Search results for: granulosa cell tumor

Authors: Mahdi Rahimi, Mohammad Mahdi Mojahedian, Mohammad Reza Aref

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In this paper, a cellular communication scenario with a transmitter and an authorized user is considered to analyze its secrecy in the face of eavesdroppers and the interferences propagated unintentionally through the communication network. It is also assumed that some D2D pairs and eavesdroppers are randomly located in the cell. Assuming hardware impairment, perfect connection probability is analytically calculated, and upper bound is provided for the secrecy outage probability. In addition, a method based on random activation of D2Ds is proposed to improve network security. Finally, the analytical results are verified by simulations.

Keywords: physical layer security, stochastic geometry, device-to-device, hardware impairment

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Authors: Rodrigo Fernandes da Silva, Daniela Maira Cardozo, Paulo Cesar Martins Alves, Sophie Françoise Derchain, Fernando Guimarães

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T-reg lymphocytes are important for the control of peripheral tolerance. They control the adaptive immune system and prevent autoimmunity through its suppressive action on CD4+ and CD8+ lymphocytes. The suppressive action also includes B lymphocytes, dendritic cells, monocytes/macrophages and recently, studies have shown that T-reg are also able to inhibit NK cells, therefore they exert their control of the immune response from innate to adaptive response. Most tumors express self-ligands, therefore it is believed that T-reg cells induce tolerance of the immune system, hindering the development of successful immunotherapies. T-reg cells have been linked to the suppression mechanisms of the immune response against tumors, including ovarian cancer. The goal of this study was to disclose the sub-population of the expanded CD3+ lymphocytes reported by previous studies, using the long-term culture model designed by Carlens et al 2001, to generate effector cell suspensions enriched with cytotoxic CD3-CD56+ NK cells, from PBMC of ovarian neoplasia patients. Methods and Results: Blood was collected from 12 patients with ovarian neoplasia after signed consent: 7 benign (Bng) and 5 malignant (Mlg). Mononuclear cells were separated by Ficoll-Paque gradient. Long-term culture was conducted by a 21 day culturing process with SCGM CellGro medium supplemented with anti-CD3 (10ng/ml, first 5 days), IL-2 (1000UI/ml) and FBS (10%). After 21 days of expansion, there was an increase in the population of CD3+ lymphocytes in the benign and malignant group. Within CD3+ population, there was a significant decrease in the population of CD4+ lymphocytes in the benign (median Bgn D-0=73.68%, D-21=21.05%) (p<0.05) and malignant (median Mlg D-0=64.00%, D-21=11.97%) (p < 0.01) group. Inversely, after 21 days of expansion, there was an increase in the population of CD8+ lymphocytes within the CD3+ population in the benign (median Bgn D-0=16.80%, D-21=38.56%) and malignant (median Mlg D-0=27.12%, D-21=72.58%) group. However, this increase was only significant on the malignant group (p<0.01). Within the CD3+CD4+ population, there was a significant increase (p < 0.05) in the population of T-reg lymphocytes in the benign (median Bgn D-0=9.84%, D-21=39.47%) and malignant (median Mlg D-0=3.56%, D-21=16.18%) group. Statistical analysis inter groups was performed by Kruskal-Wallis test and intra groups by Mann Whitney test. Conclusion: The CD4+ and CD8+ sub-population of CD3+ lymphocytes shifts with the culturing process. This might be due to the process of the immune system to produce a cytotoxic response. At the same time, T-reg lymphocytes increased within the CD4+ population, suggesting a modulation of the immune response towards cells of the immune system. The expansion of the T-reg population can hinder an immune response against cancer. Therefore, an immunotherapy using this expansion procedure should aim to halt the expansion of T-reg or its immunosuppresion capability.

Keywords: regulatory T cells, CD8+ T cells, CD4+ T cells, NK cell expansion

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Authors: D. ChobfroushKhoei, S. K. Heidari , Sh. Dariadel

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Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.

Keywords: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation

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Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Shalini Menon, K. Girish Kumar

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Norepinephrine (NE) is one of the naturally occurring catecholamines which act both as a neurotransmitter and a hormone. Catecholamine levels are used for the diagnosis and regulation of phaeochromocytoma, a neuroendocrine tumor of the adrenal medulla. The development of simple, rapid and cost-effective sensors for NE still remains a great challenge. Herein, a dual-channel sensor has been developed for the determination of NE. A mixture of AgNO₃, NaOH, NH₃.H₂O and cetrimonium bromide in appropriate concentrations was taken as the working solution. To the thoroughly vortexed mixture, an appropriate volume of NE solution was added. After a particular time, the fluorescence and absorbance were measured. Fluorescence measurements were made by exciting at a wavelength of 400 nm. A dual-channel optical sensor has been developed for the colorimetric as well as the fluorimetric determination of NE. Metal enhanced fluorescence property of nanoparticles forms the basis of the fluorimetric detection of this assay, whereas the appearance of brown color in the presence of NE leads to colorimetric detection. Wide linear ranges and sub-micromolar detection limits were obtained using both the techniques. Moreover, the colorimetric approach was applied for the determination of NE in synthetic blood serum and the results obtained were compared with the classic high-performance liquid chromatography (HPLC) method. Recoveries between 97% and 104% were obtained using the proposed method. Based on five replicate measurements, relative standard deviation (RSD) for NE determination in the examined synthetic blood serum was found to be 2.3%. This indicates the reliability of the proposed sensor for real sample analysis.

Keywords: norepinephrine, colorimetry, fluorescence, silver nanoparticles

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Authors: Yasser Mahmoudi, Nader Karimi

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The present work examines analytically the effect internal heat generation on temperature fields in a channel partially-filled with a porous under local thermal non-equilibrium condition. The Darcy-Brinkman model is used to represent the fluid transport through the porous material. Two fundamental models (models A and B) represent the thermal boundary conditions at the interface between the porous medium and the clear region. The governing equations of the problem are manipulated, and for each interface model, exact solutions for the solid and fluid temperature fields are developed. These solutions incorporate the porous material thickness, Biot number, fluid to solid thermal conductivity ratio Darcy number, as the non-dimensional energy terms in fluid and solid as parameters. Results show that considering any of the two models and under zero or negative heat generation (heat sink) and for any Darcy number, an increase in the porous thickness increases the amount of heat flux transferred to the porous region. The obtained results are applicable to the analysis of complex porous media incorporating internal heat generation, such as heat transfer enhancement (THE), tumor ablation in biological tissues and porous radiant burners (PRBs).

Keywords: porous media, local thermal non-equilibrium, forced convection, heat transfer, exact solution, internal heat generation

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Authors: Elena Maria Scalisi

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The increasing production and the use of TiO₂ nanoparticles (NPs) have inevitably led to their release into the environment, thereby posing a threat to organisms and also for human. Human exposure to TiO₂-NPs may occur during both manufacturing and use. TiO₂-NPs are common in consumer products for dermal application, toothpaste, food colorants, and nutritional supplements, then oral exposure may occur during use of such products. Into the body, TiO₂-NPs thanks to their small size (<100 nm), can, through testicular blood barrier inducing effect on testis and then on male reproductive health. The nanoscale size of TiO₂ increase the surface-to-volume ratio making them more reactive in a cell, then TiO₂ NPs increase their ability to produce reactive oxygen species (ROS). In male germ cells, ROS may have important implications in maintaining the normal functions of mature spermatozoa at physiological levels, moreover, in spermatozoa they are important signaling molecules for their hyperactivation and acrosome reaction. Nevertheless, an excess of ROS by external inputs such as NPs can increased the oxidative stress (OS), which results in damage DNA and apoptosis. The aim of our study has been investigate the impact of TiO₂ NPs on human spermatozoa, evaluating DNA damage and the expression of proteins involved in cell stress. According WHO guidelines 2021, we have exposed human spermatozoa in vitro to TiO₂ NP at concentrations 50 ppm, 100 ppm, 250 ppm, and 500 ppm for 1 hour (at 37°C and CO₂ at 5%). DNA damage was evaluated by Sperm Chromatin Dispersion Test (SCD) and TUNEL assay; moreover, we have evaluated the expression of biomarkers of oxidative stress like Heat Shock Protein 70 (HSP70) and Metallothioneins (MTs). Also, sperm parameters as motility viability have been evaluated. Our results not report a significant reduction in motility of spermatozoa at the end of the exposure. On the contrary, the progressive motility was increased at the highest concentration (500 ppm) and was statistically significant compared to control (p <0.05). Also, viability was not changed by exposure to TiO₂-NPs (p <0.05). However, increased DNA damage was observed at all concentrations, and the TUNEL assay highlighted the presence of single strand breaks in the DNA. The spermatozoa responded to the presence of TiO₂-NPs with the expression of Hsp70, which have a protective function because they allow the maintenance of cellular homeostasis in stressful/ lethal conditions. A positivity for MTs was observed mainly for the concentration of 4 mg/L. Although the biological and physiological function of the metallothionein (MTs) in the male genital organs is unclear, our results highlighted that the MTs expressed by spermatozoa maintain their biological role of detoxification from metals. Our results can give additional information to the data in the literature on the toxicity of TiO₂-NPs and reproduction.

Keywords: human spermatozoa, DNA damage, TiO₂-NPs, biomarkers

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Authors: Emílie Kučerová, Tereza Veverková, Marina Morozovová, Eva Kudová, Jitka Viktorová

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The blood-brain barrier (BBB) is a key element regulating the transport of substances between the blood and the central nervous system (CNS). The BBB protects the CNS from potentially harmful substances and maintains a suitable environment for nervous activity in the CNS, but at the same time, it represents a significant obstacle to the entry of drugs into the CNS. Pharmacoresistant epilepsy is a form of epilepsy that cannot be suppressed using two (or more) appropriately chosen antiepileptic drugs. In many cases, pharmacoresistant epilepsy is characterized by an increased concentration of efflux pumps on the luminal sides of the endothelial cells that form the BBB and an increased number of drug-metabolizing enzymes in the BBB cells, thereby preventing the effective transport of antiepileptic drugs into the CNS. Currently, a number of scientific groups are focusing on the preparation and improvement of BBB models in vitro in order to study cell interactions or transport mechanisms. However, in pathological conditions such as pharmacoresistant epilepsy, there are changes in BBB structure, and current BBB models are insufficient for related research. Our goal is to develop a suitable BBB model for pharmacoresistant epilepsy in vitro and use it to test the transfer of potential antiepileptic drugs. This model is created by co-culturing immortalized human cerebral microvascular endothelial cells, human vascular pericytes and immortalized human astrocytes. The BBB in vitro is cultivated in the form of a 2D transwell model and the integrity of the barrier is verified by measuring transendothelial electrical resistance (TEER). From the current results, a contact cell arrangement with the cultivation of endothelial cells on the upper side of the insert and the co-cultivation of astrocytes and pericytes on the lower side of the insert is selected as the most promising for BBB model cultivation. The pharmacoresistance of the BBB model is achieved by long-term cultivation of endothelial cells in an increasing concentration of selected antiepileptic drugs, which should lead to increased production of efflux pumps and drug-metabolizing enzymes. The pharmacoresistant BBB model in vitro will be further used for the screening of substances that could act both as antiepileptics and at the same time as inhibitors of efflux pumps in endothelial cells. This project was supported by the Technology Agency of the Czech Republic (TACR), Personalized Medicine: Translational research towards biomedical applications, No. TN02000109 and by the Academy of Sciences of the Czech Republic (AS CR) – grant RVO 61388963.

Keywords: antiepileptic drugs, blood-brain barrier, efflux transporters, pharmacoresistance

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Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

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Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

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Authors: Young-Su Ryu, Su-Hyun Jung, Myoung-Jin Kim, Hyoung-Kyu Song

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In this paper, improved performance scheme for joint transmission is proposed in downlink (DL) coordinated multi-point(CoMP) in case of constraint transmission power. This scheme is that serving transmission point (TP) request a joint transmission to inter-TP and selects one pre-coding technique according to channel state information(CSI) from user equipment(UE). The simulation results show that the bit error rate(BER) and throughput performances of the proposed scheme provide high spectral efficiency and reliable data at the cell edge.

Keywords: CoMP, joint transmission, minimum mean square error, zero-forcing, zero-forcing dirty paper coding

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Authors: Pallab Datta, Jyotirmoy Chatterjee, Santanu Dhara

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Over the past few years, phosphorous containing polymers have received widespread attention for applications such as high performance optical fibers, flame retardant materials, drug delivery and tissue engineering. Being pentavalent, phosphorous can exist in different chemical environments in these polymers which increase their versatility. In human biochemistry, phosphorous based compounds exert their functions both in soluble and insoluble form occurring as inorganic or as organophosphorous compounds. Specifically in case of biomacromolecules, phosphates are critical for functions of DNA, ATP, phosphoproteins, phospholipids, phosphoglycans and several coenzymes. Inspired by the role of phosphorous in functional biomacromolecules, design and synthesis of biomimetic materials are thus carried out by several authors to study macromolecular function or as substitutes in clinical tissue regeneration conditions. In addition, many regulatory signals of the body are controlled by phoshphorylation of key proteins present either in form of growth factors or matrix-bound scaffold proteins. This inspires works on synthesis of phospho-peptidomimetic amino acids for understanding key signaling pathways and this is extended to obtain molecules with potentially useful biological properties. Apart from above applications, phosphate groups bound to polymer backbones have also been demonstrated to improve function of osteoblast cells and augment performance of bone grafts. Despite the advantages of phosphate grafting, however, there is limited understanding on effect of degree of phosphorylation on macromolecular physicochemical and/or biological properties. Such investigations are necessary to effectively translate knowledge of macromolecular biochemistry into relevant clinical products since they directly influence processability of these polymers into suitable scaffold structures and control subsequent biological response. Amongst various techniques for fabrication of biomimetic scaffolds, nanofibrous scaffolds fabricated by electrospinning technique offer some special advantages in resembling the attributes of natural extracellular matrix. Understanding changes in physico-chemical properties of polymers as function of phosphorylation is therefore going to be crucial in development of nanofiber scaffolds based on phosphorylated polymers. The aim of the present work is to investigate the effect of phosphorous grafting on the electrospinning behavior of polymers with aim to obtain biomaterials for bone regeneration applications. For this purpose, phosphorylated derivatives of two polymers of widely different electrospinning behaviors were selected as starting materials. Poly(vinyl alcohol) is a conveniently electrospinnable polymer at different conditions and concentrations. On the other hand, electrospinning of chitosan backbone based polymers have been viewed as a critical challenge. The phosphorylated derivatives of these polymers were synthesized, characterized and electrospinning behavior of various solutions containing these derivatives was compared with electrospinning of pure poly (vinyl alcohol). In PVA, phosphorylation adversely impacted electrospinnability while in NMPC, higher phosphate content widened concentration range for nanofiber formation. Culture of MG-63 cells on electrospun nanofibers, revealed that degree of phosphate modification of a polymer significantly improves cell adhesion or osteoblast function of cultured cells. It is concluded that improvement of cell response parameters of nanofiber scaffolds can be attained as a function of controlled degree of phosphate grafting in polymeric biomaterials with implications for bone tissue engineering applications.

Keywords: bone regeneration, chitosan, electrospinning, phosphorylation

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Authors: Achiron Anat, Mathilda Mandel, Mayust Sue, Achiron Reuven, Gurevich Michael

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Introduction: As coronavirus disease 2019 (COVID-19) vaccination is currently spreading around the world, it is of importance to assess the ability of multiple sclerosis (MS) patients to mount an appropriate immune response to the vaccine in the context of disease-modifying treatments (DMT’s). Objectives: Evaluate immunity generated following COVID-19 vaccination in MS patients, and assess factors contributing to protective humoral and cellular immune responses in MS patients vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus infection. Methods: Review our recent data related to (1) the safety of PfizerBNT162b2 COVID-19 mRNA vaccine in adult MS patients; (2) the humoral post-vaccination SARS-CoV2 IgG response in MS vaccinees using anti-spike protein-based serology; and (3) the cellular immune response of memory B-cells specific for SARS-CoV-2 receptor-binding domain (RBD) and memory T-cells secreting IFN-g and/or IL-2 in response to SARS-CoV2 peptides using ELISpot/Fluorospot assays in MS patients either untreated or under treatment with fingolimod, cladribine, or ocrelizumab; (4) covariate parameters related to mounting protective immune responses. Results: COVID-19 vaccine proved safe in MS patients, and the adverse event profile was mainly characterised by pain at the injection site, fatigue, and headache. Not any increased risk of relapse activity was noted and the rate of patients with acute relapse was comparable to the relapse rate in non-vaccinated patients during the corresponding follow-up period. A mild increase in the rate of adverse events was noted in younger MS patients, among patients with lower disability, and in patients treated with DMTs. Following COVID-19 vaccination protective humoral immune response was significantly decreased in fingolimod- and ocrelizumab- treated MS patients. SARS-CoV2 specific B-cell and T-cell cellular responses were respectively decreased. Untreated MS patients and patients treated with cladribine demonstrated protective humoral and cellular immune responses, similar to healthy vaccinated subjects. Conclusions: COVID-19 BNT162b2 vaccine proved as safe for MS patients. No increased risk of relapse activity was noted post-vaccination. Although COVID-19 vaccination is new, accumulated data demonstrate differences in immune responses under various DMT’s. This knowledge can help to construct appropriate COVID-19 vaccine guidelines to ensure proper immune responses for MS patients.

Keywords: covid-19, vaccination, multiple sclerosis, IgG

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Authors: Christopher Hardly Joseph, Nicola Pelagalli, Davide Mencarelli, Luca Pierantoni

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In this contribution, we report the electromagnetic response of a split ring resonator (SRR) based magnetic metamaterial unit cell in free space nature by means of a full-wave electromagnetic simulation. The effective parameters of these designed structures have been analyzed. The structures have been specifically designed to work at high frequency considering the development of many microwave and lower mm-wave devices. In addition to that, the application of the designed metamaterial structures is also proposed, namely metamaterial loaded planar transmission lines, potentially useful to optimize size and quality factor of circuit components and radiating elements.

Keywords: CPW, Microwave Components, Negative Permeability, Split Ring Resonator (SRR)

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Authors: Sarah Fahad Alajmi, Tamer Ezzat Youssef

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Here, we report a simple method for the direct conversion of 6-Nitro-1H-indole into N-substituted indoles via electrochemical dehydrogenative reaction with halogenated reagents under strongly basic conditions through N–R bond formation. The N-protected indoles have been prepared under moderate and scalable electrolytic conditions. The conduct of the reactions was performed in a simple divided cell under constant current without oxidizing reagents or transition-metal catalysts. The synthesized products have been characterized via UV/Vis spectrophotometry, 1H-NMR, and FTIR spectroscopy. A possible reaction mechanism is discussed based on the N-protective products. This methodology could be applied to the synthesis of various biologically active N-substituted indole derivatives.

Keywords: green chemistry, 1H-indole, heteroaromatic, organic electrosynthesis

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Authors: Sukrat Sinha, Abhay Kumar, Shanthy Sundaram

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The Leishmania homologue of activated C kinase (LACK) is known T cell epitope from soluble Leishmania antigens (SLA) that confers protection against Leishmania challenge. This antigen has been found to be highly conserved among Leishmania strains. LACK has been shown to be protective against L. donovani challenge. A comprehensive analysis of several LACK sequences was completed. The analysis shows a high level of conservation, lower variability and higher antigenicity in specific portions of the LACK protein. This information provides insights for the potential consideration of LACK as a putative candidate in the context of visceral Leishmaniasis vaccine target.

Keywords: bioinformatics, genome assembly, leishmania activated protein kinase c (lack), next-generation sequencing

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Authors: Janis Zarins, Kristaps Blums, Oskars Radzins, Renars Deksnis, Atis Svare, Santa Salaka

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Wide tumor resection remains the first choice method for tumors of the oral cavity. Nevertheless, remained tissue defect impacts patients functional and aesthetical outcome, which could be improved using microvascular tissue transfers. Mandibular reconstruction is challenging due to the complexity of composite tissue defects and occlusal relationships for normal eating, chewing, and pain free jaw motions. Individual 3-D virtual planning would provide better symmetry and functional outcome. The main goal of preoperative planning is to develop a customized surgical approach with patient specific cutting guides of the mandible, osteotomy guides of the fibula, pre-bended osteosynthesis plates to perform more precise reconstruction, to decrease the surgery time and reach the best outcome. Our study is based on the analysis of 32 patients operated on between 2019 to 2021. All patients underwent mandible reconstruction with vascularized fibula flaps. Patients characteristics, surgery profile, survival, functional outcome, and quality of life was evaluated. Preoperative planning provided a significant decrease of surgery time and the best arrangement of bone closely similar as before the surgery. In cases of bone asymmetry, deformity and malposition, a new mandible was created using 3D planning to restore the appearance of lower jaw anatomy and functionality.

Keywords: mandibular, 3D planning, cutting guides, fibula flap, reconstruction

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Authors: Jos Olijve

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Introduction and Purpose: Endotoxins are found in the outer membrane of gram-negative bacteria and have profound in vitro and in vivo responses. They can trigger strong immune responses and negatively affect various cellar activities particular cells expressing toll-like receptors. They are therefore unwanted contaminants of biomaterials sourced from natural raw materials, and their activity must be as low as possible. Collagen and gelatin are natural extracellular matrix components and have, due to their low allergenic potential, suitable biological properties, and tunable physical characteristics, high potential in biomedical applications. The purpose of this study was to determine the influence of autoclave sterilization of gelatin on physical properties and endotoxin level compared to surfactant purified gelatin. Methods: Type A gelatin from Sigma-Aldrich (G1890) with endotoxin level of 35000 endotoxin units (EU) per gram gelatin and type A gelatins from Rousselot Gent with endotoxin activity of 30000 EU per gram were used. A 10 w/w% G1890 gelatin solution was autoclave sterilized during 30 minutes at 121°C and 1 bar over pressure. The physical properties and the endotoxin level of the sterilized G1890 gelatin were compared to a type A gelatin from Rousselot purified with Triton X100 surfactant. The Triton X100 was added to a concentration of 0.5 w/w% which is above the critical micellar concentration. The gelatin surfactant mixtures were kept for 30-45 minutes under constant stirring at 55-60°C. The Triton X100 was removed by active carbon filtration. The endotoxin levels of the gelatins were measured using the Endozyme recombinant factor C method from Hyglos GmbH (Germany). Results and Discussion: Autoclave sterilization significantly affect the physical properties of gelatin. Molecular weight of G1890 decreased from 140 to 50kDa, and gel strength decreased from 300 to 40g. The endotoxin level of the gelatin reduced after sterilization from 35000 EU/g to levels of 400-500 EU/g. These endotoxin levels are however still far above the upper endotoxin level of 0.05 EU/ml, which resembles 5 EU/g gelatin based on a 1% gelatin solution, to avoid cell proliferation alteration. Molecular weight and gel strength of Rousselot gelatin was not altered after Triton X100 purification and remained 150kDa and 300g respectively. The endotoxin levels of Triton X100 purified Rousselot gelatin was < 5EU/g gelatin. Conclusion: Autoclave sterilization of gelatin is, in comparison to Triton X100 purification, not efficient to inactivate endotoxin levels in gelatin to levels below the upper limit to avoid cell proliferation alteration. Autoclave sterilization gave a significant decrease in molecular weight and gel strength which makes autoclave sterilized gelatin, in comparison to Triton X100 purified gelatin, not suitable for 3D printing.

Keywords: endotoxin, gelatin, molecular weight, sterilization, Triton X100

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Authors: Zerrin Orbak, Busra Demir

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Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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Authors: Ke-Jing Lee, Cheng-Jung Lee, Yu-Chi Chang, Li-Wen Wang, Yeong-Her Wang

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To avoid the cross-talk issue of only resistive random access memory (RRAM) cell, one transistor and one resistor (1T1R) architecture with a TiO₂-based RRAM cell connected with solution barium zirconate nickelate (BZN) organic thin film transistor (OTFT) device is successfully demonstrated. The OTFT were fabricated on a glass substrate. Aluminum (Al) as the gate electrode was deposited via a radio-frequency (RF) magnetron sputtering system. The barium acetate, zirconium n-propoxide, and nickel II acetylacetone were synthesized by using the sol-gel method. After the BZN solution was completely prepared using the sol-gel process, it was spin-coated onto the Al/glass substrate as the gate dielectric. The BZN layer was baked at 100 °C for 10 minutes under ambient air conditions. The pentacene thin film was thermally evaporated on the BZN layer at a deposition rate of 0.08 to 0.15 nm/s. Finally, gold (Au) electrode was deposited using an RF magnetron sputtering system and defined through shadow masks as both the source and drain. The channel length and width of the transistors were 150 and 1500 μm, respectively. As for the manufacture of 1T1R configuration, the RRAM device was fabricated directly on drain electrodes of TFT device. A simple metal/insulator/metal structure, which consisting of Al/TiO₂/Au structures, was fabricated. First, Au was deposited to be a bottom electrode of RRAM device by RF magnetron sputtering system. Then, the TiO₂ layer was deposited on Au electrode by sputtering. Finally, Al was deposited as the top electrode. The electrical performance of the BZN OTFT was studied, showing superior transfer characteristics with the low threshold voltage of −1.1 V, good saturation mobility of 5 cm²/V s, and low subthreshold swing of 400 mV/decade. The integration of the BZN OTFT and TiO₂ RRAM devices was finally completed to form 1T1R configuration with low power consumption of 1.3 μW, the low operation current of 0.5 μA, and reliable data retention. Based on the I-V characteristics, the different polarities of bipolar switching are found to be determined by the compliance current with the different distribution of the internal oxygen vacancies used in the RRAM and 1T1R devices. Also, this phenomenon can be well explained by the proposed mechanism model. It is promising to make the 1T1R possible for practical applications of low-power active matrix flat-panel displays.

Keywords: one transistor and one resistor (1T1R), organic thin-film transistor (OTFT), resistive random access memory (RRAM), sol-gel

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Majid Javanmard

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In this study, the effects of coating with whey protein concentrate (7.5% w/v) alone and/or in combination with rice bran oil (0.2, 0.4, 0.6 g in 100 ml coating solution) and Zataria multiflora extract (1 and 2 μL in 100 ml coating solution) on the quality attributes and egg shelf life were carefully observed and analyzed. Weight loss, Haugh index, yolk index, pH, air cell depth, shell strength and the impact of this coating on the microbial load of the eggs surface were studied at the end of each week (during the 4 weeks of storage in a room environment temperature and humidity). After 4 weeks of storage, it was observed that the weight loss in all of the treated eggs with whey protein concentrate and 0.2 gr of rice bran oil (experimental group) was significantly lower than that of the control group(P < 0/05). With regard to Haugh index and yolk index, egg shelf life increased about 4 weeks compared with the control samples. Haugh Index changes revealed that the coated samples remained at grade A after 3 weeks of storage, while the control samples were relegated from grade AA to B after one week. Haugh and yolk Indices in all coated eggs were more than those of the control group. In the coated groups, Haugh and yolk indices of the coated samples with whey protein concentrate and 0.2 g rice bran oil and with whey protein concentrate and 0.2g of rice bran oil and 1 micro liter of Zataria multiflora extract were more than those of the other coated eggs and the control group eggs. PH values of the control group were higher than those of the coated groups during the storage of the eggs. The shell strength of the coated group was more than that of the control group (uncoated) and in coated samples, whey protein concentrate and 0.2 gr of rice bran oil coated samples had high shell strength. In the other treatments, no significant differences were observed. The depth of the air cell of the coated groups was determined to be less than that of the control group during the storage period. The minimum inhibitory concentration was 1 μL of Zataria multiflora extract. The results showed that 1 μL concentration of Zataria multiflora extract reduces the microbial load of the egg shell surface to 87% and 2 μL reduced total bacterial load to zero. In sensory evaluation, from evaluator point of view, the coated eggs had more overall acceptance than the uncoated group (control), and in the treatment group coated eggs, those containing a low percentage of rice bran oil had higher overall acceptability. In conclusion, coating as a practical and cost effective method can maintain the quality parameters of eggs and lead to durability of supply conditions in addition to the product marketability.

Keywords: edible coating, chicken egg, whey protein concentrate, rice bran oil, Zataria multiflora extract, shelf life

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Authors: Jon Ajuria, Edurne Redondo, Roman Mysyk, Eider Goikolea

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Hybrid capacitor configurations are now of increasing interest to overcome the current energy limitations of supercapacitors entirely based on non-Faradaic charge storage. Among them, Li-ion capacitors including a negative battery-type lithium intercalation electrode and a positive capacitor-type electrode have achieved tremendous progress and have gone up to commercialization. Inexpensive electrode materials from renewable sources have recently received increased attention since cost is a persistently major criterion to make supercapacitors a more viable energy solution, with electrode materials being a major contributor to supercapacitor cost. Additionally, Na-ion battery chemistries are currently under development as less expensive and accessible alternative to Li-ion based battery electrodes. In this work, we are presenting both lithium and sodium ion capacitor (LIC & NIC) entirely based on electrodes prepared from carbon materials derived from recycled olive pits. Yearly, around 1 million ton of olive pit waste is generated worldwide, of which a third originates in the Spanish olive oil industry. On the one hand, olive pits were pyrolized at different temperatures to obtain a low specific surface area semigraphitic hard carbon to be used as the Li/Na ion intercalation (battery-type) negative electrode. The best hard carbon delivers a total capacity of 270mAh/g vs Na/Na+ in 1M NaPF6 and 350mAh/g vs Li/Li+ in 1M LiPF6. On the other hand, the same hard carbon is chemically activated with KOH to obtain high specific surface area -about 2000 m2g-1- activated carbon that is further used as the ion-adsorption (capacitor-type) positive electrode. In a voltage window of 1.5-4.2V, activated carbon delivers a specific capacity of 80 mAh/g vs. Na/Na+ and 95 mAh/g vs. Li/Li+ at 0.1A /g. Both electrodes were assembled in the same hybrid cell to build a LIC/NIC. For comparison purposes, a symmetric EDLC supercapacitor cell using the same activated carbon in 1.5M Et4NBF4 electrolyte was also built. Both LIC & NIC demonstrates considerable improvements in the energy density over its EDLC counterpart, delivering a maximum energy density of 110Wh/Kg at a power density of 30W/kg AM and a maximum power density of 6200W/Kg at an energy density of 27 Wh/Kg in the case of NIC and a maximum energy density of 110Wh/Kg at a power density of 30W/kg and a maximum power density of 18000W/Kg at an energy density of 22 Wh/Kg in the case of LIC. In conclusion, our work demonstrates that the same biomass waste can be adapted to offer a hybrid capacitor/battery storage device overcoming the limited energy density of corresponding double layer capacitors.

Keywords: hybrid supercapacitor, Na-Ion capacitor, supercapacitor, Li-Ion capacitor, EDLC

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Authors: Ling Ai, Ziyu Zhao, Zeyu Zhou, Xiaochen Yang, Heng Zhai, Stuart Holmes

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Optimizing the catalyst layer structure is crucial for enhancing the performance of proton exchange membrane fuel cells (PEMFCs) with low Platinum (Pt) loading. Current works focused on the utilization, durability, and site activity of Pt particles on support, and performance enhancement has been achieved by loading Pt onto porous support with different morphology, such as graphene, carbon fiber, and carbon black. Some schemes have also incorporated cost considerations to achieve lower Pt loading. However, the design of the catalyst layer (CL) structure in the membrane electrode assembly (MEA) must consider the interactions between the layers. Addressing the crucial aspects of water management, low contact resistance, and the establishment of effective three-phase boundary for MEA, multi-walled carbon nanotubes (MWCNTs) are promising CL support due to their intrinsically high hydrophobicity, high axial electrical conductivity, and potential for ordered alignment. However, the drawbacks of MWCNTs, such as strong agglomeration, wall surface chemical inertness, and unopened ends, are unfavorable for Pt nanoparticle loading, which is detrimental to MEA processing and leads to inhomogeneous CL surfaces. This further deteriorates the utilization of Pt and increases the contact resistance. Robust chemical oxidation or nitrogen doping can introduce polar functional groups onto the surface of MWCNTs, facilitating the creation of open tube ends and inducing defects in tube walls. This improves dispersibility and load capacity but reduces length and conductivity. Consequently, a trade-off exists between maintaining the intrinsic properties and the degree of functionalization of MWCNTs. In this work, MWCNTs were modified based on the operational requirements of the MEA from the viewpoint of interlayer interactions, including the search for the optimal degree of oxidation, N-doping, and micro-arrangement. MWCNT were functionalized by oxidizing, N-doping, as well as micro-alignment to achieve lower contact resistance between CL and proton exchange membrane (PEM), better hydrophobicity, and enhanced performance. Furthermore, this work expects to construct a more continuously distributed three-phase boundary by aligning MWCNT to form a locally ordered structure, which is essential for the efficient utilization of Pt active sites. Different from other chemical oxidation schemes that used HNO3:H2SO4 (1:3) mixed acid to strongly oxidize MWCNT, this scheme adopted pure HNO3 to partially oxidize MWCNT at a lower reflux temperature (80 ℃) and a shorter treatment time (0 to 10 h) to preserve the morphology and intrinsic conductivity of MWCNT. The maximum power density of 979.81 mw cm-2 was achieved by Pt loading on 6h MWCNT oxidation time (Pt-MWCNT6h). This represented a 59.53% improvement over the commercial Pt/C catalyst of 614.17 (mw cm-2). In addition, due to the stronger electrical conductivity, the charge transfer resistance of Pt-MWCNT6h in the electrochemical impedance spectroscopy (EIS) test was 0.09 Ohm cm-2, which was 48.86% lower than that of Pt/C. This study will discuss the developed catalysts and their efficacy in a working fuel cell system. This research will validate the impact of low-functionalization modification of MWCNTs on the performance of PEMFC, which simplifies the preparation challenges of CL and contributing for the widespread commercial application of PEMFCs on a larger scale.

Keywords: carbon nanotubes, electrocatalyst, membrane electrode assembly, proton exchange membrane fuel cell

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Authors: S. Zith Dey Babu, S. Kour, S. Verma, C. Verma, V. Pathania, A. Agrawal, V. Chaudhary, A. Manoj Puthur, R. Goyal, A. Pal, T. Danti Dey, A. Kumar, K. Wadhwa, O. Ved

Abstract:

Background: Skin cancer is now is the buzzing button in the field of medical science. The cyst's pandemic is drastically calibrating the body and well-being of the global village. Methods: The extracted image of the skin tumor cannot be used in one way for diagnosis. The stored image contains anarchies like the center. This approach will locate the forepart of an extracted appearance of skin. Partitioning image models has been presented to sort out the disturbance in the picture. Results: After completing partitioning, feature extraction has been formed by using genetic algorithm and finally, classification can be performed between the trained and test data to evaluate a large scale of an image that helps the doctors for the right prediction. To bring the improvisation of the existing system, we have set our objectives with an analysis. The efficiency of the natural selection process and the enriching histogram is essential in that respect. To reduce the false-positive rate or output, GA is performed with its accuracy. Conclusions: The objective of this task is to bring improvisation of effectiveness. GA is accomplishing its task with perfection to bring down the invalid-positive rate or outcome. The paper's mergeable portion conflicts with the composition of deep learning and medical image processing, which provides superior accuracy. Proportional types of handling create the reusability without any errors.

Keywords: computer-aided system, detection, image segmentation, morphology

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Authors: N. Ibrahim-Rassoul, A. Kessi, E. K. Si-Ahmed, N. Djilali, J. Legrand

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The static and dynamic formation of liquid water bridges is analyzed using a combination of visualization experiments in a microchannel with a mathematical model. This paper presents experimental and theoretical findings of water plug/capillary bridge formation in a 250 μm squared microchannel. The approach combines mathematical and numerical modeling with experimental visualization and measurements. The generality of the model is also illustrated for flow conditions encountered in manipulation of polymeric materials and formation of liquid bridges between patterned surfaces. The predictions of the model agree favorably the observations as well as with the experimental recordings.

Keywords: green energy, mathematical modeling, fuel cell, water plug, gas diffusion layer, surface of revolution

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Authors: Henok Mezemr Besfat, Haftom Gebreslassie Gebregwergs

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wireless network is one of the most important mediums of transmission of information from one device to another devices. Wireless communication has a broad range of applications, including mobile communications through cell phones and satellites, Internet of Things (IoT) connecting several devices, wireless sensor networks for traffic management and environmental monitoring, satellite communication for weather forecasting and TV without requiring any cable or wire or other electronic conductors, by using electromagnetic waves like IR, RF, satellite, etc. This paper summarizes different wireless network technologies, applications of different wireless technologies and different types of wireless networks. Generally, wireless technology will further enhance operations and experiences across sectors with continued innovation. This paper suggests different strategies that can improve wireless networks and technologies.

Keywords: wireless senser, wireless technology, wireless network, internet of things

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Authors: Chun-Chuan Yang, Jeng-Yueng Chen, Yi-Ting Mai, Hsieh-Hua Liu

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By introduction of Relay Nodes (RNs), LTE-Advanced can provide enhanced coverage and capacity at cell edges and hot-spot areas. The authors have been researching the issue of power saving in mobile communications technology such as WiMax and LTE for some years. Based on the idea of Load-Based Power Saving (LBPS), three efficient power saving schemes for the user equipment (UE) were proposed in the authors’ previous work. In this paper, three revised schemes of the previous work in order to integrate RN and UE in power saving are proposed. Simulation study shows the proposed schemes can achieve significantly better power saving efficiency than the standard based scheme at the cost of moderately increased delay.

Keywords: DRX, LTE-A, power saving, RN

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Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

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Authors: Wael M. Rabeh, Cesar Carrasco-Lopez, Juliana C. Ferreira, Pance Naumov

Abstract:

Bioluminescence, the emission of light from a biological process, is found in various living organisms including bacteria, fireflies, beetles, fungus and different marine organisms. Luciferase is an enzyme that catalyzes a two steps oxidation of luciferin in the presence of Mg2+ and ATP to produce oxyluciferin and releases energy in the form of light. The luciferase assay is used in biological research and clinical applications for in vivo imaging, cell proliferation, and protein folding and secretion analysis. The luciferase enzyme consists of two domains, a large N-terminal domain (1-436 residues) that is connected to a small C-terminal domain (440-544) by a flexible loop that functions as a hinge for opening and closing the active site. The two domains are separated by a large cleft housing the active site that closes after binding the substrates, luciferin and ATP. Even though all insect luciferases catalyze the same chemical reaction and share 50% to 90% sequence homology and high structural similarity, they emit light of different colors from green at 560nm to red at 640 nm. Currently, the majority of the structural and biochemical studies have been conducted on green-emitting firefly luciferases. To address the color emission mechanism, we expressed and purified two luciferase enzymes with blue-shifted green and red emission from indigenous Brazilian species Amydetes fanestratus and Phrixothrix, respectively. The two enzymes naturally emit light of different colors and they are an excellent system to study the color-emission mechanism of luciferases, as the current proposed mechanisms are based on mutagenesis studies. Using a vapor-diffusion method and a high-throughput approach, we crystallized and solved the crystal structure of both enzymes, at 1.7 Å and 3.1 Å resolution respectively, using X-ray crystallography. The free enzyme adopted two open conformations in the crystallographic unit cell that are different from the previously characterized firefly luciferase. The blue-shifted green luciferase crystalized as a monomer similar to other luciferases reported in literature, while the red luciferases crystalized as an octamer and was also purified as an octomer in solution. The octomer conformation is the first of its kind for any insect’s luciferase, which might be relate to the red color emission. Structurally designed mutations confirmed the importance of the transition between the open and close conformations in the fine-tuning of the color and the characterization of other interesting mutants is underway.

Keywords: bioluminescence, enzymology, structural biology, x-ray crystallography

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