Fine-tuning thio-pyridazinediones as SMDC scaffolds (with intracellular thiol release via a novel self-immolative linker)

Herein we report the synthesis of a library of thioalkyl- and thioaryl-pyridazinediones for thiol-based self-immolative release of cargo. A bisthioaryl-pyridazinedione is shown to be stable to serum protein albumin but unstable in intracellular conditions. A derivatised analogue underwent self-immolative degradation in cellular thiol conditions as evidenced by LC-MS/release of a turn-on fluorescence fluorophore; versatility of the thiol-pyridazinedione is demonstrated through synthesis of SMDC precursors that contain three different functional groups on the same central molecule

Pattern of mandibular third molar impaction: A cross‑sectional study in northeast of Iran

Objectives: Impacted teeth, if left untreated, have a potential to induce various complications. The aim of the current study was to determine the prevalence and pattern of impacted mandibular third molar in the Iranian population.Study Design: This cross‑sectional study was performed in patients who were referred to the Department of Oral Radiology between July 2009 and October 2010 to obtain an orthopantomogram (OPG). Data were collected regarding age and gender, prevalence of impacted mandibular third molars, angulation of impacted teeth (Winter’s classification), level of impaction (Pell and Gregory classification), and relationship of the mandibular third molar with the ramus (Pell and Gregory classification). The collected data were analyzed using SPSS software version 11.0 with a confidence interval of 95%.Results: Among the 1433 patients included in the study, 489 (34.12%) patients were male and 944 (65.88%) were female. Of the total OPGs performed, 871 (60.78%) OPGs demonstrated at least one impacted mandibular third molar. In addition, of the 2866 mandibular third molars investigated, 1397 (48.74%) were found to be impacted. A significant association was observed between gender and the number of impacted teeth or the presence of impaction of any mandibular tooth (or teeth) (P < 0.05). The most common type of tooth angulation was mesioangular (48.67%). In addition, the most prevalent type of impaction level and ramus relationship was level B (63.85%) and Class II (48.46%), respectively. There were no significant differences between the two sides of the mandible for the prevalence of impacted third molar (P > 0.05).Conclusion: The pattern of mandibular third molars in the Northeast region of Iran revealed a high prevalence of impaction, which was mostly mesioangular, level B, and Class II with a gender predilection for females.Keywords: Impaction, Iran, mandibular third molar, orthopantomogram, patter

The urban heat island in an urban context: A case study of Mashhad, Iran

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. In this study, the spatio-temporal changes of urban heat island (UHI) in a mega city located in a semi-arid region and the relationships with normalized difference vegetation index (NDVI) and normalized difference built-up index (NDBI) are appraised using Landsat TM/OLI images with the help of ENVI and ArcGIS software. The results reveal that the relationships between NDBI, NDVI and land surface temperature (LST) varied by year in the study area and they are not suitable indices to study the land surface temperature in arid and semi-arid regions. The study also highlights the importance of weather conditions when appraising the relationship of these indices with land surface temperature. Overall, it can be concluded that LST in arid and steppe regions is most influenced by barren soil. As a result, built-up areas surrounded by soil or bituminous asphalt experience higher land surface temperatures compared to densely built-up areas. Therefore, apart from setting-up more green areas, an effective way to reduce the intensity of UHI in these regions is to develop the use of cool and smart pavements. The experiences from this paper may be of use to cities, many of which are struggling to adapt to a changing climate

Molecular Dynamics Insights into the Structural and Water Transport Properties of a Forward Osmosis Polyamide Thin-Film Nanocomposite Membrane Modified with Graphene Quantum Dots

An approach combining molecular dynamics (MD) simulations and laboratory experiments was applied to provide new theoretical insights into the chemical structure of polyamide (PA) thin-film composite (TFC) membranes modified with graphene quantum dots (GQDs). Interaction energies, fractional free volumes, mean-square displacements, densities, and water diffusion coefficients were computed for PA and four likely chemical structures of the GQD-embedded PA membranes. These theoretical results aided with experimentally measured water fluxes allowed for determining the most likely structure of the GQD-PA membrane. The compatibility of the GQDs and PA chains was found to be due to the formation of hydrogen and covalent bonds to m-phenylenediamine units. The modified membrane has a higher water diffusivity but a lower overall free volume, compared to the pristine PA membrane. MD simulations in concert with laboratory experiments were found to provide a good understanding of the relationship between the microscopic characteristics and macroscopic transport properties of TFC membranes

Application of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) to patients with cataract

OBJECTIVES: Cataract is a prevalent disease in the elderly, and negatively influences patients' quality of life. This study was conducted to study the application of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) to patients with cataract. METHODS: In this cross-sectional study, 300 patients with cataract were studied in Neyshabur, Iran from July to October 2014. The Iranian version of the WHOQOL-BREF questionnaire was used to measure their quality of life. Cronbach's alpha coefficient, Pearson's correlation coefficient, the paired t-test, the independent t-test, and a linear regression model were used to analyze the data in SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). RESULTS: The mean age of the participants was 68.11±11.98 years, and most were female (53). The overall observed Cronbach's alpha coefficient for the WHOQOL-BREF was 0.889, ranging from 0.714 to 0.810 in its four domains. The total mean score of the respondents on the WHOQOL-BREF was 13.19. The highest and lowest mean scores were observed in the social relationship domain (14.11) and the physical health domain (12.29), respectively. A backward multiple linear regression model found that duration of disease and marital status were associated with total WHOQOL scores, while age, duration of disease, marital status, and income level were associated with domains one through four, respectively (p<0.05). CONCLUSIONS: The reliability analysis conducted in this study indicated that the WHOQOL-BREF scale exhibited an acceptable degree of internal consistency in the measurement of the quality of life of patients with cataract. It was also found that the patients with cataract who were surveyed reported a relatively moderate quality of life

A novel thiol-labile cysteine protecting group for peptide synthesis based on a pyridazinedione (PD) scaffold

Herein we report a thiol-labile cysteine protecting group based on an unsaturated pyridazinedione (PD) scaffold. We establish compatibility of the PD in conventional solid phase peptide synthesis (SPPS), showcasing this in the on-resin synthesis of biologically relevant oxytocin. Furthermore, we establish the applicability of the PD protecting group towards both microwave-assisted SPPS and native chemical ligation (NCL) in a model system

Toward Sustainable Tackling of Biofouling Implications and Improved Performance of TFC FO Membranes Modified by Ag-MOF Nanorods

In this work, nanorods with high antibacterial properties were synthesized with silver acetate as the metal source and 2-aminoterephthalic acid as the organic linker and were then embedded into thin-film composite (TFC) membranes to amend their performance as well as to alleviate biofouling. Silver metal-organic framework (Ag-MOF) nanorods with a length smaller than 40 nm were incorporated within the polyamide thin selective layer of the membranes during interfacial polymerization. The interaction of the synthesized nanorods with the polyamide was favored because of the presence of amine-containing functional groups on the nanorod's surface. The results of X-ray photoelectron spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and atomic force microscopy characterizations proved the presence of Ag-MOF nanorods in the selective layer of thin-film nanocomposite (TFN) membranes. TFN membranes demonstrated improved water permeance, salt selectivity, and superior antibacterial properties. Specifically, the increased hydrophilicity and antibacterial potential of the TFN membranes led to a synergetic effect toward biofouling mitigation. The number of live bacteria attached to the surface of the neat TFC membrane decreased by more than 92% when a low amount of Ag-MOF nanorods (0.2 wt %) was applied. Following contact of the TFN membrane surface with Escherichia coli and Staphylococcus aureus, full inactivation, and degradation of bacteria cells were observed with microscopy, colony-forming unit tests, and disc inhibition zone analyses. This result translated to a negligible amount of the biofilm formed on the active layer. Indeed, the incorporation of Ag-MOF nanorods decreased the metal-ion release rate and therefore provided prolonged antibacterial performance

Application of the world health organization quality of life instrument, short form (WHOQOL-BREF) to patients with cataract

OBJECTIVES: Cataract is a prevalent disease in the elderly, and negatively influences patients' quality of life. This study was conducted to study the application of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) to patients with cataract. METHODS: In this cross-sectional study, 300 patients with cataract were studied in Neyshabur, Iran from July to October 2014. The Iranian version of the WHOQOL-BREF questionnaire was used to measure their quality of life. Cronbach's alpha coefficient, Pearson's correlation coefficient, the paired t-test, the independent t-test, and a linear regression model were used to analyze the data in SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). RESULTS: The mean age of the participants was 68.11 ± 11.98 years, and most were female (53). The overall observed Cronbach's alpha coefficient for the WHOQOL-BREF was 0.889, ranging from 0.714 to 0.810 in its four domains. The total mean score of the respondents on the WHOQOL-BREF was 13.19. The highest and lowest mean scores were observed in the social relationship domain (14.11) and the physical health domain (12.29), respectively. A backward multiple linear regression model found that duration of disease and marital status were associated with total WHOQOL scores, while age, duration of disease, marital status, and income level were associated with domains one through four, respectively (p < 0.05). CONCLUSIONS: The reliability analysis conducted in this study indicated that the WHOQOL-BREF scale exhibited an acceptable degree of internal consistency in the measurement of the quality of life of patients with cataract. It was also found that the patients with cataract who were surveyed reported a relatively moderate quality of life. © 2016, Korean Society of Epidemiolog

Modular synthesis of semiconducting graft co-polymers to achieve ‘clickable’ fluorescent nanoparticles with long circulation and specific cancer targeting

Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, a method for achieving colloidally stable and low-fouling SPNs is described by grafting poly(ethylene glycol) (PEG) onto the backbone of the fluorescent semiconducting polymer, poly(9,9′-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole), in a simple one-step substitution reaction, postpolymerization. Further, by utilizing azide-functionalized PEG, anti-human epidermal growth factor receptor 2 (HER2) antibodies, antibody fragments, or affibodies are site-specifically “clicked” onto the SPN surface, which allows the functionalized SPNs to specifically target HER2-positive cancer cells. In vivo, the PEGylated SPNs are found to have excellent circulation efficiencies in zebrafish embryos for up to seven days postinjection. SPNs functionalized with affibodies are then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics

Modular Synthesis of Semiconducting Graft Co-polymers to Achieve "clickable" Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

Semiconducting polymer nanoparticles (SPNs) have been explored for applications in cancer theranostics because of their high absorption coefficients, photostability and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, we describe a method for achieving colloidally stable and low-fouling SPNs by grafting PEG onto the backbone of the fluorescent semiconducting polymer, poly(9,9'-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole) (F8BT-F), in a simple one-step substitution reaction, post-polymerisation. Further, by utilising azide-functionalised PEG we site-specifically "click" anti-HER2 antibodies, Fab fragments, or affibodies onto the SPN surface, which allows the functionalised SPNs to specifically target HER2-positive cancer cells. In vivo, our PEGylated SPNs were found to have excellent circulation efficiencies in zebrafish embryos for up to seven days post-injection. SPNs functionalised with affibodies were then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics. This article is protected by copyright. All rights reserved