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991.
Dongdong Wang Huihui Wu Wei Qi Lim Soo Zeng Fiona Phua Pengping Xu Qianwang Chen Zhen Guo Yanli Zhao 《Advanced materials (Deerfield Beach, Fla.)》2019,31(27)
Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen (1O2). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal–organic frameworks (MOFs) is presented for in situ generation of endogenous O2 to enhance the PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese‐based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post‐modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O2 generation through the catalytic reaction between the catalytic amount NE and the endogenous H2O2, the hypoxic tumor microenvironment is relieved. Thus, Ce6‐loaded NE serves as a H2O2‐activated oxygen supplier to increase the local O2 concentration for significantly enhanced antitumor PDT efficacy in vitro and in vivo. In addition, the NE also shows T2‐weighted magnetic resonance imaging ability for its in vivo tracking. This work presents an interesting biomedical use of MOF‐derived mesoporous NE as a multifunctional theranostic agent in cancer therapy. 相似文献
992.
Personalized Cardio‐Metabolic Responses to an Anti‐Inflammatory Nutrition Intervention in Obese Adolescents: A Randomized Controlled Crossover Trial 下载免费PDF全文
Aoibheann M. McMorrow Ruth M. Connaughton Tiago R. Magalhães Fiona C. McGillicuddy Maria F. Hughes David Cheishvili Melissa J. Morine Sean Ennis Marie‐Louise Healy Edna F. Roche Richard E. Tremblay Moshe Szyf Fiona E. Lithander Helen M. Roche 《Molecular nutrition & food research》2018,62(10)
1 Scope
Chronic inflammation and hypoadiponectinemia are characteristics of obesity‐induced insulin resistance (IR). The effect of an anti‐inflammatory nutrition supplement (AINS) on IR and adiponectin biology in overweight adolescents was investigated. The secondary objective was to examine the extent to which individuals’ biomarker profiles, derived from baseline phenotypes, predicted response or not to the AINS. Additionally, the impact of DNA methylation on intervention efficacy was assessed.2 Methods and results
Seventy overweight adolescents (13–18 years) were recruited to this randomized controlled crossover trial. Participants received an AINS (long chain n‐3 PUFA, vitamin C, α‐tocopherol, green tea extract, and lycopene) and placebo for 8 weeks each. Homeostatic model assessment (HOMA)‐IR, adiponectin, inflammatory profiles, and DNA methylation were assessed. HOMA‐IR was unchanged in the total cohort. High‐molecular‐weight (HMW) adiponectin was maintained following the AINS while it decreased over time following the placebo intervention. HOMA‐IR decreased in 40% of subjects (responders) following the AINS. Responders’ pretreatment phenotype was characterized by higher HOMA‐IR, total and LDL cholesterol, but similar BMI in comparison to nonresponders. HMW adiponectin response to the AINS was associated with bidirectional modulation of adipogenic gene methylation.3 Conclusion
The AINS modulated adiponectin biology, an early predictor of type 2 diabetes risk, was associated with bidirectional modulation of adipogenic gene methylation in weight‐stable overweight adolescents. HOMA‐IR decreased in a sub‐cohort of adolescents with an adverse metabolic phenotype. Thus, suggesting that more stratified or personalized nutrition approaches may enhance efficacy of dietary interventions. 相似文献993.
Christopher J. Stephens Sophie F. Ladden Fiona C. Meldrum Hugo K. Christenson 《Advanced functional materials》2010,20(13):2108-2115
Biominerals typically form within localized volumes, affording organisms great control over the mineralization process. The influence of such confinement on crystallization is studied here by precipitating CaCO3 within the confines of an annular wedge, formed around the contact point of two crossed half‐cylinders. The cylinders are functionalized with self‐assembled monolayers of mercaptohexadecanoic acid on gold. This configuration enables a systematic study of the effects of confinement since the surface separation increases continuously from zero at the contact point to macroscopic (mm) separations. While oriented rhombohedral calcite crystals form at large (>10 µm) separations, particles with irregular morphologies and partial crystallinity are observed as the surface separation approaches the dimensions of the unconfined crystals (5–10 µm). Further increase in the confinement has a significant effect on the crystallization process with flattened amorphous CaCO3 (ACC) particles being formed at micrometer separations. These ACC particles show remarkable stability when maintained within the wedge but rapidly crystallize on separation of the cylinders. A comparison of bulk and surface free‐energy terms shows that ACC cannot be thermodynamically stable at these large separations, and the stability is attributed to kinetic factors. This study therefore shows that the environment in which minerals form can have a significant effect on their stability and demonstrates that ACC can be stabilized with respect to the crystalline polymorphs of CaCO3 by confinement alone. That ACC was stabilized at such large (micrometer) separations is striking, and demonstrates the versatility of this strategy, and its potential value in biological systems. 相似文献
994.
995.
Protein phosphorylation is an important and ubiquitous post-translational modification in eukaryotic biological systems. The KAYAK (Kinase ActivitY Assay for Kinome profiling) assay measures the phosphorylation rates of dozens of peptide substrates simultaneously, directly from cell lysates. Here, we simplified the assay by removing the phosphopeptide enrichment step, increasing throughput while maintaining similar data quality. We term this new method, direct-KAYAK, because kinase activities were measured directly from reaction mixtures after desalting. In addition, new peptides were included to profile additional kinase pathways and redundant substrate peptides were removed. Finally, the method is now performed in 96-well plate format using a benchtop orbitrap mass spectrometer and the Pinpoint software package for improved data analysis. We applied the new high-throughput method to measure IC(50) values for kinases involved in monocyte-to-macrophage differentiation, a process important for inflammation and the immune response. 相似文献
996.
A. Monfardini A. Benoit A. Bideaud N. Boudou M. Calvo P. Camus C. Hoffmann F.-X. Désert S. Leclercq M. Roesch K. Schuster P. Ade S. Doyle P. Mauskopf E. Pascale C. Tucker A. Bourrion J. Macias-Perez C. Vescovi A. Barishev J. Baselmans L. Ferrari S. J. C. Yates A. Cruciani P. De Bernardis S. Masi C. Giordano B. Marghesin H. G. Leduc L. Swenson 《Journal of Low Temperature Physics》2012,167(5-6):834-839
We are developing an instrument based on Kinetic Inductance Detectors (KID) known as the Néel IRAM KID Array (NIKA). Leveraging the experience gained from the first generation NIKA in 2009, an improved, dual-band (150?GHz and 240?GHz) instrument has been designed and tested at the Institut of RadioAstronomie Millimetrique (IRAM) 30-meter telescope in October 2010. The performances, in terms of sensitivity on-the-sky at 150?GHz, are already comparable to existing state-of-the-art bolometer-based instruments. NIKA represents thus the first real proof that KID are a viable technology for ground-based Astronomy. We will describe the instrument, the most recent results and the future plans for building a large resident mm-wave camera. 相似文献
997.
Sen. Lect. Fiona Moore 《Management International Review》2012,52(5):619-642
- This paper uses an incident in which a diorama was set up at the entrance to the Final Assembly section of the BMW MINI plant near Oxford to anlayse the impact of gender and ethnic identities on cross-cultural management, through the anthropological concept of the ??native category??. Its aims are to explore the ways in which the diorama symbolically exposed tensions in the workplace relating to ethnicity and gender; to consider the role of a German dominance effect on the workforce; and to examine the implications of these for cross-cultural management.
- The data was gathered through participant-observation on the assembly line and managers?? offices, and through both unstructured and semi-structured interviews with managers and workers, during two fieldwork periods, the first in 2003 and the second involving intermittent visits from 2003?C2006.
- The paper explores the ways in which the diorama reflected and contributed to unspoken tensions within the workplace relating to ethnicity and gender, and assesses the role of the German dominance effect on the workforce. It investigates the impact of tacit discourses on organisations, and considers ways in which cross-cultural management activities can be successfully carried out in MNCs.
- The management of gender and ethnicity within BMW were affected by the ??native categories?? of British and German managers and workers; furthermore, taking a native categories approach to cross-cultural management reveals areas of friction, and sheds light on normally-overlooked problems in merged organisations.
998.
Because of their critical biological roles, hemoglobin and myoglobin are among the most extensively studied proteins in human history, while nitrite tops the list of most-studied small molecules. And although the reactions between them have been examined for more than 140 years, a series of unusual and critical allosterically modulated reactions have only recently been characterized. In this Account, we review three novel metal- and nitrite-catalyzed reaction pathways in the context of historical studies of nitrite and hemoglobin chemistry and attempt to place them in the biological framework of hypoxic signaling. Haldane first described the reaction between nitrite and deoxymyoglobin, forming iron-nitrosylated myoglobin, in his analysis of the meat-curing process more than a century ago. The reaction of nitrous acid with deoxyhemoglobin to form nitric oxide (NO) and methemoglobin was more fully characterized by Brooks in 1937, while the mechanism and unusual behavior of this reaction were further detailed by Doyle and colleagues in 1981. During the past decade, multiple physiological studies have surprisingly revealed that nitrite represents a biological reservoir of NO that can regulate hypoxic vasodilation, cellular respiration, and signaling. Importantly, chemical analysis of this new biology suggests a vital role for deoxyhemoglobin- and deoxymyoglobin-dependent nitrite reduction in these processes. The use of UV-vis deconvolution and electron paramagnetic resonance (EPR) spectroscopy, in addition to refined gas-phase chemiluminescent NO detection, has led to the discovery of three novel and unexpected chemistries between nitrite and deoxyhemoglobin that may contribute to and facilitate hypoxic NO generation and signaling. First, R-state, or allosteric, autocatalysis of nitrite reduction increases the rate of NO generation by deoxyhemoglobin and results in maximal NO production at approximately 50% hemoglobin oxygen saturation, which is physiologically associated with greatest NO-dependent vasodilation. Second, oxidative denitrosylation of the iron-nitrosyl product formed in the deoxyhemoglobin-nitrite reaction allows for NO formation and release in a partially oxygenated environment. Finally, the deoxyhemoglobin-nitrite reaction participates in a nitrite reductase/anhydrase redox cycle that catalyzes the anaerobic conversion of two molecules of nitrite into dinitrogen trioxide (N(2)O(3)). N(2)O(3) may then nitrosate proteins, diffuse across hydrophobic erythrocyte membrane channels such as aquaphorin or Rh, or reconstitute NO via homolysis to NO and NO(2)(*). Importantly, the nitrite reductase/anhydrase redox pathway also represents a novel mechanism of both anaerobic and metal-catalyzed N(2)O(3) formation and S-nitrosation and may thus play a vital role in NO-dependent signaling in a hypoxic and heme-rich environment. We consider how these reactions may contribute to physiological and pathological hypoxic signaling. 相似文献
999.
Amanda K. Petrus Damian G. Allis Dr. Robert P. Smith Timothy J. Fairchild Prof. Robert P. Doyle Prof. 《ChemMedChem》2009,4(3):297-297
The cover picture shows three views of a vitamin B12–insulin conjugate bound to transcobalamin II, docked in the insulin receptor (IR). This study reveals how the structure of an orally deliverable insulin changes in solution after vitamin B12 conjugation and its effect on IR binding capacity. The results demonstrate that chemical modification of insulin by linking relatively large pendant groups does not interfere with IR recognition. For more details, see the Full Paper by T. J. Fairchild, R. P. Doyle, et al. on p. 421 ff.
1000.
Shire D.B. Kelly S.K. Jinghua Chen Doyle P. Gingerich M.D. Cogan S.F. Drohan W.A. Mendoza O. Theogarajan L. Wyatt J.L. Rizzo J.F. 《IEEE transactions on bio-medical engineering》2009,56(10):2502-2511
A wirelessly operated, minimally invasive retinal prosthesis was developed for preclinical chronic implantation studies in Yucatan minipig models. The implant conforms to the outer wall of the eye and drives a microfabricated polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially designed ab externo surgical technique that fixes the bulk of the prosthesis to the outer surface of the sclera. The implanted device is fabricated on a host polyimide flexible circuit. It consists of a 15-channel stimulator chip, secondary power and data receiving coils, and discrete power supply components. The completed device is encapsulated in poly(dimethylsiloxane) except for the reference/counter electrode and the thin electrode array. In vitro testing was performed to verify the performance of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation patterns as well as pulse strength, duration, and frequency were programmed wirelessly using custom software and a graphical user interface. Wireless operation of the retinal implant has been verified both in vitro and in vivo in three pigs for more than seven months, the latter by measuring stimulus artifacts on the eye surface using contact lens electrodes. 相似文献