RESUMO
Enterovirus 71 (EV71) is one of the major pathogens causing hand, foot, and mouth disease in children under 5 years old, which can result in severe neurological complications and even death. Due to limited treatments for EV71 infection, the identification of novel host factors and elucidation of mechanisms involved will help to counter this viral infection. N-terminal acetyltransferase 6 (NAT6) was identified as an essential host factor for EV71 infection with genome-wide CRISPR/Cas9 screening. NAT6 facilitates EV71 viral replication depending on its acetyltransferase activity but has little effect on viral release. In addition, NAT6 is also required for Echovirus 7 and coxsackievirus B5 infection, suggesting it might be a pan-enterovirus host factor. We further demonstrated that NAT6 is required for Golgi integrity and viral replication organelle (RO) biogenesis. NAT6 knockout significantly inhibited phosphatidylinositol 4-kinase IIIß (PI4KB) expression and PI4P production, both of which are key host factors for enterovirus infection and RO biogenesis. Further mechanism studies confirmed that NAT6 formed a complex with its substrate actin and one of the PI4KB recruiters-acyl-coenzyme A binding domain containing 3 (ACBD3). Through modulating actin dynamics, NAT6 maintained the integrity of the Golgi and the stability of ACBD3, thereby enhancing EV71 infection. Collectively, these results uncovered a novel mechanism of N-acetyltransferase supporting EV71 infection.IMPORTANCEEnterovirus 71 (EV71) is an important pathogen for children under the age of five, and currently, no effective treatment is available. Elucidating the mechanism of novel host factors supporting viral infection will reveal potential antiviral targets and aid antiviral development. Here, we demonstrated that a novel N-acetyltransferase, NAT6, is an essential host factor for EV71 replication. NAT6 could promote viral replication organelle (RO) formation to enhance viral replication. The formation of enterovirus ROs requires numerous host factors, including acyl-coenzyme A binding domain containing 3 (ACBD3) and phosphatidylinositol 4-kinase IIIß (PI4KB). NAT6 could stabilize the PI4KB recruiter, ACBD3, by inhibiting the autophagy degradation pathway. This study provides a fresh insight into the relationship between N-acetyltransferase and viral infection.
Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Acetiltransferases N-Terminal , Fosfotransferases (Aceptor do Grupo Álcool) , Criança , Pré-Escolar , Humanos , 1-Fosfatidilinositol 4-Quinase/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antivirais , Coenzima A/metabolismo , Infecções por Coxsackievirus , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/metabolismo , Infecções por Enterovirus/virologia , Proteínas de Membrana/metabolismo , Acetiltransferases N-Terminal/metabolismo , Biogênese de Organelas , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Replicação Viral/fisiologiaRESUMO
Three sulfonate-containing polyelectrolytes are elaborately designed and used to passivate perovskite film with the anti-solvent method. Under the influence of the secondary monomer, three copolymers present various chemical configurations and deliver different modification effects. Fluorene-thiophene copolymer STF has linear and highly-conjugated chain. STF-perovskite film presents large crystal grains. Fluorene-carbazole copolymer SCF has flexible chain and easily enters into grain boundary areas. SCF-perovskite film is homogenous and continuous. Fluorene-fluorene copolymer SPF agglomerates on the surface and is not applicable to the anti-solvent method. The full investigation demonstrates that STF and SCF not only conduct surface defect passivation, but also improve the film quality by being involved in the perovskite's crystallization process. Compared with the control device, the devices with STF and SCF deliver high efficiency and excellent stability. The unencapsulated devices with STF and SCT maintain ≈80% of the initial power conversion efficiency (PCE) after 40 days of storage under 30-40% relative humidity. SCF performs better and the device maintains 60% of the initial PCE after 20 days of storage under 60-80% relative humidity.
Assuntos
Compostos de Cálcio , Óxidos , Polímeros , Titânio , Polieletrólitos , Alcanossulfonatos , Fluorenos , SolventesRESUMO
Enterovirus 71 (EV71) is deemed a reemergent pathogen, with recent outbreaks worldwide. EV71 infection causes hand, foot, and mouth disease (HFMD) and has been associated with severe cardiac and central nervous system complications and even death. Viruses need host factors to complete their life cycle; therefore, the identification of the host factors for EV71 infection is pivotal to new antiviral research. Emerging evidence has highlighted the importance of protein acetylation during infection by various human viruses. The endoplasmic reticulum (ER), as the prominent organelle of EV71 replication, also has a unique acetylation regulation mechanism. However, the pathogenesis of EV71 and its relationship with the ER-based acetylation machinery are not fully understood. In this study, we demonstrated for the first time that the ER-resident acetyltransferase N-acetyltransferase 8 (NAT8) is a host factor for EV71 infection. Inhibiting NAT8 with CRISPR or a small compound significantly suppressed EV71 infection in SK-N-SH cells. NAT8 promoted EV71 replication in an acetyltransferase-activity-dependent manner. Additionally, we found that NAT8 facilitates EV71 infection by interacting with EV71 2B, 3AB, and 3C proteins and increasing the stability of these proteins. These results uncovered a novel function of NAT8 and elucidated a new mechanism underlying the regulation of EV71 replication. IMPORTANCE EV71 is one of the most common pathogens causing HFMD in young children, and some patients experience severe or fatal neurological consequences. To ensure efficient replication, the virus must hijack multiple host factors for its own benefit. Here, we show that the ER-resident acetyltransferase NAT8 is a host factor for EV71 infection. EV71 fails to complete its infection in various cells in the absence of NAT8. We further show that NAT8 benefits EV71 replication in an acetyltransferase-activity-dependent manner. Finally, we show that NAT8 facilitates EV71 infection by interacting with EV71 2B, 3AB, and 3C proteins and increasing the stability of these proteins. These results uncovered a novel function of NAT8 in EV71 infection and elucidated a new mechanism underlying the regulation of EV71 replication.
Assuntos
Acetiltransferases , Enterovirus Humano A , Infecções por Enterovirus , Proteínas não Estruturais Virais , Replicação Viral , Acetiltransferases/metabolismo , Enterovirus Humano A/fisiologia , Humanos , Proteínas não Estruturais Virais/metabolismoRESUMO
Herein we report a novel spiropyran (SP)-based organic-inorganic composite nanogel (NG), which was prepared using upconverting nanoparticles, spiropyran, acrylic acid and N,N'-bis(acryloyl)cystamine (BAC) compounds under emulsion polymerisation. Compared with other polymer nanoparticles, the crosslinked multi-stimulus responsive nanogels can adjust the release rate by altering more of the parameters and this can meet the needs of a complex biological environment to control the release of drugs. Doxorubicin hydrochlorides were used as a simulated drug to test the drug loading performance and controllable drug release performance of the composite NGs. Under near-infrared light (NIR) irradiation, an acidic environment or a reducing agent, the delivery of the loaded drugs was by controlled release over 24 hours. Under mild triple stimulation (NIR light, pH 6, and 4 mM reducing agent), the loaded drug could be released more efficiently. The organic-inorganic composite NGs with highly-efficient and controllable release performance for loaded drugs provide many choices for novel stimulus responsive nanocarriers.
Assuntos
Substâncias Redutoras , Nanogéis , Preparações de Ação Retardada , Oxirredução , Concentração de Íons de HidrogênioRESUMO
Among the common treatment/disposal routes of excessive activated sludge from municipal wastewater treatment plant, dewatering process functions as an essential pre-/post-treatment for volume minimization and transportation facilitation. Since inorganic coagulants have long been criticized for their high dosage and solid residue in sludge cake, there is an urgent need for investigations regarding the potential of applying organic chemicals as the conditioner. In this study, combined use of poly dimethyldiallylammonium chloride (PDMD) and tannic acid (TA) were investigated as an all-organic co-conditioning method for sewage sludge pre-treatment. Results showed that this all-organic conditioning strategy can effectively improve the dewaterability of sewage sludge. The capillary suction time reduced from 128.8 s to 23.1 s, and the filtration resistance reduced from 1.24 × 1012 cm/g to 7.38 × 1010 cm/g. The moisture content of dewatered sludge cake decreased to as low as 55.83%, showing the highest dewatering efficiency reported so far. In addition, the combination of PDMD and TA maximized the treating efficiency with very limited consumption of conditioners (added up to 4% of total solid). Based on the physic-chemical and rheological property investigation, it was proposed that the intermediate molecular weight polymer-based flocculation process and the TA agent-based protein precipitation process, could remarkably strengthen the compactness and structure robustness of sludge. In all, this PDMD-TA-based conditioning method suggested practical significance in consideration of its cost-effectiveness and disposal convenience of sludge cake.
Assuntos
Esgotos , Purificação da Água , Esgotos/química , Taninos , Compostos Orgânicos , Polímeros , Cloretos , Filtração , Eliminação de Resíduos Líquidos/métodos , Água/químicaRESUMO
Vav2 is a ubiquitous guanine nucleotide exchange factor (GEF) for Rho family GTPases that is involved in regulating a wide range of biological processes. It interacts with several tyrosine-phosphorylated cell surface receptors, including the Eph family receptors, through its SH2 domain. The interaction of Vav2 with EphA2 is crucial for EphA2-mediated tumor angiogenesis. Here we show that Vav2-SH2 domain is a lipid-binding module that can recognize PI(4,5)P2 and PI(3,4,5)P3 lipids weakly but specifically. The specific lipid-binding site in Vav2-SH2 domain was identified by NMR chemical shift perturbation experiments using the head groups of PI(4,5)P2 and PI(3,4,5)P3, both of which bind to Vav2-SH2 with millimolar binding affinities. In addition, the interaction between Vav2-SH2 and the phosphorylated juxtamembrane region (JM) of EphA2 (Y594 phosphorylated) was investigated using NMR techniques. Furthermore, by using a nickel-lipid containing peptide-based nanodiscs system, we studied the binding of Vav2-SH2 to the phosphorylated JM region of EphA2 on lipid membrane and uncovered a role of membrane environment in modulating this protein-protein recognition.
Assuntos
Efrina-A2/química , Membranas Artificiais , Fosfatidilinositol 4,5-Difosfato/química , Fosfatos de Fosfatidilinositol/química , Proteínas Proto-Oncogênicas c-vav/química , Efrina-A2/metabolismo , Humanos , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Proteínas Proto-Oncogênicas c-vav/metabolismo , Receptor EphA2 , Domínios de Homologia de srcRESUMO
BACKGROUND: The polymer-based drug/gene delivery is promising for the treatment of inherent or acquire disease, because of the polymer's structural flexibility, larger capacity for therapeutic agent, low host immunogenicity and less cost. Antisense therapy is an approach to fighting genetic disorders or infections using antisense oligonucleotides (AOs). Unfortunately, the naked AOs showed low therapeutic efficacy in vivo and in clinical trial due to their poor cellular uptake and fast clearance in bloodstream. In this study, a series of triazine-cored amphiphilic polymers (TAPs) were investigated for their potential to enhance delivery of AOs, 2'-O-methyl phosphorothioate RNA (2'-OMePS) and phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. RESULTS: TAPs significantly enhanced AO-induced exon-skipping in a GFP reporter-based myoblast and myotube culture system, and observed cytotoxicity of the TAPs were lower than Endoporter, Lipofectamine-2000 or PEI 25K. Application of optimized formulations of TAPs with AO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. The best ones for PMO and 2'-OMePS delivery have reached to 11-, 15-fold compared with the AO only in mdx mice, respectively. CONCLUSION: The study of triazine-cored amphiphilic polymers for AO delivery in vitro and in mdx mice indicated that the carrier's performances are related to the molecular size, compositions and hydrophilic-lipophilic balance (HLB) of the polymers, as well as the AO's structure. Improved exon-skipping efficiency of AOs observed in vitro and in mdx mice accompanied with low cytotoxicity demonstrated TAP polymers are potentials as safe and effective delivery carrier for gene/drug delivery.
Assuntos
Portadores de Fármacos/química , Oligonucleotídeos Antissenso/química , Polímeros/química , Triazinas/química , Animais , Permeabilidade da Membrana Celular , Distrofina/química , Feminino , Técnicas de Transferência de Genes , Terapia Genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Masculino , Camundongos Endogâmicos mdx , Estrutura Molecular , Morfolinos/química , Mioblastos/metabolismo , Polietilenoimina/química , Relação Estrutura-Atividade , TransfecçãoRESUMO
BACKGROUNDS: Surgical resection and adjunct chemotherapy or radio-therapy has been applied for the therapy of superficial malignant tumor in clinics. Whereas, there are still some problems limit its clinical use, such as severe pains and side effect. Thus, it is urgent need to develop effective, minimally invasive and low toxicity therapy stagey for superficial malignant tumor. Topical drug administration such as microneedle patches shows the advantages of reduced systemic toxicity and nimble application and, as a result, a great potential to treat superficial tumors. METHODS: In this study, microneedle (MN) patches were fabricated to deliver photosensitizer IR820 and chemotherapy agent cisplatin (CDDP) for synergistic chemo-photodynamic therapy against breast cancer. RESULTS: The MN could be completely inserted into the skin and the compounds carrying tips could be embedded within the target issue for locoregional cancer treatment. The photodynamic therapeutic effects can be precisely controlled and switched on and off on demand simply by adjusting laser. The used base material vinylpyrrolidone-vinyl acetate copolymer (PVPVA) is soluble in both ethanol and water, facilitating the load of both water-soluble and water-insoluble drugs. CONCLUSIONS: Thus, the developed MN patch offers an effective, user-friendly, controllable and low-toxicity option for patients requiring long-term and repeated cancer treatments.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Verde de Indocianina/farmacologia , Fotoquimioterapia/métodos , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Tratamento Farmacológico , Feminino , Humanos , Verde de Indocianina/análogos & derivados , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/administração & dosagem , Povidona/análogos & derivadosRESUMO
With the rapid development of portable and wearable electronic devices, self-supporting flexible supercapacitors have attracted much attention, and higher requirements have been put forward for the electrode of the device, that is, it is necessary to have good mechanical properties while satisfying excellent electrochemical performance. In this work, a facile method was invented to obtain excellent self-supported flexible electrode materials with high mechanical properties and outstanding electrochemical performance by combining cellulose nanofibrils (CNFs) and reduced graphene oxide (RGO). We focused on the effect of the ratio of the addition of CNFs and the formation process of the film on the electrochemical and mechanical properties. The results show that the CNFs/RGO12 (where the ratio of CNFs to GO is 1:2) film displayed outstanding comprehensive properties; its tensile strength and conductivity were up to 83 MPa and 202.94 S/m, respectively, and its CA value was as high as 146 mF cm-2 under the current density of 5 mA cm-2. Furthermore, the initial retention rate of the specific capacitance was about 83.7% when recycled 2000 times; moreover, its capacitance did not change much after perpendicular bending 200 times. Therefore, the films prepared by this study have great potential in the field of flexible supercapacitors.
Assuntos
Celulose/química , Capacitância Elétrica , Condutividade Elétrica , Grafite/química , Membranas Artificiais , Nanofibras/químicaRESUMO
Zymomonas mobilis is an ethanologenic microbe that has a demonstrated potential for use in lignocellulosic biorefineries for bioethanol production. Z. mobilis exhibits a number of desirable characteristics for use as an ethanologenic microbe, with capabilities for metabolic engineering and bioprocess modification. Many advanced genetic tools, including mutation techniques, screening methods and genome editing have been successively performed to improve various Z. mobilis strains as potential consolidated ethanologenic microbes. Many bioprocess strategies have also been applied to this organism for bioethanol production. Z. mobilis biofilm reactors have been modified with various benefits, including high bacterial populations, less fermentation times, high productivity, high cell stability, resistance to the high concentration of substrates and toxicity, and higher product recovery. We suggest that Z. mobilis biofilm reactors could be used in bioethanol production using lignocellulosic substrates under batch, continuous and repeated batch processes.
Assuntos
Etanol/metabolismo , Zymomonas/genética , Biofilmes , Reatores Biológicos/microbiologia , Fermentação , Edição de Genes , Lignina/metabolismo , Engenharia Metabólica , Microrganismos Geneticamente Modificados/genética , Mutagênese , Nitrogênio/metabolismo , Zymomonas/metabolismoRESUMO
Carbon fiber mesh reinforced cement-based composites (CMCCs) have received extensive attention in the field of engineering repair and structural reinforcement due to their outstanding properties such as two-way force, rust prevention, high specific strength, and low base surface requirements. However, the development of this material has been slowed down to some extent due to the poor interfacial bonding between the carbon fiber mesh and the cement matrix. In this paper, a novel fabrication strategy was proposed in which the carbon fiber mesh was modified with epoxy resin and silane coupling agent (SCA) to increase its surface chemical activity. Meanwhile, the hydroxymethyl cellulose (HMC) was also filled into the concrete matrix to improve the mechanical strength of the matrix as well as the load transfer behaviors between the mortar and carbon fiber (CF) mesh. The potential to employ SCA and HMC was evaluated for the making of CMCCs via the above methods. The results showed that the longitudinal shear strength of composites with SCA and SCA&HMC increased by 26.6% and 56.1% compared to those of CF with epoxy resin (EP) reinforced composites, respectively. The flexural strength of composite with SCA&HMC increases by 147.6% compared to I-(F) without CF. The novel II-HCM&CF/EP-SCA composites with excellent performance are promised to be applied in practical uses.
Assuntos
Fibra de Carbono/química , Resinas Compostas/química , Cumarínicos/química , Cimentos de Resina/química , Silanos/química , Resinas Epóxi/química , Teste de Materiais/métodos , Resistência ao Cisalhamento , Estresse Mecânico , Propriedades de Superfície , Telas CirúrgicasRESUMO
Squaraine dyes have excellent photostability with intensive absorption and strong fluorescence in the near-infrared (NIR) region. However, they display a strong tendency to aggregate in aqueous media because of their poor water solubility, often causing fluorescence quenching that severely limits their in vivo applications, especially for detecting or imaging diagnostic enzymes. In this work, an oligo(ethylene glycol)-functionalized squaraine fluorophore has been developed as an NIR-fluorescent probe that can detect and image the activities of a diagnostic enzyme (leucine aminopeptidase) both in vitro and in vivo. The probe shows near-infrared absorption and emission, a low detection limit (0.61 ng/mL), relatively good aqueous solubility, high selectivity, and little toxicity. In addition, the probe herein was successfully used to track endogenous leucine aminopeptidase both in vitro and in vivo with a nude-mouse model.
Assuntos
Ciclobutanos/química , Corantes Fluorescentes/química , Fenóis/química , Polietilenoglicóis/química , Animais , Linhagem Celular , Humanos , Leucil Aminopeptidase , Limite de Detecção , Camundongos , Camundongos Nus , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Biorefinery of biomass-based biofuels and biochemicals by microorganisms is a competitive alternative of traditional petroleum refineries. Zymomonas mobilis is a natural ethanologen with many desirable characteristics, which makes it an ideal industrial microbial biocatalyst for commercial production of desirable bioproducts through metabolic engineering. In this review, we summarize the metabolic engineering progress achieved in Z. mobilis to expand its substrate and product ranges as well as to enhance its robustness against stressful conditions such as inhibitory compounds within the lignocellulosic hydrolysates and slurries. We also discuss a few metabolic engineering strategies that can be applied in Z. mobilis to further develop it as a robust workhorse for economic lignocellulosic bioproducts. In addition, we briefly review the progress of metabolic engineering in Z. mobilis related to the classical synthetic biology cycle of "Design-Build-Test-Learn", as well as the progress and potential to develop Z. mobilis as a model chassis for biorefinery practices in the synthetic biology era.
Assuntos
Engenharia Metabólica/métodos , Biologia Sintética/métodos , Zymomonas/genética , Zymomonas/metabolismo , Lignina/genética , Lignina/metabolismoRESUMO
Fibrillar materials have gained much attention recently because of their unique properties and potential applications. Although many methods have been developed to fabricate materials, it remains challenging to prepare fibrillar materials containing multicomponent materials or even with complex structures. Here, a facile strategy is developed to fabricate bamboo-shaped fibers by treating electrospun polymer core-shell fibers with solvent vapor annealing. Electrospun polystyrene (PS)/poly(methyl methacrylate) (PMMA) core-shell fibers are first prepared by electrospinning PS/PMMA blend solutions via a phase separation process. When the PS/PMMA core-shell fibers are annealed with the vapor of cyclohexane, which swells and delocalizes the PS domains selectively, the fibers transform into bamboo-shaped structures. The bamboo-shaped structures can be further examined by swelling and delocalizing the PMMA domains selectively, revealing the undulated PS structures. The thermal insulation properties of the fibers with bamboo-shaped structures are observed to be enhanced compared with the original polymer core-shell fibers.
Assuntos
Acetatos/química , Polimetil Metacrilato/química , Poliestirenos/química , Temperatura , Estrutura Molecular , Tamanho da Partícula , Solventes/química , Propriedades de SuperfícieRESUMO
Present research aims to investigate the repairing effect of polylactic acid-trimethylene carbonate/GNDF slow-release catheter on the injured femoral nerve fiber. Adult SD male rats as the subjects were divided into two groups, the GDNF group and the control group, and received the surgery to remove the nerve from the exposed left femoral nerves. Thereafter, rats in the GNDF group and the control group received the GNDF or normal saline, and we evaluated the changes in rats, including the morphological, functional and electrophysiological changes of regenerated nerves. Regenerated axons were found in each group, but enormous regeneration of axons was only identified in GDNF group. Further analysis showed that: At the 4th, 8th and 12th weeks, areas of the regenerated nerves in GDNF group were (0.95±0.06) mm2, (1.14±0.07) mm2 and (1.22±0.06) mm2, respectively; in the control group, these were (0.15±0.01) mm2, (0.25±0.07) mm2 and (0.52±0.05) mm2, respectively. These showed that the outcome of GDNF group was superior to that of control group. In GDNF group, quantities of the myelinated fiber were (0.8119×104±0.0637×104), (1.3371×104±0.0460×104) and (1.7669×104±0.0542×104); while in control group, these were (0.2179×104±0.0097×104), (0.3490×104±0.0329×104) and (0.7737×l04±0.0788×104). Again, these results also indicated that the outcome of GDNF group was superior to that of the control group (p<0.05). In GDNF group, the average diameters of myelinated fibers were (2.25±0.17) µm, (2.42±0.14) µm and (2.80±0.10) µm, which were significantly better than (1.24±0.08) µm, (1.43±0.14) µm and (1.82±0.14) µm in the control group. Degrees of fiber myelination in the GDNF group were (0.71±0.03), (0.64±0.03) and (0.6l±0.0l), respectively, which were also significantly higher than (0.02±0.01), (0.04±0.01) and (0.06±0.02) in the control group (p<0.01). At the 12th week after surgery, HE staining was performed to observe the histological changes in quadriceps femoris for evaluation of atrophy in each group. In the GDNF group, significant amelioration was found in the atrophy of quadriceps femoris with an average area of myofiber of (84.95±3.92) %, while the area of the control group was (57.95±5.78) %, suggesting that the outcome of the GDNF group was better than that of the control group (p<0.05). Electrophysiological examination of nerves was employed to detect the recovery of neurological functions after repair of nerve defect. At the 4th, 8th and 12th weeks after surgery, CMAP amplitudes in the GDNF group were (9.34±0.52) mV, (14.40±0.69) mV and (19.18±0.48) mV, significantly better than (0.39±0.07) mV, (1.44±0.41) mV and (9.27±0.40) in the control group (p<0.01). Polylactic acid-trimethylene carbonate/GNDF slow-release catheter can accelerate the functional recovery of injured nerves, thus promoting the regeneration efficiency of femoral nerves.
Assuntos
Catéteres , Dioxanos/química , Nervo Femoral/lesões , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Poliésteres/química , Potenciais de Ação/fisiologia , Animais , Atrofia/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/uso terapêutico , Nervo Femoral/patologia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/administração & dosagem , Fator Neurotrófico Derivado de Linhagem de Célula Glial/química , Masculino , Bainha de Mielina/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/patologia , Músculo Quadríceps/patologia , Ratos , Recuperação de Função Fisiológica/fisiologia , Fatores de TempoRESUMO
Wnts and Fgfs regulate various tissues development in vertebrates. However, how regional Wnt or Fgf activities are established and how they interact in any given developmental event is elusive. Here, we investigated the Wnt-mediated craniofacial cartilage development in zebrafish and found that fgf3 expression in the pharyngeal pouches is differentially reduced along the anteroposterior axis in wnt5b mutants and wntless (wls) morphants, but its expression is normal in wnt9a and wnt11 morphants. Introducing fgf3 mRNAs rescued the cartilage defects in Wnt5b- and Wls-deficient larvae. In wls morphants, endogenous Wls expression is not detectable but maternally deposited Wls is present in eggs, which might account for the lack of axis defects in wls morphants. Secretion of endogenous Wnt5b but not Wnt11 was affected in the pharyngeal tissue of Wls morphants, indicating that Wls is not involved in every Wnt secretion event. Furthermore, cell proliferation but not apoptosis in the developing jaw was affected in Wnt5b- and Wls-deficient embryos. Therefore, Wnt5b requires Wls for its secretion and regulates the proliferation of chondrogenic cells through fine-tuning the expression of fgf3 during jaw cartilage development.
Assuntos
Cartilagem/crescimento & desenvolvimento , Proliferação de Células , Condrogênese/fisiologia , Fator 3 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Receptores Acoplados a Proteínas G/metabolismo , Proteínas Wnt/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Apoptose , Cartilagem/metabolismo , Células Cultivadas , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário , Técnicas Imunoenzimáticas , Hibridização In Situ , Morfolinos/farmacologia , Proteína Wnt-5a , Peixe-Zebra/metabolismoRESUMO
Landing of bacteria for adhesion on a surface is a common phenomenon in our life. However, how surface properties are involved in this process remains largely unclear. Using digital holographic microscopy, we investigated the three-dimensional motions of flagellate Escherichia coli swimming near polymeric surfaces with different properties in aqueous solution before adhesion. We monitored the bacteria landing dynamics, which shows that the density distribution, the probability, and the orientation for collisions of the bacteria are determined by their motility but are slightly affected by the surface properties. However, surface hydrophobicity reduces the near-wall velocity of the bacteria through collisions and slightly increases the collision duration. This promotes the landing and adhesion of bacteria. By contrast, most bacteria collide with the surface using their flagella, which resist adhesion.
Assuntos
Aderência Bacteriana , Escherichia coli/fisiologia , Polímeros/química , Interações Hidrofóbicas e Hidrofílicas , Movimento (Física) , Propriedades de SuperfícieRESUMO
Electrospun core-shell fibers have great potentials in many areas, such as tissue engineering, drug delivery, and organic solar cells. Although many core-shell fibers have been prepared and studied, the morphology transformation of core-shell fibers have been rarely studied. In this work, the morphology evolution of electrospun core-shell polymer fibers driven by the Plateau-Rayleigh instability is investigated. Polystyrene/poly(methyl methacrylate) (PS/PMMA) core-shell fibers are first prepared by using blend solutions and a single axial electrospinning setup. After PS/PMMA core-shell fibers are annealed on a PS film, the fibers undulate and sink into the polymer film, forming core-shell hemispheres. The evolution process, which can be observed in situ by optical microscopy, is mainly driven by achieving lower surface and interfacial energies. The morphologies of the transformed structures can be confirmed by a selective removal technique, and polymer microbowls can be obtained.
Assuntos
Polimetil Metacrilato/química , Poliestirenos/química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
In this work, a facile aqueous synthesis method is optimized to produce Mn:ZnSe/ZnS/ZnMnS sandwiched quantum dots (SQDs). In this core-shell co-doped system, paramagnetic Mn(2+) ions are introduced as core and shell dopants to generate Mn phosphorescence and enhance the magnetic resonance imaging signal, respectively. T1 relaxivity of the nanoparticles can be improved and manipulated by raising the shell doping level. Steady state and time-resolved optical measurements suggest that, after high level shell doping, Mn phosphorescence of the core can be sustained by the sandwiched ZnS shell. Because the SQDs are free of toxic heavy metal compositions, excellent biocompatibility of the prepared nanocrystals is verified by in vitro MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To explore the theranostic applications of SQDs, liposome-SQD assemblies are prepared and used for ex vivo optical and magnetic resonance imaging. In addition, these engineered SQDs as nanocarrier for gene delivery in therapy of Panc-1 cancer cells are employed. The therapeutic effects of the nanocrystals formulation are confirmed by gene expression analysis and cell viability assay.
Assuntos
Compostos de Manganês/química , Manganês/química , Imagem Multimodal/métodos , Pontos Quânticos/química , Compostos de Selênio/química , Sulfetos/química , Nanomedicina Teranóstica/métodos , Compostos de Zinco/química , Linhagem Celular Tumoral , Humanos , Hidrodinâmica , Lipossomos , Luminescência , Imageamento por Ressonância Magnética , Microscopia de Fluorescência , Sondas Moleculares/química , Tamanho da Partícula , Pontos Quânticos/ultraestrutura , RNA Interferente Pequeno/metabolismo , Espectrofotometria Ultravioleta , TransfecçãoRESUMO
A simple and low-cost method is reported here for synthesizing polymer dots (PDs) using branched polyethyleneimine and peryleneimide derivatives as precursors heated in dimethylacetamide. The as-prepared PDs can be well-dispersed in water and show excitation-dependent fluorescence, stable fluorescence over a wide range (pH = 5.0 - 9.0), and high photostability. It is demonstrated that the prepared PDs can be used as a novel fluorescent sensing platform for sensitive and selective detection of Fe (III) ions. The fluorescent PDs may be applied to promising applications in chemical sensors for metal ions, as well as biological imaging or biological labeling for their excellent fluorescence properties.