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1.
Nat Commun ; 12(1): 5743, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593817

RESUMO

Machine learning has been increasingly used for protein engineering. However, because the general sequence contexts they capture are not specific to the protein being engineered, the accuracy of existing machine learning algorithms is rather limited. Here, we report ECNet (evolutionary context-integrated neural network), a deep-learning algorithm that exploits evolutionary contexts to predict functional fitness for protein engineering. This algorithm integrates local evolutionary context from homologous sequences that explicitly model residue-residue epistasis for the protein of interest with the global evolutionary context that encodes rich semantic and structural features from the enormous protein sequence universe. As such, it enables accurate mapping from sequence to function and provides generalization from low-order mutants to higher-order mutants. We show that ECNet predicts the sequence-function relationship more accurately as compared to existing machine learning algorithms by using ~50 deep mutational scanning and random mutagenesis datasets. Moreover, we used ECNet to guide the engineering of TEM-1 ß-lactamase and identified variants with improved ampicillin resistance with high success rates.


Assuntos
Aprendizado Profundo , Evolução Molecular , Engenharia de Proteínas/métodos , Sequência de Aminoácidos/genética , Conjuntos de Dados como Assunto , Aptidão Genética , Ensaios de Triagem em Larga Escala , Mutação , Homologia de Sequência de Aminoácidos , Resistência beta-Lactâmica/genética , beta-Lactamases/genética
2.
ACS Appl Mater Interfaces ; 13(39): 47163-47173, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34555902

RESUMO

Solid polymer electrolytes (SPEs) of superior ionic conductivity, long-term cycling stability, and good interface compatibility are regarded as promising candidates to enable the practical applications of solid lithium metal batteries (SLMBs). Here, a mixed-matrix SPE (MMSE) with incorporated metal-organic frameworks (MOFs) and ionic liquid is prepared. The dissociation of Li salt in MMSE can be promoted effectively due to the introduction of MOF via the Fourier-transform infrared spectroscopy (FT-IR) analysis, density functional theory calculation, and molecular dynamics simulation. The as-formed MMSE exhibits an ultralow thickness of 20 µm with a satisfactory ionic conductivity and lithium-ion transference number (1.1 mS cm-1 at 30 °C, 0.72). The optimized SLMBs with high-voltage LiMn0.75Fe0.25PO4 (LMFP) exhibit an excellent cyclability at 4.2 V under room temperature. Moreover, Li/MMSE/LiFePO4 cells have desirable cycle performance from -20 to 100 °C, and their capacity remains 143.3 mA h g-1 after being cycled 300 times at 10 C at 100 °C. The Li/LiFePO4 pouch cells also show excellent safety under extreme conditions. The Li symmetric cells can work steadily even at a supreme current density of 4 mA cm-2 at 100 °C. From the above analysis, these MMSEs present new opportunities for the development of SLMBs with good electrochemical properties.

3.
Nat Commun ; 12(1): 4880, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385444

RESUMO

Accurate and imperceptible monitoring of electrophysiological signals is of primary importance for wearable healthcare. Stiff and bulky pregelled electrodes are now commonly used in clinical diagnosis, causing severe discomfort to users for long-time using as well as artifact signals in motion. Here, we report a ~100 nm ultra-thin dry epidermal electrode that is able to conformably adhere to skin and accurately measure electrophysiological signals. It showed low sheet resistance (~24 Ω/sq, 4142 S/cm), high transparency, and mechano-electrical stability. The enhanced optoelectronic performance was due to the synergistic effect between graphene and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), which induced a high degree of molecular ordering on PEDOT and charge transfer on graphene by strong π-π interaction. Together with ultra-thin nature, this dry epidermal electrode is able to accurately monitor electrophysiological signals such as facial skin and brain activity with low-motion artifact, enabling human-machine interfacing and long-time mental/physical health monitoring.


Assuntos
Eletrodos , Eletrofisiologia/métodos , Epiderme/fisiologia , Desenho de Equipamento/métodos , Monitorização Fisiológica/métodos , Dispositivos Eletrônicos Vestíveis , Artefatos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Condutividade Elétrica , Eletrofisiologia/instrumentação , Eletrofisiologia/normas , Desenho de Equipamento/normas , Grafite/química , Humanos , Estrutura Molecular , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/normas , Movimento (Física) , Polímeros/química , Poliestirenos/química , Pele
4.
Int J Biol Sci ; 17(12): 3173-3187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421358

RESUMO

Pharmacological stimulation of adipose tissue remodeling and thermogenesis to increase energy expenditure is expected to be a viable therapeutic strategy for obesity. Berberine has been reported to have pharmacological activity in adipose tissue to anti-obesity, while the mechanism remains unclear. Here, we observed that berberine significantly reduced the body weight and insulin resistance of high-fat diet mice by promoting the distribution of brown adipose tissue and thermogenesis. We have further demonstrated that berberine activated energy metabolic sensing pathway AMPK/SIRT1 axis to increase the level of PPARγ deacetylation, which leads to promoting adipose tissue remodeling and increasing the expression of the thermogenic protein UCP-1. These findings suggest that berberine that enhances the AMPK/SIRT1 pathway can act as a selective PPARγ activator to promote adipose tissue remodeling and thermogenesis. This study proposes a new mechanism for the regulation of berberine in adipose tissue and offers a great prospect for berberine in obesity treatment.

5.
Acta Biomater ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34303866

RESUMO

Adhesion often occurs after tendon injury, and results in sliding disorder and movement limitation with no ideal solution for it in clinic. In this study, an anti-adhesion membrane, i.e., decellularized tendon matrix (DTM) for tendon is successfully prepared by an optimized tendon decellularization method from homologous extracellular matrix. Microsection technology has been used to optimize the method of decellularization in order to better preserve the bioactive components in tissues and reduce the chemical reagent residues on the premise of effective decellularization with relatively shorter time and less reagents for decellularization. The physic-chemical properties and biological functions of DTM are evaluated, and high-throughput and high-precision tandem mass tags (TMT) labeling proteomics technology is used to analyze protein components of DTM, which may provide the scientific support for application of the innovative product. In vitro biosafety tests show that DTM not only is non-toxic but also promote cell proliferation. Subcutaneous implantation test confirms that DTM is completely degraded after 12 weeks and there is no obvious inflammatory reaction. The results of Achilles tendon repair in rabbits show that DTM can not only prevent tendon adhesion but also improve the quality of tendon repair, which demonstrates its tremendous application potential. STATEMENT OF SIGNIFICANCE: There is no ideal solution for adhesion after tendon injury. In this study, a dense tendon anti-adhesion membrane (DTM) was successfully prepared from homologous extracellular matrix (ECM). This DTM could effectively retain bioactive ingredients, and prevent adhesion as well as improve the quality of tendon repair in vivo. An optimized decellularization method was used which could effectively decellularize tendon in a short time, better preserve bioactive components, and reduce reagent residues. For the first time, high-throughput and high-precision tandem mass tags (TMT) labeling proteomics technology was used to qualitatively and quantitatively analyze the protein composition of fresh tendon, acellular tendon and DTM, which provided not only scientific support for the application of DTM, but also comprehensive and accurate data support for related research of bovine tendons and decellularization.

6.
Chem Rev ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34297541

RESUMO

Directed evolution aims to expedite the natural evolution process of biological molecules and systems in a test tube through iterative rounds of gene diversifications and library screening/selection. It has become one of the most powerful and widespread tools for engineering improved or novel functions in proteins, metabolic pathways, and even whole genomes. This review describes the commonly used gene diversification strategies, screening/selection methods, and recently developed continuous evolution strategies for directed evolution. Moreover, we highlight some representative applications of directed evolution in engineering nucleic acids, proteins, pathways, genetic circuits, viruses, and whole cells. Finally, we discuss the challenges and future perspectives in directed evolution.

7.
J Chem Inf Model ; 61(7): 3376-3385, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34161083

RESUMO

Liquid-liquid extraction (LLE) is an important technique to separate aromatics from aliphatics since these compounds have very similar boiling points and cannot be separated by distillation. Ionic liquids (ILs) are considered as potential extractants to extract aromatics from aliphatics. In this paper, molecular dynamics (MD) simulations were used to predict the extraction property (i.e., capacity and selectivity) of ILs for the LLE of aromatics from aliphatics. The extraction properties of seven different ILs including [C2mim][Tf2N], [C2mim][TFO], [C2mim][SCN], [C2mim][DCA], [C2mim][TCM], [C4mim][Tf2N], and [C8mim][Tf2N] were investigated. Results show that ILs with shorter alkyl chain cations and [Tf2N]- anion exhibit better extraction efficiency than other ILs, which is in agreement with previously reported experimental data on the extraction of toluene from aliphatics and further validated the reliability of the proposed model. The binding energies between ILs and organic molecules were calculated by the density functional theory, which help explain the different extraction behaviors of different ILs. The symmetry-adapted perturbation theory analysis was performed to further understand the interaction mechanisms between ILs and organics. Our study shows that the [Tf2N]- anion also has the best extraction capability for heavier aromatics (o-xylene, m-xylene, and p-xylene) from common aliphatics (heptane and octane). The MD modeling approach can be a low-cost in silico tool for the high-throughput fast screening of ILs for the LLE of aromatics from aliphatics.


Assuntos
Líquidos Iônicos , Ânions , Extração Líquido-Líquido , Simulação de Dinâmica Molecular , Reprodutibilidade dos Testes
8.
Phys Chem Chem Phys ; 23(22): 12541-12548, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-33998614

RESUMO

Sterically hindered frustrated Lewis pairs (FLPs) have the ability to activate hydrogen molecules, and their reactivity is strongly determined by the geometric parameters of the Lewis acids and bases. A recent experimental study showed that ionic liquids (ILs) could largely improve the effective configuration of FLPs. However, the detailed mechanistic profile is still unclear. Herein, we performed molecular dynamics (MD) simulations to reveal the effects of ILs on the structures of FLPs, in particular, the association of Lewis acids and bases. For this purpose, mixed systems were adopted consisting of the ILs [Cnmim][NTf2] (n = 6, 10, 14), [C6mim][PF6] and [C6mim][CTf3] and the typical FLP (tBu)3P/B(C6F5)3 for MD simulations. Radial distribution functions (RDFs) results show that toluene competes with (tBu)3P to interact with B(C6F5)3, resulting in a relatively low effective (tBu)3P/B(C6F5)3 complex, while [C10mim][NTf2] shows less competition with (tBu)3P, which increases the amount of effective FLPs. Spatial distribution functions (SDFs) results show that toluene forms a continuum solvation-shell, which hinders the interactions between (tBu)3P and B(C6F5)3, while [C10mim][NTf2] leaves relatively large empty spaces, which are accessible for (tBu)3P or B(C6F5)3 molecules, resulting in higher probabilities of effective FLP structures. Lastly, we find that the longer alkyl chain length of [Cnmim]+ cations, the higher the amount of effective (tBu)3P/B(C6F5)3 pairs, and the anion [CTf3]- shows negative effects, for which even less effective (tBu)3P/B(C6F5)3 pairs have been found compared to those of toluene.

9.
ACS Appl Mater Interfaces ; 13(19): 22819-22827, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33945252

RESUMO

Constructing a bilayer system with defined twist angles is an effective way to engineer the physical properties of two-dimensional (2D) materials, opening up a new research area of twistronics. How to achieve high-quality bilayer 2D materials in a controlled and mass production way is of primary importance to this emerging area. In this work, we present a strategy for the large-scale fabrication of twisted bilayer molybdenum disulfide (MoS2) through photolithography patterning and folding of single-crystal monolayer MoS2. Atomic resolution transmission electron spectroscopy directly confirms that the as-achieved folded bilayer MoS2 is of high quality with targeted twist angles. Various twist angles result in tuning Raman mode frequencies and direct optical transition energies. Due to the weak interlayer coupling between the twisted layers, folded bilayers exhibit an extremely high photoluminescence with doubled intensity as compared to the unfolded monolayer, indicating a possible application in optoelectronic devices. Our work provides a new strategy to tailor the properties of MoS2, which will be beneficial to twistable electronics.

10.
Proc Natl Acad Sci U S A ; 118(16)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33846255

RESUMO

Great efforts have been made to build integrated devices to enable future wearable electronics; however, safe, disposable, and cost-effective power sources still remain a challenge. In this paper, an all-solid-state power source was developed by using graphene materials and can be printed directly on an insulating substrate such as paper. The design of the power source was inspired by electric eels to produce programmable voltage and current by converting the chemical potential energy of the ion gradient to electric energy in the presence of moisture. An ultrahigh voltage of 192 V with 175 cells in series printed on a strip of paper was realized under ambient conditions. For the planar cell, the mathematical fractal design concept was adapted as printed patterns, improving the output power density to 2.5 mW cm-3, comparable to that of lithium thin-film batteries. A foldable three-dimensional (3D) cell was also achieved by employing an origami strategy, demonstrating a versatile design to provide green electric energy. Unlike typical batteries, this power source printed on flexible paper substrate does not require liquid electrolytes, hazardous components, or complicated fabrication processes and is highly customizable to meet the demands of wearable electronics and Internet of Things applications.

11.
Bioact Mater ; 6(9): 2927-2945, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33732964

RESUMO

Sterilization is the process of killing all microorganisms, while disinfection is the process of killing or removing all kinds of pathogenic microorganisms except bacterial spores. Biomaterials involved in cell experiments, animal experiments, and clinical applications need to be in the aseptic state, but their physical and chemical properties as well as biological activities can be affected by sterilization or disinfection. Decellularized matrix (dECM) is the low immunogenicity material obtained by removing cells from tissues, which retains many inherent components in tissues such as proteins and proteoglycans. But there are few studies concerning the effects of sterilization or disinfection on dECM, and the systematic introduction of sterilization or disinfection for dECM is even less. Therefore, this review systematically introduces and analyzes the mechanism, advantages, disadvantages, and applications of various sterilization and disinfection methods, discusses the factors influencing the selection of sterilization and disinfection methods, summarizes the sterilization and disinfection methods for various common dECM, and finally proposes a graphical route for selecting an appropriate sterilization or disinfection method for dECM and a technical route for validating the selected method, so as to provide the reference and basis for choosing more appropriate sterilization or disinfection methods of various dECM.

12.
Curr Neuropharmacol ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535957

RESUMO

Peripheral nerve injury has a high incidence and often leads to severe losses of sensory and motor functions in the afflicted limb. Autologous nerve grafts are widely accepted as the gold standard for peripheral nerve repair, but the presence of inherent drawbacks dramatically reduces their usability. Numerous tissue engineering nerve grafts are developed as alternatives of autologous nerve grafts, and a variety of cells and neurotrophic factors were introduced into these grafts for improvement. However, they are still difficult to obtain satisfactory clinical results. Peripheral nerve regeneration following injury remains a significant challenge for researchers and clinicians. Exosomes are extracellular membranous nanovesicles that are secreted by most cells. As the key players of intercellular communication, exosomes play a fundamental role in the physiological and pathological processes of the nervous system. Accumulating evidence has suggested that exosomes can exert neurotherapeutic effects via mediating axonal regrowth, Schwann cell activation, vascular regeneration, and inflammatory regulation. Exosomes are emerging as a promising approach for treating peripheral nerve injury. Furthermore, they also provide possibilities for enhancing the repair capacity of various nerve grafts. This review primarily highlights the regenerative effects of exosomes on peripheral nerve injury. The exosomes from distinct sources reported so far in literature are summarized to understand their roles in the process of nerve repair. Moreover, the challenges that must be addressed in their clinical transformation are outlined as well. This review also provides further insight into the potential application of exosomes for peripheral nerve repair. Keywords: Exosome, nerve regeneration, peripheral nerve injury, Schwann cell, axonal regrowth, inflammation, vascular regeneration.

13.
Int J Biol Macromol ; 167: 1452-1467, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33212106

RESUMO

This investigation is vital contribution to the healthcare system utilizing techniques of nanobiotechnology. It interestingly applies chitosan capped CuO nanoparticles in the field of medicine and restorative dentistry. The CuO nanoparticles and CuO-Chitosan nanoparticles are prepared by co-precipitation, and their characterization is performed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray (EDX). The average crystallite size of these nanoparticles has been found to be in the dimensions of <40 nm and <35 nm, respectively. CuO-Chitosan nanoparticles show significant enhancement in in vitro antibacterial, antioxidant, cytotoxic, and antidiabetic activity as compared to CuO nanoparticles. In addition, the successful amalgamation of CuO nanoparticles and CuO-Chitosan nanoparticles into dentine bonding agents results in providing efficient remedy against secondary caries. CuO-Chitosan nanoparticles reinforced dental adhesive discs cause significant upsurge in reduction of Lactobacillus acidophillus and Streptococcus mutans. Also, the augmentation of mechanical properties, water sorption and solubility plus slow and sustained release profile and slight variation of shear bond strength is attained. Taken together, the chemically synthesized CuO nanoparticles and CuO-Chitosan nanoparticles have proven to be promising candidates having enormous potential to be utilized in drug delivery and nanotheranostics.


Assuntos
Antibacterianos/química , Antioxidantes/química , Quitosana/química , Cobre/química , Sistemas de Liberação de Medicamentos/métodos , Hipoglicemiantes/química , Nanopartículas Metálicas/química , Nanomedicina/métodos , Animais , Artemia , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/fisiologia , Biofilmes/efeitos dos fármacos , Cárie Dentária/tratamento farmacológico , Odontologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Lactobacillus acidophilus/efeitos dos fármacos , Lactobacillus acidophilus/fisiologia , Nanopartículas Metálicas/análise , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Solubilidade , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Streptococcus/efeitos dos fármacos , Streptococcus/genética , Difração de Raios X
14.
Am J Emerg Med ; 38(10): 2101-2109, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33184025

RESUMO

INTRODUCTION: Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic. METHODS: This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs. RESULTS: Through February 29 th 2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (n = 99,949) in compared to January 2020 (n = 313,125) and February 2019 (n = 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year. CONCLUSION: The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.


Assuntos
COVID-19/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Índice de Gravidade de Doença , China/epidemiologia , Estado Terminal/epidemiologia , Estudos Transversais , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2
15.
Thromb Res ; 194: 82-90, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788125

RESUMO

INTRODUCTION: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. However, the risk of bleeding and all-cause mortality in patients with edoxaban versus vitamin K antagonists (VKAs) is unclear. METHODS: We systematically searched all published studies of edoxaban versus VKAs. PubMed, CENTRAL databases and www.clinicaltrial.gov were searched for relevant articles published from January 1966 to 20 February 2020. All phase III randomized controlled trials (RCTs) comparing the risk of bleeding and all-cause mortality in patients with edoxaban versus VKAs were included in our meta-analysis. Both random- and fixed-effects models were used to pool data across phase III RCTs. RESULTS: We included four trials that met our inclusion criteria (n = 33,077). They included patients with atrial fibrillation (3 trials, n = 24,847), venous thromboembolism (VTE) or pulmonary embolism (PE) (1 trial, n = 8240). Edoxaban was associated with reduced risks of major or clinically relevant nonmajor bleeding (CRNM) events (OR: 0.78, 95% CI: 0.68-0.89), any bleeding events (OR: 0.76, 95% CI: 0.72-0.80), and intracranial bleeding events (OR: 0.38, 95% CI: 0.29-0.48). They had a similar risk of gastro-intestinal bleeding (OR: 0.95, 95% CI: 0.79-1.13), death from any cause (OR: 0.97, 95% CI: 0.80-1.19), stroke (OR: 1.00, 95% CI: 0.88-1.14) and systemic embolic events (OR: 0.93, 95% CI: 0.57-1.51) between edoxaban and VKAs. CONCLUSIONS: Compared to VKAs, edoxaban is safe as a direct oral anticoagulant, with respect to reduced risk of major or CRNM, intracranial bleeding events, and similar risk of gastro-intestinal bleeding events and all-cause mortality.


Assuntos
Fibrilação Atrial , Fibrinolíticos , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Piridinas , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiazóis , Vitamina K
16.
Acta Biomater ; 115: 235-249, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771587

RESUMO

Acellular nerve allografts are promising alternatives to autologous nerve grafts, but still have many drawbacks which greatly limit their curative effects. Here, we developed an optimized acellular nerve allograft with multiple axial channels by a modified decellularization method. These allografts were confirmed to preserve more extracellular matrix components and factors, and remove cellular components effectively. Meanwhile, macrochannels and microchannels were introduced to optimize internal microstructure of allografts, which increases porosity and water absorption, without significant loss of mechanical strength. The in vitro experiments demonstrated that the multichannel allografts showed superior ability of facilitating proliferation and penetration of Schwann cells. Additionally, in the in vivo experiments, the multichannel allografts were used to bridge 10 mm rat sciatic nerve defects. They exhibited better capacity to guide regenerative nerve fibers through the defective segment and restore innervation of target organs, thus achieving better recovery of muscle and motor function, in comparison with conventional acellular allografts. These findings indicate that this multichannel acellular nerve allograft has great potential for clinical application and provides a new prospective for future investigations of nerve regeneration. STATEMENT OF SIGNIFICANCE: Acellular nerve allografts, with preservation of natural extracellular matrix, are officially approved to repair peripheral nerve injury in some countries. However, bioactive component loss and compact internal structure result in variable clinical effects of conventional acellular allografts. In the present study, we fabricated an optimized acellular nerve allograft with multiple axial channels, which could both enable decellularization to be easily accomplished and reduce the amount of detergents in the preparation process. Characterization of the multichannel acellular allografts was confirmed to have better preservation of ECM bioactive molecules and regenerative factors. Efficiency evaluation showed the multichannel allografts could facilitate Schwann cells to migrate inside them in vitro, and enhance regrowth and myelination of axons as well as recovery of muscle and motor function in vivo.


Assuntos
Regeneração Nervosa , Nervo Isquiático , Aloenxertos , Animais , Estudos Prospectivos , Ratos , Células de Schwann
17.
Artigo em Inglês | MEDLINE | ID: mdl-32328131

RESUMO

Periodontitis is an infectious disease whereby the chronic inflammatory process of the periodontium stimulated by bacterial products induces specific host cell responses. The activation of the host cell immune system upregulates the production of inflammatory mediators, comprising cytokines and proteolytic enzymes, which contribute to inflammation and bone destruction. It has been well known that periodontitis is related to systemic inflammation which links to numerous systemic diseases, including diabetes and arteriosclerosis. Furthermore, periodontitis has been reported in association with neurodegenerative diseases such as Alzheimer's disease (AD) in the brain. Regarding immune responses and inflammation, cathepsin B (CatB) plays pivotal role for the induction of IL-1ß, cathepsin K- (CatK-) dependent active toll-like receptor 9 (TLR9) signaling, and cathepsin S (CatS) which involves in regulating both TLR signaling and maturation of the MHC class II complex. Notably, both the production and proteolytic activities of cathepsins are upregulated in chronic inflammatory diseases, including periodontitis. In the present review, we focus on the roles of cathepsins in the innate and adaptive immune responses within periodontitis. We believe that understanding the roles of cathepsins in the immune responses in periodontitis would help to elucidate the therapeutic strategies of periodontitis, thus benefit for reduction of systemic diseases as well as neurodegenerative diseases in the global aging society.

18.
ACS Appl Mater Interfaces ; 12(1): 1486-1494, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31793286

RESUMO

Stretchable conductors have been achieved by stacking conductive nanomaterials onto the surfaces of elastomeric substrates. However, many of them show a dramatic decrease in conductivity under strain without an efficient way for the conductive layer to release strain. Here, we report a transparent, stretchable, and self-healing conductor with excellent mechanoelectrical stability by introducing dynamic bonding between conductive nanomaterials and an elastomeric substrate. We prepare the conductor by semiembedding Ag nanowires (AgNWs) into a self-healing polydimethylsiloxane (PDMS)-based elastomer, which is modified with bipyridine (Bpy) ligand and further cross-linked by adding Zn2+ as coordinator (Zn-Bpy-PDMS). The dynamic Ag-N bonds not only improve the wettability of the substrate and facilitate the spreading of AgNWs but also reversibly break and reform to accommodate the deformation of AgNWs. As a result, the resistance increase of Zn-Bpy-PDMS/AgNWs is much smaller than that without the dynamic bonding (PDMS/AgNWs). Besides, this conductor exhibits excellent conductivity (76.2 Ω/sq) and transparency (86.6% @ 550 nm), as well as extraordinary self-healing property with a low resistance increase (ΔR/R0 ∼ 1.4) after healing at room temperature for 1 day. This work provides insights into the future design of integrated electronic skin with transparency, stretchability, conductivity, and self-healing capability for applications in wearable optoelectronic devices.


Assuntos
Dimetilpolisiloxanos/química , Elastômeros/química , Nanofios/química , Dispositivos Eletrônicos Vestíveis , Dipeptídeos , Elasticidade , Condutividade Elétrica , Humanos , Nanoestruturas/química , Prata/química
19.
Biomed Mater ; 15(1): 015013, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31747647

RESUMO

This study addresses the fabrication of an extracellular matrix material of the acellular sheep periosteum and the systematic evaluation of its biocompatibility to explore its potential application in guided bone regeneration. Sheep periosteum was harvested and decellularized by a combined decellularization protocol. The effectiveness of cell removal was proved and residual α-Gal antigen was also quantitatively detected. Then, mouse MC3T3-E1 cells were seeded onto the acellular periosteum. A scanning electron microscope (SEM) was used to record the whole process of cell adhesion. The CCK-8 assay suggested that the acellular periosteum not only had zero toxic effect on pre-osteoblasts, but played a positive role in cell proliferation. We also tested whether the acellular periosteum possesses favorable osteogenesis induction activity using an alkaline phosphatase (ALP) assay and a quantitative real-time PCR (Col I, Runx2, OCN) assay. An in vivo study of a subcutaneous implantation test using Sprague Dawley (SD) rats was performed to detect the changes in IL-2, IFN-γ and IL-4 in serum and elucidate the host's local response to acellular periosteum through hematoxylin and eosin (HE) and immunohistochemical staining. The results show that acellular sheep periosteum did not elicit a severe immunogenic response via the Th1 pathway, unlike fresh sheep periosteum. In conclusion, acellular sheep periosteum possesses favorable biocompatibility to be employed for guided bone regeneration.


Assuntos
Materiais Biocompatíveis/química , Regeneração Óssea , Regeneração Tecidual Guiada/métodos , Periósteo/metabolismo , Células 3T3 , Fosfatase Alcalina/metabolismo , Animais , Adesão Celular , Proliferação de Células , Matriz Extracelular/metabolismo , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Camundongos , Osteogênese , Ratos , Ratos Sprague-Dawley , Ovinos
20.
J Biomed Mater Res A ; 108(1): 19-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430044

RESUMO

The objective of this study was to fabricate an acellular sheep periosteum and explore its potential application in guided bone regeneration. Sheep periosteum was collected and decellularized by a modified decellularization protocol. The effectiveness of cell removal was proved by hematoxylin and eosin and 4',6-diamidino-2-phenylindole staining, DNA quantitative test, and agarose gel electrophoresis. After decellularization, its microstructure was found to become more porous while the integrality of collagen fibers remained undamaged, and the contents of collagen and glycosaminoglycan were not decreased significantly. Biomechanical analysis showed that the elastic modulus was significantly declined, while the yield stress was not affected, probably due to the collagen integrality. In vitro study of CCK-8 assay demonstrated that the acellular periosteum not only had no toxic effect to the MC3T3-E1 cells, but benefited the cell proliferation to some degree. In vivo experiment of guided bone regeneration was performed using a rabbit cranial model. Micro-CT and histological results revealed that the acellular periosteum not only effectively prevented the ingrowth of fibrous connective tissues, but also potentially facilitated bone regeneration. In conclusion, acellular sheep periostea, with wider sources, less costs, and more convenient fabrication process, would have great potential in the employment for guided bone regeneration.


Assuntos
Regeneração Óssea/fisiologia , Regeneração Tecidual Guiada , Periósteo/fisiologia , Animais , Morte Celular , Proliferação de Células , Matriz Extracelular/metabolismo , Masculino , Periósteo/diagnóstico por imagem , Periósteo/ultraestrutura , Coelhos , Reprodutibilidade dos Testes , Ovinos , Crânio/diagnóstico por imagem , Crânio/cirurgia , Microtomografia por Raio-X
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