Search results for: hydrogen inhibition

Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: Vivek Kumar Gupta, Kripi Vohra, Monika Gupta

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Pulses have been a vital ingredient of the balanced human diet in India. Lentil (Lens culinaris Medikus or Lens esculenta Moench.) is a common legume known since biblical times. Lentil seeds, with or without hulls, are cooked as dhal and this has been the main dish for millennia in the South Asian region. Oxidative stress can damage lipids, proteins, enzymes, carbohydrates and DNA in cells and tissues, resulting in membrane damage, fragmentation or random cross linking of molecules like DNA, enzymes and structural proteins and even lead to cell death induced by DNA fragmentation and lipid peroxidation. These consequences of oxidative stress construct the molecular basis in the development of cancer, neurodegenerative disorders, cardiovascular diseases, diabetes and autoimmune. The aim of the present work is to assess the antioxidant potential of the peteroleum ether, acetone, methanol and water extract of the Lens esculenta seeds. In vitro antioxidant assessment of the extracts was carried out using 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity, hydroxyl radical scavenging activity, reducing power assay. The quantitative estimation of total phenolic content, total flavonoid content in extracts and in plant material, total saponin content, total alkaloid content, crude fibre content, total volatile content, fat content and mucilage content in drug material was also carried out. Though all the extracts exhibited dose dependent reducing power activity the acetone extract was found to possess significant hydrogen donating ability in DPPH (45.83%-93.13%) and hydroxyl radical scavenging system (28.7%-46.41%) than the peteroleum ether, methanol and water extracts. Total phenolic content in the acetone and methanol extract was found to be 608 and 188 mg gallic acid equivalent of phenol/g of sample respectively. Total flavonoid content of acetone and methanol extract was found to be 128 and 30.6 mg quercetin equivalent/g of sample respectively. It is evident that acetone extract of Lentil seeds possess high levels of polyphenolics and flavonoids that could be utilized as antioxidants and neutraceuticals.

Keywords: antioxidant, flavanoids, Lens esculenta, polyphenols

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection

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Authors: Yawen Dai, Ping Cheng, Jian Ru Gong

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Photoelctrochemical (PEC) water splitting using semiconductors (SCs) provides a convenient way to convert sustainable but intermittent solar energy into clean hydrogen energy, and it has been regarded as one of most promising technology to solve the energy crisis and environmental pollution in modern society. However, the record energy conversion efficiency of a PEC cell (~3%) is still far lower than the commercialization requirement (~10%). The sluggish kinetics of oxygen evolution reaction (OER) half reaction on photoanodes is a significant limiting factor of the PEC device efficiency, and electrocatalysts (ECs) are always deposited on SCs to accelerate the hole injection for OER. However, an active EC cannot guarantee enhanced PEC performance, since the newly emerged SC-EC interface complicates the interfacial charge behavior. Herein, α-Fe2O3 photoanodes coated with Co3O4 and CoO ECs are taken as the model system to glean fundamental understanding on the EC-dependent interfacial charge behavior. Intensity modulated photocurrent spectroscopy and electrochemical impedance spectroscopy were used to investigate the competition between interfacial charge transfer and recombination, which was found to be dominated by the charge storage capacities of ECs. The combined results indicate that both ECs can store holes and increase the hole density on photoanode surface. It is like a double-edged sword that benefit the multi-hole participated OER, as well as aggravate the SC-EC interfacial charge recombination due to the Coulomb attraction, thus leading to a nonmonotonic PEC performance variation trend with the increasing surface hole density. Co3O4 has low hole storage capacity which brings limited interfacial charge recombination, and thus the increased surface holes can be efficiently utilized for OER to generate enhanced photocurrent. In contrast, CoO has overlarge hole storage capacity that causes severe interfacial charge recombination, which hinders hole transfer to electrolyte for OER. Therefore, the PEC performance of α-Fe2O3 is improved by Co3O4 but decreased by CoO despite the similar electrocatalytic activity of the two ECs. First-principle calculation was conducted to further reveal how the charge storage capacity depends on the EC’s intrinsic property, demonstrating that the larger hole storage capacity of CoO than that of Co3O4 is determined by their Co valence states and original Fermi levels. This study raises up a new strategy to manipulate interfacial charge behavior and the resultant PEC performance by the charge storage capacity of ECs, providing insightful guidance for the interface design in PEC devices.

Keywords: charge storage capacity, electrocatalyst, interfacial charge behavior, photoelectrochemistry, water-splitting

Procedia PDF Downloads 109

Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

Procedia PDF Downloads 98

Authors: Nélio Veiga, Paula Ferreira, Tiago Correia, Maria J. Correia, Carlos Pereira, Odete Amaral, Ilídio J. Correia

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Introduction: The application of fissure sealants is considered to be an important primary prevention method used in dental medicine. However, the formation of microleakage gaps between tooth enamel and the fissure sealant applied is one of the most common reasons of dental caries development in teeth with fissure sealants. The association between various dental biomaterials may limit the major disadvantages and limitations of biomaterials functioning in a complementary manner. The present study consists in the incorporation of a cariostatic agent – silver diamine fluoride (SDF) – in a resin-based fissure sealant followed by the study of release kinetics by spectrophotometry analysis of the association between both biomaterials and assessment of the inhibitory effect on the growth of the reference bacterial strain Streptococcus mutans (S. mutans) in an in vitro study. Materials and Methods: An experimental in vitro study was designed consisting in the entrapment of SDF (Cariestop^® 12% and 30%) into a commercially available fissure sealant (Fissurit^®), by photopolymerization and photocrosslinking. The same sealant, without SDF was used as a negative control. The effect of the sealants on the growth of S. mutans was determined by the presence of bacterial inhibitory halos in the cultures at the end of the incubation period. In order to confirm the absence of bacteria in the surface of the materials, Scanning Electron Microscopy (SEM) characterization was performed. Also, to analyze the release profile of SDF along time, spectrophotometry technique was applied. Results: The obtained results indicate that the association of SDF to a resin-based fissure sealant may be able to increase the inhibition of S. mutans growth. However, no SDF release was noticed during the in vitro release studies and no statistical significant difference was verified when comparing the inhibitory halo sizes obtained for test and control group.  Conclusions: In this study, the entrapment of SDF in the resin-based fissure sealant did not potentiate the antibacterial effect of the fissure sealant or avoid the immediate development of dental caries. The development of more laboratorial research and, afterwards, long-term clinical data are necessary in order to verify if this association between these biomaterials is effective and can be considered for being used in oral health management. Also, other methodologies for associating cariostatic agents and sealant should be addressed.

Keywords: biomaterial, fissure sealant, primary prevention, silver diamine fluoride

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Authors: Chyuan Haur Kao, Hsiang Chen, Yu Sheng Tsai, Chen Hao Hung, Yu Shan Lee

Abstract:

Dielectric electrolyte-insulator-semiconductor sensing membranes-based biosensors have been intensively investigated because of their simple fabrication, low cost, and fast response. However, to enhance their sensing performance, it is worthwhile to explore alternative materials, distinct processes, and novel treatments. An ISFET can be viewed as a variation of MOSFET with the dielectric oxide layer as the sensing membrane. Then, modulation on the work function of the gate caused by electrolytes in various ion concentrations could be used to calculate the ion concentrations. Recently, owing to the advancement of CMOS technology, some high dielectric materials substrates as the sensing membranes of electrolyte-insulator-semiconductor (EIS) structures. The EIS with a stacked-layer of SiO₂ layer between the sensing membrane and the silicon substrate exhibited a high pH sensitivity and good long-term stability. IGZO is a wide-bandgap (~3.15eV) semiconductor of the III-VI semiconductor group with several preferable properties, including good transparency, high electron mobility, wide band gap, and comparable with CMOS technology. IGZO was sputtered by reactive radio frequency (RF) on a p-type silicon wafer with various gas ratios of Ar:O₂ and was treated with rapid thermal annealing in O₂ ambient. The sensing performance, including sensitivity, hysteresis, and drift rate was measured and XRD, XPS, and AFM analyses were also used to study the material properties of the IGZO membrane. Moreover, IGZO was used as a sensing membrane in dielectric EIS bio-sensor structures. In addition to traditional pH sensing capability, detection for concentrations of Na+, K+, urea, glucose, and creatinine was performed. Moreover, post rapid thermal annealing (RTA) treatment was confirmed to improve the material properties and enhance the multi-analyte sensing capability for various ions or chemicals in solutions. In this study, the IGZO sensing membrane with annealing in O₂ ambient exhibited a higher sensitivity, higher linearity, higher H+ selectivity, lower hysteresis voltage and lower drift rate. Results indicate that the IGZO dielectric sensing membrane on the EIS structure is promising for future bio-medical device applications.

Keywords: dielectric sensing membrane, IGZO, hydrogen ion, plasma, rapid thermal annealing

Procedia PDF Downloads 228

Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

Procedia PDF Downloads 32

Authors: D. Zhao, Y. Wang, G. Chen

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Gas sensors that utilize carbonaceous materials as sensing media offer numerous advantages, making them the preferred choice for constructing chemical sensors over those using other sensing materials. Carbonaceous materials, particularly nano-sized ones like carbon nanotubes (CNTs), provide these sensors with high sensitivity. Additionally, carbon-based sensors possess other advantageous properties that enhance their performance, including high stability, low power consumption for operation, and cost-effectiveness in their construction. These properties make carbon-based sensors ideal for a wide range of applications, especially in miniaturized devices created through MEMS or NEMS technologies. To capitalize on these properties, a group of chemoresistance-type carbon-based gas sensors was developed and tested against various volatile organic compounds (VOCs) and volatile inorganic compounds (VICs). The results demonstrated exceptional sensitivity to both VOCs and VICs, along with the sensor’s long-term stability. However, this broad sensitivity also led to poor selectivity towards specific gases. This project aims at addressing the selectivity issue by modifying the carbon-based sensing materials and enhancing the sensor's specificity to individual gas. Multiple groups of sensors were manufactured and modified using proprietary techniques. To assess their performance, we conducted experiments on representative sensors from each group to detect a range of VOCs and VICs. The VOCs tested included acetone, dimethyl ether, ethanol, formaldehyde, methane, and propane. The VICs comprised carbon monoxide (CO), carbon dioxide (CO2), hydrogen (H2), nitric oxide (NO), and nitrogen dioxide (NO2). The concentrations of the sample gases were all set at 50 parts per million (ppm). Nitrogen (N2) was used as the carrier gas throughout the experiments. The results of the gas sensing experiments are as follows. In Group 1, the sensors exhibited selectivity toward CO2, acetone, NO, and NO2, with NO2 showing the highest response. Group 2 primarily responded to NO2. Group 3 displayed responses to nitrogen oxides, i.e., both NO and NO2, with NO2 slightly surpassing NO in sensitivity. Group 4 demonstrated the highest sensitivity among all the groups toward NO and NO2, with NO2 being more sensitive than NO. In conclusion, by incorporating several modifications using carbon nanotubes (CNTs), sensors can be designed to respond well to NOx gases with great selectivity and without interference from other gases. Because the response levels to NO and NO2 from each group are different, the individual concentration of NO and NO2 can be deduced.

Keywords: gas sensors, carbon, CNT, MEMS/NEMS, VOC, VIC, high selectivity, modification of sensing materials

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Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

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Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: Jineetkumar Gawad, Chandrakant Bonde

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Tuberculosis (TB) is a major worldwide concern whose control has been exacerbated by HIV, the rise of multidrug-resistance (MDR-TB) and extensively drug resistance (XDR-TB) strains of Mycobacterium tuberculosis. The interest for newer and faster acting antitubercular drugs are more remarkable than any time. To search potent compounds is need and challenge for researchers. Here, we tried to design lead for inhibition of Decaprenyl phosphoryl-β-D-ribose 2′-epimerase (DprE1) enzyme. Arabinose is an essential constituent of mycobacterial cell wall. DprE1 is a flavoenzyme that converts decaprenylphosphoryl-D-ribose into decaprenylphosphoryl-2-keto-ribose, which is intermediate in biosynthetic pathway of arabinose. Latter, DprE2 converts keto-ribose into decaprenylphosphoryl-D-arabinose. We had a selection of 23 compounds from azaindole series for computational study, and they were drawn using marvisketch. Ligands were prepared using Maestro molecular modeling interface, Schrodinger, v10.5. Common pharmacophore hypotheses were developed by applying dataset thresholds to yield active and inactive set of compounds. There were 326 hypotheses were developed. On the basis of survival score, ADRRR (Survival Score: 5.453) was selected. Selected pharmacophore hypotheses were subjected to virtual screening results into 1000 hits. Hits were prepared and docked with protein 4KW5 (oxydoreductase inhibitor) was downloaded in .pdb format from RCSB Protein Data Bank. Protein was prepared using protein preparation wizard. Protein was preprocessed, the workspace was analyzed using force field OPLS 2005. Glide grid was generated by picking single atom in molecule. Prepared ligands were docked with prepared protein 4KW5 using Glide docking. After docking, on the basis of glide score top-five compounds were selected, (5223, 5812, 0661, 0662, and 2945) and the glide docking score (-8.928, -8.534, -8.412, -8.411, -8.351) respectively. There were interactions of ligand and protein, specifically HIS 132, LYS 418, TRY 230, ASN 385. Pi-pi stacking was observed in few compounds with basic Imidazo [4,5-b] pyridine ring. We had basic azaindole ring in parent compounds, but after glide docking, we received compounds with Imidazo [4,5-b] pyridine as a basic ring. That might be the new lead in the process of drug discovery.

Keywords: DprE1 inhibitors, in silico drug designing, imidazo [4, 5-b] pyridine, lead, tuberculosis

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Authors: Weirong Wang, Shenghong Huang, Xisheng Luo, Zhenyu Li

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Material mixing process and related dynamic issues at extreme compressing conditions have gained more and more concerns in last ten years because of the engineering appealings in inertial confinement fusion (ICF) and hypervelocity aircraft developments. However, there lacks models and methods that can handle fully coupled turbulent material mixing and complex fluid evolution under conditions of high energy density regime up to now. In aspects of macro hydrodynamics, three numerical methods such as direct numerical simulation (DNS), large eddy simulation (LES) and Reynolds-averaged Navier–Stokes equations (RANS) has obtained relative acceptable consensus under the conditions of low energy density regime. However, under the conditions of high energy density regime, they can not be applied directly due to occurrence of dissociation, ionization, dramatic change of equation of state, thermodynamic properties etc., which may make the governing equations invalid in some coupled situations. However, in view of micro/meso scale regime, the methods based on Molecular Dynamics (MD) as well as Monte Carlo (MC) model are proved to be promising and effective ways to investigate such issues. In this study, both classical MD and first-principle based electron force field MD (eFF-MD) methods are applied to investigate Richtmyer-Meshkov Instability of metal Lithium and gas Hydrogen (Li-H2) interface mixing at different shock loading speed ranging from 3 km/s to 30 km/s. It is found that: 1) Classical MD method based on predefined potential functions has some limits in application to extreme conditions, since it cannot simulate the ionization process and its potential functions are not suitable to all conditions, while the eFF-MD method can correctly simulate the ionization process due to its ‘ab initio’ feature; 2) Due to computational cost, the eFF-MD results are also influenced by simulation domain dimensions, boundary conditions and relaxation time choices, etc., in computations. Series of tests have been conducted to determine the optimized parameters. 3) Ionization induced by strong shock compression has important effects on Li-H2 interface evolutions of RMI, indicating a new micromechanism of RMI under conditions of high energy density regime.

Keywords: first-principle, ionization, molecular dynamics, material mixture, Richtmyer-Meshkov instability

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Authors: Gopala Krishna Darbha

Abstract:

Microplastics (MPs) are secondary fragments of large-sized plastic debris released into the environment and fall in the size range of less than 5 mm. Though reports indicate the abundance of MPs in both riverine and soil environments, their fate is still not completely understood due to the complexity of natural conditions. Mineral particles are ubiquitous in the rivers and may play a vital role in accumulating MPs to the riverbed, thus affecting the benthic life and posing a threat to the river's health. Apart, the chemistry (pH, ionic strength, humics) at the interface can be very prominent. The MPs can also act as potential vectors to transport other contaminants in the environment causing secondary water pollution. The present study focuses on understanding the interaction of MPs with weathering sequence of minerals (feldspar, kaolinite and gibbsite) under batch mode under relevant environmental and natural conditions. Simultaneously, we performed stability studies and transport (column) experiments to understand the mobility of MPs under varying soil solutions (SS) chemistry and the influence of contaminants (CuO nanoparticles). Results showed that the charge and morphology of the gibbsite played an significant role in sorption of NPs (108.1 mg/g) compared to feldspar (7.7 mg/g) and kaolinite (11.9 mg/g). The Fourier transform infrared spectroscopy data supports the complexation of NPs with gibbsite particles via hydrogen bonding. In case of feldspar and kaolinite, a weak interaction with NPs was observed which can be due to electrostatic repulsions and low surface area to volume ration of the mineral particles. The study highlights the enhanced mobility in presence of feldspar and kaolinite while gibbsite rich zones can cause entrapment of NPs accumulating in the riverbeds. In the case of soils, in the absence of MPs, a very high aggregation of CuO NPs observed in SS extracted from black, lateritic, and red soils, which can be correlated with ionic strength (IS) and type of ionic species. The sedimentation rate (Ksed(1/h)) for CuO NPs was >0.5 h−1 in the case of these SS. Interestingly, the stability and sedimentation behavior of CuO NPs varied significantly in the presence of MPs. The Ksed for CuO NPs decreased to half and found <0.25 h−1 in the presence of MPs in all SS. C/C0 values in breakthrough curves increased drastically (black < alluvial < laterite < red) in the presence of MPs. Results suggest that the release of MPs in the terrestrial ecosystem is a potential threat leading to increased mobility of metal nanoparticles in the environment.

Keywords: microplastics, minerals, sorption, soils

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Authors: Raghuram Kandimalla, Sanjeeb Kalita, Bhaswati Choudhury, Jibon Kotoky

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The quest for developing an ideal suture material prompted our interest to develop a novel suture with advantageous characteristics to market available ones. We developed novel suture biomaterial from muga silk (Antheraea assama) and ramie (Boehmeria nivea) plant fiber. Field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR) and thermo gravimetric analysis (TGA) results revealed the physicochemical properties of the fibers which supports the suitability of fibers for suture fabrication. Tensile properties of the prepared sutures were comparable with market available sutures and it found to be biocompatible towards human erythrocytes and nontoxic to mammalian cells. The prepared sutures completely healed the superficial deep wound incisions within seven days in adult male wister rats leaving no rash and scar. Histopathology studies supports the wound healing ability of sutures, as rapid synthesis of collagen, connective tissue and other skin adnexal structures were observed within seven days of surgery. Further muga suture surface modified by exposing the suture to oxygen plasma which resulted in formation of nanotopography on suture surface. Broad spectrum antibiotic amoxicillin was functionalized on the suture surface to prepare an advanced antimicrobial muga suture. Surface hydrophilicity induced by oxygen plasma results in an increase in drug-impregnation efficiency of modified muga suture by 16.7%. In vitro drug release profiles showed continuous and prolonged release of amoxicillin from suture up to 336 hours. The advanced muga suture proves to be effective against growth inhibition of Staphylococcus aureus and Escherichia coli, whereas normal muga suture offers no antibacterial activity against both types of bacteria. In vivo histopathology studies and colony-forming unit count data revealed accelerated wound healing activity of advanced suture over normal one through rapid synthesis and proliferation of collagen, hair follicle and connective tissues.

Keywords: sutures, biomaterials, silk, Ramie

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Authors: Ronaldo de Lima Cardoso, Thiago V. C. Marcos, Felipe J. da Costa, Antonio C. da Oliveira, Paulo G. P. Toro

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The 14-X is a strategic project of the Brazil Air Force Command to develop a technological demonstrator of a hypersonic air-breathing propulsion system based on supersonic combustion programmed to flight in the Earth's atmosphere at 30 km of altitude and Mach number 10. The 14-X is under development at the Laboratory of Aerothermodynamics and Hypersonic Prof. Henry T. Nagamatsu of the Institute of Advanced Studies. The program began in 2007 and was planned to have three stages: development of the wave rider configuration, development of the scramjet configuration and finally the ground tests in the hypersonic shock tunnel T3. The install configuration of the model based in the scramjet of the 14-X in the test section of the hypersonic shock tunnel was made to proportionate and test the flight conditions in the inlet of the combustion chamber. Experimental studies with hypersonic shock tunnel require special techniques to data acquisition. To measure the pressure along the experimental model geometry tested we used 30 pressure transducers model 122A22 of PCB®. The piezoeletronic crystals of a piezoelectric transducer pressure when to suffer pressure variation produces electric current (PCB® PIEZOTRONIC, 2016). The reading of the signal of the pressure transducers was made by oscilloscope. After the studies had begun we observed that the pressure inside in the combustion chamber was lower than expected. One solution to improve the pressure inside the combustion chamber was install an obstacle to providing high temperature and pressure. To confirm if the combustion occurs was selected the spectroscopy emission technique. The region analyzed for the spectroscopy emission system is the edge of the obstacle installed inside the combustion chamber. The emission spectroscopy technique was used to observe the emission of the OH*, confirming or not the combustion of the mixture between atmospheric air in supersonic speed and the hydrogen fuel inside of the combustion chamber of the model. This paper shows the results of experimental studies of the supersonic combustion induced by shock wave performed at the Hypersonic Shock Tunnel T3 using the scramjet 14-X model. Also, this paper provides important data about the combustion studies using the model based on the engine of 14-X (second stage of the 14-X Program). Informing the possibility of necessaries corrections to be made in the next stages of the program or in other models to experimental study.

Keywords: 14-X, experimental study, ground tests, scramjet, supersonic combustion

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Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung

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Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.

Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2

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Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

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The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

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Authors: Hamsasew Hankebo Lemago, Dóra Hessz, Zoltán Erdélyi, Imre Miklós Szilágyi

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Metal oxide inverse opals are a unique class of photocatalysts with a hierarchical structure that mimics the natural opal gemstone. They are composed of a network of interconnected pores, which provides a large surface area and efficient pathways for the transport of light and reactants. Atomic layer deposition (ALD) is a versatile technique for the synthesis of high-precision metal oxide thin films, including inverse opals. ALD allows for precise control over the thickness, composition, and morphology of the synthesized films, making it an ideal technique for the fabrication of photocatalysts with tailored properties. In this study, we report the synthesis of TiO2, ZnO, and Al2O3 inverse opal photocatalysts using thermal or plasma-enhanced ALD. The synthesized photocatalysts were characterized using a variety of techniques, including scanning electron microscopy (SEM)-energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Raman spectroscopy, photoluminescence (PL), ellipsometry, and UV-visible spectroscopy. The results showed that the ALD-synthesized metal oxide inverse opals had a highly ordered structure and a tunable pore size. The PL spectroscopy results showed low recombination rates of photogenerated electron-hole pairs, while the ellipsometry and UV-visible spectroscopy results showed tunable optical properties and band gap energies. The photocatalytic activity of the samples was evaluated by the degradation of methylene blue under visible light irradiation. The results showed that the ALD-synthesized metal oxide inverse opals exhibited high photocatalytic activity, even under visible light irradiation. The composites photocatalysts showed even higher activity than the individual metal oxide inverse opals. The enhanced photocatalytic activity of the composites can be attributed to the synergistic effect between the different metal oxides. For example, Al2O3 can act as a charge carrier scavenger, which can reduce the recombination of photogenerated electron-hole pairs. The ALD-synthesized metal oxide inverse opals and their composites are promising photocatalysts for a variety of applications, such as wastewater treatment, air purification, and energy production. For example, they can be used to remove organic pollutants from wastewater, decompose harmful gases in the air, and produce hydrogen fuel from water.

Keywords: ALD, metal oxide inverse opals, composites, photocatalysis

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Authors: Takuya Suzuki, Atsushi Shirai, Takashi Seki

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Acupuncture therapy is one of the treatments in traditional Chinese medicine. Recently, some reports have shown the effectiveness of acupuncture. However, its full acceptance has been hindered by the lack of understanding on mechanism of the therapy. Acupuncture applied to Zusanli (ST-36) enhances blood flow volume in superior mesenteric artery (SMA), yielding peripheral vascular resistance – regulated blood flow of SMA dominated by the parasympathetic system and inhibition of sympathetic system. In this study, a lumped-parameter approximation model of blood flow in the systemic arteries was developed. This model was extremely simple, consisting of the aorta, carotid arteries, arteries of the four limbs and SMA, and their peripheral vascular resistances. Here, the individual artery was simplified to a tapered tube and the resistances were modelled by a linear resistance. We numerically investigated contribution of the peripheral vascular resistance of SMA to the systemic blood distribution using this model. In addition to the upstream end of the model, which correlates with the left ventricle, two types of boundary condition were applied; mean left ventricular pressure which correlates with blood pressure (BP) and mean cardiac output which corresponds to cardiac index (CI). We examined it to reproduce the experimentally obtained hemodynamic change, in terms of the ratio of the aforementioned hemodynamic parameters from their initial values before the acupuncture, by regulating the peripheral vascular resistances and the upstream boundary condition. First, only the peripheral vascular resistance of SMA was changed to show contribution of the resistance to the change in blood flow volume in SMA, expecting reproduction of the experimentally obtained change. It was found, however, this was not enough to reproduce the experimental result. Then, we also changed the resistances of the other arteries together with the value given at upstream boundary. Here, the resistances of the other arteries were changed simultaneously in the same amount. Consequently, we successfully reproduced the hemodynamic change to find that regulation of the upstream boundary condition to the value experimentally obtained after the stimulation is necessary for the reproduction, though statistically significant changes in BP and CI were not observed in the experiment. It is generally known that sympathetic and parasympathetic tones take part in regulation of whole the systemic circulation including the cardiac function. The present result indicates that stimulation to ST-36 could induce vasodilation of peripheral circulation of SMA and vasoconstriction of that of other arteries. In addition, it implies that experimentally obtained small changes in BP and CI induced by the acupuncture may be involved in the therapeutic response.

Keywords: acupuncture, hemodynamics, lumped-parameter approximation, modeling, systemic vascular resistance

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Authors: F. Mutelet, L. Cesari

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Development of safer and environmentally friendly processes and products is needed to achieve sustainable production and consumption patterns. Ionic liquids, which are of great interest to the chemical and related industries because of their attractive properties as solvents, should be considered. Ionic liquids are comprised of an asymmetric, bulky organic cation and a weakly coordinating organic or inorganic anion. A large number of possible combinations allows for the ability to ‘fine tune’ the solvent properties for a specific purpose. Physical and chemical properties of ionic liquids are not only influenced by the nature of the cation and the nature of cation substituents but also by the polarity and the size of the anion. These features infer to ionic liquids numerous applications, in organic synthesis, separation processes, and electrochemistry. Separation processes required a good knowledge of the behavior of organic compounds with ionic liquids. Gas chromatography is a useful tool to estimate the interactions between organic compounds and ionic liquids. Indeed, retention data may be used to determine infinite dilution thermodynamic properties of volatile organic compounds in ionic liquids. Among others, the activity coefficient at infinite dilution is a direct measure of solute-ionic liquid interaction. In this work, infinite dilution thermodynamic properties of volatile organic compounds in specific bis(trifluoromethylsulfonyl)imide based ionic liquids measured by gas chromatography is presented. It was found that apolar compounds are not miscible in this family of ionic liquids. As expected, the solubility of organic compounds is related to their polarity and hydrogen-bond. Through activity coefficients data, the performance of these ionic liquids was evaluated for different separation processes (benzene/heptane, thiophene/heptane and pyridine/heptane). Results indicate that ionic liquids may be used for the extraction of polar compounds (aromatics, alcohols, pyridine, thiophene, tetrahydrofuran) from aliphatic media. For example, 1-benzylpyridinium bis(trifluoromethylsulfonyl) imide and 1-cyclohexylmethyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide are more efficient for the extraction of aromatics or pyridine from aliphatics than classical solvents. Ionic liquids with long alkyl chain length present important capacity values but their selectivity values are low. In conclusion, we have demonstrated that specific bis(trifluoromethylsulfonyl)imide based ILs containing polar chain grafted on the cation (for example benzyl or cyclohexyl) increases considerably their performance in separation processes.

Keywords: interaction organic solvent-ionic liquid, gas chromatography, solvation model, COSMO-RS

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Authors: R. Prinsloo

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis, and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: best interest of the child, children's rights, parent and child relationship, parental responsibilities and rights

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Authors: Damian Stanislaw Nakonieczny, Grazyna Simha Martynkova, Marianna Hundakova, G. Kratosová, Karla Cech Barabaszova

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The main aim of the research was to functionalize the surface of spherical aluminum silicates in the form of so-called cenospheres. Cenospheres are light ceramic particles with a density between 0.45 and 0.85 kgm-3 hat can be obtained as a result of separation from fly ash from coal combustion. However, their occurrence is limited to about 1% by weight of dry ash mainly derived from anthracite. Hence they are very rare and desirable material. Cenospheres are characterized by complete chemical inertness. Mohs hardness in range of 6 and completely smooth surface. Main idea was to prepare the surface by chemical etching, among others hydrofluoric acid (HF) and hydrogen peroxide, caro acid, silanization using (3-aminopropyl) triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) to obtain the maximum development and functionalization of the surface to improve chemical and mechanical connection with biomedically used polymers, i.e., polyacrylic methacrylate (PMMA) and polyetheretherketone (PEEK). These polymers are used medically mainly as a material for fixed and removable dental prostheses and PEEK spinal implants. The problem with their use is the decrease in mechanical properties over time and bacterial infections fungal during implantation and use of dentures. Hence, the use of a ceramic filler that will significantly improve the mechanical properties, improve the fluidity of the polymer during shape formation, and in the future, will be able to support bacteriostatic substances such as silver and zinc ions seem promising. In order to evaluate our laboratory work, several instrumental studies were performed: chemical composition and morphology with scanning electron microscopy with Energy-Dispersive X-Ray Probe (SEM/EDX), determination of characteristic functional groups of Fourier Transform Infrared Spectroscopy (FTIR), phase composition of X-ray Diffraction (XRD) and thermal analysis of Thermo Gravimetric Analysis/differentia thermal analysis (TGA/DTA), as well as assessment of isotherm of adsorption with Brunauer-Emmett-Teller (BET) surface development. The surface was evaluated for the future application of additional bacteria and static fungus layers. Based on the experimental work, it was found that orated methods can be suitable for the functionalization of the surface of cenosphere ceramics, and in the future it can be suitable as a bacteriostatic filler for biomedical polymers, i.e., PEEK or PMMA.

Keywords: bioceramics, composites, functionalization, surface development

Procedia PDF Downloads 101

Authors: Nelson R. Osungbemiro, O. A. Bello-Olusoji, M. Oladipupo

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This study was carried out to determine the effects of probiotics Pseudomonas fluorescens on the growth performance, histology examination and immune modulation of African Catfish, (Clarias gariepinus) challenged with Clostridium botulinum. P. fluorescens, and C. botulinum isolates were removed from the gut, gill and skin organs of procured adult samples of Clarias gariepinus from commercial fish farms in Akure, Ondo State, Nigeria. The physical and biochemical tests were performed on the bacterial isolates using standard microbiological techniques for their identification. Antibacterial activity tests on P. fluorescens showed inhibition zone with mean value of 3.7 mm which indicates high level of antagonism. The experimental diets were prepared at different probiotics bacterial concentration comprises of five treatments of different bacterial suspension, including the control (T1), T2 (10³), T3 (10⁵), T4 (10⁷) and T5 (10⁹). Three replicates for each treatment type were prepared. Growth performance and nutrients utilization indices were calculated. The proximate analysis of fish carcass and experimental diet was carried out using standard methods. After feeding for 70 days, haematological values and histological test were done following standard methods; also a subgroup from each experimental treatment was challenged by inoculating Intraperitonieally (I/P) with different concentration of pathogenic C. botulinum. Statistically, there were significant differences (P < 0.05) in the growth performance and nutrient utilization of C. gariepinus. Best weight gain and feed conversion ratio were recorded in fish fed T4 (10⁷) and poorest value obtained in the control. Haematological analyses of C. gariepinus fed the experimental diets indicated that all the fish fed diets with P. fluorescens had marked significantly (p < 0.05) higher White Blood Cell than the control diet. The results of the challenge test showed that fish fed the control diet had the highest mortality rate. Histological examination of the gill, intestine, and liver of fish in this study showed several histopathological alterations in fish fed the control diets compared with those fed the P. fluorescens diets. The study indicated that the optimum level of P. fluorescens required for C. gariepinus growth and white blood cells formation is 10⁷ CFU g⁻¹, while carcass protein deposition required 10⁵ CFU g⁻¹ of P. fluorescens concentration. The study also confirmed P. fluorescens as efficient probiotics that is capable of improving the immune response of C. gariepinus against the attack of a virulent fish pathogen, C. botulinum.

Keywords: Clarias gariepinus, Clostridium botulinum, probiotics, Pseudomonas fluorescens

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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Authors: Harish Kuruva, Vedasri Bai Khavala, Tiju Thomas, K. Murugan, B. S. Murty

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Industries are growing day to day to increase the economy of the country. The biggest problem with industries is wastewater treatment. Releasing these wastewater directly into the river is more harmful to human life and a threat to aquatic life. These industrial effluents contain many dissolved solids, organic/inorganic compounds, salts, toxic metals, etc. Phenols, pesticides, dioxins, herbicides, pharmaceuticals, and textile dyes were the types of industrial effluents and more challenging to degrade eco-friendly. So many advanced techniques like electrochemical, oxidation process, and valorization have been applied for industrial wastewater treatment, but these are not cost-effective. Industrial effluent degradation is complicated compared to commercially available pollutants (dyes) like methylene blue, methylene orange, rhodamine B, etc. TiO₂ is one of the widely used photocatalysts which can degrade organic compounds using solar light and moisture available in the environment (organic compounds converted to CO₂ and H₂O). TiO₂ is widely studied in photocatalysis because of its low cost, non-toxic, high availability, and chemically and physically stable in the atmosphere. This study mainly focused on valorizing the mineralogical product TiO₂ (IREL, India). This mineralogical graded TiO₂ was characterized and compared with its structural and photocatalytic properties (industrial effluent degradation) with the commercially available Degussa P-25 TiO₂. It was testified that this mineralogical TiO₂ has the best photocatalytic properties (particle shape - spherical, size - 30±5 nm, surface area - 98.19 m²/g, bandgap - 3.2 eV, phase - 95% anatase, and 5% rutile). The industrial effluent was characterized by TDS (total dissolved solids), ICP-OES (inductively coupled plasma – optical emission spectroscopy), CHNS (Carbon, Hydrogen, Nitrogen, and sulfur) analyzer, and FT-IR (fourier-transform infrared spectroscopy). It was observed that it contains high sulfur (S=11.37±0.15%), organic compounds (C=4±0.1%, H=70.25±0.1%, N=10±0.1%), heavy metals, and other dissolved solids (60 g/L). However, the organo-sulfur industrial effluent was degraded by photocatalysis with the industrial mineralogical product TiO₂. In this study, the industrial effluent pH value (2.5 to 10), catalyst concentration (50 to 150 mg) were varied, and effluent concentration (0.5 Abs) and light exposure time (2 h) were maintained constant. The best degradation is about 80% of industrial effluent was achieved at pH 5 with a concentration of 150 mg - TiO₂. The FT-IR results and CHNS analyzer confirmed that the sulfur and organic compounds were degraded.

Keywords: wastewater treatment, industrial mineralogical product TiO₂, photocatalysis, organo-sulfur industrial effluent

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

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Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

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Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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Authors: Dong Zhao

Abstract:

Abstract—Extensive research on obtaining applicable room temperature superconductors meets the major barrier, and the record Tc of 135 K achieved via cuprate has been idling for decades. Even though, the accomplishment of higher Tc than the cuprate was made through pressurizing certain compounds composed of light elements, such as for the LaH10 and for the metallic hydrogen. Room temperature superconductivity under ambient pressure is still the preferred approach and is believed to be the ultimate solution for many applications. While racing to find the breakthrough method to achieve this room temperature Tc milestone in superconducting research, a report stated a discovery of a possible high-temperature superconductor, i.e., the thorium sulfide ThS. Apparently, ThS’s Tc can be at room temperature or even higher. This is because ThS revealed an unusual property of the ‘coexistence of high electrical conductivity and diamagnetism’. Noticed that this property of coexistence of high electrical conductivity and diamagnetism is in line with superconductors, meaning ThS is also at its superconducting state. Surprisingly, ThS owns the property of superconductivity at least at room temperature and under atmosphere pressure. Further study of the ThS’s electrical and magnetic properties in comparison with thorium di-iodide ThI2 concluded its molecular configuration as [Th4+(e-)2]S. This means the ThS’s cation is composed of a [Th4+(e-)2]2+ cation core. It is noticed that this cation core is built by an oxidation state +4 of thorium atom plus an electron pair on this thorium atom that resulted in an oxidation state +2 of this [Th4+(e-)2]2+ cation core. This special construction of [Th4+(e-)2]2+ cation core may lead to the ThS’s room temperature superconductivity because of this characteristic electron lone pair residing on the thorium atom. Since the study of thorium chemistry was carried out in the period of before 1970s. the exploration about ThS’s possible room temperature superconductivity would require resynthesizing ThS. This re-preparation of ThS will provide the sample and enable professionals to verify the ThS’s room temperature superconductivity. Regrettably, the current regulation prevents almost everyone from getting access to thorium metal or thorium compounds due to the radioactive nature of thorium-232 (Th-232), even though the radioactive level of Th-232 is extremely low with its half-life of 14.05 billion years. Consequently, further confirmation of ThS’s high-temperature superconductivity through experiments will be impossible unless the use of corresponding thorium metal and related thorium compounds can be deregulated. This deregulation would allow researchers to obtain the necessary starting materials for the study of ThS. Hopefully, the confirmation of ThS’s room temperature superconductivity can not only establish a method to obtain applicable superconductors but also to pave the way for fully understanding the mechanism of superconductivity.

Keywords: co-existence of high electrical conductivity and diamagnetism, electron pairing and electron lone pair, room temperature superconductivity, the special molecular configuration of thorium sulfide ThS

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Authors: Vanda Ferreira Ribeiro, Daiane Tomacheski, Douglas Naue Simões, Michele Pitto, Ruth Marlene Campomanes Santana

Abstract:

Indoor environments, such as car cabins and public transportation vehicles are places where users are subject to air quality. Microorganisms (bacteria, fungi, yeasts) enter these environments through windows, ventilation systems and may use the organic particles present as a growth substrate. In addition, atmospheric pollutants can act as potential carbon and nitrogen sources for some microorganisms. Compounds base SEBS copolymers, poly(styrene-b-(ethylene-co-butylene)-b-styrene, are a class of thermoplastic elastomers (TPEs), fully recyclable and largely used in automotive parts. Metals, such as cooper and silver, have biocidal activities and the production of the SEBS compounds by melting blending with these agents can be a good option for producing compounds for use in plastic parts of ventilation systems and automotive air-conditioning, in order to minimize the problems caused by growth of pathogenic microorganisms. In this sense, the aim of this work was to evaluate the effect of copper microparticles as antimicrobial agent in compositions based on SEBS/PP/oil/calcite. Copper microparticles were used in weight proportion of 0%, 1%, 2% and 4%. The compounds were prepared using a co-rotating double screw extruder (L/D ratio of 40/1 and 16 mm screw diameter). The processing parameters were 300 rpm of screw rotation rate, with a temperature profile between 150 to 190°C. SEBS based TPE compounds were injection molded. The compounds emission were characterized by gravimetric fogging test. Compounds were characterized by physical (density and staining by contact), mechanical (hardness and tension properties) and rheological properties (melt volume rate – MVR). Antibacterial properties were evaluated against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains. To avaluate the abilities toward the fungi have been chosen Aspergillus niger (A. niger), Candida albicans (C. albicans), Cladosporium cladosporioides (C. cladosporioides) and Penicillium chrysogenum (P. chrysogenum). The results of biological tests showed a reduction on bacteria in up to 88% in E.coli and up to 93% in S. aureus. The tests with fungi showed no conclusive results because the sample without copper also demonstrated inhibition of the development of these microorganisms. The copper addition did not cause significant variations in mechanical properties, in the MVR and the emission behavior of the compounds. The density increases with the increment of copper in compounds.

Keywords: air conditioner, antimicrobial, cooper, SEBS

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