Intervention-Free Graphitization of Carbon Microspheres from a Non-Graphitizing Polymer at Low Temperature: Nanopores as Dynamic Nanoreactors.

Graphitizability of organic precursors is the topic of numerous investigations due to the wide applications of graphitic materials in the industry and emerging technologies of supercapacitors, batteries, etc. Most polymers, such as polydivinyl benzene (PDVB) are classified as non-graphitizings that do not convert to Graphite even after heating to 3000℃. Here, for the first time, the development of graphitic structure in the hierarchal porous sulfonated-PDVB microspheres without employing specific equipment or additives like metal catalysts, organic ingredients, or graphite particles, at 1100°C is reported. The abnormal additive-free graphitic structure formation is confirmed by Raman spectroscopy (ID /IG = 0.87), high-resolution transmission electron microscopy (HRTEM), and selected area diffraction patterns (SAED), as well as x-ray diffraction patterns (XRD), while preservation of aromatic compounds from the carbonization is detected by Fourier transform infrared (FTIR) analysis. Polymer evolution from room temperature to 1100°C is also studied by FTIR, Raman spectroscopy, and XRD techniques. Based on the obtained results, it is suggested that the hierarchal and complicated ink-bottle pore network with a high surface area besides super micropores in the sulfonated-PDVB microspheres has served as nano-sized reaction media. These pores, hereafter referred as "dynamic nanoreactors", are expected to have confined the in-situ produced thermal decomposition products containing broken bond benzene rings, while changing dimensionally and structurally during the designed carbonization regime. This confinement has led to the benzene rings fusion at 250°C, a remarkable extension of them at 450°C, their growth to graphene sheets at 900°C and finally, the stacking of curved graphene layers at 1100°C. The results of this research put stress on the capability of nanopores as nanoreactors to facilitate reactions of decomposition products at low temperatures and ambient pressures to form stacked layers of graphene; A transformation that normally requires catalysts and very high pressures for only specific polyaromatic hydrocarbons.

Well-distributed 1T/2H MoS2 nanocrystals in the N-doped nanoporous carbon framework by direct pyrolysis.

Molybdenum disulfide (MoS2) has been a promising anode material in lithium-ion batteries (LIBs) because of its high theoretical capacity and large interlayer spacing. However, its intrinsic poor electrical conductivity and large volume changes during the lithiation/delithiation reactions limit its practical application. An efficient synthesis strategy was developed to prepare the MoS2 nanocrystals well-anchored into the N-doped nanoporous carbon framework to deal with these challenges by a confined reaction space in an acrylonitrile-based porous polymer during the carbonization process. The prepared hybrid material comprises small 1T/2H-MoS2 nanoparticles surrounded by a nanoporous carbon matrix. In addition to the highly crystalline nature of the synthesized MoS2, the low ID/IG of the Raman spectrum demonstrated the development of graphitic domains in the carbon support during low-temperature pyrolysis (700 °C). This novel three-dimensional (3D) hierarchical composite shows superior advantages, such as decreased diffusion lengths of lithium ions, preventing the agglomeration of MoS2 nanocrystals, and maintaining the whole structural stability. The prepared C/MoS2 hybrid demonstrated fast rate performance and satisfactory cycling stability as an anode material for LIBs.

A hydrophilic carbon foam/molybdenum disulfide composite as a self-floating solar evaporator.

Solar-driven interfacial evaporation has gained increasing attention as an emerging and sustainable technology for wastewater treatment and desalinization. The carbon/molybdenum disulfide (C/MoS2) composite has attracted more attention due to its outstanding light absorption capability and optoelectronic properties as a solar steam generator. However, the hydrophobic nature of carbon and MoS2-based materials hinders their wettability, which is crucial to the effective and facile operation of a solar generator of steam. Herein, a pH-controlled hydrothermal method was utilized to deposit a promising photothermal MoS2 coating on melamine-derived carbon foams (CFs). The hydrophilic CF/MoS2 composite, which can easily be floatable on the water surface, is a high-efficiency solar steam evaporator with a rapid increase in temperature under photon irradiation. Due to the localized heat confinement effect, the self-floating composite foam on the surface of water has the potential to produce a significant temperature differential. The porous structure effectively facilitates fast water vapor escape, leading to an impressively high evaporation efficiency of 94.5% under a light intensity of 1000 W m-2.

A novel and easy to prepare azo-based bioreductive linker and its application in hypoxia-sensitive cationic liposomal doxorubicin: Synthesis, characterization, in vitro and in vivo studies in mice bearing C26 tumor.

This study designed and synthesized a cost-effective azo-based hypoxia-sensitive linker (AHSL) using commercially accessible, inexpensive raw materials and simple methods to apply in cationic nanoliposomes. Then, AHSL was post-inserted into the cationic liposome (Cat-lip), and PEG-Azo-Cat-lip was prepared and characterized using DLS. The decrease in the zeta-potential of formulation from + 18.4 mV for Cat-lip to + 6.1 mV and the increase in the size of the PEG-Azo-Cat-lip indicated the successful post insertion of AHSL into the liposomes. The Doxorubicin (Dox) release study showed that PEGylation results in a more stable PEG-Azo-Cat-lip than the Cat-lip. The increased cytotoxicity of the PEG-Azo-Cat-lip in the hypoxic condition also indicated the cleavage of the AHSL in the hypoxic environment. In vivo biodistribution using animal imaging has shown higher tumor accumulation of the MPEG-Azo-Cat-lip than Cat-lip during the 120 h of the study. The results of anti-tumor activities and biosafety of the formulations also showed the higher efficiency of the MPEG-Azo-Cat-lip compared with the Cat-lip. The results of this study indicated the antitumor efficacy of this hypoxia-sensitive which merits further investigation.

Lipid-liquid crystals for 2 months controlled risperidone release: In-vitro evaluation and pharmacokinetics in rabbits.

In this study, a drug delivery system based on lipid liquid crystal (LLC) was developed for the long-term delivery of risperidone to improve psychological treatment. Optimal LLC formulation was achieved based on maximum release after 60 days with different ratios of phosphatidylcholine (PC) to sorbitol monooleate (PC: SMO), tween grade 80 (w/w %), and tocopherol acetate (TA) (w/w %) using the Box-Behnken method. In vitro and ex vivo studies, pharmacokinetics, and histopathological examination in rabbits were conducted to compare the optimal LLC with Risperdal CONSTA®. The optimum formulation containing the PC to SMO ratio of 58.6%, tween 0.82% w/w, and TA 3.6% w/w was selected because it had the highest drug release percentage (100%) during about two months. Polarized optical microscopy (POM) revealed HII mesophase with a 2-dimensional structure. Cell culture also revealed moderate cytotoxicity for LLC-risperidone. Pharmacokinetic data displayed that the optimal LLC created a more consistent drug serum level within 60 days, and histopathology results demonstrated slight to moderate damage in rabbits' organs. Furthermore, the accelerated stability test confirmed optimum stability for LLC and risperidone. This study confirmed the better pharmacokinetic potentials of SMO-based LLC systems compared with Risperdal CONSTA®, which would promote patient compliance and obviate the difficulties of additional oral therapy.

Design and synthesis of new carbamates as inhibitors for fatty acid amide hydrolase and cholinesterases: Molecular dynamic, in vitro and in vivo studies.

As anandamide (N-arachidonoylethanolamine, AEA) shows neuroprotective effects, the inhibition of its degradative enzyme, fatty acid amide hydrolase (FAAH) has been considered as a hopeful avenue for the treatment of neurodegenerative diseases, like Alzheimer's disease (AD). Memory loss, cognitive impairment and diminution of the cholinergic tone, due to the dying cholinergic neurons in the basal forebrain, are common hallmarks in patients with AD. By taking advantage of cholinesterase inhibitors (ChEIs), the degradation of acetylcholine (ACh) is decreased leading to enhanced cholinergic neurotransmission in the aforementioned region and ultimately improves the clinical condition of AD patients. In this work, new carbamates were designed as inhibitors of FAAH and cholinestrases (ChEs) (acetylcholinestrase (AChE), butyrylcholinestrase (BuChE)) inspired by the structure of the native substrates, structure of active sites and the SARs of the well-known inhibitors of these enzymes. All the designed compounds were synthesized using different reactions. All the target compounds were tested for their inhibitory activity against FAAH and ChEs by employing the Cayman assay kit and Elman method respectively. Generally, compounds possessing aminomethyl phenyl linker was more potent compared to their corresponding compounds possessing piperazinyl ethyl linker. The inhibitory potential of the compounds 3a-q extended from 0.83 ± 0.03 µM (3i) to ˃100 µM (3a) for FAAH, 0.39 ± 0.02 µM (3i) to 24% inhibition in 113 ± 4.8 µM (3b) for AChE, and 1.8 ± 3.2 µM (3i) to 23.2 ± 0.2 µM (3b) for BuChE. Compound 3i a heptyl carbamate analog possessing 2-oxo-1,2-dihydroquinolin ring and aminomethyl phenyl linker showed the most inhibitory activity against three enzymes. Also, compound 3i was investigated for memory improvement using the Morris water maze test in which the compound showed better memory improvement at 10 mg/kg compared to reference drug rivastigmine at 2.5 mg/kg. Molecular docking and molecular dynamic studies of compound 3i into the enzymes displayed the possible interactions of key residues of the active sites with compound 3i. Finally, kinetic study indicated that 3i inhibits AChE through the mixed- mode mechanism and non-competitive inhibition mechanism was revealed for BuChE.

Improving anti-tumour efficacy of PEGylated liposomal doxorubicin by dual targeting of tumour cells and tumour endothelial cells using anti-p32 CGKRK peptide.

The aim of this study was to surface-functionalize PEGylated liposomal doxorubicin (PLD) using anti-p32 CGKRK peptide to evaluate its anti-angiogenic and anti-tumour activities. CGKRK was conjugated to DSPE-mPEG2000-maleimide and post-inserted into PLD at 25, 50, 100, 200 and 400 peptides per each liposome and characterised for their size, zeta potential, drug loading, release properties; and cell binding, cell uptake and cytotoxicity on three C26, 4T1 and human umbilical vein endothelial cell (HUVEC) cell lines. The in vitro results indicated the better efficiency of the PLD-100 (PLD with 100 CGKRK) formulation on 4T1 and HUVEC cell lines. The results of anti-tube formation and spheroid assay indicated the efficiencies of the PLD-100 formulation compared with Caelyx®in vitro. The in vivo studies indicated the higher tumour accumulation of PLD-100 formulation in comparison with Caelyx® which also implied the higher survival rates in mice treated with PLD-100 formulation. Histological evaluations demonstrated that PLD-100 had no side-effects on major organs. In conclusion, the results of this study indicated that PLD-CGKRK- could efficiently target endothelial and tumour parenchymal cells which enhance the therapeutic efficacy of PLD and merits further investigation.

Redox-sensitive nanoscale drug delivery systems for cancer treatment.

Pharmaceutical nanotechnology introduces novel strategies in designing smart nanoscale drug delivery systems (NDDSs) capable of responding to specific conditions. These smart responsive NDDSs respond to specific conditions already established in the tumor microenvironment (TME) resulting in greater drug release following accumulation through enhanced permeation and retention (EPR) effect. Among various specific conditions, reactive oxygen species (ROS) and glutathione (GSH) have been extensively used to improve tumor targeting. While cells of the tumor microenvironment including immune cells, cancer-associated fibroblasts, endothelial cells and tumor invasive cells are responsible for the production and elevation of ROS levels, high levels of GSH inside tumor cells establish highly reducing environment, which in turn maintain cell survival. Abnormal ROS generation in the tumor microenvironment helps with designing highly specific ROS-sensitive NDDSs with the potential to release the payload next to the tumor cells. On the other hand, elevated levels of tumor GSH allows for designing NDDSs bearing reductively cleavable linkage to enhance drug release exploiting the dramatic higher intracellular GSH. The aim of the current review is to emphasize the requirements for developing various NDDSs including liposomes, polymeric nanoparticles, micelles, mesoporous silica nanoparticles, nanogels and prodrugs, capable of responding to TME using their Redox-sensitive moieties.

Endogenous stimuli-responsive linkers in nanoliposomal systems for cancer drug targeting.

There are various drug delivery systems (DDSs) among which nanoliposomal formulations are among the most prominent. Despite the superiority of nanoliposomal DDSs compared to conventional drug delivery methods, recent reports have claimed that they can deliver small amounts of the injected dose to target site by passive targeting. However, our understanding of tumor microenvironment features, including dysregulation of pH, the high intracellular concentration of glutathione, change in the amount and expression of some enzymes, reactive oxygen species, hypoxia, and ATP concentrations, has driven the scope of research into the use of these endogenous stimuli for a design of smart linkers. These linkers optimize the release of payloads in favorable target sites and avoid premature releasing in non-favorable off-target sites. In this review, we discuss particular linkers, which are able to respond to the specific endogenous conditions, and could be used in nanoliposomal DDSs, based on pathophysiological changes that occur in tumors. Furthermore, structural and chemical properties of these linkers and other potential linkers, which could be used in nanoliposomal DDSs, have been reviewed.

Electrochemical-based biosensors for detection of Mycobacterium tuberculosis and tuberculosis biomarkers.

Early detection of tuberculosis (TB) reduces the interval between infection and the beginning of treatment. However, commercially available tests cannot discriminate between BCG-vaccinated healthy persons and patients. Also, they are not suitable to be used for immunocompromised persons. In recent years, biosensors have attracted great attention due to their simple utility, accessibility, and real-time outputs. These sensors are increasingly being considered as pioneering tools for point-of-care diagnostics in communities with a high burden of TB and limited accessibility to reference laboratories. Among other types of biosensors, the electrochemical sensors have the advantages of low-cost operation, fast processing, simultaneous multi-analyte analyzing, operating with turbid samples, comparable sensitivity and readily available miniaturization. Electrochemical biosensors are sub-divided into several categories including: amperometric, impedimetric, potentiometric, and conductometric biosensors. The biorecognition element in electrochemical biosensors is usually based on antibodies (immunosensors), DNAs or PNAs (genosensors), and aptamers (aptasensors). In either case, whether an interaction of the antigen-antibody/aptamer or the hybridization of probe with target mycobacterial DNA is detected, a change in the electrical current occurs that is recorded and displayed as a plot. Therefore, impedimetric-based methods evaluate resistance to electron transfer toward an electrode by a Nyquist plot and amperometric/voltammetric-based methods weigh the electrical current by means of cyclic voltammetry, square wave voltammetry, and differential pulse voltammetry. Electrochemical biosensors provide a promising scope for the new era of diagnostics. As a consequence, they can improve detection of Mycobacterium tuberculosis traces even in attomolar scales.

Influenza A (H1N1) in Hamedan Province, Western Iran in 2009: A Case-Control Study.

BACKGROUND: The novel influenza A (H1N1) virus was first detected in March 2009 in Mexico and then disseminated to many other countries worldwide. In this study, we assessed the potential risk factors of swine flu as well as the most important clinical manifestations of this infectious disease among confirmed cases during early phase of pandemic H1N1. METHODS: Subjects (cases and controls) were selected from those patients with signs and symptoms of respiratory tract infection who referred to health centers of eight cities throughout Hamedan Province, western Iran form July to December 2009. Characteristics of the participants were obtained by interviewers using pre-determined questionnaire. Cases were distinguished by pharyngeal soap speci-mens positive for influenza A virus using polymerase chain reaction (PCR). Logistic regression model was conducted at 0.05 significance level using Stata 9.1 statistical software to assess the effects of various risk factors on H1N1 influenza infection. RESULTS: Totally, 245 confirmed cases of H1N1 influenza were compared with 388 controls. Case fatality rate of influenza infection was about 2.86%. In comparison with age group of 1-19 yr old, adjusted odds ratio estimates was 1.91 [95% CI: 1.06, 3.46] for age group of 20-39 yr old, 0.94 [0.37, 2.38] for age group of 40-59 yr old, and 0.34 [0.09, 1.37] for age group of 60-79 yr old. Adjusted odds ratio estimates of influenza A infection was 8.12 [95% CI: 3.11, 21.6] for pregnant women compared to non-pregnant women; 1.84 [95% CI: 1.32, 2.86] for high educated individuals in comparison with low educated individuals; 2.11 [95% CI: 1.25, 3.57] for whose who had close contact with suspected influenza patients; and 2.15 [95% CI: 1.16, 3.98] for individuals with normal body mass index (BMI= 25-30) compared with underweight individuals (BMI< 20). There were no significant differences in clinical manifestations between cases and controls. CONCLUSION: The risk of influenza A infection is highest among children and adolescents, pregnant women, high educated individuals, and those who had close contact with suspected influenza patients during pandemic phase. In addition, there is no pathogonomonic sign or symptom to distinguish influenza infection clinically from other kinds of respiratory track infections.