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Echinoderms (starfish, sea-urchins and their close relations) possess a unique type of collagenous tissue that is innervated by the motor nervous system and whose mechanical properties, such as tensile strength and elastic stiffness, can be altered in a time frame of seconds. Intensive research on echinoderm 'mutable collagenous tissue' (MCT) began over 50 years ago, and over 20 years ago, MCT first inspired a biomimetic design. MCT, and sea-cucumber dermis in particular, is now a major source of ideas for the development of new mechanically adaptable materials and devices with applications in diverse areas including biomedical science, chemical engineering and robotics. In this review, after an up-to-date account of present knowledge of the structural, physiological and molecular adaptations of MCT and the mechanisms responsible for its variable tensile properties, we focus on MCT as a concept generator surveying biomimetic systems inspired by MCT biology, showing that these include both bio-derived developments (same function, analogous operating principles) and technology-derived developments (same function, different operating principles), and suggest a strategy for the further exploitation of this promising biological resource.
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Materiales Biomiméticos , Pepinos de Mar , Animales , Equinodermos , Biomimética , Ingeniería QuímicaRESUMEN
Site-selective functionalization strategies are in high demand to prepare well-defined homogeneous proteins for basic research and biomedical applications. In this regard, cysteine-based reactions have enabled a broad set of transformations to produce modified proteins for various applications. However, these approaches were mainly employed to modify a single reactive site with a specific transformation. Achieving site selectivity or multiple transformations, essential for preparing complex biomolecules, remains challenging. Herein we demonstrate the power of combining palladium(II)-mediated C-S bond formation and C-S bond cleavage reactions to selectively edit desired cysteine sites in complex and uniquely modified proteins. We developed an orthogonal palladium(II) strategy for rapid and effective diversification of multiple cysteine sites (3-6 residues) with various transformations. Importantly, we employed our approach to prepare 10 complex analogues, including modified, stapled, and multimeric proteins on a milligram scale. Furthermore, we also synthesized a focused library of stabilized artificial transcription factors that displayed enhanced stability and potent DNA binding activity. Our approach enables rapid and effective protein editing and opens new avenues to engineer new biomolecules for fundamental research and therapeutic applications.
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Cisteína , Factores de Transcripción , Cisteína/química , Paladio/química , Ingeniería Química , CatálisisRESUMEN
Single-atom nanozymes (SAzymes), with well-defined and uniform atomic structures, are an emerging type of natural enzyme mimics. Currently, it is important but challenging to rationally design high-performance SAzymes and deeply reveal the interaction mechanism between SAzymes and substrate molecules. Herein, this work reports the controllable fabrication of a unique Cu-N1S2-centred SAzyme (Cu-N/S-C) via a chemical vapor deposition-based sulfur-engineering strategy. Benefiting from the optimized geometric and electronic structures of single-atom sites, Cu-N/S-C SAzyme shows boosted enzyme-like activity, especially in catalase-like activity, with a 13.8-fold increase in the affinity to hydrogen peroxide (H2O2) substrate and a 65.2-fold increase in the catalytic efficiency when compared to Cu-N-C SAzyme with Cu-N3 sites. Further theoretical studies reveal that the increased electron density around single-atom Cu is achieved through electron redistribution, and the efficient charge transfer between Cu-N/S-C and H2O2 is demonstrated to be more beneficial for the adsorption and activation of H2O2. The as-designed Cu-N/S-C SAzyme possesses an excellent antitumor effect through the synergy of catalytic therapy and oxygen-dependent phototherapy. This study provides a strategy for the rational design of SAzymes, and the proposed electron redistribution and charge transfer mechanism will help to understand the coordination environment effect of single-atom metal sites on H2O2-mediated enzyme-like catalytic processes.
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Peróxido de Hidrógeno , Neoplasias , Humanos , Ingeniería , Ingeniería Química , Fototerapia , Catálisis , Gases , Neoplasias/terapiaRESUMEN
The manipulation of internal interactions at the molecular level within biological fibers is of particular importance but challenging, severely limiting their tunability in macroscopic performances and applications. It thus becomes imperative to explore new approaches to enhance biological fibers' stability and environmental tolerance and to impart them with diverse functionalities, such as mechanical recoverability and stimulus-triggered responses. Herein, we develop a dynamic imine fiber chemistry (DIFC) approach to engineer molecular interactions to fabricate strong and tough protein fibers with recoverability and actuating behaviors. The resulting DIF fibers exhibit extraordinary mechanical performances, outperforming many recombinant silks and synthetic polymer fibers. Remarkably, impaired DIF fibers caused by fatigue or strong acid treatment are quickly recovered in water directed by the DIFC strategy. Reproducible mechanical performance is thus observed. The DIF fibers also exhibit exotic mechanical stability at extreme temperatures (e.g., -196 °C and 150 °C). When triggered by humidity, the DIFC endows the protein fibers with diverse actuation behaviors, such as self-folding, self-stretching, and self-contracting. Therefore, the established DIFC represents an alternative strategy to strengthen biological fibers and may pave the way for their high-tech applications.
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Ingeniería Química , Iminas , Iminas/química , SedaRESUMEN
Background: Boron neutron capture therapy (BNCT) is a promising cancer treatment that eliminates tumor cells by triggering high-energy radiation within cancer cells. Aim: In vivo evaluation of poly(vinyl alcohol)/boric acid crosslinked nanoparticles (PVA/BA NPs) for BNCT. Materials & methods: PVA/BA NPs were synthesized and intravenously injected into tumor-bearing mice for BNCT. Results: The in vitro boron uptake of PVA/BA NPs in tumor cells was 70-fold higher than the required boron uptake for successful BNCT. In an in vivo study, PVA/BA NPs showed a 44.29% reduction in tumor size compared with clinically used boronophenylalanine for oral cancer in a murine model. Conclusion: PVA/BA NPs exhibited effective therapeutic results for oral cancer treatments in BNCT.
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Terapia por Captura de Neutrón de Boro , Neoplasias de la Boca , Nanopartículas , Animales , Ratones , Terapia por Captura de Neutrón de Boro/métodos , Neoplasias de la Boca/radioterapia , Modelos Animales de Enfermedad , Ingeniería Química , MasculinoRESUMEN
Continuous process safety (PS) development is the key to maintaining a good PS system, and its competency plays a substantial role. However, PS incompetency can still be demonstrated in several process-related accidents, particularly major catastrophic incidents. To mitigate this gap, universities' PS education is analysed. Because PS is an important element of chemical engineering (CE), this study seeks to identify the most prevalent PS subjects taught in the top 300 Quacquarelli Symonds ranking (2019) universities. Findings indicate that PS education remains insufficiently addressed in undergraduate CE curricula over the years. Twelve common topics, i.e., human factors; management of hazards, incidents, and risk; design; fire and explosion; legislation and standards; sustainability; process control; economics; toxicology; and software are identified. Notably, sustainability is acknowledged to be a new common PS topic, depicting its demand for industrial evolution. Ultimately, strengthening the collaboration between universities and industries is required to develop graduates' PS competency.Abbreviations: ALARP: as low as reasonably practicable; CAD: computer-aided design; CE: chemical engineering; ETA: event tree analysis; FTA: fault tree analysis; FMEA: failure mode and effect analysis; HAZAN: hazard analysis; HAZID: hazard identification; HAZOP: hazard and operability; HSE: health, safety and environment; HYSYS: Hyprotech Systems; LCA: life cycle analysis; LOPA: layer of protection analysis; MS: Microsoft; ORP: occupational risk prevention; PC: personal computer; PHA: process hazard analysis; PS: process safety; PSM: process safety management; QS: Quacquarelli Symonds; SMS: safety management system.
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Ingeniería Química , Administración de la Seguridad , Humanos , Industrias , CurriculumRESUMEN
The limited capabilities of teaching laboratories, combined with an increasing number of students enrolled in university, require constant augmentation of instructional approaches. By enhancing laboratory demonstrations with digital technology, these structural issues can be addressed while at the same time enhancing student understanding and learning. Our case study focuses on the fermentation lab part of the Reaction Equilibria and Thermodynamics (RET) module, a first-year chemical engineering course at the University of Birmingham. Video demonstrations were used to introduce students to the laboratory set-ups and walk them through each step and technique. The video demonstrations allowed the students to attend the in-person lab sessions having established knowledge and understanding of the processes involved and the outcomes desired, which decreased the burden on the facilities and the staff. A knowledge-based quiz and a student survey conducted at the end of the module showed that the pre-lab videos encouraged more active participation in the laboratory sessions and reinforced learning. Approximately 70% of the students polled in the first survey conducted within this project felt more confident going into the laboratory sessions after watching the pre-lab videos and attempting the knowledge quiz, while 92% of the students polled in the second survey judged the pre-lab video sessions as beneficial to them. Overall, the teaching method has the potential to improve student participation and access, boost confidence and learning, and provided a more structured and flexible approach to laboratory learning outcomes.
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Ingeniería Química , Laboratorios , Humanos , Aprendizaje , EstudiantesRESUMEN
Small interfering RNAs are a new class of drugs, exhibiting sequence-driven, potent, and sustained silencing of gene expression in vivo. We recently demonstrated that siRNA chemical architectures can be optimized to provide efficient delivery to the CNS, enabling development of CNS-targeted therapeutics. Many genetically-defined neurodegenerative disorders are dominant, favoring selective silencing of the mutant allele. In some cases, successfully targeting the mutant allele requires targeting single nucleotide polymorphism (SNP) heterozygosities. Here, we use Huntington's disease (HD) as a model. The optimized compound exhibits selective silencing of mutant huntingtin protein in patient-derived cells and throughout the HD mouse brain, demonstrating SNP-based allele-specific RNAi silencing of gene expression in vivo in the CNS. Targeting a disease-causing allele using RNAi-based therapies could be helpful in a range of dominant CNS disorders where maintaining wild-type expression is essential.
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Enfermedad de Huntington , Alelos , Animales , Ingeniería Química , Silenciador del Gen , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/terapia , Ratones , Proteínas del Tejido Nervioso/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismoRESUMEN
Microfluidic devices and systems have entered many areas of chemical engineering, and the rate of their adoption is only increasing. As we approach and adapt to the critical global challenges we face in the near future, it is important to consider the capabilities of flow chemistry and its applications in next-generation technologies for sustainability, energy production, and tailor-made specialty chemicals. We present the introduction of microfluidics into the fundamental unit operations of chemical engineering. We discuss the traits and advantages of microfluidic approaches to different reactive systems, both well-established and emerging, with a focus on the integration of modular microfluidic devices into high-efficiency experimental platforms for accelerated process optimization and intensified continuous manufacturing. Finally, we discuss the current state and new horizons in self-driven experimentation in flow chemistry for both intelligent exploration through the chemical universe and distributed manufacturing.
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Dispositivos Laboratorio en un Chip , Microfluídica , Ingeniería QuímicaRESUMEN
Lateral flow immunoassay (LFIA) with gold nanoparticles (AuNPs) as signal reporters is a popular point-of-care diagnostic technique. However, given the weak absorbance of traditional 20-40 nm spherical AuNPs, their sensitivity is low, which greatly limits the wide application of AuNP-based LFIA. With the rapid advances in materials science and nanotechnology, the synthesis of noble metal nanoparticles (NMNPs) has enhanced physicochemical properties such as optical, plasmonic, catalytic, and multifunctional activity by simply engineering their physical parameters, including the size, shape, composition, and external structure. Using these engineered NMNPs as an alternative to traditional AuNPs, the sensitivity of LFIA has been significantly improved, thereby greatly expanding the working range and application scenarios of LFIA, particularly in trace analysis. Therefore, in this review, we will focus on the design of engineered NMNPs and their demonstration in improving LFIA. We highlight the strategies available for tailoring NMNP designs, the effect of NMNP engineering on their performance, and the working principle of each engineering design for enhancing LFIA. Finally, current challenges and future improvements in this field are briefly discussed.
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Inmunoensayo/instrumentación , Nanopartículas del Metal/química , Ingeniería Química , Diseño de Fármacos , Oro , Humanos , Magnetismo , Fenómenos Ópticos , Tamaño de la PartículaRESUMEN
Aromatic cyclic ß2,3-amino acids (cßAAs), such as 2-aminobenzoic acid and 3-aminothiophene-2-carboxylic acid, are building blocks that can induce unique folding propensities of peptides. Although their ribosomal elongation had been a formidable task due to the low nucleophilicity of their amino groups, we have recently overcome this issue by means of an engineered tRNAPro1E2 that enhances their incorporation efficiency into nascent peptide chains. Here we report ribosomal synthesis of a random macrocyclic peptide library containing aromatic and aliphatic cßAAs, and its application to de novo discovery of binders against human IFNGR1 and FXIIa as model targets. The potent binding peptides showed not only high inhibitory activity but also high protease resistance in human serum. Moreover, these cßAAs play a critical role in exhibiting their properties, establishing a discovery platform for de novo foldamer-like macrocycles containing such unique building blocks.
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Ácidos Carboxílicos/química , Compuestos Macrocíclicos/química , Péptidos Cíclicos/química , ortoaminobenzoatos/química , Secuencia de Aminoácidos , Ingeniería Química , Humanos , Compuestos Macrocíclicos/metabolismo , Biblioteca de Péptidos , Péptidos Cíclicos/metabolismo , Unión Proteica , Ribosomas , SueroRESUMEN
Chemical reaction engineering is interested in elucidating the reaction kinetics through the determination of the fundamental influencing variables. The understanding of enzyme kinetics is needed to implement the potential of enzymes to satisfy determined production targets and for the design of the reactor. The quantification of the enzyme kinetics is implemented by the elucidation and building of the kinetic model (it includes one or more kinetic equations). In the context of process development, the kinetic model is not only useful to identify feasibility and for optimizing reaction conditions but also, at an early stage of development it is very useful to anticipate implementation bottlenecks, and so guide reactor setup. In this chapter we describe theoretical and practical considerations to illustrate the methodological framework of kinetic analysis. We take as study cases four archetypal kinetic cases by using as example the hydrolysis of cellobiose catalyzed by a beta-glucosidase. We show the different experimental data that can be obtained by the monitoring of enzymatic reactions in different configuration of free enzyme homogeneous ideal reactors; we show step-by-step the visualization, treatment, and analysis of data to elucidate kinetic models and the procedure for the quantification of kinetic constants. Finally, the performance of different reactors is compared in the interplay with the enzyme kinetics. This book chapter aims at being useful for a broad multidisciplinary audience and different levels of academic development.
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Ingeniería Química , Reactores Biológicos , Hidrólisis , Cinética , beta-GlucosidasaRESUMEN
There is growing interest in the role of microorganisms in human health and disease, with evidence showing that new types of biotherapy using engineered bacterial therapeutics, including bacterial derivatives, can address specific mechanisms of disease. The complex interactions between microorganisms and metabolic/immunologic pathways underlie many diseases with unmet medical needs, suggesting that targeting these interactions may improve patient treatment. Using tools from synthetic biology and chemical engineering, non-pathogenic bacteria or bacterial products can be programmed and designed to sense and respond to environmental signals to deliver therapeutic effectors. This review describes current progress in biotherapy using live bacteria and their derivatives to achieve therapeutic benefits against various diseases.
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Bacterias/metabolismo , Ingeniería Química/métodos , Sistemas de Liberación de Medicamentos/métodos , Inmunoterapia/métodos , Biología Sintética/métodos , Animales , Bacterias/genética , Membrana Externa Bacteriana/metabolismo , HumanosRESUMEN
Smart attachable systems have attracted much attention owing to their capabilities in terms of body performance evaluation, disease diagnostics, and drug delivery. Recent advances in chemical and engineering techniques provide many opportunities to improve device fabrication and applications owing to the advantages of being lightweight and easy to control as well as their battery absence and functional diversity. This review highlights the latest developments in the field of chemical engineering-based lightweight and miniaturized attachable systems, which are mainly inspired by the natural world. Their applications for real-time monitoring, point-of-care sampling, biomarker detection, and controlled release are discussed thoroughly with respect to specific products/prototypes. The perspectives of the field, including persistence guarantee, burden reduction, and personality improvement, are also discussed. It is believed that chemical engineering-based lightweight and miniaturized attachable systems have good potential in both clinical and industrial fields, indicating a large potential to improve human lives in the near future.
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Ingeniería Química , Sistemas de Atención de Punto , Sistemas de Liberación de Medicamentos , Suministros de Energía Eléctrica , HumanosRESUMEN
PURPOSE: Rebamipide (REB) a potent anti-ulcer agent, has not been exploited to its full potential, owing to it extremely poor solubility, leading to highly diminutive bioavailability (<10%). The purpose is to carry out its solid-state modification. METHOD: Cocrystallisation was done with three GRAS coformers namely citric acid (CA), 3,4-dihydroxybenzoic acid (DHBA) and oxalic acid (OXA) employing the liquid-assisted grinding method. Cocrystal formation was based upon amide-carboxyl and amide-hydroxyl supramolecular synthons. Characterization of novel cocrystals i.e. RCA, RDHBA and ROXA was carried out by DSC, PXRD and additionally by FT-IR spectroscopy. Chemical structures have been determined utilizing the PXRD pattern by Material Studio®. Furthermore, cocrystals were subjected to solubility and intrinsic dissolution rate (IDR) evaluation. Also, pharmacodynamic and pharmacokinetic studies were performed and compared with pure rebamipide. RESULT: The appearances of a single sharp melting endotherm in DSC, along with novel characteristic peaks in PXRD infer the existence of a new crystalline form. Shifting in characteristic vibrations in FT-IR spectroscopy supports the establishment of distinct hydrogen-bonded networks. Structural determination revealed that RCA crystallizes in 'Bb2b' space groups whereas RDHBA in 'P1' and ROXA crystallize out in the 'P-1' space group. All the cocrystals exhibited superior apparent solubility and almost 7-13 folds increase in IDR. Furthermore, 1.6-2.5 folds enhancement in relative bioavailability and remarkable amplification in anti-ulcer, anti-inflammatory and the antioxidant potential of these cocrystals were observed. CONCLUSION: The study ascertains the advantages of cocrystallization, with RCA showing greatest potential and suggests a viable alternative approach for improved formulation of rebamipide.
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Alanina/análogos & derivados , Productos Biológicos/química , Ingeniería Química , Edema/tratamiento farmacológico , Quinolonas/química , Úlcera Gástrica/tratamiento farmacológico , Alanina/administración & dosificación , Alanina/química , Alanina/farmacocinética , Animales , Disponibilidad Biológica , Productos Biológicos/farmacocinética , Carragenina/administración & dosificación , Carragenina/inmunología , Química Farmacéutica/métodos , Cristalización , Modelos Animales de Enfermedad , Composición de Medicamentos/métodos , Edema/inducido químicamente , Edema/inmunología , Humanos , Enlace de Hidrógeno , Indometacina , Masculino , Difracción de Polvo , Quinolonas/administración & dosificación , Quinolonas/farmacocinética , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Úlcera Gástrica/inducido químicamenteRESUMEN
Although great progress has been made in artificial enzyme engineering, their catalytic performance is far from satisfactory as alternatives of natural enzymes. Here, we report a novel and efficient strategy to access high-performance nanozymes via direct atomization of platinum nanoparticles (Pt NPs) into single atoms by reversing the thermal sintering process. Atomization of Pt NPs into single atoms makes metal catalytic sites fully exposed and results in engineerable structural and electronic properties, thereby leading to dramatically enhanced enzymatic performance. As expected, the as-prepared thermally stable Pt single-atom nanozyme (PtTS-SAzyme) exhibited remarkable peroxidase-like catalytic activity and kinetics, far exceeding the Pt nanoparticle nanozyme. The following density functional theory calculations revealed that the engineered P and S atoms not only promote the atomization process from Pt NPs into PtTS-SAzyme but also endow single-atom Pt catalytic sites with a unique electronic structure owing to the electron donation of P atoms, as well as the electron acceptance of N and S atoms, which simultaneously contribute to the substantial enhancement of the enzyme-like catalytic performance of PtTS-SAzyme. This work demonstrates that thermal atomization of the metal nanoparticle-based nanozymes into single-atom nanozymes is an effective strategy for engineering high-performance nanozymes, which opens up a new way to rationally design and optimize artificial enzymes to mimic natural enzymes.
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Ingeniería Química/métodos , Enzimas/síntesis química , Enzimas/metabolismo , Nanopartículas del Metal/química , Platino (Metal)/química , CatálisisRESUMEN
Recently, the design and development of nanozyme-based logic gates have received much attention. In this work, by engineering the stability of the nanozyme-catalyzed product, we demonstrated that the chromogenic system of 3, 3', 5, 5'-tetramethylbenzidine (TMB) can act as a visual output signal for constructing various Boolean logic operations. Specifically, cerium oxide or ferroferric oxide-based nanozymes can catalyze the oxidation of colorless TMB to a blue color product (oxTMB). The blue-colored solution of oxTMB could become colorless by some reductants, including the reduced transition state of glucose oxidase and xanthine oxidase. As a result, by combining biocatalytic reactions, the color change of oxTMB could be controlled logically. In our logic systems, glucose oxidase, ß-galactosidase, and xanthine oxidase acted as inputs, and the state of oxTMB solution was used as an output. The logic operation produced a colored solution as the readout signal, which was easily distinguished with the naked eye. More importantly, the study of such a decolorization process allows the transformation of previously designed AND and OR logic gates into NAND and NOR gates. We propose that this work may push forward the design of novel nanozyme-based biological gates and help us further understand complex physiological pathways in living systems.
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Bencidinas/química , Ingeniería Química/métodos , Compuestos Cromogénicos/química , Colorimetría/métodos , Enzimas/química , Nanotecnología , Biocatálisis , Catálisis , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
We designed and synthesized a fatty aldehyde surrogate containing a formyl thioester group, which can be reduced by fatty aldehyde reductase (FALR) with stoichiometric formaldehyde generation. It can be rapidly visualized and quantified using the Purpald assay. We demonstrated its successful application in the high throughput screening of FALR engineering.
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Aldehído Oxidorreductasas/química , Aldehído Oxidorreductasas/metabolismo , Aldehídos/química , Ingeniería Química/métodos , Ácidos Grasos/química , Ensayos Analíticos de Alto Rendimiento/métodosRESUMEN
The study investigated the toxicity effects of 'form specific' engineered nanomaterials (ENMs) and ions released from nano-enabled products (NEPs), namely sunscreens, sanitisers, body creams and socks on Pseudokirchneriella subcapitata, Spirodela polyrhiza, and Daphnia magna. Additionally, risk estimation emanating from the exposures was undertaken. The ENMs and the ions released from the products both contributed to the effects to varying extents, with neither being a uniform principal toxicity agent across the exposures; however, the effects were either synergistic or antagonistic. D. magna and S. polyrhiza were the most sensitive and least sensitive test organisms, respectively. The most toxic effects were from ENMs and ions released from sanitisers and sunscreens, whereas body creams and sock counterparts caused negligible effects. The internalisation of the ENMs from the sunscreens could not be established; only adsorption on the biota was evident. It was established that ENMs and ions released from products pose no imminent risk to ecosystems; instead, small to significant adverse effects are expected in the worst-case exposure scenario. The study demonstrates that while ENMs from products may not be considered to pose an imminent risk, increasing nanotechnology commercialization may increase their environmental exposure and risk potential; therefore, priority exposure cases need to be examined.