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1.
Environ Pollut ; 349: 123933, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38583795

RESUMO

The effects of two benthonic species, Perinereis aibuhitensis and Matuta planipes Fabricius, on the release of polycyclic aromatic hydrocarbons (PAHs) from sediments were investigated using a sediment-seawater microcosm. A Level IV fugacity model was used to simulate the behavior and fate of PAHs in the environment. This study revealed that both benthos significantly influenced the release of PAHs, and Matuta planipes Fabricius had a stronger disturbance effect than another. The final concentrations of Matuta planipes Fabricius group, Perinereis aibuhitensis group and the control group in the seawater phase reached 10.8, 9.94 and 7.90 µg/L, respectively. There were certain differences in the behaviour of the two benthonic species. Matuta planipes Fabricius caused more sediment resuspension, while Perinereis aibuhitensis increased the total organic carbon (TOC) content in the environment. The vertical concentration distribution of sediment indicated that vertical mixing was slightly stronger in the Matuta planipes Fabricius group than that in the Perinereis aibuhitensis group. The fugacity model effectively simulated the release behavior of PAHs, providing insight into PAH transport and distribution. The results demonstrated that bioturbation could promote the release of PAHs from seawater. The amount of PAHs released was significantly correlated with the biological habits of the benthos.


Assuntos
Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos , Água do Mar , Poluentes Químicos da Água , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/química , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Água do Mar/química , Monitoramento Ambiental , Animais
2.
J Am Chem Soc ; 146(10): 6856-6865, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38413090

RESUMO

A comprehensive understanding of carrier transport in photoisomeric molecular junctions is crucial for the rational design and delicate fabrication of single-molecule functional devices. It has been widely recognized that the conductance of azobenzene (a class of photoisomeric molecules) based molecular junctions is mainly determined by photoinduced conformational changes. In this study, it is demonstrated that the most probable conductance of amine-anchored azobenzene-based molecular junctions increases continuously upon UV irradiation. In contrast, the conductance of pyridyl-anchored molecular junctions with an identical azobenzene core exhibits a contrasting trend, highlighting the pivotal role that anchoring groups play, potentially overriding (even reversing) the effects of photoinduced conformational changes. It is further demonstrated that the molecule with cis-conformation cannot be fully mechanically stretched into the trans-conformation, clarifying that it is a great challenge to realize a reversible molecular switch by purely mechanical operation. Additionally, it is revealed that the coupling strength of pyridyl-anchored molecules is dramatically weakened when the UV irradiation time is prolonged, whereas it is not observed for amine-anchored molecules. The mechanisms for these observations are elucidated with the assistance of density functional theory calculations and UV-Vis spectra combined with flicker noise measurements which confirm the photoinduced conformational changes, providing insight into understanding the charge transport in photoisomeric molecular junctions and offering a routine for logical designing synchro opto-mechanical molecular switches.

3.
J Hazard Mater ; 460: 132351, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37625296

RESUMO

To understand the pollution status and risk levels in the Laizhou Bay, the spatiotemporal distribution, source, and ecological risk of 16 polycyclic aromatic hydrocarbons (PAHs) and 20 substituted PAHs (SPAHs) were studied in surface sediments in 2022. The findings indicated significant seasonal differences in the concentrations of PAHs and SPAHs under the influences of precipitation, temperature, light, and human activities, with higher storage levels in summer than in spring, and there was also a spatial distribution trend of estuary > coast > offshore. 2-Nitrofluorene (2-NF) and 2-methylnaphthalene (2-MN) were the most abundant components of SPAHs in both spring and summer, with levels of 21.44 ng/g and 17.89 ng/g in spring, 43.22 ng/g and 25.51 ng/g in summer, respectively. The results of the diagnostic ratio and principal component analysis - multiple linear regression identified sources of PAHs and SPAHs as combustion sources, including petroleum, coal, and biomass. The risk level of PAHs was low-to-moderate according to the toxicity equivalent quotient (TEQ) and risk quotient. A novel calculation method based on TEQ was proposed to assess the ecological risk of SPAHs, and the results indicated that the risk level of SPAHs was moderate-to-high.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Humanos , Baías , Biomassa , China , Medição de Risco
4.
Urban Stud ; 60(9): 1750-1770, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37416836

RESUMO

The ongoing coronavirus disease (COVID-19) pandemic has had a far-reaching impact on urban living, prompting emergency preparedness and response from public health governance at multiple levels. The Chinese government has adopted a series of policy measures to control infectious disease, for which cities are the key spatial units. This research traces and reports analyses of those policy measures and their evolution in four Chinese cities: Zhengzhou, Hangzhou, Shanghai and Chengdu. The theoretical framework stems from conceptualisations of urban governance and its role in public health emergencies, wherein crisis management and emergency response are highlighted. In all four cities, the trend curves of cumulative diagnosed cases, critical policies launched in key time nodes and local governance approaches in the first wave were identified and compared. The findings suggest that capable local leadership is indispensable for controlling the coronavirus epidemic, yet local governments' approaches are varied, contributing to dissimilar local epidemic control policy pathways and positive outcomes in the fight against COVID-19. The effectiveness of disease control is determined by how local governments' measures have adapted to geospatial and socioeconomic heterogeneity. The coordinated actions from central to local governments also reveal an efficient, top-down command transmission and execution system for coping with the pandemic. This article argues that effective control of pandemics requires both a holistic package of governance strategies and locally adaptive governance measures/processes, and concludes with proposals for both a more effective response at the local level and identification of barriers to achieving these responses within diverse subnational institutional contexts.

5.
Sci Total Environ ; 891: 164340, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37236473

RESUMO

Estuarine sediments are key storage sites for persistent organic pollutants (POPs), and estuaries are strongly influenced by tides throughout the year. Although much work has been done concerning on POPs release, related questions on tidal action have not been considered in the release process. Herein, polycyclic aromatic hydrocarbons (PAHs) release from sediment to seawater was investigated under tidal action by combining a tidal microcosm with level IV fugacity model. The results showed that PAHs release with tidal action was 2.0-3.5 times the accumulation of that without tidal action. Tidal action was confirmed to influence strongly PAHs release from sediment to seawater. We also quantified suspended substance (SS) in the overlying water, and an obvious positive correlation between the PAHs concentration and SS content was found. In addition, an increase in seawater depth enhanced the intensity of tidal action, and more PAHs were released, especially dissolved PAHs. Moreover, the fugacity model results showed a good fit with the experimental results. The simulated values demonstrated that the PAHs release was accomplished via two processes, "rapid release" and "slow release". And the sediment played a key role in the fate of PAHs and was a major sink in the sediment-seawater system.

6.
Materials (Basel) ; 16(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37110065

RESUMO

The manipulation of single molecules has attracted extensive attention because of their promising applications in chemical, biological, medical, and materials sciences. Optical trapping of single molecules at room temperature, a critical approach to manipulating the single molecule, still faces great challenges due to the Brownian motions of molecules, weak optical gradient forces of laser, and limited characterization approaches. Here, we put forward localized surface plasmon (LSP)-assisted trapping of single molecules by utilizing scanning tunneling microscope break junction (STM-BJ) techniques, which could provide adjustable plasmonic nanogap and characterize the formation of molecular junction due to plasmonic trapping. We find that the plasmon-assisted trapping of single molecules in the nanogap, revealed by the conductance measurement, strongly depends on the molecular length and the experimental environments, i.e., plasmon could obviously promote the trapping of longer alkane-based molecules but is almost incapable of acting on shorter molecules in solutions. In contrast, the plasmon-assisted trapping of molecules can be ignored when the molecules are self-assembled (SAM) on a substrate independent of the molecular length.

7.
Small Methods ; 7(4): e2201427, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36732898

RESUMO

The ability to precisely regulate the size of a nanogap is essential for establishing high-yield molecular junctions, and it is crucial for the control of optical signals in extreme optics. Although remarkable strategies for the fabrication of nanogaps are proposed, wafer-compatible nanogaps with freely adjustable gap sizes are not yet available. Herein, two approaches for constructing in situ adjustable metal gaps are proposed which allow Ångstrom modulation resolution by employing either a lateral expandable piezoelectric sheet or a stretchable membrane. These in situ adjustable nanogaps are further developed into in-plane molecular break junctions, in which the gaps can be repeatedly closed and opened thousands of times with self-assembled molecules. The conductance of the single 1,4-benzenediamine (BDA) and the BDA molecular dimer is successfully determined using the proposed strategy. The measured conductance agreeing well with the data by employing another well-established scanning tunneling microscopy break junction technique provides insight into the formation of molecule dimer via hydrogen bond at single molecule level. The wafer-compatible nanogaps and in-plane dynamical break-junctions provide a potential approach to fabricate highly compacted devices using a single molecule as a building block and supply a promising in-plane technique to address the dynamical properties of single molecules.

8.
ACS Omega ; 8(1): 599-613, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643483

RESUMO

The Permian Fengcheng Formation in the Mahu Sag was deposited in a volcanic-alkaline lacustrine evaporative environment and contains a unique variety of fine-grained sediments. This study examines, at a millimeter-scale, the influence of sedimentary microfacies on variability of lamina quality in fine-grained sediments in the second member of the Fengcheng Formation (P1f2). The methods used include thin-section identification, X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy (SEM), nitrogen adsorption, and nuclear magnetic resonance (NMR). Six types of lamina were identified in two different lithofacies: fan-delta front facies (FDFF) and semideep/deep lacustrine facies (SDDLF). The laminae in FDFF are predominantly feldspar-quartz laminae (FQL), reedmergnerite laminae (RL), shortite laminae (SL), alkaline mineral laminae (AML), and chert laminae (CL). The laminae in SDDLF are predominantly FQL, RL, SL, CL, and dolomite laminae (DOL). Variations in reservoir quality, oil-bearing properties, and the fracability of laminae in different sedimentary facies are determined by the combined effects of lamina density, mineral composition, rock structure, organic matter abundance, and microfractures. Analysis of these factors indicates superior reservoir qualities in FDFF. In SDDLF, the pore structure is limited by high lamina density, chert content, and fine grain size with the NMR porosities of FQL, RL, SL, and CL being 1.32, 0.18, 0.84, and 0.39%, respectively. However, in FDFF, the combination of high organic matter content, feldspar, pyrite, and clay minerals has a superior effect on the organic matter and minerals deposited resulting in better pore structure and more storage space for shale oil. The NMR porosities of FQL, RL, SL, and CL are 2.81, 2.53, 1.80, and 1.12%, respectively. Overall, analysis of lamina variations and their relationships with sedimentary facies indicates that the reservoir in FDFF may offer more favorable targets for "sweet spot" evaluation.

9.
Health Place ; 79: 102971, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36682263

RESUMO

Automobile dependence and physical inactivity have become common health challenges for residents in large suburban residential areas. Limited literature has examined the associations between the built environment and active travel in such residential areas and the differences in these associations among residents from different neighborhoods. To avoid inaccurate results potentially derived from residence-based measures, we adopt a mobility-based approach for environmental exposure assessment. Using GPS data from 530 trips made by 98 participants in a large residential area in Shanghai, we investigate the relationships between neighborhood types, pollution perceptions, built environment features and active travel. The results indicate that residents in affordable and relocation housing make fewer active trips than those in market-rate housing, while the built environment seems to mitigate this difference. Sports facilities promote active travel while commercial facilities and road intersections discourage it. We identify significant interactions between the percentage of green space and neighborhood type, as well as floor area ratio and air pollution perception. Interventions promoting active travel include active-travel-friendly design for commercial facilities and road intersections, the provision of more sports facilities, a careful increase in floor area ratio, and the provision of more green space that is attractive to residents from different neighborhoods.


Assuntos
Ambiente Construído , Viagem , Humanos , China , Habitação , Características de Residência , Planejamento Ambiental , Caminhada
10.
Sci Total Environ ; 850: 158014, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35981573

RESUMO

INTRODUCTION: Lung cancer is a major health concern and is influenced by air pollution, which can be affected by the density of urban built environment. The spatiotemporal impact of urban density on lung cancer incidence remains unclear, especially at the sub-city level. We aimed to determine cumulative effect of community-level density attributes of the built environment on lung cancer incidence in high-density urban areas. METHODS: We selected 78 communities in the central city of Shanghai, China as the study site; communities included in the analysis had an averaged population density of 313 residents per hectare. Using data from the city cancer surveillance system, an age-period-cohort analysis of lung cancer incidence was performed over a five-year period (2009-2013), with a total of 5495 non-smoking/non-secondhand smoking exposure lung cancer cases. Community-level density measures included the density of road network, facilities, buildings, green spaces, and land use mixture. RESULTS: In multivariate models, built environment density and the exposure time duration had an interactive effect on lung cancer incidence. Lung cancer incidence of birth cohorts was associated with road density and building coverage across communities, with a relative risk of 1·142 (95 % CI: 1·056-1·234, P = 0·001) and 1·090 (95 % CI: 1·053-1·128, P < 0·001) at the baseline year (2009), respectively. The relative risk increased exponentially with the exposure time duration. As for the change in lung cancer incidence over the five-year period, lung cancer incidence of birth cohorts tended to increase faster in communities with a higher road density and building coverage. CONCLUSION: Urban planning policies that improve road network design and building layout could be important strategies to reduce lung cancer incidence in high-density urban areas.


Assuntos
Poluição do Ar , Neoplasias Pulmonares , Ambiente Construído , China/epidemiologia , Estudos de Coortes , Humanos , Neoplasias Pulmonares/epidemiologia
11.
J Clin Lab Anal ; 36(2): e24190, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34951053

RESUMO

BACKGROUND: The mechanism of cancer occurrence and development could be understood with multi-omics data analysis. Discovering genetic markers is highly necessary for predicting clinical outcome of lung adenocarcinoma (LUAD). METHODS: Clinical follow-up information, copy number variation (CNV) data, single nucleotide polymorphism (SNP), and RNA-Seq were acquired from The Cancer Genome Atlas (TCGA). To obtain robust biomarkers, prognostic-related genes, genes with SNP variation, and copy number differential genes in the training set were selected and further subjected to feature selection using random forests. Finally, a gene-based prediction model for LUAD was validated in validation datasets. RESULTS: The study filtered 2071 prognostic-related genes and 230 genomic variants, 1878 copy deletions, and 438 significant mutations. 218 candidate genes were screened through integrating genomic variation genes and prognosis-related genes. 7 characteristic genes (RHOV, CSMD3, FBN2, MAGEL2, SMIM4, BCKDHB, and GANC) were identified by random forest feature selection, and many genes were found to be tumor progression-related. A 7-gene signature constructed by Cox regression analysis was an independent prognostic factor for LUAD patients, and at the same time a risk factor in the test set, external validation set, and training set. Noticeably, the 5-year AUC of survival in the validation set and training set was all ˃ 0.67. Similar results were obtained from multi-omics validation datasets. CONCLUSIONS: The study builds a novel 7-gene signature as a prognostic marker for the survival prediction of patients with LUAD. The current findings provided a set of new prognostic and diagnostic biomarkers and therapeutic targets.


Assuntos
Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Marcadores Genéticos , Neoplasias Pulmonares/genética , Variações do Número de Cópias de DNA , Humanos , Mutação , Polimorfismo de Nucleotídeo Único , Prognóstico , Modelos de Riscos Proporcionais
12.
Cities ; 118: 103396, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34334868

RESUMO

Effective control of the COVID-19 pandemic via appropriate management of the built environment is an urgent issue. This study develops a research framework to explore the relationship between COVID-19 incidence and influential factors related to protection of vulnerable populations, intervention in transmission pathways, and provision of healthcare resources. Relevant data for regression analysis and structural equation modeling is collected during the first wave of the pandemic in the United States, from counties with over 100 confirmed cases. In addition to confirming certain factors found in the existing literature, we uncover six new factors significantly associated with COVID-19 incidence. Furthermore, incidence during the lockdown is found to significantly affect incidence after the reopening, highlighting that timely quarantining and treating of patients is essential to avoid the snowballing transmission over time. These findings suggest ways to mitigate the negative effects of subsequent waves of the pandemic, such as special attention of infection prevention in neighborhoods with unsanitary and overcrowded housing, minimization of social activities organized by neighborhood associations, and contactless home delivery service of healthy food. Also worth noting is the need to provide support to people less capable of complying with the stay-at-home order because of their occupations or socio-economic disadvantage.

13.
Nanoscale Horiz ; 6(5): 386-392, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949578

RESUMO

We developed a method based on the mechanically controllable break junction technique to investigate the electron transport properties of single molecular junctions upon fiber waveguided light. In our strategy, a metal-coated tapered optical fiber is fixed on a flexible substrate, and this tapered fiber serves as both the optical waveguide and metal electrodes after it breaks. For an imidazole bridged single-molecule junction, two probable conductance values below 1G0 are observed. The higher value shows an approximately 40% enhancement under illumination, while the lower one does not show distinguishable difference under illumination. Theoretical calculations reveal these two conductance values resulting from the imidazole monomer junction and the imidazole dimer junction linked via a hydrogen bond, respectively. In imidazole monomer junctions, the absorption of a single photon strongly shifts the transmission function resulting in optical-induced conductance enhancement. In contrast, the transmission function of imidazole dimer junctions remains at the same level in the bias window despite the light illumination. This work provides a robust experimental framework for studying the underlying mechanisms of photoconductivity in single-molecule junctions and offers tools for tuning the optoelectronic performance of single-molecule devices in situ.

14.
FASEB J ; 34(1): 1198-1210, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914655

RESUMO

Early pro-inflammatory signaling in the endocrine pancreas involves activation of NF-κB, which is believed to be important for determining the ultimate fate of ß-cells and hence progression of type 1 diabetes (T1D). Thus, early non-invasive detection of NF-κB in pancreatic islets may serve as a potential strategy for monitoring early changes in pancreatic endocrine cells eventually leading to T1D. We investigated the feasibility of optical imaging of NF-κB transcription factor activation induced by low-dose streptozocin (LD-STZ) treatment in the immunocompetent SKH1 mouse model of early stage diabetes. In this model, we showed that the levels of NF-κB may be visualized and measured by fluorescence intensity of specific near-infrared (NIR) fluorophore-labeled oligodeoxyribonucleotide duplex (ODND) probes. In addition, NF-κB activation following LD-STZ treatment was validated using immunofluorescence and transgenic animals expressing NF-κB inducible imaging reporter. We showed that LD-STZ-treated SKH1 mice had significantly higher (2-3 times, P < .01) specific NIR FI in the nuclei and cytoplasm of islets cells than in non-treated control mice and this finding was corroborated by immunoblotting and electrophoretic mobility shift assays. Finally, using semi-quantitative confocal analysis of non-fixed pancreatic islet microscopy we demonstrated that ODND probes may be used to distinguish between the islets with high levels of NF-κB transcription factor and control islet cells.


Assuntos
Núcleo Celular/metabolismo , Citoplasma/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Ilhotas Pancreáticas/metabolismo , NF-kappa B/metabolismo , Animais , Núcleo Celular/patologia , Citoplasma/patologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Feminino , Corantes Fluorescentes/farmacologia , Ilhotas Pancreáticas/patologia , Masculino , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência , NF-kappa B/genética , Oligodesoxirribonucleotídeos/farmacologia
15.
Nanotheranostics ; 2(1): 1-11, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29291159

RESUMO

Constitutively activated signal transducer and activator of transcription 3 (STAT3) factor is an important therapeutic target in head and neck cancer (HNC). Despite early promising results, a reliable systemic delivery system for STAT3- targeted oligonucleotide (ODN) drugs is still needed for future clinical translation of anti-STAT3 therapies. We engineered and tested a novel ODN duplex/gold nanoparticle (AuNP)-based system carrying a therapeutic STAT3 decoy (STAT3d) payload. This strategy is two-pronged because of the additive STAT3 antagonism and radiosensitizing properties of AuNP. The specificity to head and neck cancer cell surface was imparted by using a nucleolin aptamer (NUAP) that was linked to AuNP for taking the advantage of an aberrant presentation of a nuclear protein nucleolin on the cell surface. STAT3d and nucleolin aptamer constructs were independently linked to AuNPs via Au-S bonds. The synthesized AuNP constructs (AuNP-NUAP-STAT3d) exhibited internalization in cells that was quantified by using radiolabeled STAT3d. AuNP-NUAP-STAT3d showed radiosensitizing effect in human HNC FaDu cell culture experiments that resulted in an increase of cell DNA damage as determined by measuring γ-H2AX phosphorylation levels by flow cytometry. The radiosensitization study also demonstrated that AuNP-NUAP-STAT3d as well as STAT3d alone resulted in the efficient inhibition of A431 cell proliferation. While FaDu cells did not show instant proliferation inhibition after incubating with AuNP-NUAP-STAT3d, the cell DNA damage in these cells showed nearly a 50% increase in AuNP-NUAP-STAT3d group after treating with radiation. Compared with anti-EGFR humanized antibody (Cetuximab), AuNP-NUAP-STAT3d system had an overall stronger radiosensitization effect in both A431 and FaDu cells.

16.
Theranostics ; 7(13): 3354-3368, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28900515

RESUMO

Short oligonucleotide sequences are now being widely investigated for their potential therapeutic properties. The modification of oligonucleotide termini with short fluorinated residues is capable of drastically altering their behavior in complex in vitro and in vivo systems, and thus may serve to greatly enhance their therapeutic potential. The main goals of our work were to explore: 1) how modification of STAT3 transcription factor-binding oligodeoxynucleotide (ODN) duplexes (ODND) with one or two short fluorocarbon (FC)-based residues would change their properties in vitro and in vivo, and if so, how this would affect their intracellular uptake by cancer cells, and 2) the ability of such modified ODND to form non-covalent complexes with FC-modified carrier macromolecule. The latter has an inherent advantage of producing a 19F-specific magnetic resonance (MR) imaging signature. Thus, we also tested the ability of such copolymers to generate 19F-MR signals. Materials and Methods. Fluorinated nucleic acid residues were incorporated into ODN by using automated synthesis or via activated esters on ODN 5'-ends. To quantify ODND uptake by the cells and to track their stability, we covalently labeled ODN with fluorophores using internucleoside linker technology; the FC-modified carrier was synthesized by acylation of pegylated polylysine graft copolymer with perfluoroundecanoic acid (M5-gPLL-PFUDA). Results. ODN with a single FC group exhibited a tendency to form duplexes with higher melting points and with increased stability against degradation when compared to control non-modified ODNs. ODND carrying fluorinated residues showed complex formation with M5-gPLL-PFUDA as predicted by molecular dynamics simulations. Moreover, FC groups modulated the specificity of ODND binding to the STAT3 target. Finally, FC modification resulted in greater cell uptake (2 to 4 fold higher) when compared to the uptake of non-modified ODND as determined by quantitative confocal fluorescence imaging of A431 and INS-1 cells. Conclusion. ODND modification with FC residues enables fine-tuning of protein binding specificity to double-strand binding motifs and results in an increased internalization by A431 and INS-1 cells in culture. Our results show that modification of ODN termini with FC residues is both a feasible and powerful strategy for developing more efficient nucleic acid-based therapies with the added benefit of allowing for non-invasive MR imaging of ODND therapeutic targeting and response.


Assuntos
Fluorocarbonos/química , Espaço Intracelular/metabolismo , Imagem Molecular , Oligodesoxirribonucleotídeos/química , Fator de Transcrição STAT3/metabolismo , Carbocianinas/química , Linhagem Celular Tumoral , Ensaio de Desvio de Mobilidade Eletroforética , Ácidos Graxos/química , Humanos , Simulação de Dinâmica Molecular , Sondas Moleculares/química , Oligodesoxirribonucleotídeos/síntese química , Polilisina/química , Espectroscopia de Prótons por Ressonância Magnética
17.
J Antibiot (Tokyo) ; 69(10): 741-746, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26932407

RESUMO

Ciprofloxacin is a quinolone antibiotic used to treat Klebsiella pneumoniae infections in the clinic. Previous studies have demonstrated that berberine exhibits antibacterial activity and less acquired resistance related to efflux pumps. The multidrug efflux pump acrAB-tolC can be stimulated to expel as much toxic material as possible from the cells, but a detrimental effect can be produced owing to an overcrowded periplasm with excess expression products, which inhibits bacterial growth. In this study, the in vitro antibacterial activities of ciprofloxacin in combination with berberine were evaluated and compared with those of ciprofloxacin and berberine alone by evaluating the MIC, MBC and summation fractional IC against 20 clinical multidrug-resistant K. pneumoniae isolates, 1 quality control bacterium and 1 induced-resistance bacterium. Susceptibility tests showed that the MIC for the combination of berberine and ciprofloxacin was 1/2 that of the individual agents or less. Antimicrobial activities of 18.18% synergy and 77.27% additivity were found. Furthermore, synergism was verified through a time-kill assay, which suggested that the synergistic antibacterial effect of the two-drug combination may, to some extent, be related to the high expression of the acrAB-tolC and acrR multidrug efflux pumps. Indeed, the expression of these genes was increased >14-fold in the isolates affected by ciprofloxacin-berberine combination synergism.


Assuntos
Antibacterianos/farmacologia , Berberina/farmacologia , Ciprofloxacina/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Concentração Inibidora 50 , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Testes de Sensibilidade Microbiana
18.
Bioconjug Chem ; 27(2): 383-90, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26603129

RESUMO

Magnetic resonance (MR) and photoacoustic (PA) imaging are currently being investigated as complementing strategies for applications requiring sensitive detection of cells in vivo. While combined MR/PAI detection of cells requires biocompatible cell labeling probes, water-based synthesis of dual-modality MR/PAI probes presents significant technical challenges. Here we describe facile synthesis and characterization of hybrid modular dextran-stabilized gold/iron oxide (Au-IO) multimetallic nanoparticles (NP) enabling multimodal imaging of cells. The stable association between the IO and gold NP was achieved by priming the surface of dextran-coated IO with silver NP resulting from silver(I) reduction by aldehyde groups, which are naturally present within the dextran coating of IO at the level of 19-23 groups/particle. The Au-IO NP formed in the presence of silver-primed Au-IO were stabilized by using partially thiolated MPEG5-gPLL graft copolymer carrying residual amino groups. This stabilizer served as a carrier of near-infrared fluorophores (e.g., IRDye 800RS) for multispectral PA imaging. Dual modality imaging experiments performed in capillary phantoms of purified Au-IO-800RS NPs showed that these NPs were detectible using 3T MRI at a concentration of 25 µM iron. PA imaging achieved approximately 2.5-times higher detection sensitivity due to strong PA signal emissions at 530 and 770 nm, corresponding to gold plasmons and IRDye integrated into the coating of the hybrid NPs, respectively, with no "bleaching" of PA signal. MDA-MB-231 cells prelabeled with Au-IO-800RS retained plasma membrane integrity and were detectable by using both MR and dual-wavelength PA at 49 ± 3 cells/imaging voxel. We believe that modular assembly of multimetallic NPs shows promise for imaging analysis of engineered cells and tissues with high resolution and sensitivity.


Assuntos
Meios de Contraste/química , Dextranos/química , Compostos Férricos/química , Ouro/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Técnicas Fotoacústicas/métodos , Linhagem Celular Tumoral , Meios de Contraste/farmacocinética , Dextranos/farmacocinética , Compostos Férricos/farmacocinética , Ouro/farmacocinética , Humanos , Nanopartículas Metálicas , Imagem Multimodal/métodos
19.
Exp Ther Med ; 12(6): 3877-3884, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28105120

RESUMO

Curcumin is a natural polyphenol with powerful antioxidant and anti-inflammatory properties. The present study evaluated the protective effect of curcumin on myocardial injury in rats as well as the mechanisms underlying these effects, and examined the expression of nuclear factor-κB (NF-κB), peroxisome proliferator-activated receptor-γ (PPAR-γ) and B-cell leukemia/lymphoma-2 (Bcl-2) following myocardial infarction. A rat model of myocardial infarction was successfully established. Hematoxylin and eosin staining showed cellular atrophy and hyperchromatic cytoplasm in the myocardial infarction area. The myocardial cells displayed lysis and breakage of cardiac muscle fibers, karyopyknosis and karyorrhexis associated with infiltration of inflammatory cells and proliferation of fibrous tissue. Curcumin treatment at a dosage of 150 mg/kg/body weight resulted in an increase in surviving cells, fewer apoptotic cells, decreased proliferation of fibrous tissue and reduced infiltration of inflammatory cells, though necrosis was still present compared with the rats without curcumin treatment. The immunohistochemical assay demonstrated that curcumin treatment inhibited the expression of NF-κB, but increased the expression of PPAR-γ. The results of the reverse transcription-polymerase chain reaction indicated that curcumin treatment significantly increased the mRNA expression levels of Bcl-2 (P<0.01). Therefore, curcumin antagonizes cardiomyocyte apoptosis and inhibits inflammatory cell infiltration following myocardial infarction, which may be associated with its inhibitory effects on the expression of NF-κB, and activating effects on the expression of PPAR-γ and Bcl-2 in myocardial cells. Curcumin may be useful in clinical practice for saving more living heart muscle in the area of myocardial infarction and improving cardiac function following the elective opening of obstructed coronary arteries.

20.
Neuropeptides ; 49: 37-45, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25499095

RESUMO

Calcitonin gene-related peptide (CGRP) is an important cardioprotective neuropeptide. Few studies have shown that calcium supplementation may increase CGRP levels transiently. However, the relationship between CGRP and calcium is poorly known. This study was to explore the correlation between serum calcium and CGRP in coronary artery disease (CAD), and observe whether short-term calcium/vitamin D supplementation would increase fasting serum CGRP. A randomized, placebo-controlled and double-blind clinical trial, and a supplementary study for further analysis of the correlations were conducted. The results showed that the correlation between serum calcium and CGRP was positive in CAD without myocardial infarction (MI) (r = 0.487, P = 0.029), but negative in acute and healing MI (r = -0.382, P = 0.003). Moreover, we found a positive correlation between lg (amino-terminal pro-B-type natriuretic peptide, NT-proBNP) and CGRP (r = 0.312, P = 0.027), but a negative correlation between lg (NT-proBNP) and serum calcium (r = -0.316, P = 0.025) in acute and healing MI. As to the clinical trial, participants subjected to CAD but without evolving or acute MI, together with blood calcium ≤ 2.4 mmol/L, were randomized into three groups. Among the groups of placebo, caltrate (600 mg elemental calcium; 125 IU vitamin D3, per tablet) 1 tablet/d and caltrate 2 tablets/d, there were no significant differences in baseline characteristics. After short-term (5 days) treatments, the results indicated that the effect of grouping was not statistically significant (P = 0.915). In conclusion, the correlations between serum calcium and CGRP in different types of CAD are inconsistent, and the main reason may be associated with elevated natriuretic peptides after acute MI. Further, our study shows that short-term calcium/vitamin D supplementation cannot significantly increase fasting serum CGRP levels.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/sangue , Cálcio/administração & dosagem , Cálcio/sangue , Doença da Artéria Coronariana/sangue , Vitamina D/administração & dosagem , Idoso , Doença da Artéria Coronariana/complicações , Suplementos Nutricionais , Método Duplo-Cego , Jejum/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações
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