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1.
Proc Natl Acad Sci U S A ; 116(9): 3722-3727, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808758

RESUMO

Staphylococcus aureus is a notorious human bacterial pathogen with considerable capacity to develop antibiotic resistance. We have observed that human infections caused by highly drug-resistant S. aureus are more prolonged, complicated, and difficult to eradicate. Here we describe a metabolic adaptation strategy used by clinical S. aureus strains that leads to resistance to the last-line antibiotic, daptomycin, and simultaneously affects host innate immunity. This response was characterized by a change in anionic membrane phospholipid composition induced by point mutations in the phospholipid biosynthesis gene, cls2, encoding cardiolipin synthase. Single cls2 point mutations were sufficient for daptomycin resistance, antibiotic treatment failure, and persistent infection. These phenotypes were mediated by enhanced cardiolipin biosynthesis, leading to increased bacterial membrane cardiolipin and reduced phosphatidylglycerol. The changes in membrane phospholipid profile led to modifications in membrane structure that impaired daptomycin penetration and membrane disruption. The cls2 point mutations also allowed S. aureus to evade neutrophil chemotaxis, mediated by the reduction in bacterial membrane phosphatidylglycerol, a previously undescribed bacterial-driven chemoattractant. Together, these data illustrate a metabolic strategy used by S. aureus to circumvent antibiotic and immune attack and provide crucial insights into membrane-based therapeutic targeting of this troublesome pathogen.


Assuntos
Farmacorresistência Bacteriana/genética , Proteínas de Membrana/genética , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Antibacterianos/farmacologia , Daptomicina/farmacologia , Farmacorresistência Bacteriana/imunologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Evasão da Resposta Imune/genética , Evasão da Resposta Imune/imunologia , Proteínas de Membrana/metabolismo , Staphylococcus aureus Resistente à Meticilina/imunologia , Staphylococcus aureus Resistente à Meticilina/metabolismo , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
2.
Langmuir ; 37(44): 13046-13058, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34696591

RESUMO

We have examined the spatial distributions of polymer chains in blend films of weakly segregated polystyrene-block-poly(methyl methacrylate) [P(S-b-MMA)] and deuterated polystyrene (dPS). By fine-tuning the composition (ϕPS+dPS = 63.8 vol %) of the total PS/dPS component and annealing temperature (230 and 270 °C), P(S-b-MMA)/dPS blend films mainly form perforated layers with a parallel orientation (hereafter PLs//). The distributions of dPS in PLs// were probed by grazing-incidence small-angle neutron scattering (GISANS) and time-of-flight neutron reflectivity (ToF-NR). GISANS and ToF-NR results offer evidence that dPS chains preferentially locate at the free surface and within the PS layers for blend films that were annealed at 230 °C. Upon annealing at 270 °C, dPS chains distribute within PS layers and perforated PMMA layers. Nevertheless, dPS chains still retain a surface preference for thin films. In contrast, such surface segregation of dPS chains is prohibited for thick films when annealed at 270 °C.

3.
Langmuir ; 35(43): 14017-14030, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31577149

RESUMO

Ultraviolet irradiation (UVI) of varied duration caused cross-linking and neutralization of polystyrene (PS) homopolymers of molar mass (Mn) from 6 to 290 kg mol-1 on a silicon-oxide surface. An optimal neutral skin layer on the surface of the PS was obtained via brief UVI in air (UVIA), by which the PS had no preferential interaction with either block in the copolymer. UVI in an inert environment (gaseous dinitrogen) (UVIN) stabilized the PS layers via cross-linking and enabled the PS networks to have an effective adhesive contact with the underlying substrate. Thorough examination of domain orientations and spatial orders of a series of block copolymer, polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA), thin films deposited on these UVI-treated PS support layers yielded clear evidence that a dense layer of neutralized PS chains was required for the perpendicular orientation of PS-b-PMMA nanodomains. In particular, in addition to neutralization, two factors-the densities of physical entanglements and of chemical crosslinks-both in UVI-treated PS should be considered for the perpendicular orientation of nanolamellae and nanocylinders in symmetric and asymmetric PS-b-PMMA thin films. The density of physical entanglement in PS depends intrinsically on Mn of the PS, whereas the density of chemical cross-links was controlled with a varied duration of UVIN. Sufficiently large densities of physical entanglements and chemical cross-links can prevent PS-b-PMMA chains from penetrating through the neutral skin layer. The total density of physical entanglements and chemical cross-links required for the perpendicular orientation is correlated with the dimensions of the PS-b-PMMA chains.

4.
Langmuir ; 34(25): 7416-7427, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29863876

RESUMO

We investigated the relationship between the self-assembled morphology of poly( tert-butyl acrylate)- block-poly(6-[4-(4'-methoxyphenylazo)phenoxy]hexyl methacrylate) (P tBA- b-PAzoMA) block copolymers and their photoresponsive and fluorescence behaviors. The morphology of P tBA- b-PAzoMA copolymers was manipulated by dissolving them in mixed dimethylformamide (DMF)/hexanol solvents. When P tBA- b-PAzoMA was dissolved in DMF-rich (neutral) solvents, a favorable interaction between the DMF molecules and both blocks resulted in a random-coiled conformation. The unconfined morphology facilitated the formation of both nonassociated and head-to-head organized azobenzene mesogens, which promoted fluorescence emission. When hexanol, a P tBA-selective solvent, was added to DMF, the solvency of P tBA- b-PAzoMA worsened, leading to its assembly into micelles, with PAzoMA in the micelle core. The confinement of azobenzene moieties in the micelle core hindered their trans-to- cis photoisomerization, thereby considerably decreasing the kinetics of photoisomerization and the population of cis isomers. Additionally, a nanoconfined geometry resulted in compactly packed chromophores, causing fluorescence loss. When P tBA- b-PAzoMA was exposed to UV light, the increased number of cis isomers hampered the closely packed mesogens, resulting in a substantial enhancement of fluorescence emission. When the mole fraction of the PAzoMA block was increased, P tBA- b-PAzoMA formed clusters, causing the slow kinetics of photoisomerization and fluorescence quenching.

5.
Langmuir ; 32(46): 12166-12174, 2016 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-27802053

RESUMO

The interactions between ions and phospholipids are closely associated with the structures and functions of cell membrane. Instead of conventional aqueous systems, we systematically investigated the effects of inorganic ions on the self-assembly of lecithin, a zwitterionic phosphatidylcholine, in cyclohexane. Previous studies have shown that addition of inorganic salts with specific divalent and trivalent cations can transform lecithin organosols into organogels. In this study, we focused on the effect of monovalent alkali halides. Fourier transform infrared spectroscopy was used to demonstrate that the binding strength of the alkali cations with the phosphate of lecithin is in the order Li+ > Na+ > K+. More importantly, the cation-phosphate interaction is affected by the paired halide anions, and the effect follows the series I- > Br- > Cl-. The salts of stronger interactions with lecithin, including LiCl, LiBr, LiI, and NaI, were found to induce cylindrical micelles sufficiently long to form organogels, while others remain organosols. A mechanism based on the charge density of ions and the enthalpy change of the ion exchange between alkali halides and lecithin headgroup is provided to explain the contrasting interactions and the effectiveness of the salts to induce organogelation.

6.
Cell Physiol Biochem ; 35(3): 913-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25633526

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. After surgery, radiotherapy is the mainstay of treatment for GBM patients. Unfortunately, the vast majority of GBM patients fail responding to radiotherapy because GBM cells remain highly resistant to radiation. Radiotherapy-induced DNA damage response may correlate with therapeutic resistance. METHODS: Ionizing radiation (IR) was used to induce DNA damage. Cell proliferation and migration were detected by wound-healing, MTT and apoptosis assays. Dual-luciferase assays and Western blot analysis were performed to evaluate NF-κB activation and validate microRNA targets. Real-time PCR was used to study mRNA and microRNA levels. RESULTS: IR-induced DNA damage activated NF-κB in GBM cells which promoted expression of IL-6, IL-8 and Bcl-xL, thereby contributing to cell survival and invasion. Knockdown SENP2 expression enhanced NF-κB essential modulator (NEMO) SUMOylation and NF-κB activity following IR exposure. miR-181b targets SENP2 and positively regulated NF-κB activity. CONCLUSION: NF-κB activation by DNA damage in GBM cells confers resistance to radiation-induced death.


Assuntos
Neoplasias Encefálicas/genética , Cisteína Endopeptidases/metabolismo , Glioblastoma/genética , MicroRNAs/biossíntese , Apoptose/efeitos da radiação , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Cisteína Endopeptidases/genética , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Glioblastoma/radioterapia , Humanos , MicroRNAs/metabolismo , NF-kappa B/genética , Radiação Ionizante , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação
7.
BMC Musculoskelet Disord ; 15: 40, 2014 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-24517217

RESUMO

BACKGROUND: Currently, Posterior Short Segment Pedicle Screw Fixation is a popular procedure for treating unstable thoracolumbar/lumbar burst fracture. But progressive kyphosis and a high rate of hardware failure because of lack of the anterior column support remains a concern. The efficacy of different methods remains debatable and each technique has its advantages and disadvantages. METHODS: A consecutive series of 20 patients with isolated thoracolumbar/lumbar burst fractures were treated by posterior short segment pedicle screw fixation and transforaminal thoracolumbar/lumbar interbody fusion (TLIF) between January 2005 and December 2007. All patients were followed up for a minimum of 2 years. Demographic data, neurologic status, anterior vertebral body heights, segmental Cobb angle and treatment-related complications were evaluated. RESULTS: The mean operative time was 167 minutes (range, 150-220). Blood loss was 450 ~ 1200 ml, an average of 820 ml. All patients recovered with solid fusion of the intervertebral bone graft, without main complications like misplacement of the pedicle screw, nerve or vessel lesion or hard ware failure. The post-operative radiographs demonstrated a good fracture reduction and it was well maintained until the bone graft fusion. Neurological recovery of one to three Frankel grade was seen in 14 patients with partial neurological deficit, three grades of improvement was seen in one patient, two grades of improvement was observed in 6 patients and one grade of improvement was found in 6 patients. All the 6 patients with no paraplegia on admission remained neurological intact, and in one patient with Frankel D on admission no improvement was observed. CONCLUSION: Posterior short-segment pedicle fixation in conjunction with TLIF seems to be a feasible option in the management of selected thoracolumbar/lumbar burst fractures, thereby addressing all the three columns through a single approach with less trauma and good results.


Assuntos
Parafusos Ósseos , Fixação de Fratura/instrumentação , Vértebras Lombares/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Fusão Vertebral/instrumentação , Vértebras Torácicas/cirurgia , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Transplante Ósseo , Feminino , Fixação de Fratura/efeitos adversos , Consolidação da Fratura , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Osseointegração , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Desenho de Prótese , Radiografia , Recuperação de Função Fisiológica , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/fisiopatologia , Fusão Vertebral/efeitos adversos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Vértebras Torácicas/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Sci Rep ; 14(1): 18489, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122932

RESUMO

In low-light environments, the amount of light captured by the camera sensor is reduced, resulting in lower image brightness. This makes it difficult to recognize or completely lose details in the image, which affects subsequent processing of low-light images. Low-light image enhancement methods can increase image brightness while better-restoring color and detail information. A generative adversarial network is proposed for low-quality image enhancement to improve the quality of low-light images. This network consists of a generative network and an adversarial network. In the generative network, a multi-scale feature extraction module, which consists of dilated convolutions, regular convolutions, max pooling, and average pooling, is designed. This module can extract low-light image features from multiple scales, thereby obtaining richer feature information. Secondly, an illumination attention module is designed to reduce the interference of redundant features. This module assigns greater weight to important illumination features, enabling the network to extract illumination features more effectively. Finally, an encoder-decoder generative network is designed. It uses the multi-scale feature extraction module, illumination attention module, and other conventional modules to enhance low-light images and improve quality. Regarding the adversarial network, a dual-discriminator structure is designed. This network has a global adversarial network and a local adversarial network. They determine if the input image is actual or generated from global and local features, enhancing the performance of the generator network. Additionally, an improved loss function is proposed by introducing color loss and perceptual loss into the conventional loss function. It can better measure the color loss between the generated image and a normally illuminated image, thus reducing color distortion during the enhancement process. The proposed method, along with other methods, is tested using both synthesized and real low-light images. Experimental results show that, compared to other methods, the images enhanced by the proposed method are closer to normally illuminated images for synthetic low-light images. For real low-light images, the images enhanced by the proposed method retain more details, are more apparent, and exhibit higher performance metrics. Overall, compared to other methods, the proposed method demonstrates better image enhancement capabilities for both synthetic and real low-light images.

9.
Sci Rep ; 14(1): 12382, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811675

RESUMO

Remote sensing is gradually playing an important role in the detection of ground information. However, the quality of remote-sensing images has always suffered from unexpected natural conditions, such as intense haze phenomenon. Recently, convolutional neural networks (CNNs) have been applied to deal with dehazing problems, and some important findings have been obtained. Unfortunately, the performance of these classical CNN-based methods still needs further enhancement owing to their limited feature extraction capability. As a critical branch of CNNs, the generative adversarial network (GAN), composed of a generator and discriminator, has become a hot research topic and is considered a feasible approach to solving the dehazing problems. In this study, a novel dehazed generative adversarial network (GAN) is proposed to reconstruct the clean images from the hazy ones. For the generator network of the proposed GAN, the color and luminance feature extraction module and the high-frequency feature extraction module aim to extract multi-scale features and color space characteristics, which help the network to acquire texture, color, and luminance information. Meanwhile, a color loss function based on hue saturation value (HSV) is also proposed to enhance the performance in color recovery. For the discriminator network, a parallel structure is designed to enhance the extraction of texture and background information. Synthetic and real hazy images are used to check the performance of the proposed method. The experimental results demonstrate that the performance can significantly improve the image quality with a significant increment in peak-signal-to-noise ratio (PSNR). Compared with other popular methods, the dehazing results of the proposed method closely resemble haze-free images.

10.
ACS Appl Mater Interfaces ; 16(1): 1370-1379, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38117479

RESUMO

The extracellular matrix (ECM) is the fundamental acellular element of human tissues, providing their mechanical structure while delivering biomechanical and biochemical signals to cells. Three-dimensional (3D) tissue models commonly use hydrogels to recreate the ECM in vitro and support the growth of cells as organoids and spheroids. Collagen-nanocellulose (COL-NC) hydrogels rely on the blending of both polymers to design matrices with tailorable physical properties. Despite the promising application of these biomaterials in 3D tissue models, the architecture and network organization of COL-NC remain unclear. Here, we investigate the structural effects of incorporating NC fibers into COL hydrogels by small-angle neutron scattering (SANS) and ultra-SANS (USANS). The critical hierarchical structure parameters of fiber dimensions, interfiber distance, and coassembled open structures of NC and COL in the absence and presence of cells were determined. We found that NC expanded and increased the homogeneity in the COL network without affecting the inherent fiber properties of both polymers. Cells cultured as spheroids in COL-NC remodeled the hydrogel network without a significant impact on its architecture. Our study reveals the polymer organization of COL-NC hydrogels and demonstrates SANS and USANS as exceptional techniques to reveal nano- and micron-scale details on polymer organization, which leads to a better understanding of the structural properties of hydrogels to engineer novel ECMs.


Assuntos
Matriz Extracelular , Hidrogéis , Humanos , Hidrogéis/química , Matriz Extracelular/química , Colágeno/química , Organoides
11.
J Phys Condens Matter ; 36(21)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38354419

RESUMO

We present a comprehensive investigation of the crystal and magnetic structures of the van der Waals antiferromagnetα-RuCl3using single crystal x-ray and neutron diffraction. The crystal structure at room temperature is a monoclinic (C2/m). However, with decreasing temperature, a remarkable first-order structural phase transition is observed, leading to the emergence of a rhombohedral (R3-) structure characterized by three-fold rotational symmetry forming an isotropic honeycomb lattice. On further cooling, a zigzag-type antiferromagnetic order develops belowTN=6∼6.6K. The critical exponent of the magnetic order parameter was determined to beß=0.11(1), which is close to the two-dimensional Ising model. Additionally, the angular dependence of the magnetic critical field of the zigzag antiferromagnetic order for the polarized ferromagnetic phase reveals a six-fold rotational symmetry within theab-plane. These findingsreflect the symmetry associated with the Ising-like bond-dependent Kitaev spin interactions and underscore the universality of the Kitaev interaction-dominated antiferromagnetic system.

12.
Nanomaterials (Basel) ; 13(7)2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37049350

RESUMO

Supercapacitors are candidates with the greatest potential for use in sustainable energy resources. Extensive research is being carried out to improve the performances of state-of-art supercapacitors to meet our increased energy demands because of huge technological innovations in various fields. The development of high-performing materials for supercapacitor components such as electrodes, electrolytes, current collectors, and separators is inevitable. To boost research in materials design and production toward supercapacitors, the up-to-date collection of recent advancements is necessary for the benefit of active researchers. This review summarizes the most recent developments of water-in-salt (WIS) and deep eutectic solvents (DES), which are considered significant electrolyte systems to advance the energy density of supercapacitors, with a focus on two-dimensional layered nanomaterials. It provides a comprehensive survey of 2D materials (graphene, MXenes, and transition-metal oxides/dichalcogenides/sulfides) employed in supercapacitors using WIS/DES electrolytes. The synthesis and characterization of various 2D materials along with their electrochemical performances in WIS and DES electrolyte systems are described. In addition, the challenges and opportunities for the next-generation supercapacitor devices are summarily discussed.

13.
IEEE Trans Neural Netw Learn Syst ; 34(2): 799-813, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34406948

RESUMO

While the celebrated graph neural networks (GNNs) yield effective representations for individual nodes of a graph, there has been relatively less success in extending to the task of graph similarity learning. Recent work on graph similarity learning has considered either global-level graph-graph interactions or low-level node-node interactions, however, ignoring the rich cross-level interactions (e.g., between each node of one graph and the other whole graph). In this article, we propose a multilevel graph matching network (MGMN) framework for computing the graph similarity between any pair of graph-structured objects in an end-to-end fashion. In particular, the proposed MGMN consists of a node-graph matching network (NGMN) for effectively learning cross-level interactions between each node of one graph and the other whole graph, and a siamese GNN to learn global-level interactions between two input graphs. Furthermore, to compensate for the lack of standard benchmark datasets, we have created and collected a set of datasets for both the graph-graph classification and graph-graph regression tasks with different sizes in order to evaluate the effectiveness and robustness of our models. Comprehensive experiments demonstrate that MGMN consistently outperforms state-of-the-art baseline models on both the graph-graph classification and graph-graph regression tasks. Compared with previous work, multilevel graph matching network (MGMN) also exhibits stronger robustness as the sizes of the two input graphs increase.

14.
Pharmaceutics ; 15(3)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36986601

RESUMO

Nanomedicine has garnered significant interest owing to advances in drug delivery, effectively demonstrated in the treatment of certain diseases. Here, smart supermagnetic nanocomposites based on iron oxide nanoparticles (MNPs) coated with Pluronic F127 (F127) were developed for the delivery of doxorubicin (DOX) to tumor tissues. The XRD patterns for all samples revealed peaks consistent with Fe3O4, as shown by their indices (220), (311), (400), (422), (511), and (440), demonstrating that the structure of Fe3O4 did not change after the coating process. After loading with DOX, the as-prepared smart nanocomposites demonstrated drug-loading efficiency and drug-loading capacity percentages of 45 ± 0.10 and 17 ± 0.58% for MNP-F127-2-DOX and 65 ± 0.12 and 13 ± 0.79% for MNP-F127-3-DOX, respectively. Moreover, a better DOX release rate was observed under acidic conditions, which may be credited to the pH sensitivity of the polymer. In vitro analysis demonstrated the survival rate of approximately 90% in HepG2 cells treated with PBS and MNP-F127-3 nanocomposites. Furthermore, after treatment with MNP-F127-3-DOX, the survival rate decreased, confirming cellular inhibition. Hence, the synthesized smart nanocomposites showed great promise for drug delivery in liver cancer treatment, overcoming the limitations of traditional therapies.

15.
J Colloid Interface Sci ; 652(Pt B): 1609-1619, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37666193

RESUMO

HYPOTHESIS: Poly(N-isopropylacrylamide) [PNIPAM]-grafted cellulose nanofibers (CNFs) are new thermo-responsive hydrogels which can be used for a wide range of applications. Currently, there is no clear understanding of the precise mechanism by which CNFs and PNIPAM interact together. Here, we hypothesize that the physical crosslinking of grafted PNIPAM on CNF inhibits the free movement of individual CNF, which increases the gel strength while sustaining its thermo-responsive properties. EXPERIMENTS: The thermo-responsive behaviour of PNIPAM-grafted CNFs (PNIPAM-g-CNFs), synthesized via silver-catalyzed decarboxylative radical polymerization, and PNIPAM-blended CNFs (PNIPAM-b-CNFs) was studied. Small angle neutron scattering (SANS) combined with Ultra-SANS (USANS) revealed the nano to microscale conformation changes of these polymer hybrids as a function of temperature. The effect of temperature on the optical and viscoelastic properties of hydrogels was also investigated. FINDINGS: Grafting PNIPAM from CNFs shifted the lower critical solution temperature (LCST) from 32 °C to 36 °C. Below LCST, the PNIPAM chains in PNIPAM-g-CNF sustain an open conformation and poor interaction with CNF, and exhibit water-like behaviour. At and above LCST, the PNIPAM chains change conformation to entangle and aggregate nearby CNFs. Large voids are formed in solution between the aggregated PNIPAM-CNF walls. In comparison, PNIPAM-b-CNF sustains liquid-like behaviour below LCST. At and above LCST, the blended PNIPAM phase separates from CNF to form large aggregates which do not affect CNF network and thus PNIPAM-b-CNF demonstrates low viscosity. Understanding of temperature-dependent conformation of PNIPAM-g-CNFs engineer thermo-responsive hydrogels for biomedical and functional applications.

16.
Commun Biol ; 6(1): 124, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721030

RESUMO

Group A Streptococcus (GAS) is a strict human pathogen possessing a unique pathogenic trait that utilizes the cooperative activity of NAD+-glycohydrolase (NADase) and Streptolysin O (SLO) to enhance its virulence. How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracellular survival is a long-standing question. Here, the structure and dynamic nature of the NADase/SLO complex are elucidated by X-ray crystallography and small-angle scattering, illustrating atomic details of the complex interface and functionally relevant conformations. Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection. Furthermore, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated in a murine infection model. Overall, this work delivers the structure-functional relationship of the NADase/SLO complex and pinpoints the key interacting residues that are central to the coordinated actions of NADase and SLO in the pathogenesis of GAS infection.


Assuntos
Streptococcus , Estreptolisinas , Humanos , Animais , Camundongos , Proteínas de Bactérias , NAD+ Nucleosidase
17.
J Neurooncol ; 107(2): 307-14, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22160627

RESUMO

ß-Elemene, an active component of herb medicine Curcuma wenyujin, has been shown to antagonize glioblastoma cells by inducing apoptosis. However, how ß-elemene induces apoptosis of these cells remains unclear. In this study, we report that ß-elemene disrupted the formation of the Hsp90/Raf-1 complex, a key step in maintaining the conformation stability of Raf-1, and caused deactivation of Raf-1 and inhibition of the ERK pathway, thereby leading to apoptosis of glioblastoma cells. Specifically, treatment of glioblastoma cell lines with ß-elemene attenuated phosphorylation of multiple members of the kinase families in the Ras/Raf/MEK/ERK cascade, including Raf-1 and ERK as well as downstream signaling targets such as Bcl-2. These results suggest that the Hsp90/Raf-1 complex could be a promising molecular target for new drug development for the treatment of glioblastoma.


Assuntos
Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas Proto-Oncogênicas c-raf/metabolismo , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Neoplasias Encefálicas/dietoterapia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Citometria de Fluxo , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Imunoprecipitação , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/metabolismo
18.
Analyst ; 137(24): 5770-6, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23092986

RESUMO

A series of triazolyl coumarin derivatives L1-L4, with and without spacer groups between the coumarin and the triazole groups, were synthesized as fluorescent sensors to study their binding ability and selectivity toward metal ions. Ligand L3, which contains an acetyl linker between the triazole and the coumarin, exhibited a high selectivity toward Hg(2+) in polar protic solvents MeOH-CHCl(3) (9 : 1, v/v) with fluorescent enhancement, furthermore, it was found to bind two Hg(2+) at a high concentration (>12.5 mM) of Hg(ClO(4))(2). In contrast, L4, in which position 4 of the triazole unit was replaced by a benzyl group instead of the 4-tert-butylphenoxymethyl group used in L1-L3, showed a binding stoichiometry toward only one Hg(2+). On the basis of the fluorescent sensing, IR, and (1)H NMR titration results of ligands L1-L4, we proposed that not only the acetyl C=O but also the ether group of the 4-tert-butylphenoxymethyl of assisted the triazole nitrogen atoms in the complexation of Hg(2+) to form a 1 : 2 complex (L3·(Hg(2+))(2)).


Assuntos
Técnicas de Química Analítica/instrumentação , Cumarínicos/química , Cumarínicos/síntese química , Desenho de Fármacos , Mercúrio/análise , Mercúrio/química , Triazóis/química , Técnicas de Química Sintética , Espectrometria de Fluorescência
19.
IEEE Trans Cybern ; 52(5): 3745-3756, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32946405

RESUMO

Fuzzing is a technique of finding bugs by executing a target program recurrently with a large number of abnormal inputs. Most of the coverage-based fuzzers consider all parts of a program equally and pay too much attention to how to improve the code coverage. It is inefficient as the vulnerable code only takes a tiny fraction of the entire code. In this article, we design and implement an evolutionary fuzzing framework called V-Fuzz, which aims to find bugs efficiently and quickly in limited time for binary programs. V-Fuzz consists of two main components: 1) a vulnerability prediction model and 2) a vulnerability-oriented evolutionary fuzzer. Given a binary program to V-Fuzz, the vulnerability prediction model will give a prior estimation on which parts of a program are more likely to be vulnerable. Then, the fuzzer leverages an evolutionary algorithm to generate inputs which are more likely to arrive at the vulnerable locations, guided by the vulnerability prediction result. The experimental results demonstrate that V-Fuzz can find bugs efficiently with the assistance of vulnerability prediction. Moreover, V-Fuzz has discovered ten common vulnerabilities and exposures (CVEs), and three of them are newly discovered.


Assuntos
Algoritmos
20.
Sci Rep ; 12(1): 775, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031677

RESUMO

We report on experimental evidence of non-conversional pairing in In and Sn nanoparticle assemblies. Spontaneous magnetizations are observed, through extremely weak-field magnetization and neutron-diffraction measurements, to develop when the nanoparticles enter the superconducting state. The superconducting transition temperature TC shifts to a noticeably higher temperature when an external magnetic field or magnetic Ni nanoparticles are introduced into the vicinity of the superconducting In or Sn nanoparticles. There is a critical magnetic field and a critical Ni composition that must be reached before the magnetic environment will suppress the superconductivity. The observations may be understood when assuming development of spin-parallel superconducting pairs on the surfaces and spin-antiparallel superconducting pairs in the core of the nanoparticles.

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