering and regenerative medicine. The requirements for alginates used in biomedical applications differ significantly from those for technical applications. Particularly, the generation of novel niches for stem cells requires reliable and predictable properties of the resulting hydrogel. Ultra-high viscosity (UHV) alginates possess alginates with special physicochemical properties, and thus far, numerical simulations for the gelation process are currently lacking but highly relevant for future designs of stem cell niches and cell-based models. In this article, the gelation of UHV alginates is studied using a microscopic approach for disc- and sphere-shaped hydrogels. Based on the collected data, a multiphase continuum model was implemented to describe the cross-linking process of UHV alginate polysaccharides. The model utilizes four coupled kinetic equations based on mixture theory, which are solved using finite element software. A good agreement between simulation results and experimental data was found, establishing a foundation for future refinements in the development of an interactive tool for cell biologists and material scientists.

Xun Zhong, Yuxuan Yang, Jiating Chen et al.

Nano-silica is widely used to enhance gel properties, but its size, concentrations, and aggregation behaviors all matter. The influencing rules of these factors remain unclear especially in harsh reservoir conditions. This study presented a comprehensive investigation into the gelation, rheological, and plugging properties of phenolic polymer gels reinforced by modified nano-silica (GSNP) of different sizes and concentrations in harsh reservoir conditions. Specifically, the nano-silica was modified with a highly soluble silane, and gel properties were evaluated through rheological, differential scanning calorimetry (DSC), and sandpack flooding tests. The results showed that the incorporation of GSNP prolonged the gelation time, enhanced gel strength, and improved stability, allowing the gelation solution to enter deeper into the formation while maintaining long-time effectiveness. The optimal gel system was obtained with 0.4 wt.% GSNP-30, under which condition the storage modulus increased by approximately 14 times, and the content of non-freezable bound water more than doubled. This system exhibited plugging efficiency exceeding 80% in formations with permeabilities ranging from 1000 to 6000 millidarcy and enhanced the oil recovery factor by over 25%. The reinforcement mechanisms were attributed to the adsorption of GSNP onto polymer chains and its role in filling the gel matrix, which enhanced polymer hydrophilicity, suppressed polymer aggregation/curling, prevented ion penetration, and promoted the formation of a more uniform gel network. Careful optimization of nanoparticle size and concentration was essential to avoid the detrimental effects due to nanoparticle overfilling and aggregation. The novelty of this study lies in the practicable formulation of thermal and salt-tolerant gel systems with facile modified nano-silica of varying sizes and the systematic study of size and concentration effects. These findings offer practical guidance for tailoring nanoparticle parameters to cater for high-temperature and high-salinity reservoir conditions.

Dongnian Chen, Hui Yu, Jiajia Hao et al.

Kelp is a natural hydrogel material, which has been widely used in food industry. However, as a natural material, its properties have not been well explored. In this work, the surface and mechanical properties of kelp were investigated. The surface of kelp exhibited superoleophobicity and a self-clean property. The friction coefficient (COF) of the kelp surface was also low (<0.1). Interestingly, kelp demonstrated anisotropic mechanical properties either with or without metal ions. The tensile strength and toughness of kelp along with the growth direction (H) were better than those at the direction vertical to the growth direction (V). The adsorption of metal ions would significantly enhance the mechanical properties and ionic conductivity. Triboelectric nanogenerator (TENG) was assembled using kelp with NaCl, which showed excellent output performance (open-circuit voltage of 30 V, short-circuit current of 0.73 μA and charge transfer on contact of 10.5 nC). A writing tablet was prepared to use as the kelp-based self-powered tactile sensor. This work provides a new insight into natural kelp, which may be used as a renewable material.

Yugyung Lee, Chi H. Lee

Collagen is a versatile material, and collagen in the human body strengthens the muscles and related organs, allowing good substances to be absorbed into the bloodstream while preventing the absorption of toxic substances. Thus, collagen has been broadly applied in regenerative medicine and tissue engineering. A comprehensive framework for various collagen products has been created by integrating collagen resources with additive components. The application of 3D-bioprinting technologies for designing physiological models further allows for the introduction of enhanced preclinical testing tools that can contribute to successful elucidation of the mechanisms behind host–pathogen interactions, and subsequent prevention and treatment of various diseases. In this review, novel strategies for the 3D-printing production of collagen-sourced biomedical devices, as well as diverse applications customized with advanced artificial intelligence (AI) technologies, were thoroughly examined. Ongoing challenges, including the inherent limitations in the mechanical weakness of collagen-based bioinks, such as printability and stability, along with cell viability and bioavailability, and advanced strategies addressing those challenges, were also reviewed. An integration of 3D printing with collagen as a bioink is enormously efficient in biomedical applications, demonstrating its great potential for clinical translation against infectious diseases, including cardiovascular diseases.

S. Shiva, Guru Sharan Pal, V. Pandey

Introduction: The concept of Achara Rasayana (good conduct/ethical alchemy) explained in Ayurveda is unique to all systems of medicine. This is a special Rasayana explained in Charak Samhita. It has been mentioned that to rejuvenate the body and mind, not only medicated drugs but also good nature and behavior also play an important role as Rasayana. In Achara Rasayana, specific codes are followed to conduct our lifestyles and behaviors. Acharya advocates that one who practices such behavioral conduct gains all the benefits of Rasayana therapy, like vitality, vigor, rejuvenation, and general well-being of health. It also works as an anti-aging drug. These can be achieved without physically consuming any medicinal substance. It can be called behavioral rejuvenating medicine. Objectives: In the era of character crisis, to build character in the society by teaching social, ethical, and behavioral manners. Materials and Methods: A pilot analytical study had been planned, taking 50 volunteers in this research work. The period of study was 3 months. Codes of Achara Rasayana were taught to the participants by lectures, and they were requested to follow these codes in their daily life. Follow-up was also done from time to time. Results: Paired t-test was applied for analysis of collected data. Statistical analysis of data obtained from pre-lecture and post-lecture was done. Significant changes in results were observed, i.e., p-value < 0.05. Conclusion: This result showed a good impact on the behavioral and moral ethics. Achara Rasayana is used as an answer to solve the problem of optimal longevity, including psychosomatic disorders. It also provides immunity against physical as well as mental diseases.

Yessenia Oyarzún, José Ulloa, Matías Ceballos et al.

Herein, we investigated hydrogels composed of boronic-acid-functionalized alginate and blended with polyvinyl alcohol (PVA) of different molecular weights to control the release of metoclopramide hydrochloride as a function of pH and shear stress. The functionalization of alginate introduced dynamic covalent bonding and pH-responsive properties that can modulate network connectivity. The study investigated the viscoelastic properties of the hydrogels, their drug release profiles, and their responsiveness to changes in pH and shear forces. The results showed that a higher PVA molecular weight and alkaline pH conditions increased hydrogel viscosity and stiffness due to a more stable and interconnected network structure than acidic pH. Metoclopramide release revealed that the hydrogels exhibited pH-responsive drug release behavior. The drug was more readily released under acidic conditions due to the instability of sp²-hybridized boronate ester bonds. The influence of shear forces on the release of metoclopramide was also investigated at shear rates of 1, 10, and 100 s⁻¹, revealing their effect on matrix stiffening. Research shows that AlgBA/PVA hydrogels have unique properties, such as dynamic covalent bonding, that make them sensitive to external mechanical forces. This sensitivity makes them ideal for applications where physiological conditions trigger drug release.

Julian Wangler, M. Jansky

Abstract Background Since 2020, physicians in Germany can prescribe approved digital health applications (DHAs) with the costs covered by the health system. There has so far been a lack of studies on attitudes and experiences amongst GPs in using DHAs. Objectives The aim was to elucidate the experiences and observations of GPs that have used DHAs in health care and to examine the conditions necessary for DHAs to gain a foothold in primary care according to the GPs. Methods In 2022, 96 qualitative semi-standardised interviews were conducted with German GPs with experience in prescribing DHAs. The GPs were all organised in digitalisation-oriented physicians’ associations. Fifty-four interviews were carried out in person and 42 by phone. The data were analysed according to qualitative content analysis. Results Unlike health apps, the interviewees saw DHAs as reliable tools for enhancing the relationship between GPs and their patients. They saw the DHAs they had been prescribing as useful and reported various benefits, including improvements in compliance, mobility, information for patients and weight reduction. The physicians also saw room for further improvement (usability, gamification, training, information sources). Interviewees saw the inclusion of DHAs in evidence-based guidelines as a major step forward. Conclusion The interviewees rated DHAs favourably regarding healthcare potential and as safer and more reliable than conventional health apps. Many saw benefits to healthcare from using such applications. From the interviewees’ point of view, DHAs can be integrated more effectively into patient care.

Jorge Alberto Cortes Ortega, Jacobo Hernández-Montelongo, Rosaura Hernández-Montelongo et al.

Adsorption is one of the most crucial processes in water treatment today. It offers a low-cost solution that does not require specialized equipment or state-of-the-art technology while efficiently removing dissolved contaminants, including heavy metals. This process allows for the utilization of natural or artificial adsorbents or a combination of both. In this context, polymeric materials play a fundamental role, as they enable the development of adsorbent materials using biopolymers and synthetic polymers. The latter can be used multiple times and can absorb large amounts of water per gram of polymer. This paper focuses on utilizing adsorption through hydrogels composed of poly(acrylamide-co-itaconic acid) for removing Cu²⁺ ions dissolved in aqueous media in a semi-continuous process. The synthesized hydrogels were first immersed in 0.1 M NaOH aqueous solutions, enabling OH⁻ ions to enter the gel matrix and incorporate into the polymer surface. Consequently, the copper ions were recovered as Cu(OH)₂ on the surface of the hydrogel rather than within it, allowing the solid precipitates to be easily separated by decantation. Remarkably, the hydrogels demonstrated an impressive 98% removal efficiency of the ions from the solution in unstirred conditions at 30 °C within 48 h. A subsequent study involved a serial process, demonstrating the hydrogels’ reusability for up to eight cycles while maintaining their Cu2+ ion recovery capacity above 80%. Additionally, these hydrogels showcased their capability to remove Cu²⁺ ions even from media with ion concentrations below 100 ppm.

Shuangyang Li, Qixuan Yu, Hongpeng Li et al.

Regenerative medicine is a complex discipline that is becoming a hot research topic. Skin, bone, and nerve regeneration dominate current treatments in regenerative medicine. A new type of drug is urgently needed for their treatment due to their high vulnerability to damage and weak self-repairing ability. A self-assembled peptide hydrogel is a good scaffolding material in regenerative medicine because it is similar to the cytoplasmic matrix environment; it promotes cell adhesion, migration, proliferation, and division; and its degradation products are natural and harmless proteins. However, fewer studies have examined the specific mechanisms of self-assembled peptide hydrogels in promoting tissue regeneration. This review summarizes the applications and mechanisms of self-assembled short peptide and peptide hydrogels in skin, bone, and neural healing to improve their applications in tissue healing and regeneration.

Mariana Chelu, Adina Magdalena Musuc, Monica Popa et al.

<i>Aloe vera</i>-based hydrogels have emerged as promising platforms for the delivery of therapeutic agents in wound dressings due to their biocompatibility and unique wound-healing properties. The present study provides a comprehensive overview of recent advances in the application of <i>Aloe vera</i>-based hydrogels for wound healing. The synthesis methods, structural characteristics, and properties of <i>Aloe vera</i>-based hydrogels are discussed. Mechanisms of therapeutic agents released from <i>Aloe vera</i>-based hydrogels, including diffusion, swelling, and degradation, are also analyzed. In addition, the therapeutic effects of <i>Aloe vera</i>-based hydrogels on wound healing, as well as the reduction of inflammation, antimicrobial activity, and tissue regeneration, are highlighted. The incorporation of various therapeutic agents, such as antimicrobial and anti-inflammatory ones, into <i>Aloe vera</i>-based hydrogels is reviewed in detail. Furthermore, challenges and future prospects of <i>Aloe vera</i>-based hydrogels for wound dressing applications are considered. This review provides valuable information on the current status of <i>Aloe vera</i>-based hydrogels for the delivery of therapeutic agents in wound dressings and highlights their potential to improve wound healing outcomes.

J. L. Hernández-Pastora

In the standard Einstein's theory the exterior gravitational field of any static and axially symmetric stellar object can be described by means of a single function from which we obtain a metric into a four-dimensional space-time. In this work we present a generalization of those so called Weyl solutions to a space-time-matter metric in a five-dimensional manifold within a non-compactified Kaluza-Klein theory of gravity. The arising field equations reduce to those of vacuum Einstein's gravity when the metric function associated to the fifth dimension is considered to be constant. The calculation of the geodesics allows to identify the existence or not of different behaviours of test particles, in orbits on a constant plane, between the two metrics. In addition, static solutions on the hypersurface orthogonal to the added dimension but with time dependence in the five-dimensional metric are also obtained. The consequences on the variation of the rest mass, if the fifth dimension is identified with it, are studied.

Ryuki Kido, Takiko Sasaki, Shu Takamatsu et al.

We are interested in the so-called "combined effect" of two different kinds of nonlinear terms for semilinear wave equations in one space dimension. Recently, the first result with the same formulation as in the higher dimensional case has been obtained if and only if the total integral of the initial speed is zero, namely Huygens' principle holds. In this paper, we extend the nonlinear term to the general form including the product type. Such model equations are extremely meaningful only in one space dimension because the most cases in higher dimensions possess the global-in-time existence of a classical solution in the general theory for nonlinear wave equations. It is also remarkable that our results on the lifespan estimates are partially better than those of the general theory. This fact tells us that there is a possibility to improve the general theory which was expected complete more than 30 years ago.

Tahseen Kamal, Mazhar Ul-Islam, Sher Bahadar Khan et al.

The current study was aimed at developing BC-Cactus (BCC) composite hydrogels with impressive mechanical features for their potential applications in medical and environmental sectors. BCC composites hydrogels were developed through cactus gel coating on a never dried BC matrix. The FE-SEM micrographs confirmed the saturation of BC fibrils with cactus gel. Additionally, the presence of various functional groups and alteration in crystalline behavior was confirmed through FTIR and XRD analysis. Mechanical testing illustrated a three-times increase in the strain failure and an increase of 1.6 times in the tensile strength of BCC composite. Absorption capabilities of BCC were much higher than pure BC and it retained water for a longer period of time. Additionally, the rewetting and absorption potentials of composites were also higher than pure BC. The composite efficiently adsorbed Pb, Zn, Cu, and Co metals. Biocompatibility studies against human HaCat cell line indicated much better cell adhesion and proliferation of BCC compared to BC. These findings advocate that the BCC composite could find applications in medical, pharmaceutical and environmental fields.

Lupe Carolina Espinoza, Diana Guaya, Ana Cristina Calpena et al.

Alzheimer’s disease is characterized by a progressive deterioration of neurons resulting in a steady loss of cognitive functions and memory. Many treatments encounter the challenge of overcoming the blood–brain barrier, thus the intranasal route is a non-invasive effective alternative that enhances the drug delivery in the target organ–the brain–and reduces the side effects associated with systemic administration. This study aimed at developing intranasal gels of donepezil as an approach to Alzheimer’s disease. Three different gels were elaborated and characterized in terms of pH, morphology, gelation temperature, rheology, and swelling. An in vitro release study and an ex vivo permeation in porcine nasal mucosa were conducted on Franz diffusion cells. The tolerability of the formulations was determined by the cytotoxicity in human nasal cells RPMI 2650. Results showed that pluronic gels exhibit the higher release rate and enhanced permeation compared to chitosan gel. Moreover, the combination of Pluronic F-127 and Transcutol^® P exerted a synergic effect on the permeation of donepezil through the nasal mucosa. The resulting gels showed suitable tolerance in the RPMI 2650 cell line and physicochemical characteristics for intranasal delivery, and thus gel formulations administered by nasal mucosa could be an alternative strategy to improve the bioavailability of donepezil.

Waleed Y. Rizg, Khaled M. Hosny, Samar S. Mahmoud et al.

Tongue cancer is one of the most common carcinomas of the head and neck region. The antitumor activities of statins, including lovastatin (LV), and the essential oil of eucalyptus (Eu oil), have been adequately reported. The aim of this study was to develop a nanoemulgel containing LV combined with Eu oil that could then be made into a nanoemulsion and assessed to determine its cytotoxicity against the cell line human chondrosarcoma-3 (HSC3) of carcinoma of the tongue. An I-optimal coordinate-exchange quadratic mixture design was adopted to optimize the investigated nanoemulsions. The droplet size and stability index of the developed formulations were measured to show characteristics of the nanoemulsions. The optimized LV loaded self-nanoemulsifying drug delivery system (LV-Eu-SNEDDS) was loaded into the gelling agent Carbopol 934 to develop the nanoemulgel and evaluated for its rheological properties. The cytotoxic efficiency of the optimized LV-Eu-SNEDDS loaded nanoemulgel was tested for cell viability, and the caspase-3 enzyme test was used against the HSC3 cell line of squamous carcinoma of the tongue. The optimized nanoemulsion had a droplet size of 85 nm and a stability index of 93%. The manufactured nanoemulgel loaded with the optimum LV-Eu-SNEDDS exhibited pseudoplastic flow with thixotropic behavior. The developed optimum LV-Eu-SNEDDS-loaded nanoemulgel had the best half-maximal inhibitory concentration (IC₅₀) and caspase-3 enzyme values of the formulations developed for this study, and these features improved the ability of the nanoemulsion-loaded gel to deliver the drug to the investigated target cells. In addition, the in vitro cell viability studies revealed the synergistic effect between LV and Eu oil in the treatment of tongue cancer. These findings illustrated that the LV-Eu-SNEDDS-loaded gel formulation could be beneficial in the local treatment of tongue cancer.

Hideaki Tokuyama, Ryosuke Hamaguchi

A TiO₂ nanoparticle-loaded polymer fiber web was developed as a functional material with the ability to adsorb and photo-catalytically degrade organic pollutants in aquatic media. A linear copolymer of <i>N</i>-isopropylacrylamide (primary component) and <i>N</i>-methylol acrylamide (poly(NIPA-<i>co</i>-NMA)) was prepared, and composite fibers were fabricated by electrospinning a methanol suspension containing the copolymer and commercially available TiO₂ nanoparticles. The crosslinking of the polymer via the formation of methylene bridges between NMA units was accomplished by heating, and the fiber morphology was analyzed by electron microscopy. 4-Isopropylphenol generated by the degradation of bisphenol A—one of the endocrine-disrupting chemicals—was used as the model organic pollutant. As poly(NIPA) is a thermosensitive polymer that undergoes hydrophilic/hydrophobic transition in water, the temperature-dependence of the adsorption and photocatalytic degradation of 4-isopropylphenol was investigated. The degradation rate was analyzed using a pseudo-first-order kinetic model to obtain the apparent reaction rate constant, <i>k</i>_app. The enhancement of the photocatalytic degradation rate owing to the adsorption of 4-isopropylphenol onto thermosensitive poly(NIPA)-based fibers is discussed in terms of the ratio of the <i>k</i>_app of the composite fiber to that of unsupported TiO₂ nanoparticles. Based on the results, an eco-friendly wastewater treatment process involving periodically alternated adsorption and photocatalytic degradation is proposed.

Marat R. Agliullin, Roman E. Yakovenko, Yury G. Kolyagin et al.

The formation of silicoaluminophosphate gels using boehmite, Al isopropoxide, and di-n-propylamine as a template of silicoaluminophosphate gels as well as their subsequent crystallization into SAPO-11 molecular sieves was studied in detail using X-ray fluorescence spectroscopy (XRF), powder X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and N₂ adsorption–desorption methods. The effect of the chemical and phase composition of silicoaluminophosphate gels on the physicochemical properties of SAPO-11 molecular sieves was shown. The secondary structural units that the AEL lattice is composed of were found to be formed at the initial stage of preparation involving aluminum isopropoxide. Several approaches to control their morphology and secondary porous structure are also proposed.