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1.
Diagn Microbiol Infect Dis ; 97(3): 115040, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32354459

RESUMO

Staphylococci are the most common causes of periprosthetic joint infection (PJI). TNP-2092 is an investigational hybrid drug composed of rifamycin and quinolizinone pharmacophores conjugated via a covalent linker. We determined minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm bactericidal concentration (MBBC) values of TNP-2092 against 80 PJI-associated Staphylococcus aureus and Staphylococcus epidermidis isolates compared to ciprofloxacin and rifampin alone and in combination, alongside daptomycin and vancomycin. TNP-2092 exhibited the following activity against S. aureus: MIC50/MIC90, ≤0.0075/0.015 µg/mL; MBC50/MBC90, 0.5/4 µg/mL; and MBBC50/MBBC90, 0.5/2 µg/mL, and the following activity against S. epidermidis: MIC50/MIC90, ≤0.0075/0.015 µg/mL; MBC50/MBC90, 0.015/0.125 µg/mL; and MBBC50/MBBC90, 0.06/0.25 µg/mL. TNP-2092 MIC, MBC, and MBBC values were >8 µg/mL for 1 isolate, while MIC values were ≤0.25 µg/mL and MBC and MBBC values were ≤4 µg/mL for all other isolates. Results of this study show that TNP-2092 has promising in vitro activity against PJI-associated staphylococci.

2.
Molecules ; 25(10)2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32456032

RESUMO

The introductions of the bicyclic 4-nitroimidazole and the oxazolidinone classes of antimicrobial agents represented the most significant advancements in the infectious disease area during the past two decades. Pretomanid, a bicyclic 4-nitroimidazole, and linezolid, an oxazolidinone, are also part of a combination regimen approved recently by the US Food and Drug Administration for the treatment of pulmonary, extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) Mycobacterium tuberculosis (TB). To identify new antimicrobial agents with reduced propensity for the development of resistance, a series of dual-acting nitroimidazole-oxazolidinone conjugates were designed, synthesized and evaluated for their antimicrobial activity. Compounds in this conjugate series have shown synergistic activity against a panel of anaerobic bacteria, including those responsible for serious bacterial infections.

3.
Biochem Biophys Res Commun ; 521(3): 706-715, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31699371

RESUMO

Each cell comprising an intact, healthy, confluent epithelial layer ordinarily remains sedentary, firmly adherent to and caged by its neighbors, and thus defines an elemental constituent of a solid-like cellular collective [1,2]. After malignant transformation, however, the cellular collective can become fluid-like and migratory, as evidenced by collective motions that arise in characteristic swirls, strands, ducts, sheets, or clusters [3,4]. To transition from a solid-like to a fluid-like phase and thereafter to migrate collectively, it has been recently argued that cells comprising the disordered but confluent epithelial collective can undergo changes of cell shape so as to overcome geometric constraints attributable to the newly discovered phenomenon of cell jamming and the associated unjamming transition (UJT) [1,2,5-9]. Relevance of the jamming concept to carcinoma cells lines of graded degrees of invasive potential has never been investigated, however. Using classical in vitro cultures of six breast cancer model systems, here we investigate structural and dynamical signatures of cell jamming, and the relationship between them [1,2,10,11]. In order of roughly increasing invasive potential as previously reported, model systems examined included MCF10A, MCF10A.Vector; MCF10A.14-3-3ζ; MCF10.ErbB2, MCF10AT; and MCF10CA1a [12-15]. Migratory speed depended on the particular cell line. Unsurprisingly, for example, the MCF10CA1a cell line exhibited much faster migratory speed relative to the others. But unexpectedly, across different cell lines higher speeds were associated with enhanced size of cooperative cell packs in a manner reminiscent of a peloton [9]. Nevertheless, within each of the cell lines evaluated, cell shape and shape variability from cell-to-cell conformed with predicted structural signatures of cell layer unjamming [1]. Moreover, both structure and migratory dynamics were compatible with previous theoretical descriptions of the cell jamming mechanism [2,10,11,16,17]. As such, these findings demonstrate the richness of the cell jamming mechanism, which is now seen to apply across these cancer cell lines but remains poorly understood.


Assuntos
Neoplasias da Mama/patologia , Movimento Celular , Invasividade Neoplásica/patologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Forma Celular , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Humanos
4.
Mar Pollut Bull ; 150: 110787, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791594

RESUMO

Owing to the semi-enclosed environment of the Bohai Sea, the ecological effects caused by an oil spill would be significant. A typical in- situ bioremediation engineering project for of oil-spilled marine sediments was performed in the Bohai Sea and a quantitative assessment of the ecological restoration was performed. The bioremediation efficiencies of n-alkane and PAHs in the sediment are 32.84 ± 21.66% and 50.42 ± 17.49% after 70 days of bioremediation, and 60.99 ± 10.14% and 68.01 ± 18.60% after 210 days, respectively. After 210 days of bioremediation, the degradation rates of two- to three ring PAHs and four-ring PAHs are 84.44 ± 23.03% and 26.62 ± 43.76%, respectively. In addition, the concentrations of the heavy metals first increased by 6.00% due to oil spill degradation and release, and then decreased by 72.60% with the degradation of oil caused by bioremediation or vertical migration. According to the continuous tracking monitoring, the composition of the microbial community in the restored area was similar to that in the control area and the clean area in Bohai Sea after 210 days of bioremediation. These results may provide some theoretical and scientific data to understand the degradation mechanism and assessing the ecological remediation efficiency for oil spills in open sea areas.


Assuntos
Biodegradação Ambiental , Monitoramento Ambiental , Metais Pesados , Poluição por Petróleo , Poluentes Químicos da Água , China , Sedimentos Geológicos , Oceanos e Mares
5.
Nanotechnology ; 30(49): 495706, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31437827

RESUMO

Au-graphene quantum dots (GQDs)@Pt core-shell nanodendrites are synthesized through a two-step reduction approach, in which Au forms the core, GQDs form an intermediate layer and dendritic Pt forms the shell. Among the above synthesized catalysts, the GQDs can manipulate the binding of reaction intermediates on the Pt surface as well as assemble π-π * conjugate bonds, thus forming a dendritic Pt shell instead of a compact Pt shell. The obtained core-shell structure was characterized by transmission electron microscopy, energy-dispersive x-ray and x-ray photoelectron spectroscopy. The methanol electro-oxidation was investigated in alkaline media on the Au-GQDs@Pt modified electrode via cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy analysis. In particular, we discovered that Au-Pt assembled with GQDs could dramatically improve the activity and stability of the catalysts, owing to the synergistic effect raised by the GQDs, which exhibit prominent electron conductivity and great chemical/physical stability. It was also found that the Pt/Au mole ratios could control the Pt shell thickness, which significantly affected the catalytic methanol oxidation activity of the Au-GQDs@Pt nanodendrites. The Au-GQDs@Pt nanodendrites with optimum Pt/Au mole ratios of 1.0 exhibited a 2.5 times increase in electrocatalytic activity toward methanol oxidation compared with the commercial catalyst (Pt/C), and its CO tolerance was also greatly improved. The above results show that the Au-GQDs@Pt nanocatalysts have potential application prospects in direct methanol fuel cells.

6.
Nanoscale ; 11(21): 10348-10357, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31107483

RESUMO

Among all the non-precious electrocatalysts for the oxygen evolution reaction (OER), FeNi and FeCo layered double hydroxides (LDHs) display the best activity. However, due to the unavoidable transformation of the active M3+/4+ (M = Fe, Co, and Ni) ions into inert M-O-H species, their activity dramatically decreases after about 25 h during stability tests, which means the widely-adopted stability test with a duration of 24 h is not sufficient for LDHs. Herein, the in situ growth of Fe1Co1 and Fe1Ni1 LDH nanosheets on V- and Ni-doped AlOOH nanorods was extended for the duration of stable electrocatalysis to 50 h. The V and Ni dopants were found to promote the diffusion of active Fe, Co and Ni cations along the abundant {100} planes of AlOOH single-crystalline nanorods with their {100} family of crystal planes perpendicular to the lateral facet, avoiding the aggregation of the active species and their transformation into inert species and their following nucleation and growth. Besides, the nano-channels on the nanorods generated during the subsequent in situ growth of LDHs are beneficial for the supply of OH- and the transportation of O2, which enhance the activity and stability of these composites.

7.
PLoS One ; 14(2): e0202065, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30707705

RESUMO

Loss of function of the tumor suppressor p53 is known to increase the rate of migration of cells transiting the narrow pores of the traditional Boyden chamber assay. Here by contrast we investigate how p53 impacts the rate of cellular migration within a 2D confluent cell layer and a 3D collagen-embedded multicellular spheroid. We use two human carcinoma cell lines, the bladder carcinoma EJ and the colorectal carcinoma HCT116. In the confluent 2-D cell layer, for both EJ and HCT cells the migratory speeds and effective diffusion coefficients for the p53 null cells were significantly smaller than in p53-expressing cells. Compared to p53 expressers, p53-null cells exhibited more organized cortical actin rings together with reduced front-rear cell polarity. Furthermore, loss of p53 caused cells to exert smaller traction forces upon their substrates, and reduced formation of cryptic lamellipodia. In the 3D multicellular spheroid, loss of p53 consistently reduced collective cellular migration into surrounding collagen matrix. As regards the role of p53 in cellular migration, extrapolation from the Boyden chamber assay to other cellular microenvironments is seen to be fraught even in terms of the sign of the effect. Together, these paradoxical results show that the effects of p53 on cellular migration are context-dependent.


Assuntos
Movimento Celular/fisiologia , Neoplasias Colorretais/patologia , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Colágeno/metabolismo , Neoplasias Colorretais/metabolismo , Células HCT116 , Humanos , Esferoides Celulares , Microambiente Tumoral , Neoplasias da Bexiga Urinária/metabolismo
8.
J Mech Behav Biomed Mater ; 88: 330-339, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30196189

RESUMO

Curvature as an important topological parameter of 3D extra-cellular matrix has drawn growing attention in recent years. But the underlying mechanism that curvature influences cell behaviors has remained unknown. In this study, we seeded cells on semi-cylindrical and hemispheric surfaces and tested cell alignment and polarization. We found that the surface curvature has profound effect on cell behaviors. With the decrease of diameter of the cylinder/sphere (i.e. increase of curvature), the cells would more preferentially align and polarize with large aspect ratio in the axial/peripheral direction. And the behaviors of the alignment and polarization were position-dependent. For example, at the end of the cylinder, the cells preferred to align circumferentially; while in the interior region, the cells preferred to align in the axial direction. We showed that the cell polarization and alignment were closely correlated with the in-plane stresses in cell layer. That is, the cell polarization and alignment were controlled by the maximum shear stress, which drove cells to align and polarize along the maximum principal stress. The curvature could influence the magnitude of the maximum shear stress and thus regulate cell behaviors. This study provided important insights into the mechanisms of surface curvature influencing cell behaviors in tissue morphogenesis. In addition, our theory of the stress dependent cellular polarity provides a generalized interpretation of the curvature and edge effects which might be extended to understand other steric effects in cell behaviors.


Assuntos
Fenômenos Mecânicos , Modelos Biológicos , Células 3T3 , Actinas/metabolismo , Animais , Fenômenos Biomecânicos , Núcleo Celular/metabolismo , Espaço Extracelular/metabolismo , Camundongos , Propriedades de Superfície
9.
Biophys J ; 115(3): 554-564, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30089244

RESUMO

Collective behaviors of multiple cells play important roles in various physiological and pathological processes, but the mechanisms of coordination among cells are highly unknown. Here, we build a one-dimensional cell-chain model to quantitatively study cell cooperativity. Combining experimental and theoretical approaches, we showed that the matrix stiffness, intercellular adhesion strength, and cell-chain length have a significant effect on the cooperative contraction of the cell chains. Cells have strong cooperativity, i.e., exhibiting a united contraction mode, in shorter cell chains or on softer matrix or with higher intercellular adhesion strength. In contrast, cells would exhibit a divided contraction when the cell chain was long or on stiffer matrix or with weaker adhesion strength. In addition, our quantitative results indicated that the cooperativity of cells is regulated by the coupling between matrix stiffness and intercellular adhesion, which can be quantified by an explicit parameter group. These results may provide guidelines for regulating the cooperativity of cells in their collective behaviors in tissue morphogenesis and tissue engineering in biomedical applications.


Assuntos
Fenômenos Mecânicos , Modelos Biológicos , Células 3T3 , Animais , Fenômenos Biomecânicos , Forma Celular , Sobrevivência Celular , Cães , Espaço Intracelular/metabolismo , Células Madin Darby de Rim Canino , Camundongos
10.
Proc Natl Acad Sci U S A ; 115(7): 1517-1522, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29378953

RESUMO

α-Actinin-4 (ACTN4) bundles and cross-links actin filaments to confer mechanical resilience to the reconstituted actin network. How this resilience is built and dynamically regulated in the podocyte, and the cause of its failure in ACTN4 mutation-associated focal segmental glomerulosclerosis (FSGS), remains poorly defined. Using primary podocytes isolated from wild-type (WT) and FSGS-causing point mutant Actn4 knockin mice, we report responses to periodic stretch. While WT cells largely maintained their F-actin cytoskeleton and contraction, mutant cells developed extensive and irrecoverable reductions in these same properties. This difference was attributable to both actin material changes and a more spatially correlated intracellular stress in mutant cells. When stretched cells were further challenged using a cell adhesion assay, mutant cells were more likely to detach. Together, these data suggest a mechanism for mutant podocyte dysfunction and loss in FSGS-it is a direct consequence of mechanical responses of a cytoskeleton that is brittle.


Assuntos
Actinina/genética , Podócitos/patologia , Mutação Puntual , Actinina/metabolismo , Animais , Adesão Celular , Citoesqueleto/metabolismo , Feminino , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Masculino , Camundongos Transgênicos
11.
Environ Sci Pollut Res Int ; 25(10): 9539-9546, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29354858

RESUMO

Clearing up whether spilled oil is mixed or not can strengthen the accuracy of oil spill identification. In the present study, the biomarkers in spilled oil samples were detected. The weathering modes of different types of diagnostic ratio and carbon isotope values of individual n-alkanes were also analyzed. The results showed that the diagnostic ratios of steroids, terpenes and aromatics, and weathering characteristics of carbon isotope composition (δ13C) of individual n-alkanes supported the idea that Dalian oil spill emerged from a single oil source. Furthermore, commonly used diagnostic ratios of n-alkanes indicated that the Dalian oil spill had undergone the oil mixing process. The different identifying outcomes indicate that some kinds of n-alkane-rich substance (such as oil dispersants) were mixed in the Dalian spilled oil and interfered with the routine diagnosis ratios of n-alkanes.


Assuntos
Isótopos de Carbono/análise , Poluição por Petróleo/análise , Poluentes Químicos da Água/análise , Alcanos/química , Biomarcadores , Terpenos , Tempo (Meteorologia)
12.
Nanotechnology ; 28(44): 445603, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-28836504

RESUMO

VSe2 is a typical layered semimetal TMDC, and was thought to be difficult to synthesize for many years. By changing the concentration of precursors and reaction steps in the hydrothermal method, here we successfully synthesize three different shapes of VSe2: nano-hydrangea (NH), nano-dandelion (ND) and hexagonal disk (HD). The as-prepared VSe2 HDs have a single-crystalline structure compared with the poly-crystalline structure of NHs and NDs. The as-prepared VSe2 in these three shapes also demonstrates apparent differences and intrinsic properties both in the nitrogen adsorption-desorption characterizations and UV-vis absorption analysis. Possible growth processes and mechanisms are put forward in detail to further inspire shape-design in other nanoscale materials.

13.
ACS Biomater Sci Eng ; 3(11): 2943-2953, 2017 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33418714

RESUMO

Lamellipodia (LP), a subcellular structure at cell front, plays a key role in cell spreading and migration. And its mechanosensing function is of crucial importance for cell activities. But the mechanism of the mechanosensing function remains poorly understood. Here we developed a multiscale model to consider its protrusion and retraction processes, and analyzed the forces acted on the key structural components of the LP and the effect of these forces on LP movement. Our results show that raising substrate rigidity increases the force acting on the focal adhesion (FA) and decreases the force on LP actin, thus promoting the maturation of FA while suppressing the detachment of LP actin from the cell membrane. The membrane tension also influences the LP movement, but its effect is opposite to that of the substrate rigidity. It turns out that the substrate rigidity and membrane tension together regulate the dynamics of FAs and the detachment of LP actin, which in turn determine the LP movement. Interestingly, we found that the effect of substrate rigidity and membrane tension on the LP movement both exhibit a biphasic manner. We show that our predictions agree, in general, with the experiments on cell mechanosensing behaviors at both subcellular and cellular levels.

14.
Biophys J ; 109(3): 489-500, 2015 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-26244731

RESUMO

Pattern-dependent collective behaviors of cells have recently raised intensive attention. However, the underlying mechanisms that regulate these behaviors are largely elusive. Here, we report a quantitative study, combining experiment and modeling, on cell polarization and arrangement on a micropatterned substrate. We show that cells exhibit position-dependent collective behaviors that can be regulated by geometry and stiffness of the patterned substrate. We find that the driving force for these collective behaviors is the in-plane maximum shear stress in the cell layer that directs the arrangement of cells. The larger the shear stress, the more the cells preferentially align and polarize along the direction of the maximum principal stress. We also find that the aspect ratio of cell polarization shape and the degree to which cells preferentially align along the direction of maximum principal stress exhibit a biphasic dependence on substrate rigidity, corresponding to our quantitative predictions that the magnitude of the maximum shear stress is biphasically dependent on the stiffness of the substrate. As such, the driving force of these cell collective behaviors can be quantified using the maximum shear stress.


Assuntos
Comunicação Celular , Polaridade Celular , Proliferação de Células , Animais , Linhagem Celular , Camundongos , Osteoblastos/citologia , Osteoblastos/fisiologia
15.
Mar Pollut Bull ; 90(1-2): 88-94, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25499964

RESUMO

Surface sediment samples from Bohai Bay and its adjacent river, China, were analyzed for aliphatic hydrocarbon, PAHs and biomarkers in order to determine the distribution, composition and source of organic matter in a coastal environment. Results suggested that the input of organic matter from anthropogenic activities has a more significant influence on its distribution than that from natural processes. Petroleum contamination, mainly from offshore oil exploration and discharge of pollutants from rivers, was the main source of n-alkanes. PAHs were mostly of pyrogenic origin; while some sites in Yellow River Estuary were derived mainly from the petrogenic sources. The toxic assessment suggested that the PAHs in surface sediments will not cause immediately adverse biological effects in sediments from Bohai Bay and its adjacent river, China.


Assuntos
Baías/química , Sedimentos Geológicos/química , Petróleo/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Rios/química , Poluentes Químicos da Água/análise , Alcanos/análise , Alcanos/química , China , Monitoramento Ambiental , Estuários , Hidrocarbonetos Policíclicos Aromáticos/química
16.
Mar Pollut Bull ; 71(1-2): 64-8, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23623662

RESUMO

In an attempt to analyze the chemical characterization of oil residues and examine the suitability of chemical fingerprinting methods in oil spill investigations, multiple parameters sensitive to both sources and degree of weathering were used to characterize oil residues from "7-16" Dalian oil spill, China. Oil residues collected 90 days to 120 days after the spill showed a weathering pattern where significant amounts of light to middle molecular weight normal alkanes were depleted with pristane and phytane as dominant peaks. Diagnostic ratios developed from n-alkane and selected isoprenoids (e.g. Pr/Ph, n-C17/Pr, n-C18/Ph, carbon preference index, LMW/HMW-alkanes ratio), all display obvious changes over weathering time, indicating that these ratios are not valid for oil source identification. Furthermore, the biomarker ratios of hopanes and steranes with relative standard deviations (RSDs) of 0.88-4.08% were useful for source identification even for severely weathered oil residues. In addition, RSD of δ(13)C values of individual n-alkanes in oil residue varied from 0.07% to 0.20%, which suggest that stable carbon isotope profile of n-alkanes can also be a useful tool for tracing the source of an oil spill.


Assuntos
Monitoramento Ambiental/métodos , Poluição por Petróleo , Petróleo/análise , Poluentes Químicos da Água/análise , China , Poluentes Químicos da Água/química , Tempo (Meteorologia)
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