Using chitosan-coated magnetite nanoparticles as a drug carrier for opioid delivery against breast cancer.

Over the past decades, opium derivatives have been discovered as new anticancer agents. In our study, Fe3O4 superparamagnetic nanoparticles (SPIONs) decorated with chitosan were loaded with papaverine or noscapine to surmount drug delivery-related obstacles. Modifying the magnetic nanoparticles (MNP) surface with polymeric materials such as chitosan prevents oxidation and provides a site for drug linkage, which renders them a great drug carrier. The obtained systems were characterized by DLS (20-40 nm were achieved for MNPs and drug- loaded MNPs), TEM (spherical with average size of 11-20 nm) FTIR, XRD, and VSM (71.3 - 42.8 emu/g). Contrary to noscapine, papaverine-MNPs attenuated 4T1 murine breast cancer cell proliferation (11.50 ± 1.74 µg/mL) effectively compared to the free drug (62.35 ± 2.88 µg/mL) while sparing L-929 fibroblast cells (138.14 ± 4.38 µg/mL). Furthermore, SPION and SPION-chitosan displayed no cytotoxic activity. Colony-formation assay confirmed the long-term cytotoxicity of nanostructures. Both developed formulations promoted ROS production accompanied by late apoptotic cell death. The biocompatible nanoparticle exerted an augmenting effect to deliver papaverine to metastatic breast cancer cells.

Preparation of stable colloidal dispersion of surface modified Fe3O4 nanoparticles for magnetic heating applications.

The effect of surface modification on enhancing the magnetic heating behavior of magnetic nano fluids were investigated, for this purpose Fe3O4 nanoparticles were synthesized using co-precipitation method and surface modification was done using citric acid, ascorbic acid, tetraethyl orthosilicate (TEOS), polyvinyl alcohol (PVA) and polyethylene glycol (PEG). Experimental heating tests using AC magnetic field were done in the frequency of 100 kHz and different magnetic field (H) intensities. Theoretically the specific absorption rate (SAR) in magnetic nano fluids is independent of nanoparticles concentration but the experimental results showed different behavior. The theoretical SAR value @ H = 12kA.m-1 for Nano fluids containing bare Fe3O4 nanoparticles was 11.5 W/g but in experimental tests the obtained value was 9.72 W/g for nano fluid containing 20,000 ppm of dispersed nanoparticles. The experimental SAR calculation was repeated for sample containing 10,000 ppm of nanoparticles and the results showed increase in experimental SAR that is an evidence of nanoparticles agglomeration in higher concentrations. The surface modification has improved the dispersion ability of the nanoparticles. The Ratio of SAR, experimental, 20000ppm to SAR, experimental, 10000ppm was 0.85 for bare Fe3O4 nanoparticles dispersion but in case of surface modified nanoparticles this ratio has increased up to 0.98 that shows lower agglomeration of nanoparticles as a result of surface modification, although on the other hand the surface modification agents were magnetically passive and so it is expected that in constant concentration the SAR for bare Fe3O4 nanoparticles to be higher than this variable for surface modified nanoparticles. At lower concentrations the dispersions containing bare Fe3O4 nanoparticles showed higher SAR values but at higher concentrations the surface modified Fe3O4 nanoparticles showed better results although the active agent amount was lower at them. Finally, it should be noted that the nanoparticles that were surface modified using polymeric agents showed the highest decrease in experimental SAR amounts comparing theoretical results that was because of the large molecules of polymers comparing other implemented surface modification agents.

Evaluation of Thermal Properties of Ferromagnetic Core for Treatment of Solid Tumors by Electromagnetic Induction Hyperthermia.

Background: Electromagnetic induction hyperthermia is a promising method to treat the deep-seated tumors such as brain and prostatic tumors. This technique is performed using the induction of electromagnetic waves in the ferromagnetic cores implanted at the solid tumor. Objective: This study aims at determining the conditions of the optimal thermal distribution in the different frequencies before performing the in vitro cellular study. Material and Methods: In this experimental study, the i-Cu alloy (70.4-29.6; wt%) was prepared and characterized and then the parameters, affecting the amount of induction heating in the ferromagnetic core, were investigated. Self-regulating cores in 1, 3, 6, and 9 arrangements in the water phantom with a volume of 2 cm3 were used as a replacement for solid tumor. Results: Inductively Coupled Plasma (ICP) analysis and Energy Dispersive X-ray Spectroscopy (EDS) show the uniformity of the alloy after 4 times remeling by vacuum arc remelting furnace. The Vibrating Sample Magnetometer (VSM) shows that the Curie temperature (TC) of the ferromagnetic core is less than 50 °C. Temperature profile with a frequency of 100-400 kHz for 30 min, was extracted by infrared imaging camera, indicating the increase temperature in the range of 42 °C to 46 °C. Conclusion: The optimum conditions with used hyperthermia system are supplied in the frequency of 100 kHz, 200 kHz and 400 kHz with 6, 3 and 1 seeds, respectively. It is also possible to induce a temperature up to 50 °C by increasing the number of seeds at a constant frequency and power, or by increasing the applied frequency at a constant number of seeds.

Surface ID: a geometry-aware system for protein molecular surface comparison.

MOTIVATION: A protein can be represented in several forms, including its 1D sequence, 3D atom coordinates, and molecular surface. A protein surface contains rich structural and chemical features directly related to the protein's function such as its ability to interact with other molecules. While many methods have been developed for comparing the similarity of proteins using the sequence and structural representations, computational methods based on molecular surface representation are limited. RESULTS: Here, we describe "Surface ID," a geometric deep learning system for high-throughput surface comparison based on geometric and chemical features. Surface ID offers a novel grouping and alignment algorithm useful for clustering proteins by function, visualization, and in silico screening of potential binding partners to a target molecule. Our method demonstrates top performance in surface similarity assessment, indicating great potential for protein functional annotation, a major need in protein engineering and therapeutic design. AVAILABILITY AND IMPLEMENTATION: Source code for the Surface ID model, trained weights, and inference script are available at https://github.com/Sanofi-Public/LMR-SurfaceID.

DiSiR: fast and robust method to identify ligand-receptor interactions at subunit level from single-cell RNA-sequencing data.

Most cell-cell interactions and crosstalks are mediated by ligand-receptor interactions. The advent of single-cell RNA-sequencing (scRNA-seq) techniques has enabled characterizing tissue heterogeneity at single-cell level. In the past few years, several methods have been developed to study ligand-receptor interactions at cell type level using scRNA-seq data. However, there is still no easy way to query the activity of a specific user-defined signaling pathway in a targeted way or to map the interactions of the same subunit with different ligands as part of different receptor complexes. Here, we present DiSiR, a fast and easy-to-use permutation-based software framework to investigate how individual cells are interacting with each other by analyzing signaling pathways of multi-subunit ligand-activated receptors from scRNA-seq data, not only for available curated databases of ligand-receptor interactions, but also for interactions that are not listed in these databases. We show that, when utilized to infer ligand-receptor interactions from both simulated and real datasets, DiSiR outperforms other well-known permutation-based methods, e.g. CellPhoneDB and ICELLNET. Finally, to demonstrate DiSiR's utility in exploring data and generating biologically relevant hypotheses, we apply it to COVID lung and rheumatoid arthritis (RA) synovium scRNA-seq datasets and highlight potential differences between inflammatory pathways at cell type level for control versus disease samples.

An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFß blockade therapy.

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGFß activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGFß pathway activity. Analysis of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution patterns. The digital image analysis approach achieves 74% concordance with the pathologist assessment for tumor-immune phenotypes. The transcriptomic profiling suggests that the TIL score was negatively correlated with TGFß pathway activation, together with elevated TGFß signaling activity observed in excluded and desert tumor phenotypes. The present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes: immune desert, immune excluded or immune inflamed. The association between "cold" tumor-immune phenotypes and TGFß signature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGFß blockade.

AuNP-based biosensors for the diagnosis of pathogenic human coronaviruses: COVID-19 pandemic developments.

The outbreak rate of human coronaviruses (CoVs) especially highly pathogenic CoVs is increasing alarmingly. Early detection of these viruses allows treatment interventions to be provided more quickly to people at higher risk, as well as helping to identify asymptomatic carriers and isolate them as quickly as possible, thus preventing the disease transmission chain. The current diagnostic methods such as RT-PCR are not ideal due to high cost, low accuracy, low speed, and probability of false results. Therefore, a reliable and accurate method for the detection of CoVs in biofluids can become a front-line tool in order to deal with the spread of these deadly viruses. Currently, the nanomaterial-based sensing devices for detection of human coronaviruses from laboratory diagnosis to point-of-care (PoC) diagnosis are progressing rapidly. Gold nanoparticles (AuNPs) have revolutionized the field of biosensors because of the outstanding optical and electrochemical properties. In this review paper, a detailed overview of AuNP-based biosensing strategies with the varied transducers (electrochemical, optical, etc.) and also different biomarkers (protein antigens and nucleic acids) was presented for the detection of human coronaviruses including SARS-CoV-2, SARS-CoV-1, and MERS-CoV and lowly pathogenic CoVs. The present review highlights the newest trends in the SARS-CoV-2 nanobiosensors from the beginning of the COVID-19 epidemic until 2022. We hope that the presented examples in this review paper convince readers that AuNPs are a suitable platform for the designing of biosensors.

Benchmarking computational methods for B-cell receptor reconstruction from single-cell RNA-seq data.

Multiple methods have recently been developed to reconstruct full-length B-cell receptors (BCRs) from single-cell RNA sequencing (scRNA-seq) data. This need emerged from the expansion of scRNA-seq techniques, the increasing interest in antibody-based drug development and the importance of BCR repertoire changes in cancer and autoimmune disease progression. However, a comprehensive assessment of performance-influencing factors such as the sequencing depth, read length or number of somatic hypermutations (SHMs) as well as guidance regarding the choice of methodology is still lacking. In this work, we evaluated the ability of six available methods to reconstruct full-length BCRs using one simulated and three experimental SMART-seq datasets. In addition, we validated that the BCRs assembled in silico recognize their intended targets when expressed as monoclonal antibodies. We observed that methods such as BALDR, BASIC and BRACER showed the best overall performance across the tested datasets and conditions, whereas only BASIC demonstrated acceptable results on very short read libraries. Furthermore, the de novo assembly-based methods BRACER and BALDR were the most accurate in reconstructing BCRs harboring different degrees of SHMs in the variable domain, while TRUST4, MiXCR and BASIC were the fastest. Finally, we propose guidelines to select the best method based on the given data characteristics.

Graphite nanocrystals coated paper-based electrode for detection of SARS-Cov-2 gene using DNA-functionalized Au@carbon dot core-shell nanoparticles.

Currently, the development of biosensors is an urgent need due to the rapid spread of SARS-CoV-2 and the limitations of current standard methods for the diagnosis of COVID-19. Hence, many researchers have focused on the design of high-performance biosensors for measuring coronavirus genes. In this study, a voltammetric genosensor was developed for the determination of SARS-CoV-2 RdRP gene based on the format of cDNA probe/Au@CD core-shell NPs/graphite nanocrystals (GNCs)/paper electrode. For the first time, graphite nanocrystals were used in the electrochemical biosensor design. This genosensor was exposed to different concentrations of virus gene and then the hybridization between cDNA probe and RdRP gene was monitored by redox-active toluidine blue (TB). With increasing the RdRP concentration, the reduction peak current of TB enhanced in a linear range of 0.50 pM-12.00 nM according to the regression equation of I (µA) = 7.60 log CRdRP (pM) + 25.78. The repeatability with a RSD of 2.2% clearly exhibited that the response of modified electrode is stable because of the high adhesion of GNC layer on the paper substrate and the high stability of cDNA-Au@CD bioconjugates. The spike-and-recovery studies showed the acceptable recoveries for the sputum samples (>95%).

Magnetic graphene oxide-lignin nanobiocomposite: a novel, eco-friendly and stable nanostructure suitable for hyperthermia in cancer therapy.

In this research, a novel magnetic nanobiocomposite was designed and synthesized in a mild condition, and its potential in an alternating magnetic field was evaluated for hyperthermia applications. For this purpose, in the first step, graphene oxide was functionalized with a natural lignin polymer using epichlorohydrin as the cross-linking agent. In the second step, the designed magnetic graphene oxide-lignin nanobiocomposite was fabricated by the in situ preparation of magnetic Fe3O4 nanoparticles in the presence of graphene oxide functionalized with lignin. The resultant magnetic nanobiocomposite possessed certain main properties, including stability and homogeneity in aqueous solutions, making it suitable for hyperthermia applications. The chemical and structural properties of the synthesized magnetic graphene oxide-lignin composite were characterized using FT-IR, EDX, FE-SEM, TEM, TG and VSM analyses. The saturation magnetization value of this magnetic nanocomposite was recorded as 17.2 emu g-1. Further, the maximum specific absorption rate was determined to be 121.22 W g-1. Given these results, this newly fabricated magnetic nanobiocomposite may achieve considerable performance under the alternating magnetic field in fluid hyperthermia therapy.

Nanomaterials-based hyperthermia: A literature review from concept to applications in chemistry and biomedicine.

Hyperthermia, the mild elevation of temperature to 40-45 °C, can induce cancer cell death and enhance the effects of radiotherapy and chemotherapy. Due to the nature of hyperthermia, especially their ability to combine nanotechnology, hyperthermia possesses the potential to open a novel paradigm for the therapeutic strategies. However, achievement of its full potential as a clinically relevant treatment modality has been restricted by its inability to effectively and preferentially heat malignant cells. The main challenge of current hyperthermia treatment is to adequately heat whole volumes of deep-seated tumors without overheating surrounding healthy tissues. So, hyperthermia is under clinical trials (research study with people) and is not widely available. In this Review, we summarize a basic knowledge of hyperthermia before focusing on their applications to the cancer therapy and synthesis. We try to give a comprehensive view of the role of nanomaterials in the designing of hyperthermia-based therapeutic protocols and compare the studies in this field with the purpose of providing a source of helpful information for planning forthcoming hyperthermia researches. However, establishing comparisons between hyperthermia studies is a challenge due to the widely different conditions used by different authors, which, in some cases, is aggravated by the lack of crucial information concerning a certain aspect of the procedure.

Novel enzyme-based electrochemical and colorimetric biosensors for tetracycline monitoring in milk.

Recently, there has been a growing demand to develop portable devices for the fast detection of contaminants in food safety, healthcare, and environmental fields. Herein, two biosensing methods were designed by the use of nicotinamide adenine dinucleotide phosphate (NAD(P)H)-dependent TetX2 enzyme activity and thionine as an excellent electrochemical and colorimetric mediator/probe to monitor tetracycline (TC) in milk. The nanoporous glassy carbon electrode (NPGCE) modified with polythionine was first prepared by electrochemically and then TetX2 was immobilized onto the NPGCE using polyethyleneimine. The prepared biosensor provided a high electrocatalytic response toward NAD(P)H by significantly reducing its overpotential. The proposed biosensor exhibited a detection limit of 40 nM with a linear range of 0.1-0.8 µM for TC determination. Besides, the thionine probe was used to develop a novel colorimetric assay using a simple enzymatic color reaction within a few minutes. The limit of detection for TC was experimentally achieved as 60 nM, which was lower than the safety levels established by the World Health Organization (225 nM). The correlation between change in the color of the solution and the concentration of TC was used for quality control of milk samples, as confirmed by the standard high-performance liquid chromatography method. The results show the great potential of the proposed assays as portable instruments for on-site TC measurements.

Application of an integrated computational antibody engineering platform to design SARS-CoV-2 neutralizers.

As the COVID-19 pandemic continues to spread, hundreds of new initiatives including studies on existing medicines are running to fight the disease. To deliver a potentially immediate and lasting treatment to current and emerging SARS-CoV-2 variants, new collaborations and ways of sharing are required to create as many paths forward as possible. Here, we leverage our expertise in computational antibody engineering to rationally design/engineer three previously reported SARS-CoV neutralizing antibodies and share our proposal towards anti-SARS-CoV-2 biologics therapeutics. SARS-CoV neutralizing antibodies, m396, 80R and CR-3022 were chosen as templates due to their diversified epitopes and confirmed neutralization potency against SARS-CoV (but not SARS-CoV-2 except for CR3022). Structures of variable fragment (Fv) in complex with receptor binding domain (RBD) from SARS-CoV or SARS-CoV-2 were subjected to our established in silico antibody engineering platform to improve their binding affinity to SARS-CoV-2 and developability profiles. The selected top mutations were ensembled into a focused library for each antibody for further screening. In addition, we convert the selected binders with different epitopes into the trispecific format, aiming to increase potency and to prevent mutational escape. Lastly, to avoid antibody-induced virus activation or enhancement, we suggest application of NNAS and DQ mutations to the Fc region to eliminate effector functions and extend half-life.

Treatment of Breast Cancer-Bearing BALB/c Mice with Magnetic Hyperthermia using Dendrimer Functionalized Iron-Oxide Nanoparticles.

The development of novel nanoparticles for diagnostic and therapeutic applications has been one of the most crucial challenges in cancer theranostics for the last decades. Herein, we functionalized iron oxide nanoparticles (IONPs) with the fourth generation (G4) of poly amidoamine (PAMAM) dendrimers (G4@IONPs) for magnetic hyperthermia treatment of breast cancer in Bagg albino strain C (BALB/c)mice. The survival of breast cancer cells significantly decreased after incubation with G4@IONPs and exposure to an alternating magnetic field (AMF) due to apoptosis and elevation of Bax (Bcl-2 associated X)/Bcl-2(B-cell lymphoma 2) ratio. After intratumoral injection of G4@IONPs, tumor-bearing BALB/c mice were exposed to AMF for 20 min; this procedure was repeated three times every other day. After the last treatment, tumor size was measured every three days. Histopathological and Immunohistochemical studies were performed on the liver, lung, and tumor tissues in treated and control mice. The results did not show any metastatic cells in the liver and lung tissues in the treatment group, while the control mice tissues contained metastatic breast cancer cells. Furthermore, the findings of the present study showed that magnetic hyperthermia treatment inhibited tumor growth by increasing cancer cell apoptosis, as well as reducing the tumor angiogenesis.

Preparation and Evaluation of Doxorubicin-Loaded PLA-PEG-FA Copolymer Containing Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for Cancer Treatment: Combination Therapy with Hyperthermia and Chemotherapy.

BACKGROUND: Among the novel cancer treatment strategies, combination therapy is a cornerstone of cancer therapy. MATERIALS AND METHODS: Here, combination therapy with targeted polymer, magnetic hyperthermia and chemotherapy was presented as an effective therapeutic technique. The DOX-loaded PLA-PEG-FA magnetic nanoparticles (nanocarrier) were prepared via a double emulsion method. The nanocarriers were characterized by particle size, zeta potential, morphology, saturation magnetizations and heat generation capacity, and the encapsulation efficiency, drug content and in-vitro drug release for various weight ratios of PLA:DOX. Then, cytotoxicity, cellular uptake and apoptosis level of nanocarrier-treated cells for HeLa and CT26 cells were investigated by MTT assay, flow cytometry, and apoptosis detection kit. RESULTS AND CONCLUSIONS: The synthesized nanoparticles were spherical in shape, had low aggregation and considerable magnetic properties. Meanwhile, the drug content and encapsulation efficiency of nanoparticles can be achieved by varying the weight ratios of PLA:DOX. The saturation magnetizations of nanocarriers in the maximum applied magnetic field were 59/447 emu/g and 28/224 emu/g, respectively. Heat generation capacity of MNPs and nanocarriers were evaluated in the external AC magnetic field by a hyperthermia device. The highest temperature, 44.2°C, was measured in the nanocarriers suspension at w/w ratio 10:1 (polymer:DOX weight ratio) after exposed to the magnetic field for 60 minutes. The encapsulation efficiency improved with increasing polymer concentration, since the highest DOX encapsulation efficiency was related to the nanocarriers' suspension at w/w ratio 50:1 (79.6 ± 6.4%). However, the highest DOX loading efficiency was measured in the nanocarriers' suspension at w/w ratio 10:1 (5.14 ± 0.6%). The uptake efficiency and apoptosis level of nanocarrier-treated cells were higher than those of nanocarriers (folic acid free) and free DOX-treated cells in both cell lines. Therefore, this targeted nanocarrier may offer a promising nanosystem for cancer-combined chemotherapy and hyperthermia.

A novel electrochemical immunosensor for ultrasensitive detection of CA125 in ovarian cancer.

In the current study, we report on the design and development of a novel electrochemical immunosensor for the detection of cancer antigen 125 (CA125) oncomarker. Polyamidoamine/gold nanoparticles (PAMAM/AuNPs) were used to increase the conductivity and enhance the number of antibodies (Abs) immobilized on the electrode surface. Three-dimensional reduced graphene oxide-multiwall carbon nanotubes (3DrGO-MWCNTs) were used to modify the glassy carbon electrode to improve the electrode conductivity and specific surface area. Ab and toluidine blue attached to O-succinyl-chitosan-magnetic nanoparticles (Suc-CS@MNPs) as a tracer. The poor solubility of chitosan (CS) was improved by succinic anhydride using a novel modification method. Under optimum condition, the developed immunosensor exhibited a wide linear range (0.0005-75 U/mL) and an excellent limit of detection around 6 µU/mL. The reliability of the engineered immunosensor in detecting CA125 was verified by standard addition recovery method, which was further compared to enzyme-linked immunosorbent assay (ELISA). The proposed immunosensor exhibited excellent stability, high selectivity and sensitivity, and good reproducibility. Based on the great performance of the engineered immunosensor, it is proposed as a robust and reliable diagnostic tool for the detection of CA125 in the clinic.

Photothermal enhancement in sensitivity of lateral flow assays for detection of E-coli O157:H7.

Lateral flow immunoassay (LFA) is a well-known point-of-care technology for the detection of various analytes. However, low sensitivity and lack of quantitative results are some of its critical drawbacks. Here we report a photothermal enhanced lateral flow sensor on the basis of the photothermal properties of reduced graphene oxide (rGO) for the detection of E-coli O157:H7 as a model pathogen. The calibration curve of the photothermal method exhibited a linear range from 5 × 105 to 5 × 107 CFU/ml with a correlation coefficient of R2 = 0.96 and a regression equation of y = 8.1x-43 for standard bacteria solutions in phosphate buffer. The limit of detection was ∼5 × 105 CFU/ml for standard bacteria solutions, which was a 10-fold enhancement in sensitivity compared to the qualitative results. Specificity experiments showed that the photothermal method can only detect the target bacteria among 6 types of bacteria strains. It was confirmed that the developed technique could be a highly potential method for the rapid detection field because it can provide fast quantitative results with improved sensitivity.

Comparing the efficacy of ondansetron and granisetron augmentation in treatment-resistant obsessive-compulsive disorder: a randomized double-blind placebo-controlled study.

This study aimed to assess the efficacy and tolerability of ondansetron vs. granisetron in patients with treatment-resistant obsessive-compulsive disorder. A randomized clinical trial conducted on 135 patients with a Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of obsessive-compulsive disorder, who were treatment-resistant and receiving stable treatment with selective serotonin reuptake inhibitors and antipsychotic, received 14 weeks (phase I, intervention period) of placebo (n = 45), ondansetron (n = 45, 4 mg), and granisetron (n = 45, 2 mg) daily augmentations. Patients were rated every 2 weeks using the Yale-Brown Obsessive Compulsive Scale. Upon completion of intervention course, patients were followed for 4 weeks (phase II, discontinuation period). The collected data were analyzed in SPSS Version 22, with χ test; Fisher's exact test and independent t-test, according to the intention-to-treat principle. Two-factor repeated measure analysis of variance was used to compare score changes over phases. P < 0.05 was considered to be statistically significant. At week 14, reduction in Yale-Brown Obsessive Compulsive Scale scores in ondansetron, granisetron and placebo groups was 41.5%, 39.7% and 15.2%, respectively (P = 0.001). Complete response in the ondansetron group was significantly higher than in the granisetron group ((P = 0.041), risk ratio (95% confidence interval) = 2.33 (1.18-3.045)]. Relapse occurred by three (7.31%) patients in the granisetron group, whereas it was not seen in the ondansetron group [P < 0.001, risk ratio (95% confidence interval) = 2.81 (1.016-4.51)]. The results of this present study confirm the benefit of using ondansetron and granisetron as augmenting agents in treatment-resistant obsessive-compulsive disorder. Our results supported the potential superiority of ondansetron compared to granisetron. This needs to be confirmed in further placebo-controlled augmentation studies. RANDOMIZED CONTROLLED TRIAL CLINICAL TRIAL REGISTRATION NUMBER:: IRCT20130726014170N2.

A novel electrochemical biosensor based on TetX2 monooxygenase immobilized on a nano-porous glassy carbon electrode for tetracycline residue detection.

Different carbon-based nanostructures were used to investigate direct electron transfer (DET) of TetX2 monooxygenase (TetX2), and an enzyme-based biosensor for sensitive determination of tetracycline (TC) also fabricated. A polyethyleneimine (PEI) with positive charge groups was used for immobilization of TetX2 on modified glassy carbon electrodes. Cyclic voltammetry (CV) was employed to study the electrochemical characteristics of the immobilized enzyme and the performance of the proposed biosensor. Amongst multiple carbon-modified electrodes, nano-porous glassy carbon electrode (NPGCE) was selected because of its amplified signal response for flavin adenine dinucleotide (FAD) and superior electrocatalytic behavior toward oxygen reduction. The cyclic voltammogram of PEI/TetX2/NPGCE showed two couple of well-defined and quasi-reversible redox peaks of FAD, consistent with the realization of DET. The prepared electrode was then successfully introduced as a biosensing interface based on the oxygen reduction peak current, resulting in a linear range response from 0.5 to 5 µM with a good detection limit of 18 nM. The as-fabricated electrode demonstrates a fast response and excellent stability for the detection of TC. The results indicate that this simple, rapid, eco-friendly and economic strategy of PEI/TetX2/NPGCE preparation has potential for the fabrication of an enzyme-based biosensor for the practical detection of TC in food products.

Functionalized reduced graphene oxide as a lateral flow immuneassay label for one-step detection of Escherichia coli O157:H7.

In this study, graphene oxide (GO) and reduced graphene oxide (rGO) were used as visual labels in a lateral flow assay for detection of E. coli O157:H7. The color intensity was employed for the quantitative measurements of the target bacteria. Quantitative results showed that in comparison to GO, rGO can provide higher color intensity owing to enhanced light absorption following chemical reduction. Our results confirm that the visual limit of detection of the target bacteria by rGO is ∼105 colony forming unit per milliliter (CFU/ml), which closely compares with current alternative techniques using gold nanoparticles. The performance and practicability of the rGO-based test strips for detection of the target bacteria in milk and drinking water were validated with conventional plating and colony counting techniques. Results suggest that the proposed lateral flow assay is sensitive, specific, and affordable. It has also the potential to become a widely used detection technique for E. coli O157:H7 and a wide variety of other analytes.