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1.
Artigo em Inglês | MEDLINE | ID: mdl-34613907

RESUMO

Dynamic neural network is an emerging research topic in deep learning. Compared to static models which have fixed computational graphs and parameters at the inference stage, dynamic networks can adapt their structures or parameters to different inputs, leading to notable advantages in terms of accuracy, computational efficiency, adaptiveness, etc. In this survey, we comprehensively review this rapidly developing area by dividing dynamic networks into three main categories: 1) sample-wise dynamic models that process each sample with data-dependent architectures or parameters; 2) spatial-wise dynamic networks that conduct adaptive computation with respect to different spatial locations of image data; and 3) temporal-wise dynamic models that perform adaptive inference along the temporal dimension for sequential data such as videos and texts. The important research problems of dynamic networks, e.g., architecture design, decision making scheme, optimization technique and applications, are reviewed systematically. Finally, we discuss the open problems in this field together with interesting future research directions.

2.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638868

RESUMO

Mechanical unloading contributes to significant cardiovascular deconditioning. Endothelial dysfunction in the sites of microcirculation may be one of the causes of the cardiovascular degeneration induced by unloading, but the detailed mechanism is still unclear. Here, we first demonstrated that mechanical unloading inhibited brain microvascular endothelial cell proliferation and downregulated histone deacetylase 6 (HDAC6) expression. Furthermore, HDAC6 promoted microvascular endothelial cell proliferation and attenuated the inhibition of proliferation caused by clinorotation unloading. To comprehensively identify microRNAs (miRNAs) that are regulated by HDAC6, we analyzed differential miRNA expression in microvascular endothelial cells after transfection with HDAC6 siRNA and selected miR-155-5p, which was the miRNA with the most significantly increased expression. The ectopic expression of miR-155-5p inhibited microvascular endothelial cell proliferation and directly downregulated Ras homolog enriched in brain (RHEB) expression. Moreover, RHEB expression was downregulated under mechanical unloading and was essential for the miR-155-5p-mediated promotion of microvascular endothelial cell proliferation. Taken together, these results are the first to elucidate the role of HDAC6 in unloading-induced cell growth inhibition through the miR-155-5p/RHEB axis, suggesting that the HDAC6/miR-155-5p/RHEB pathway is a specific target for the preventative treatment of cardiovascular deconditioning.


Assuntos
Proliferação de Células , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Desacetilase 6 de Histona/metabolismo , MicroRNAs/biossíntese , Microvasos/metabolismo , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Animais , Linhagem Celular , Células Endoteliais/citologia , Camundongos , Microvasos/citologia
3.
Angew Chem Int Ed Engl ; 60(50): 26087-26095, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34490693

RESUMO

Synthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self-propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane-floating cell-surface receptors in a stochastic manner and simultaneously trigger the receptor-dimerization to activate downstream signaling for cell motility. The cell membrane-associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell-driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution.

4.
Cell Prolif ; 54(9): e13104, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34323331

RESUMO

OBJECTIVES: RAB14 is a member of small GTPase RAB family which localizes at the endoplasmic reticulum (ER), Golgi apparatus and endosomal compartments. RAB14 acts as molecular switches that shift between a GDP-bound inactive state and a GTP-bound active state and regulates circulation of vesicles between the Golgi and endosomal compartments. In present study, we investigated the roles of RAB14 during oocyte meiotic maturation. MATERIALS AND METHODS: Microinjection with siRNA and exogenous mRNA for knock down and rescue, and immunofluorescence staining, Western blot and real-time RT-PCR were utilized for the study. RESULTS: Our results showed that RAB14 localized in the cytoplasm and accumulated at the cortex during mouse oocyte maturation, and it was also enriched at the spindle periphery. Depletion of RAB14 did not affect polar body extrusion but caused large polar bodies, indicating the failure of asymmetric division. We found that absence of RAB14 did not affect spindle organization but caused the spindle migration defects, and this might be due to the regulation on cytoplasmic actin assembly via the ROCK-cofilin signalling pathway. We also found that RAB14 depletion led to aberrant Golgi apparatus distribution. Exogenous Myc-Rab14 mRNA supplement could significantly rescue these defects caused by Rab14 siRNA injection. CONCLUSIONS: Taken together, our results suggest that RAB14 affects ROCK-cofilin pathway for actin-based spindle migration and Golgi apparatus distribution during mouse oocyte meiotic maturation.


Assuntos
Meiose/fisiologia , Oócitos/metabolismo , Oócitos/fisiologia , Oogênese/fisiologia , Proteínas rab de Ligação ao GTP/metabolismo , Actinas , Animais , Citoplasma/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fosforilação/fisiologia , Transdução de Sinais/fisiologia , Quinases Associadas a rho/metabolismo
5.
Acta Biomater ; 130: 138-148, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34082094

RESUMO

Precise delivery of therapeutic protein drugs that specifically modulate desired cellular responses is critical in clinical practice. However, the spatiotemporal regulation of protein drugs release to manipulate the target cell population in vivo remains a huge challenge. Herein, we have rationally developed an injectable and Near-infrared (NIR) light-responsive MXene-hydrogel composed of Ti3C2, agarose, and protein that enables flexibly and precisely control the release profile of protein drugs to modulate cellular behaviors with high spatiotemporal precision remotely. As a proof-of-concept study, we preloaded hepatic growth factor (HGF) into the MXene@hydrogel (MXene@agarose/HGF) to activate the c-Met-mediated signaling by NIR light. We demonstrated NIR light-instructed cell diffusion, migration, and proliferation at the user-defined localization, further promoting angiogenesis and wound healing in vivo. Our approach's versatility was validated by preloading tumor necrotic factor-α (TNF-α) into the composite hydrogel (MXene@agarose/TNF-α) to promote the pro-apoptotic signaling pathway, achieving the NIR light-induced programmed cell deaths (PCD) of tumor spheroids. Taking advantage of the deep-tissue penetrative NIR light, we could eradicate the deep-seated tumors in a xenograft model exogenously. Therefore, the proposed MXene-hydrogel provides the impetus for developing therapeutic synthetic materials for light-controlled drug release under thick tissue, which will find promising applications in regenerative medicine and tumor therapy. STATEMENT OF SIGNIFICANCE: Current stimuli-responsive hydrogels for therapeutic proteins delivery mainly depend on self-degradation, passive diffusion, or the responsiveness to cues relevant to diseases. However, it remains challenging to spatiotemporally deliver protein-based drugs to manipulate the target cell population in vivo in an "on-demand" manner. Therefore, we have rationally constructed an injectable and Near-infrared (NIR) light-responsive composite hydrogel by embedding Ti3C2 MXene and protein drugs within an agarose hydrogel to enable the remote control of protein drugs delivery with high spatiotemporal precision. The NIR light-controlled release of the growth factor or cytokine has been carried out to regulate receptor-mediated cellular behaviors under deep tissue for skin wound healing or cancer therapy. This system will provide the potential for precision medicine through the development of intelligent drug delivery systems.


Assuntos
Hidrogéis , Raios Infravermelhos , Liberação Controlada de Fármacos , Hidrogéis/farmacologia , Titânio , Cicatrização
6.
Adv Mater ; 33(31): e2008586, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34173269

RESUMO

The discovery of magnetism in 2D materials offers new opportunities for exploring novel quantum states and developing spintronic devices. In this work, using field-effect transistors with solid ion conductors as the gate dielectric (SIC-FETs), we have observed a significant enhancement of ferromagnetism associated with magnetic easy-axis switching in few-layered Cr2 Ge2 Te6 . The easy axis of the magnetization, inferred from the anisotropic magnetoresistance, can be uniformly tuned from the out-of-plane direction to an in-plane direction by electric field in the few-layered Cr2 Ge2 Te6 . Additionally, the Curie temperature, obtained from both the Hall resistance and magnetoresistance measurements, increases from 65 to 180 K in the few-layered sample by electric gating. Moreover, the surface of the sample is fully exposed in the SIC-FET device configuration, making further heterostructure-engineering possible. This work offers an excellent platform for realizing electrically controlled quantum phenomena in a single device.

7.
Mediators Inflamm ; 2021: 9958051, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34035661

RESUMO

Tumor angiogenesis plays a crucial role in colorectal cancer development. Dysregulation of the receptor for the advanced glycation end-products (RAGE) transmembrane signaling mediates inflammation, resulting in various cancers. However, the mechanism of the RAGE signaling pathway in modulating development of colorectal cancer has not been explored. In this study, an aptamer-based RAGE antagonist (Apt-RAGE) was used to inhibit interaction between RAGE and S100B, thus blocking downstream NFκB-mediated signal transduction. In vitro results showed that Apt-RAGE effectively inhibited S100B-dependent and S100B-independent RAGE/NFκB activation in colorectal HCT116 cancer cells, thus decreasing proliferation and migration of cells. Notably, expression and secretion of VEGF-A were inhibited, implying that Apt-RAGE can be used as an antiangiogenesis agent in tumor therapy. Moreover, Apt-RAGE inhibited tumor growth and microvasculature formation in colorectal tumor-bearing mice. Inhibition of angiogenesis by Apt-RAGE was positively correlated with suppression of the RAGE/NFκB/VEGF-A signaling. The findings of this study show that Apt-RAGE antagonist is a potential therapeutic agent for treatment of colorectal cancer.

8.
Stem Cell Reports ; 16(9): 2169-2181, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34019816

RESUMO

Duchenne muscular dystrophy (DMD) is a rare X-linked recessive disease that is associated with severe progressive muscle degeneration culminating in death due to cardiorespiratory failure. We previously observed an unexpected proliferation-independent telomere shortening in cardiomyocytes of a DMD mouse model. Here, we provide mechanistic insights using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using traction force microscopy, we show that DMD hiPSC-CMs exhibit deficits in force generation on fibrotic-like bioengineered hydrogels, aberrant calcium handling, and increased reactive oxygen species levels. Furthermore, we observed a progressive post-mitotic telomere shortening in DMD hiPSC-CMs coincident with downregulation of shelterin complex, telomere capping proteins, and activation of the p53 DNA damage response. This telomere shortening is blocked by blebbistatin, which inhibits contraction in DMD cardiomyocytes. Our studies underscore the role of fibrotic stiffening in the etiology of DMD cardiomyopathy. In addition, our data indicate that telomere shortening is progressive, contraction dependent, and mechanosensitive, and suggest points of therapeutic intervention.

9.
Basic Res Cardiol ; 116(1): 26, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33876316

RESUMO

Heart failure due to high blood pressure or ischemic injury remains a major problem for millions of patients worldwide. Despite enormous advances in deciphering the molecular mechanisms underlying heart failure progression, the cell-type specific adaptations and especially intercellular signaling remain poorly understood. Cardiac fibroblasts express high levels of cardiogenic transcription factors such as GATA-4 and GATA-6, but their role in fibroblasts during stress is not known. Here, we show that fibroblast GATA-4 and GATA-6 promote adaptive remodeling in pressure overload induced cardiac hypertrophy. Using a mouse model with specific single or double deletion of Gata4 and Gata6 in stress activated fibroblasts, we found a reduced myocardial capillarization in mice with Gata4/6 double deletion following pressure overload, while single deletion of Gata4 or Gata6 had no effect. Importantly, we confirmed the reduced angiogenic response using an in vitro co-culture system with Gata4/6 deleted cardiac fibroblasts and endothelial cells. A comprehensive RNA-sequencing analysis revealed an upregulation of anti-angiogenic genes upon Gata4/6 deletion in fibroblasts, and siRNA mediated downregulation of these genes restored endothelial cell growth. In conclusion, we identified a novel role for the cardiogenic transcription factors GATA-4 and GATA-6 in heart fibroblasts, where both proteins act in concert to promote myocardial capillarization and heart function by directing intercellular crosstalk.

10.
Biochem Biophys Res Commun ; 555: 175-181, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33819748

RESUMO

Microgravity and radiation exposure-induced bone damage is one of the most significant alterations in astronauts after long-term spaceflight. However, the underlying mechanism is still largely unknown. Recent ground-based simulation studies have suggested that this impairment is likely mediated by increased production of reactive oxygen species (ROS) during spaceflight. The small Maf protein MafG is a basic-region leucine zipper-type transcription factor, and it globally contributes to regulation of antioxidant and metabolic networks. Our research investigated the role of MafG in the process of apoptosis induced by simulated microgravity and radiation in MC3T3-E1 cells. We found that simulated microgravity or radiation alone decreased MafG expression and elevated apoptosis in MC3T3-E1 cells, and combined simulated microgravity and radiation treatment aggravated apoptosis. Meanwhile, under normal conditions, increased ROS levels facilitated apoptosis and downregulated the expression of MafG in MC3T3-E1 cells. Overexpression of MafG decreased apoptosis induced by simulated microgravity and radiation. These findings provide new insight into the mechanism of bone damage induced by microgravity and radiation during space flight.


Assuntos
Apoptose/efeitos da radiação , Fator de Transcrição MafG/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos da radiação , Proteínas Repressoras/metabolismo , Apoptose/fisiologia , Linhagem Celular , Regulação para Baixo , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Fator de Transcrição MafG/genética , Osteoblastos/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/genética , Simulação de Ausência de Peso , Raios X
11.
Acupunct Med ; 39(6): 656-662, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33715459

RESUMO

BACKGROUND: Bone loss induced by microgravity is a serious problem in space flight. However, the effects of acupuncture stimulation on osteoporosis induced by microgravity have not been studied. With the goal of developing an effective countermeasure, our aim was to evaluate the effects of electroacupuncture (EA) stimulation at BL20, BL23, and SP6 on osteoporosis induced by simulated microgravity in rats. METHODS: Thirty male Wistar rats (aged 10 weeks) were randomly divided into three groups: healthy control group (CON, n = 10), hind limb unloading by tail-suspension group (T-S, n = 10), and EA treatment group (TRE, n = 10). Rats in the T-S and TRE groups were subjected to tail-suspension at -30° for 30 days, while the CON group experienced freedom of activity. In this period, the TRE group received EA treatment at BL20, BL23, and SP6 for 30 min every other day, which continued for 30 days. The microarchitecture of the proximal tibia and the biomechanical features of the femur in the rats were analyzed. In addition, the levels of serum biomarkers bone alkaline phosphatase (BALP) and osteocalcin (BGP) were measured. RESULTS: Compared with the CON group, the value of bone volume/total volume (BV/TV) and trabecular number (Tb.N) of the tibias in the TRE group remarkably decreased (p < 0.01). However, these changes were markedly less than those of the T-S group after 4 weeks of EA treatment (p < 0.05). Moreover, the serum concentration of BGP in the TRE group was also significantly higher than that of the T-S group (p < 0.05). CONCLUSIONS: These findings indicate that EA stimulation at BL20, BL23, and SP6 retards osteoporosis induced by hind limb unloading in rats.

12.
NPJ Microgravity ; 7(1): 3, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589605

RESUMO

Microgravity is well-known to induce Osteopenia. However, the combined effects of microgravity and radiation that commonly exist in space have not been broadly elucidated. This research investigates the combined effects on MC3T3-E1 cells and rat femurs. In MC3T3-E1 cells, simulated microgravity and X-ray radiation, alone or combination, show decreased cell activity, increased apoptosis rates by flow cytometric analysis, and decreased Runx2 and increased Caspase-3 mRNA and protein expressions. In rat femurs, simulated microgravity and X-ray radiation, alone or combination, show increased bone loss by micro-CT test and Masson staining, decreased serum BALP levels and Runx2 mRNA expressions, and increased serum CTX-1 levels and Caspase-3 mRNA expressions. The strongest effect is observed in the combined group in MC3T3-E1 cells and rat femurs. These findings suggest that the combination of microgravity and radiation exacerbates the effects of either treatment alone on MC3T3-E1 cells and rat femurs.

13.
FEBS J ; 288(9): 3055-3067, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33206458

RESUMO

Protein regulator of cytokinesis 1 (PRC1) is a microtubule bundling protein that is involved in the regulation of the central spindle bundle and spindle orientation during mitosis. However, the functions of PRC1 during meiosis have rarely been studied. In this study, we explored the roles of PRC1 during meiosis using an oocyte model. Our results found that PRC1 was expressed at all stages of mouse oocyte meiosis, and PRC1 accumulated in the midzone/midbody during anaphase/telophase I. Moreover, depleting PRC1 caused defects in polar body extrusion during mouse oocyte maturation. Further analysis found that PRC1 knockdown did not affect meiotic spindle formation or chromosome segregation; however, deleting PRC1 prevented formation of the midzone and midbody at the anaphase/telophase stage of meiosis I, which caused cytokinesis defects and further induced the formation of two spindles in the oocytes. PRC1 knockdown increased the level of tubulin acetylation, indicating that microtubule stability was affected. Furthermore, KIF4A and PRC1 showed similar localization in the midzone/midbody of oocytes at anaphase/telophase I, while the depletion of KIF4A affected the expression and localization of PRC1. The PRC1 mRNA injection rescued the defects caused by PRC1 knockdown in oocytes. In summary, our results suggest that PRC1 is critical for midzone/midbody formation and cytokinesis under regulation of KIF4A in mouse oocytes.


Assuntos
Proteínas de Ciclo Celular/genética , Cinesina/genética , Meiose/genética , Fuso Acromático/genética , Anáfase/genética , Animais , Segregação de Cromossomos/genética , Citocinese/genética , Camundongos , Microtúbulos/genética , Mitose/genética , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Oogênese/genética
14.
J Hazard Mater ; 401: 123362, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32629343

RESUMO

This study examined the role of intermittent illumination/dark conditions coupled with MnO2-ammendments to regulate the mobility of As and Fe in flooded arsenic-enriched soils. Addition of MnO2 particles with intermittent illumination led to a pronounced increase in the reductive-dissolution of Fe(III) and As(V) from flooded soils compared to a corresponding dark treatments. A higher MnO2 dosage (0.10 vs 0.02 g) demonstrated a greater effect. Over a 49-day incubation, maximum Fe concentrations mobilized from the flooded soils amended with 0.10 and 0.02 g MnO2 particles were 2.39 and 1.85-fold higher than for non-amended soils under dark conditions. The corresponding maximum amounts of mobilized As were at least 92 % and 65 % higher than for non-amended soils under dark conditions, respectively. Scavenging of excited holes by soil humic/fulvic compounds increased mineral photoelectron production and boosted Fe(III)/As(V) reduction in MnO2-amended, illuminated soils. Additionally, MnO2 amendments shifted soil microbial community structure by enriching metal-reducing bacteria (e.g., Anaeromyxobacter, Bacillus and Geobacter) and increasing c-type cytochrome production. This microbial diversity response to MnO2 amendment facilitated direct contact extracellular electron transfer processes, which further enhanced Fe/As reduction. Subsequently, the mobility of released Fe(II) and As(III) was partially attenuated by adsorption, oxidation, complexation and/or coprecipitation on active sites generated on MnO2 surfaces during MnO2 dissolution. These results illustrated the impact of a semiconducting MnO2 mineral in regulating the biogeochemical cycles of As/Fe in soil and demonstrated the potential for MnO2-based bioremediation strategies for arsenic-polluted soils.


Assuntos
Arsênio , Oryza , Poluentes do Solo , Arsênio/análise , Ferro , Compostos de Manganês , Oxirredução , Óxidos , Solo , Poluentes do Solo/análise
15.
Angew Chem Int Ed Engl ; 60(12): 6733-6743, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33331089

RESUMO

Selective modulation of ligand-receptor interaction is essential in targeted therapy. In this study, we design an intelligent "scan and unlock" DNA automaton (SUDA) system to equip a native protein-ligand with cell-identity recognition and receptor-mediated signaling in a cell-type-specific manner. Using embedded DNA-based chemical reaction networks (CRNs) on the cell surface, SUDA scans and evaluates molecular profiles of cell-surface proteins via Boolean logic circuits. Therefore, it achieves cell-specific signal modulation by quickly unlocking the protein-ligand in proximity to the target cell-surface to activate its cognate receptor. As a proof of concept, we non-genetically engineered hepatic growth factor (HGF) with distinct logic SUDAs to elicit target cell-specific HGF signaling and wound healing behaviors in multiple heterogeneous cell types. Furthermore, the versatility of the SUDA strategy was shown by engineering tumor necrotic factor-α (TNFα) to induce programmed cell death of target cell subpopulations through cell-specific modulation of TNFR1 signaling.


Assuntos
DNA/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , DNA/química , Fator de Crescimento de Hepatócito/química , Humanos , Ligantes , Modelos Moleculares , Receptores Tipo I de Fatores de Necrose Tumoral/química , Transdução de Sinais
16.
ACS Omega ; 5(49): 31551-31558, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33344807

RESUMO

A novel integrated analyzer was developed for the in situ determination of two-dimensional (2D) dissolved Fe(II) distributions in sediment pore water. The analyzer utilized gel enrichment and optical imaging techniques. An image probe mainly consisting of a gel holder and portable document scanner was designed to be inserted into sediment. The gel holder exposed to the sediment was made to hold a polyacrylamide gel strip (diffusive gel) and polyacrylamide gel strip impregnated with C18 and coated with ferrozine (concentrating gel). The concentrating gel strip could accumulate the dissolved Fe(II) in pore water and produce a magenta-colored Fe(II)-ferrozine compound on the gel strip in two dimensions. The portable document scanner sealed in a transparent box and stuck onto the back of the gel holder could record gel images from the back of the concentrating gel strip. Gel images with grayscale intensities were acquired and analyzed using ImageJ software, and Fe(II) concentration was determined based on a deployment time related calibration curve established in the laboratory. The measurement accuracy and precision were investigated. The quantitative range reached up to 200 µmol L-1. The method and analyzer exhibit distinct characteristics of in situ enrichment and measurement; they were successfully applied to determine the 2D Fe(II) distribution in lake and marine sediment pore waters.

17.
Anal Chem ; 92(22): 15236-15243, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33140958

RESUMO

Lipid transferase-catalyzed protein lipidation plays critical roles in many physiological processes and it has been an increasingly attractive therapeutic target from cancer to neurodegeneration, while sensitive detection of lipid transferase activity in biological samples remains challenging. Here, we presented an AuNP-based colorimetric method with dual-product synergistically enhanced sensitivity for convenient detection of lipid transferase activity. Homo sapiens N-myristoyltransferase 1 (HsNMT1), a key lipid transferase, was selected as the model. Accordingly, positively charged substrate peptides (Pep) of HsNMT1 can induce the aggregation of AuNPs through disrupting their electrostatic repulsion, while the HsNMT1-catalyzed lipid modification generates aggregated lipidated peptides (C14-Pep) and negatively charged HS-CoA, which will eliminate the disruption and stabilize the AuNPs by the formation of Au-S bonds, respectively. Consequently, charge reversal of the biomolecules and the formation of Au-S bonds synergistically contribute to the stability of AuNPs in the presence of HsNMT1. Therefore, the HsNMT1 activity can be visually detected by the naked eye through the color change of the AuNPs originated from the change in their distance-dependent surface plasmon resonance absorptions. Here, the A520/A610 ratio can sensitively reflect the activity of HsNMT1 in the linear range of 2-75 nM with a low detection limit of 0.56 nM. Moreover, the method was successfully applied for probing the HsNMT1 activities in different cell lysates and inhibitor screening. Furthermore, given the replaceability of the substrate peptide, the proposed assay is promising for universal application to other lipid transferases and exhibits great potential in lipid transferase-targeted drug development.


Assuntos
Aciltransferases/metabolismo , Colorimetria/métodos , Ensaios Enzimáticos/métodos , Limite de Detecção , Ouro/química , Humanos , Nanopartículas Metálicas/química
18.
Anal Chem ; 92(22): 15194-15201, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33136382

RESUMO

Neurotransmitters are essential chemical mediators for neuronal communication in variable neuromodulations. However, the progress of neuroscience is hampered by the shortage of suitable sensors to track neurotransmitters with high spatial and temporal resolution. Here, we introduce a self-assembled DNA-nanoprism fluorescent probe capable of nongenetically engineering the cell surface for ultrasensitive imaging of the neurotransmitter release at a single live-cell level. The DNA-nanoprism structure conjugated with three cholesterol tails enables the probe to rapidly and stably anchor on the cell surface within 10 min. The in situ detection of neurotransmitters is achieved by equipping the DNA-nanoprism with an aptamer-based "turn-on" fluorescent sensory module for the transmitter of interest. In a proof-of-concept study, we directly visualized the transient dopamine (DA) release on the cell surface with selective responsivity and high spatiotemporal precision and further explored the dynamic correlation between DA release and calcium influx triggered by high K+. This study provides a robust and sensitive tool for cell-surface-targeted imaging of neuromodulations, which might open up a new avenue to improve the understanding of neurochemistry and advance neuroscience research.


Assuntos
DNA/química , Corantes Fluorescentes/química , Nanoestruturas/química , Neurotransmissores/química , Neurotransmissores/metabolismo , Imagem Óptica/métodos , Linhagem Celular Tumoral , Sobrevivência Celular , Dopamina/metabolismo , Humanos , Neurônios/citologia
19.
Chem Commun (Camb) ; 56(81): 12254, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33000826

RESUMO

Correction for 'Electrochemically shape-controlled synthesis of great stellated dodecahedral Au nanocrystals with high-index facets for nitrogen reduction to ammonia' by Yu-Chen Jiang et al., Chem. Commun., 2020, DOI: 10.1039/d0cc04326e.

20.
Chem Commun (Camb) ; 56(81): 12162-12165, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-32909571

RESUMO

Au great stellated dodecahedra (GSD), one of the Kepler-Poinsot solids, are synthesized by an electrochemical double-step potential method in a choline chloride-urea based deep eutectic solvent. The as-synthesized Au GSD are bound by high-index {331} facets and exhibit excellent electrocatalytic performance for the nitrogen reduction reaction with a high NH3 yield rate (49.96 µg h-1 cm-2) and faradaic efficiency (28.59%) under ambient conditions.

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