RESUMEN
Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.
Asunto(s)
Regeneración Ósea , Macrófagos , Microesferas , Staphylococcus aureus , Animales , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Regeneración Ósea/efectos de los fármacos , Células RAW 264.7 , Staphylococcus aureus/efectos de los fármacos , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Masculino , Glucólisis/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Complicaciones de la Diabetes/tratamiento farmacológico , Liposomas/química , Antibacterianos/farmacologíaRESUMEN
Infection is the most common complication after orthopedic surgery and can result in prolonged ailments such as chronic wounds, enlarged bone defects, and osteomyelitis. Iron, which is essential for bacterial metabolism and immune cell functions, is extremely important. Bacteria harness iron from nearby cells to promote biofilm formation, ensuring their survival. Iron deficiency within the infection microenvironment (IME) consequently hampers macrophage function, enabling further dissemination of the infection and hindering macrophage polarization to the M2 phenotype. Therefore, a novel approach is proposed to regulate macrophage polarization, aiming to restore the inflammatory immune environment. A composite hydrogel derived from natural polymers is developed to address infections and manage iron metabolism in macrophages. This IME-responsive hydrogel, named FCL-ECMH, is synthesized by encapsulating vermiculite functional core layers within a decellularized extracellular matrix hydrogel. It is noteworthy that FCL-ECMH can produce reactive oxygen species within the IME. Supplementary photothermal treatment enhances bacterial iron uptake, leading to ferroptosis-like death. This process also rejuvenates the iron-enriched macrophages around the IME, thereby enhancing their antibacterial and tissue repair functions. In vivo experiments confirmed the antibacterial and repair-promoting capabilities of FCL-ECMH, indicating its potential for clinical applications.
Asunto(s)
Ferroptosis , Hidrogeles , Ingeniería de Tejidos , Hidrogeles/química , Ferroptosis/efectos de los fármacos , Ratones , Animales , Ingeniería de Tejidos/métodos , Remodelación Ósea/efectos de los fármacos , Macrófagos/metabolismo , Modelos Animales de EnfermedadRESUMEN
The design and orderly layered co-immobilization of multiple enzymes on resin particles remain challenging. In this study, the SpyTag/SpyCatcher binding pair was fused to the N-terminus of an alcohol dehydrogenase (ADH) and an aldo-keto reductase (AKR), respectively. A non-canonical amino acid (ncAA), p-azido-L-phenylalanine (p-AzF), as the anchor for covalent bonding enzymes, was genetically inserted into preselected sites in the AKR and ADH. Employing the two bioorthogonal counterparts of SpyTag/SpyCatcher and azide-alkyne cycloaddition for the immobilization of AKR and ADH enabled sequential dual-enzyme coating on porous microspheres. The ordered dual-enzyme reactor was subsequently used to synthesize (S)-1-(2-chlorophenyl)ethanol asymmetrically from the corresponding prochiral ketone, enabling the in situ regeneration of NADPH. The reactor exhibited a high catalytic conversion of 74 % and good reproducibility, retaining 80 % of its initial activity after six cycles. The product had 99.9 % ee, which that was maintained in each cycle. Additionally, the double-layer immobilization method significantly increased the enzyme loading capacity, which was approximately 1.7â times greater than that of traditional single-layer immobilization. More importantly, it simultaneously enabled both the purification and immobilization of multiple enzymes on carriers, thus providing a convenient approach to facilitate cascade biocatalysis.
Asunto(s)
Alcohol Deshidrogenasa , Biocatálisis , Enzimas Inmovilizadas , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Alcohol Deshidrogenasa/metabolismo , Alcohol Deshidrogenasa/química , Alcohol Deshidrogenasa/genética , Ingeniería de Proteínas , Aldo-Ceto Reductasas/metabolismo , Aldo-Ceto Reductasas/química , Aldo-Ceto Reductasas/genética , Fenilalanina/química , Fenilalanina/metabolismo , Fenilalanina/análogos & derivados , Azidas/químicaRESUMEN
Erythromycin (Ery) is a commonly used antibiotic that can be found ubiquitously in water bodies. The increasing apprehension over the adverse effects of antibiotic remnants in aquatic environments necessitates the prompt advancement of erythromycin detection techniques that are both highly sensitive and compact. Here, we propose a non-enzyme Ery sensor that integrates a mesoporous SiO2-based low-voltage oxide electric-double-layer transistor (EDLT) with a molecular imprinting technique, featuring a molecularly imprinted polymers (MIP) functionalized gate electrode. The mesoporous SiO2-based oxide transistor exhibits excellent electrical characteristics, including an operating voltage of small than 1.0 V, an on/off ratio exceeding 106 and a mobility of 14.95 cm2V-1s-1. At an ultra-low operating voltage within 0.5 V, the sensor exhibits a linear response to the concentration range of 1 nM-10 µM of Ery, with a detection limit of 0.22 nM and a sensitivity of 23.3 mV dec-1. Besides, the single-spike dynamic sensing mode effectively reduces the power consumption of the detection. The proposed sensor provides a rapid and convenient approach to detect Ery in aqueous environments, with benefits such as miniaturization, high sensitivity, and simplicity.
RESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease.However, there are few cases of Charcot Neuro-osteoarthropathy (CN) caused by rheumatoid diseases in clinical reports. It is not easy to pay attention to the diagnosis of CN in the complications of rheumatoid disease, which greatly increases the probability of misdiagnosis and missed diagnosis. This case reported a rare complication of rheumatoid arthritis, Charcot arthritis, and the molecular mechanism and diagnosis and treatment of CN caused by RA were systematically discussed. CASE PRESENTATION: The patient, a 79-year-old woman, was hospitalized due to bilateral shoulder pain, limited activity for half a year, aggravated for 4 months to the hospital. During this period, the symptoms did not improve after treatment with acupuncture and Chinese medicine. The patient was previously diagnosed with rheumatoid arthritis for more than 3 years and intermittent irregular use of methylprednisolone and methotrexate for 2 years. She had a history of osteoporosis. PHYSICAL EXAMINATION: symmetrical malformed swelling of the finger joints of both hands; Bilateral supraspinatus and deltoid muscle atrophy, tenderness at the acromion, and attachment of the long head tendon of the biceps brachii were observed. The left Dugas test and the right Dugas test were positive.Blood test: anti-cyclic citrullinated peptide antibody (A-CCP) 33.10U/ml (normal range: 0-5RU/ml); antinuclear antibody quantification (ANA) 47.40AU/ml (normal range: Negative or < 32); anti-double stranded DNA IgG antibody quantification (dsDNA) 31.00 IU/ml (normal range: 0-100 IU/ml); D-Dimer 6.43 µg/ml (normal range: 0-0.5 mg/L); erythrocyte sedimentation rate (ESR) was 27 mm/h (normal range: < 20 mm/60 min). C-reactive protein (CRP) 39.06 mg/L(0.068-8 mg/L).MRI 3.0 T enhancement of bilateral shoulder joints, cervical spine and thoracic spine showed: 1.Large bone destruction, cartilage injury, multiple effusion, synovitis, obvious on the right side. 2.Intervertebral disc degeneration, cervical 3/4, 4/5, 5/6, 6/7 disc herniation, with cervical 3/4 obvious, posterior central herniation; CONCLUSIONS: Rheumatoid arthritis complicated with Charcot's joint is rare. Clinically, patients with rheumatoid diseases should not ignore Charcot's joint complications because of rareness. Early blood inflammatory markers, neuro electrophysiology, and imaging MRI of rheumatoid CN are of great significance for the diagnosis of this mild or early neurovascular inflammation. Early diagnosis and treatment are helpful to prevent further joint injury. The clinical diagnosis, treatment, and molecular mechanism of osteolysis in RA and peripheral sensory nerve injury remain to be further revealed.
Asunto(s)
Artritis Reumatoide , Artropatía Neurógena , Humanos , Artritis Reumatoide/complicaciones , Femenino , Anciano , Artropatía Neurógena/etiología , Artropatía Neurógena/diagnóstico por imagen , Artropatía Neurógena/diagnósticoRESUMEN
A recently emerging cell death pathway, known as copper-induced cell death, has demonstrated significant potential for treating infections. Existing research suggests that cells utilizing aerobic respiration, as opposed to those reliant on glycolysis, exhibit greater sensitivity to copper-induced death. Herein, a MnO2-loaded copper metal-organic frameworks platform is developed denoted as MCM, to enhance bacterial cuproptosis-like death via the remodeling of bacterial respiratory metabolism. The reversal of hypoxic microenvironments induced a cascade of responses, encompassing the reactivation of suppressed immune responses and the promotion of osteogenesis and angiogenesis. Initially, MCM catalyzed O2 production, alleviating hypoxia within the biofilm and inducing a transition in bacterial respiration mode from glycolysis to aerobic respiration. Subsequently, the sensitized bacteria, characterized by enhanced tricarboxylic acid cycle activity, underwent cuproptosis-like death owing to increased copper concentrations and aggregated intracellular dihydrolipoamide S-acetyltransferase (DLAT). The disruption of hypoxia also stimulated suppressed dendritic cells and macrophages, thereby strengthening their antimicrobial activity through chemotaxis and phagocytosis. Moreover, the nutritional effects of copper elements, coupled with hypoxia alleviation, synergistically facilitated the regeneration of bones and blood vessels. Overall, reshaping the infection microenvironment to enhance cuproptosis-like cell death presents a promising avenue for eradicating biofilms.
Asunto(s)
Biopelículas , Cobre , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Animales , Cobre/metabolismo , Ratones , Óxidos/farmacología , Compuestos de Manganeso , Modelos Animales de Enfermedad , Hipoxia/metabolismoRESUMEN
The onset of implant-associated infection (IAI) triggers a cascade of immune responses, which are initially dominated by neutrophils. Bacterial aggregate formation and hypoxic microenvironment, which occur shortly after implantation, may be two major risk factors that impair neutrophil function and lead to IAI. Here, the implant surface with phytic acid-Zn2+ coordinated TiO2 nanopillar arrays (PA-Zn@TiNPs) and oxygen self-supporting CaO2 nanoparticles, named as CPZTs, is mechanochemically reprogrammed. The engineered CPZTs interface integrates multiple properties to inhibit the formation of nascent biofilm, encompassing antibacterial adhesion, mechanobactericidal effect, and chemobiocidal effect. Meanwhile, continuous oxygenation fuels the neutrophils with reactive oxygen species (ROS) for efficient bacterial elimination on the implant surface and inside the neutrophils. Furthermore, this surface modulation strategy accelerates neutrophil apoptosis and promotes M2 macrophage-mediated osteogenesis both in vitro and in a rat model of IAI. In conclusion, targeting neutrophils for immunomodulation is a practical and effective strategy to prevent IAI and promote bone-implant integration.
Asunto(s)
Apoptosis , Neutrófilos , Ratas , Animales , Antibacterianos/farmacología , Macrófagos , Prótesis e ImplantesRESUMEN
mRNA emerged as an attractive therapy modality with the development of mRNA structure engineering techniques and delivery platforms. mRNA therapeutics, applied for vaccine therapy, protein replacement therapy, and chimeric antigen receptor (CAR) T cell-based therapy, has shown huge potential in treating a wide range of diseases, such as cancer and rare genetic diseases, with successful and exciting preclinical and clinical progress. In mRNA therapeutics, a potent delivery system is key to the success of its application for disease treatment. Herein, different types of mRNA delivery strategies, including nanoparticles produced from lipid or polymer materials, virus-based platforms, and exosome-based platforms, are mainly focused.
Asunto(s)
Nanopartículas , Neoplasias , Humanos , ARN Mensajero/genética , Lípidos , Neoplasias/genética , Neoplasias/terapia , Terapia Genética/métodosRESUMEN
Biofilms offer bacteria a physical and metabolic barrier, enhancing their tolerance to external stress. Consequently, these biofilms limit the effectiveness of conventional antimicrobial treatment. Recently, quorum sensing (QS) has been linked to biofilm's stress response to thermal, oxidative, and osmotic stress. Herein, a multiple synergistic therapeutic strategy that couples quorum sensing interference assisted therapy (QSIAT)-mediated enhanced thermal therapy with bacteria-triggered immunomodulation in a single nanoplatform, is presented. First, as magnetic hyperthermia amplifier, hyaluronic acid-coated ferrite (HA@MnFe2 O4 ) attenuates the stress response of biofilm by down-regulating QS-related genes, including agrA, agrC, and hld. Next, the sensitized bacteria are eliminated with magnetic heat. QS interference and heat also destruct the biofilm, and provide channels for further penetration of nanoparticles. Moreover, triggered by bacterial hyaluronidase, the wrapped hyaluronic acid (HA) decomposes into disaccharides at the site of infection and exerts healing effect. Thus, by reversing the bacterial tissue invasion mechanism for antimicrobial purpose, tissue regeneration following pathogen invasion and thermal therapy is successfully attained. RNA-sequencing demonstrates the QS-mediated stress response impairment. In vitro and in vivo experiments reveal the excellent antibiofilm and anti-inflammatory effects of HA@MnFe2 O4 . Overall, QSIAT provides a universal enhancement strategy for amplifying the bactericidal effects of conventional therapy via stress response interference.
Asunto(s)
Hipertermia Inducida , Percepción de Quorum , Ácido Hialurónico , Biopelículas , Antibacterianos/farmacología , Bacterias , Fenómenos MagnéticosRESUMEN
The popularization of financial literacy has become a global trend, with governments across the world expressing commitment to continuously enhancing the financial literacy of their citizens to improve the country's overall financial well-being. However, there is a lack of research evaluating the actual effects of financial literacy on Chinese households. This study first investigated the micro impact of financial literacy on the household stock profit level using data from the 2019 China Household Finance Survey. As most existing studies use factor analysis to measure financial literacy from a single dimension of financial knowledge, our study additionally used the entropy method to construct a composite evaluation system of financial literacy from four dimensions: financial skills, knowledge, attitudes, and behaviors. The ordinary least squares model was utilized as the primary regression model to estimate the correlation, and the average financial literacy of other households in the same community was selected as an instrumental variable. Further instrumental variable regression analysis was conducted using the two-stage least squares method. Three robustness tests were performed to ensure the reliability of the research findings. The results demonstrate that financial literacy significantly enhances household stock profit levels. The mediation effect analysis indicates that financial literacy affects stock profit levels through financial information attention. Moreover, financial literacy has a more substantial promoting effect on stock profit levels for households with members working for state-owned enterprises and those living in first-tier cities. This study confirms the value of financial literacy; identifies important channels for residents to increase their property income; and provides important guidance for the government, educational organizations, and financial institutions. This also injects more vigor into market participation to improve the persistently sluggish Chinese stock market.
Asunto(s)
Alfabetización en Salud , Renta , Humanos , Reproducibilidad de los Resultados , China , Composición Familiar , AlfabetizaciónRESUMEN
Infectious hematopoietic necrosis (IHN) is a major disease that limits the culture of rainbow trout. In practical production, it has been found that the temperature of the culture water is a crucial factor affecting its mortality. Currently, little is known about how temperature affects the immune response of rainbow trout gut microbiota and metabolites to IHNV. In this study, our main objective is to analyze the changes in gut microorganisms of rainbow trout (juvenile fish with a consistent genetic background) after 14 days of infection with IHNV (5 × 105 pfu/fish) at 12-13°C (C: injected with saline, A: injected with IHNV) and 16-17°C (D: injected with saline, B: injected with IHNV) using metagenomic and metabolomic analyses, and to screen for probiotics that are effective against IHNV. The results showed that infection with IHNV at 12-13°C caused Eukaryote loss. Compared to Group C, Group A showed a significant increase in harmful pathogens, such as Yersiniaceae, and a significant alteration of 4,087 gut metabolites. Compared to group D, group B showed a significant increase in the abundance of Streptococcaceae and Lactococcus lactis, along with significant changes in 4,259 intestinal metabolites. Compared with their respective groups, the levels of two immune-related metabolites, 1-Octadecanoyl-glycero-3-phosphoethanolamine and L-Glutamate, were significantly upregulated in groups A and B. Compared to group B, Group A showed significantly higher pathogenic bacteria including Aeromonas, Pseudomonas, and Yersiniaceae, while group B showed a significant increase in Streptococcaceae and Lactococcus lactis. Additionally, there were 4,018 significantly different metabolites between the two groups. Interestingly, 1-Octadecanoyl-sn-glycero-3-phosphoethanolamine and L-Glutamate were significantly higher in group A than in group B. Some of the different metabolites in C vs. A are correlated with Fomitopsis pinicola, while in D vs. B they were correlated with Lactococcus raffinolactis, and in A vs. B they were correlated with Hypsizygus marmoreus. This study exposed how rainbow trout gut microbiota and metabolites respond to IHNV at different temperatures, and screens beneficial bacteria with potential resistance to IHN, providing new insights and scientific basis for the prevention and treatment of IHN.
RESUMEN
PURPOSE: Obesity has been demonstrated to improve bone mineral density (BMD), according to previous research. Nevertheless, there is a dearth of clarity regarding the optimal body mass index (BMI) and waist circumference (WC) for achieving the highest beneficial BMD in postmenopausal women. The objective of this study was to establish the correlation between obesity and BMD. METHODS: The relationship between BMI, WC, and BMD was examined by using multivariate logistic regression models, fitting smoothing curves and utilizing the latest data from the National Health and Nutrition Examination Survey (NHANES) survey conducted between 2007 and 2018. Furthermore, the analysis of saturation effects was employed to examine the association of nonlinear connections among BMI, WC, and BMD. RESULTS: The research examined information from a combination of 564 participants. A significant correlation between BMD and BMI as well as WC was observed in our findings. The enduring correlation between BMI and WC with BMD was demonstrated across subgroup analyses categorized by age and race, except among other Hispanic and other race. Furthermore, the smoothing curve fitting indicated that there existed not just a linear correlation among BMI, WC, and BMD, but also a saturation threshold in the association of these three factors. CONCLUSIONS: Based on our study, we have found a strong and positive relationship between obesity and BMD. According to the results of this research, maintaining obesity at a moderate level in postmenopausal women would result in achieving an optimal equilibrium between obesity and BMD.
Asunto(s)
Densidad Ósea , Posmenopausia , Femenino , Humanos , Encuestas Nutricionales , Estudios Transversales , Obesidad/complicaciones , Obesidad/epidemiologíaRESUMEN
Regional bias of N6-methyladenosine (m6A) mRNA modification avoiding splice site region, calls for an open hypothesis whether exon-intron boundary could affect m6A deposition. By deep learning modeling, we find that exon-intron boundary represses a proportion (12% to 34%) of m6A deposition at adjacent exons (~100 nt to splice site). Experiments validate that m6A signal increases once the host gene does not undergo pre-mRNA splicing to produce the same mRNA. Inhibited m6A sites have higher m6A enhancers and lower m6A silencers locally and show high heterogeneity at different exons genome-widely, with only a small proportion (12% to 15%) of exons showing strong inhibition, enabling more stable mRNAs and flexible protein coding. m6A is majorly responsible for why mRNAs with more exons be more stable. Exon junction complex (EJC) only partially contributes to this exon-intron boundary m6A inhibition in some short internal exons, highlighting additional factors yet to be identified.
Asunto(s)
Precursores del ARN , Empalme del ARN , Intrones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Semivida , Exones/genética , Empalme del ARN/genética , Precursores del ARN/metabolismoRESUMEN
The use of engineered ketoreductases (KREDS), both as whole microbial cells and isolated enzymes, in the highly enantiospecific reduction of prochiral ketones is reviewed. The homochiral alcohol products are key intermediates in, for example, pharmaceuticals synthesis. The application of sophisticated protein engineering and enzyme immobilisation techniques to increase industrial viability are discussed.
Asunto(s)
Alcoholes , Cetonas , Estereoisomerismo , Oxidación-Reducción , Cetonas/metabolismo , Ingeniería de Proteínas , CatálisisRESUMEN
Males and females respond differently at the muscular level to various tastes and show varied responses when eating different foods. In this study, we used surface electromyography (sEMG) as a novel approach to examine gender differences in taste sensations. We collected sEMG data from 30 participants (15 males, 15 females) over various sessions for six taste states: a no-stimulation physiological state, sweet, sour, salty, bitter, and umami. We applied a Fast Fourier Transformation to the sEMG-filtered data and used a two-sample t-test algorithm to analyze and evaluate the resulting frequency spectrum. Our results showed that the female participants had more sEMG channels with low frequencies and fewer channels with high frequencies than the male participants during all taste states except the bitter taste sensation, meaning that for most sensations, the female participants had better tactile and fewer gustatory responses than the male participants. The female participants responded better to gustatory and tactile perceptions during bitter tasting because they had more channels throughout the frequency distribution. Moreover, the facial muscles of the female participants twitched with low frequencies, while the facial muscles of the male participants twitched with high frequencies for all taste states except the bitter sensation, for which the female facial muscles twitched throughout the range of the frequency distribution. This gender-dependent variation in sEMG frequency distribution provides new evidence of differentiated taste sensations between males and females.
Asunto(s)
Percepción del Gusto , Gusto , Humanos , Masculino , Femenino , Percepción del Gusto/fisiología , Gusto/fisiología , Electromiografía , Factores Sexuales , TactoRESUMEN
Objective: Focusing on the theme of "osteoporosis-related research in adolescents," a systematic visualization of the developmental lineage, current research status, hot spots, and trends of adolescent osteoporosis was conducted to provide a reference for subsequent related research, clinical diagnosis, and treatment. Method: The Web of Science core database was used as the data source to retrieve the relevant literature and the bibliometrics method. An online bibliometric platform, CiteSpace, and VOSviewer software were used to conduct co-occurrence analysis on the authors, scientific research institutions, national cooperation, keywords, and funding sources to draw the relevant knowledge map. Result: A total of 1,199 publications from the Web of Science core database were included in this study. The number of published adolescent osteoporosis (AOP) studies has shown an upward trend over the past 29 years, with the United States being the major contributor to the field with the highest number of publications (291, 24.3%) and the highest number of citations (12,186). The international collaboration map shows that the United States is the country most focused on international collaborative exchanges, with the closest collaboration between the United States and Canada. The most influential research institutions and authors are Children's Hospital and Rauch F. the United States is the primary funding source for this research area. Research hotspots were mainly focused on "bone density," "osteoporosis," and "children." Conclusion: These knowledge maps review the research hotpots in adolescent osteoporosis research over time, analyze and summarize the research process over the past 29 years, and predict future research directions.
Asunto(s)
Osteoporosis , Adolescente , Niño , Humanos , Bibliometría , Densidad Ósea , CanadáRESUMEN
Restoring skin integrity after wound infection remains a tougher health challenge due to the uncontrolled antibiotic-resistant pathogens caused by antibiotic abuse. Herein, an injectable hydrogel with dual antibacterial and anti-inflammatory activities composed of gold nanoclusters (GNCs) and carbomer (CBM) is developed for wound dressing to overcome multidrug-resistant infection. Firstly, both experimental investigations and molecular dynamics simulation validate the protonation state of 6-mercaptohexanoic acid (MHA) ligands play an important role in its antibacterial action of GNCs. The self-organizing GNCs-CBM composite hydrogel is then spontaneously cross-linked by the dimeric hydrogen bonds (H-bonds) between the MHA ligands and the acrylic acid groups of CBM. Benefitting from the dimeric H-bonds, the hydrogel becomes thickening enough as an ideal wound dressing and the GNCs exist in the hydrogel with a high protonation level that contributes to the enhanced bactericidal function. In all, by combining bactericidal and immunomodulatory actions, the GNCs-CBM hydrogel demonstrated excellent synergy in accelerating wound healing in animal infection models. Hence, the dimeric H-bonds strengthening strategy makes the GNCs-CBM hydrogel hold great potential as a safe and effective dressing for treating infected wounds.
RESUMEN
The covalent immobilisation of enzymes generally involves the use of highly reactive crosslinkers, such as glutaraldehyde, to couple enzyme molecules to each other or to carriers through, for example, the free amino groups of lysine residues, on the enzyme surface. Unfortunately, such methods suffer from a lack of precision. Random formation of covalent linkages with reactive functional groups in the enzyme leads to disruption of the three dimensional structure and accompanying activity losses. This review focuses on recent advances in the use of bio-orthogonal chemistry in conjunction with rec-DNA to affect highly precise immobilisation of enzymes. In this way, cost-effective combination of production, purification and immobilisation of an enzyme is achieved, in a single unit operation with a high degree of precision. Various bio-orthogonal techniques for putting this precision and elegance into enzyme immobilisation are elaborated. These include, for example, fusing (grafting) peptide or protein tags to the target enzyme that enable its immobilisation in cell lysate or incorporating non-standard amino acids that enable the application of bio-orthogonal chemistry.
Asunto(s)
Enzimas Inmovilizadas , Enzimas Inmovilizadas/químicaRESUMEN
Ideal immobilization with enhanced biocatalyst activity and thermostability enables natural enzymes to serve as a powerful tool to yield synthetically useful chemicals in industry. Such an enzymatic method strategy becomes easier and more convenient with the use of genetic and protein engineering. Here, we developed a covalent programmable polyproteam of tyrosine ammonia lyases (TAL-CLEs) by fusing SpyTag and SpyCatcher peptides into the N-terminal and C-terminal of the TAL, respectively. The resulting circular enzymes were clear after the spontaneous isopeptide bonds formed between the SpyTag and SpyCatcher. Furthermore, the catalytic performance of the TAL-CLEs was measured via a synthesis sample of p-Coumaric acid. Our TAL-CLEs showed excellent catalytic efficiency, with 98.31 ± 1.14% yield of the target product-which is 4.15 ± 0.08 times higher than that of traditional glutaraldehyde-mediated enzyme aggregates. They also showed over four times as much enzyme-activity as wild-type TAL does and demonstrated good reusability, and so may become a good candidate for industrial enzymes.
Asunto(s)
Amoníaco-Liasas , Amoníaco-Liasas/genética , Amoníaco-Liasas/metabolismo , Ácidos Cumáricos/metabolismo , Ingeniería de Proteínas , Tirosina/metabolismoRESUMEN
Silent speech decoding (SSD), based on articulatory neuromuscular activities, has become a prevalent task of brain-computer interfaces (BCIs) in recent years. Many works have been devoted to decoding surface electromyography (sEMG) from articulatory neuromuscular activities. However, restoring silent speech in tonal languages such as Mandarin Chinese is still difficult. This paper proposes an optimized sequence-to-sequence (Seq2Seq) approach to synthesize voice from the sEMG-based silent speech. We extract duration information to regulate the sEMG-based silent speech using the audio length. Then, we provide a deep-learning model with an encoder-decoder structure and a state-of-the-art vocoder to generate the audio waveform. Experiments based on six Mandarin Chinese speakers demonstrate that the proposed model can successfully decode silent speech in Mandarin Chinese and achieve a character error rate (CER) of 6.41% on average with human evaluation.