Search results for: white blood cell detection

Authors: Ratih Fitria Putri, Josaphat Tetuko Sri Sumantyo, Hiroaki Kuze

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Jakarta Metropolitan City is located on the northwest coast of West Java province with geographical location between 106º33’ 00”-107º00’00”E longitude and 5º48’30”-6º24’00”S latitude. Jakarta urban area has been suffered from land subsidence in several land use type as trading, industry and settlement area. Land subsidence hazard is one of the consequences of urban development in Jakarta. This hazard is caused by intensive human activities in groundwater extraction and land use mismanagement. Geologically, the Jakarta urban area is mostly dominated by alluvium fan sediment. The objectives of this research are to make an analysis of Jakarta urban land use type on land subsidence zone areas. The process of producing safer land use and settlements of the land subsidence areas are very important. Spatial distributions of land subsidence detection are necessary tool for land use management planning. For this purpose, Differential Synthetic Aperture Radar Interferometry (DInSAR) method is used. The DInSAR is complementary to ground-based methods such as leveling and global positioning system (GPS) measurements, yielding information in a wide coverage area even when the area is inaccessible. The data were fine tuned by using X-Band image satellite data from 2010 to 2013 and land use mapping data. Our analysis of land use type that land subsidence movement occurred on the northern part Jakarta Metropolitan City varying from 7.5 to 17.5 cm/year as industry and settlement land use type areas.

Keywords: land use analysis, land subsidence mapping, urban area, X-band satellite image

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Authors: Wen-Jay Lee, Kuo-Ning Chiang

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The graphene binding with silicon substrate has apparently Schottky barriers property, which can be used in the application of solar cell and light source. Because graphene has only one atom layer, the atomistic structure of graphene binding with the silicon surface plays an important role to affect the properties of graphene. In this work, temperature effect on the morphology of graphene sheet attached on different crystal planes of silicon substrates are investigated by Molecular dynamics (MD) (LAMMPS, developed by Sandia National Laboratories). The results show that the covered graphene sheet would cause the structural deformation of the surface Si atoms of stubtrate. To achieve a stable state in the binding process, the surface Si atoms would adjust their position and fit the honeycomb structure of graphene after the graphene attaches to the Si surface. The height contour of graphene on different plane of silicon surfaces presents different pattern, leading the local residual stress at the interface. Due to the high density of dangling bond on the Si (111)7x7 surface, the surface of Si(111)7x7 is not matching with the graphene so well in contrast with Si(100)2x1and Si(111)2x1. Si(111)7x7 is found that only partial silicon adatoms are rearranged on surface after the attachment when the temperature is lower than 200K, As the temperature gradually increases, the deformation of surface structure becomes significant, as well as the residue stress. With increasing temperature till the 815K, the graphene sheet begins to destroy and mixes with the silicon atoms. For the Si(100)2x1 and Si(111)2x1, the silicon surface structure keep its structural arrangement with a higher temperature. With increasing temperature, the residual stress gradually decrease till a critical temperatures. When the temperature is higher than the critical temperature, the residual stress gradually increases and the structural deformation is found on the surface of the Si substrates.

Keywords: molecular dynamics, graphene, silicon, Schottky barriers, interface

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Authors: Digby Wrede, Stephen Gray, Syed Hussainy

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Microalgae are extremely useful organisms but notoriously hard to harvest. The use of fungal pellets has been found to be an efficient way to flocculate numerous species of algae. However, only the flocculation of single species of algae has been investigated. Algae are generally found in complex communities in the environment comprising of numerous species of algae ranging from simple single cell algae such as Chlorella to more complex or communal algae such as Dictyosphaerium. This study investigated the flocculation capabilities of Aspergillus oryzae to flocculate four species of algae; Chlorella vulgaris, Scenedesmus quadricauda, Scenedesmus acuminatus and Dictyosphaerium sp., and the algal communities in four different types of domestic effluent from a lagoon-based treatment plant; primary effluent, secondary effluent and the high rate algal pond effluent at a natural and at a lowered pH level. Spectrophotometry was used to measure the changes in algal population. C. vulgaris, S. acuminatus and S. quadricauda, had over 90% reduction of algal in suspension after 24 hours. Dictyosphaerium sp. showed a little to no removal after 24 hours. The primary, secondary, and natural pH level HRAP had roughly a 50% removal after 24 hours, the HRAP which was grown at a lower pH level had over a 90% removal after 24 hours. pH has been shown previously to affect fungal flocculation. Fungal and algae pellets have been shown to be able to treat wastewater and can be converted to biofuels in a very similar method to how algae are currently converted. The mixture of both fungi and algae has also been shown to provide a higher yield of oils then separately and are able to more efficiently treat wastewater then algae or fungi by themselves.

Keywords: algae harvesting, Aspergillus oryzae, fungal flocculation, wastewater treatment

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Authors: Mar Cañada Soriano, Rafael Royo-Pastor, Carolina Aparicio-Fernández, Jose-Luis Vivancos

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The lack of insulation, along with the existence of air leakages, constitute a meaningful impact on the energy performance of buildings. Both of them lead to increases in the energy demand through additional heating and/or cooling loads. Additionally, they cause thermal discomfort. In order to quantify these uncontrolled air currents, pressurization and depressurization tests can be performed. Among them, the Blower Door test is a standardized procedure to determine the airtightness of a space which characterizes the rate of air leakages through the envelope surface, calculating to this purpose an air flow rate indicator. In this sense, the low-energy buildings complying with the Passive House design criteria are required to achieve high levels of airtightness. Due to the invisible nature of air leakages, additional tools are often considered to identify where the infiltrations take place. Among them, the infrared thermography entails a valuable technique to this purpose since it enables their detection. The aim of this study is to assess the airtightness of a typical Mediterranean dwelling house located in the Valencian orchad (Spain) restored under the Passive House standard using to this purpose the blower-door test. Moreover, the building energy performance modelling tools TRNSYS (TRaNsient System Simulation program) and TRNFlow (TRaNsient Flow) have been used to determine its energy performance, and the infiltrations’ identification was carried out by means of infrared thermography. The low levels of infiltrations obtained suggest that this house may comply with the Passive House standard.

Keywords: airtightness, blower door, trnflow, infrared thermography

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Authors: Ankit Kumar Yadav, Nagendra R. Velaga

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Driving under the influence of alcohol impairs the driving performance and increases the crash risks worldwide. The present study investigated the effect of different Blood Alcohol Concentrations (BAC) on the accelerating and braking behaviour of drivers with the help of driving simulator experiments. Eighty-two licensed Indian drivers drove on the rural road environment designed in the driving simulator at BAC levels of 0.00%, 0.03%, 0.05%, and 0.08% respectively. Driving performance was analysed with the help of vehicle control performance indicators such as mean acceleration and mean brake pedal force of the participants. Preliminary analysis reported an increase in mean acceleration and mean brake pedal force with increasing BAC levels. Generalized linear mixed models were developed to quantify the effect of different alcohol levels and explanatory variables such as driver’s age, gender and other driver characteristic variables on the driving performance indicators. Alcohol use was reported as a significant factor affecting the accelerating and braking performance of the drivers. The acceleration model results indicated that mean acceleration of the drivers increased by 0.013 m/s², 0.026 m/s² and 0.027 m/s² for the BAC levels of 0.03%, 0.05% and 0.08% respectively. Results of the brake pedal force model reported that mean brake pedal force of the drivers increased by 1.09 N, 1.32 N and 1.44 N for the BAC levels of 0.03%, 0.05% and 0.08% respectively. Age was a significant factor in both the models where one year increase in drivers’ age resulted in 0.2% reduction in mean acceleration and 19% reduction in mean brake pedal force of the drivers. It shows that driving experience could compensate for the negative effects of alcohol to some extent while driving. Female drivers were found to accelerate slower and brake harder as compared to the male drivers which confirmed that female drivers are more conscious about their safety while driving. It was observed that drivers who were regular exercisers had better control on their accelerator pedal as compared to the non-regular exercisers during drunken driving. The findings of the present study revealed that drivers tend to be more aggressive and impulsive under the influence of alcohol which deteriorates their driving performance. Drunk driving state can be differentiated from sober driving state by observing the accelerating and braking behaviour of the drivers. The conclusions may provide reference in making countermeasures against drinking and driving and contribute to traffic safety.

Keywords: alcohol, acceleration, braking behaviour, driving simulator

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Authors: Sena Park

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Background: The concurrent presentation with colorectal cancer in the inguinal hernia has been extremely rare. Due to its rarity, its presentation may lead to diagnostic and therapeutic dilemmas. We aim to review all the reported cases on colorectal cancer incarcerated in the inguinal hernia in the last 20 years, and discuss the operative approaches. Methods: We identified all case reports on colorectal cancer within inguinal hernia using PUBMED (2002-2022) and MEDLINE (2002-2022). The search strategy included the following keywords: colorectal cancer (title/abstract) AND inguinal hernia (title/abstract) OR incarceration (title/abstract). The search did not include letters, book chapters, systemic reviews, meta-analysis and editorials. Results: In the last 20 years, a total of 19 cases on colorectal cancer within the inguinal hernia were identified. The age of the patients ranged between 48 and 89. Majority of the patients were male (95%). Most commonly involved part of the large intestine was sigmoid colon (79%). Of all the cases, 79 percent of patients received open procedure and 21 percent had laparoscopic procedure. Discussion: Inguinal hernias are common with an incidence of approximately 1.7 percent. Colorectal cancer is the one of the leading causes of cancer-related mortality worldwide. However, their concurrent presentation has been extremely rare. In the last 20 years, 19 cases on concurrent presentation of colorectal cancer and inguinal hernia have been reported. Most patients who had open procedures had two incisions of groin incision and a midline laparotomy. There were 4 cases where the oncological resection was performed laparoscopically. The advantages of laparoscopic resection include reduced blood lost, reduced post-operative pain, reduced length of hospital stay and similar number of lymph nodes taken. From the review of the cases in the last 20 years, both open and laparoscopic approaches seemed to be safe and achieve adequate oncological resections. Conclusion: This is a brief overview of reported cases of colorectal cancer presenting with inguinal hernia concurrently. Due to its rarity, there are no current guidelines on operative approach in clinical practice. The experience in the last 20 years supports both open and laparoscopic approach.

Keywords: colorectal cancer, inguinal hernia, incarceration, operative approach

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Authors: Dake Xiong, Ben Hankamer, Ian Ross

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The most urgent challenge of our time is to replace the depleting resources of fossil fuels by sustainable environmentally friendly alternatives. Hydrogen is a promising CO2-neutral fuel for a more sustainable future especially when produced photo-biologically. Hydrogen can be photosynthetically produced in unicellular green alga like Chlamydomonas reinhardtii, catalysed by the inducible highly active and bidirectional [FeFe]-hydrogenase enzymes (HydA). However, evolutionary and physiological constraints severely restrict the hydrogen yield of algae for industrial scale-up, mainly due to its competition among other metabolic pathways on photosynthetic electrons. Among them, a major challenge to be resolved is the inferior competitiveness of hydrogen production (catalysed by HydA) with NADPH production (catalysed by ferredoxin-NADP+-reductase (FNR)), which is essential for cell growth and takes up ~95% of photosynthetic electrons. In this work, the in vivo hydrogen production efficiency of mutants with ferredoxin-hydrogenase (Fd*-HydA1*) fusion protein construct, where the electron donor ferredoxin (Fd*) is fused to HydA1* and expressed in the model organism C. reinhardtii was investigated. Once Fd*-HydA1* fusion gene is expressed in algal cells, the fusion enzyme is able to draw the redistributed photosynthetic electrons and use them for efficient hydrogen production. From preliminary data, mutants with Fd*-HydA1* transgene showed a ~2-fold increase in the photosynthetic hydrogen production rate compared with its parental strain, which only possesses the native HydA in vivo. Therefore, a solid method of having more efficient hydrogen production in microalgae can be achieved through the expression of the synthetic enzymes.

Keywords: Chlamydomonas reinhardtii, ferredoxin, fusion protein, hydrogen production, hydrogenase

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Authors: Katie Emerson, Sara Perez-Ojalvo, Jim Komorowski, Danielle Greenberg

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The purpose of this study was to evaluate arginase activity levels in response to combinations of an inositol-stabilized arginine silicate (ASI; Nitrosigine®), L-arginine, and Inositol. Arginine acts as a vasodilator that promotes increased blood flow resulting in enhanced delivery of oxygen and nutrients to the brain and other tissues. ASI alone has been shown to improve performance on cognitive tasks. Arginase, found in human serum, catalyzes the conversion of arginine to ornithine and urea, completing the last step in the urea cycle. Decreasing arginase levels maintains arginine and results in increased nitric oxide production. This study aimed to determine the most effective combination of ASI, L-arginine and inositol for minimizing arginase levels and therefore maximize ASI’s effect on cognition. Serum was taken from untreated healthy donors by separation from clotted factors. Arginase activity of serum in the presence or absence of test products was determined (QuantiChrom™, DARG-100, Bioassay Systems, Hayward CA). The remaining ultra-filtrated serum units were harvested and used as the source for the arginase enzyme. ASI alone or combined with varied levels of Inositol were tested as follows: ASI + inositol at 0.25 g, 0.5 g, 0.75 g, or 1.00 g. L-arginine was also tested as a positive control. All tests elicited changes in arginase activity demonstrating the efficacy of the method used. Adding L-arginine to serum from untreated subjects, with or without inositol only had a mild effect. Adding inositol at all levels reduced arginase activity. Adding 0.5 g to the standardized amount of ASI led to the lowest amount of arginase activity as compared to the 0.25g 0.75g or 1.00g doses of inositol or to L-arginine alone. The outcome of this study demonstrates an interaction of the pairing of inositol with ASI on the activity of the enzyme arginase. We found that neither the maximum nor minimum amount of inositol tested in this study led to maximal arginase inhibition. Since the inhibition of arginase activity is desirable for product formulations looking to maintain arginine levels, the most effective amount of inositol was deemed preferred. Subsequent studies suggest this moderate level of inositol in combination with ASI leads to cognitive improvements including reaction time, executive function, and concentration.

Keywords: arginine, inositol, arginase, cognitive benefits

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Authors: Muhammad S. Sajid, Asim Shamim, Muhammad Nisar Khan, Ashfaq A. Chatta, Muhammad Saqib

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Goats (Capra hircus) are a valued asset for resource poor farmers globally. But the parasitic infection especially Haemonchus contortus (Trichostrongylid), impact the health and production of goats globally. The present study intended to evaluate resilient and resistance to Haemonchus contortus in indigenous goat breeds (Teddy and Beetal) of Punjab, Pakistan. Out of 60, 30 goats of each breed were divided into 6 groups and each group contain five goats. Two group of each breed received challenged infection with 12000 and 18000 L3 (third stage) larvae of Haemonchus contortus under two infection protocol that is early and trickle and remaining two group of each breed was kept as control. Resilient and resistance of each breed was then measured on the basis of their phenotypic markers like: faecal egg counts, packed cell volume, FAMACHA score system, body weight, total protein, albumin and worm count on 2nd, 4th, 6th, and 8th week of post infection. Variation in response of each goat breeds to Haemonchus contortus was observed. Teddy breed showed significant (P < 0.05)resistance as compared to Beetal. It is probably first attempt to report an evaluation of goat breed response towards Haemonchus contortus in Pakistan. It was concluded that Teddy goats have a greater genetic tendency to resist against to the Haemonchus contortus infection and this breed could be kept and bred from the economic point of view. Evaluation of genetic markers are like: gene, protein expression, Immunoglobulin, Histamines and interleukins determination are recommended for future studies which can be helpful to be fined resistant breed of goats.

Keywords: goat, beetal, teddy, haemonchus contortus, resistance, resilience, phenotypic markers

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Authors: Khushbu Priyadarshi, Chandramani Pathak

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Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.

Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein

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Authors: Ágota Ábrahám, Md Nurul Islam, Karimane Zeghbib, Gábor Kemenesi, Sazeda Akter

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Collecting palm sap as a food source is an everyday practice in some parts of the world. However, the consumption of palm juice has been associated with regular infections and epidemics in parts of Bangladesh. This is attributed to fruit-eating bats and other vertebrates or invertebrates native to the area, contaminating the food with their body secretions during the collection process. The frequent intake of palm juice, whether as a processed food product or in its unprocessed form, is a common phenomenon in large areas. The range of pathogens suitable for human infection resulting from this practice is not yet fully understood. Additionally, the high sugar content of the liquid makes it an ideal culture medium for certain bacteria, which can easily propagate and potentially harm consumers. Rapid diagnostics, especially in remote locations, could mitigate health risks associated with palm juice consumption. The primary objective of this research is the rapid genomic detection and risk assessment of bacteria that may cause infections in humans through the consumption of palm juice. Utilizing state-of-the-art third-generation Nanopore metagenomic sequencing technology based on 16S rRNA, and identified bacteria primarily involved in fermenting processes. The swift metagenomic analysis, coupled with the widespread availability and portability of Nanopore products (including real-time analysis options), proves advantageous for detecting harmful pathogens in food sources without relying on extensive industry resources and testing.

Keywords: raw date palm sap, NGS, metabarcoding, food safety

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Authors: Ahmed F. Azmy, Amal E. Saafan, Tamer M. Essam, Magdy A. Amin, Shaban H. Ahmed

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Bacterial strains capable of degradation of malathion from the domestic sewage were isolated by an enrichment culture technique. Three bacterial strains were screened and identified as Acinetobacter baumannii (AFA), Pseudomonas aeruginosae (PS1),andPseudomonas mendocina (PS2) based on morphological, biochemical identification and 16S rRNA sequence analysis. Acinetobacter baumannii AFA was the most efficient malathion degrading bacterium, so used for further biodegradation study. AFA was able to grow in mineral salt medium (MSM) supplemented with malathion (100 mg/l) as a sole carbon source, and within 14 days, 84% of the initial dose was degraded by the isolate measured by high performance liquid chromatography. Strain AFA could also degrade other organophosphorus compounds including diazenon, chlorpyrifos and fenitrothion. The effect of different culture conditions on the degradation of malathion like inoculum density, other carbon or nitrogen sources, temperature and shaking were examined. Degradation of malathion and bacterial cell growth were accelerated when culture media were supplemented with yeast extract, glucose and citrate. The optimum conditions for malathion degradation by strain AFA were; an inoculum density of 1.5x 1012CFU/ml at 30°C with shaking. A specific polymerase chain reaction primers were designed manually using multiple sequence alignment of the corresponding carboxylesterase enzymes of Acinetobacter species. Sequencing result of amplified PCR product and phylogenetic analysis showed low degree of homology with the other carboxylesterase enzymes of Acinetobacter strains, so we suggested that this enzyme is a novel esterase enzyme. Isolated bacterial strains may have potential role for use in bioremediation of malathion contaminated.

Keywords: Acinetobacter baumannii, biodegradation, malathion, organophosphate pesticides

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Authors: Nikolai Nosik, Vladislav Podmasterjev, Nina Kondrashina, Marina Chataeva, Olga Lobach, Dmitry Noosik, Sergei Razumovskii

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Virucidal activity of ozone is well known: dissolved in water it kill viruses very fast. The virucidal capacity of ozone in ozone-air mixture is less known. The goal of the study was to investigate the virucidal potentials of the ozone–air mixture and kinetics of virus inactivation. Materials and methods. Ozone (O3 ) was generated from oxygen with ozonizer ( 1.0 – 75.0 mg\l). The ozone concentration was determined by the spectrophotometric methods. Virus contaminated samples were placed into the flowing reactor. Viruses: poliovirus type 1, vaccine strain (Sabin) and adenovirus, type 5, were obtained from the State virus collection. Titrations of viruses were carried out in appropriate cell cultures. CxT value ( mg\l x min) was calculated. Results. Metallic, polycarbonic and fiber “Kevlar” samples were contaminated with virus, dried and treated with ozone-air mixture in the flowing reactor. Kinetics of poliovirus inactivation: in 15 min at 5.0 mg\l -2.0 lg TCID50 inhibition , in 15 min at 10 mg\l – 2.5 lg TCID50 , 4.0 lg TCID50 inactivation of poliovirus was achieved after 75min at ozone concentration 20.0mg\l (99.99%). ( CxT = 75, 150 and 1500 mg\l x min on all three types of surfaces). It was found that the inactivation of poliovirus was more effective when the virus contaminated samples were wet (in 15 min at 20mg\l inhibition of virus in dry samples was 2.0 TCID50 , in wet samples – 4.0 TCID50). Adenovirus was less resistant to ozone treatment then poliovirus: 4.0 lg TCID50 inhibition was observed after 30 min of the treatment with ozone at 20mg\l ( CxT mg\l x min = 300 for adenovirus as for poliovirus it was 1500). Conclusion. It was found that ozone-air mixture inactivates viruses at rather high concentrations (compared to the reported effect of ozone dissolved in water). Despite of that there is a difference in the resistance to ozone action between viruses – poliovirus is more resistant then adenovirus-ozone-air mixture can be used for disinfection of large rooms. The maintaining of the virus-contaminated surfaces in wet condition allow to decrease the ozone load for virus inactivation.

Keywords: adenovirus, disinfection, ozone, poliovirus

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Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and has been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. The prickly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, the southwestern region of Korea, and used as a functional food. The present study investigated the effects of OFS on adipogenesis, lipolysis, glucose uptake, and glucose transporter (GLUT4) expression using preadipocyte 3T3-L1 cells. Adipogenesis was determined by preadipocyte differentiation and triglyceride accumulation assessed by Oil Red O staining. Lipolysis was determined as the rate of glycerol release. Insulin-stimulated glucose uptake and GLUT4 expression were measured using fluorescent glucose analogue, 2-NBDG, and ELISA, respectively. Quantitative real-time RT-PCR was performed to investigate the effects of OFS on the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation. Ethanol extracts of OFS dose-dependently enhanced adipocyte differentiation and cellular triglyceride levels indicating the enhancement of the differentiation of preadipocytes into adipocytes. Insulin-stimulated glucose uptake and GLUT4 expression were also dose-dependently increased by OFS treatment. Furthermore, OFS treatment also increased the mRNA levels of PPARγ. These effects of OFS on adipocytes suggest that OFS is potentially beneficial for type 2 diabetes by due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

Keywords: 3T3-L1 preadipocyte cell, adipogenesis, GLUT4, lipolysis, Opuntia ficus-indica var. Saboten, PPARγ, prickly pear cactus

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Authors: Afifa Hafidh, Hedia Chaabane

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This work mainly focused on the synthetic strategies and biological activities associated with pyrazoles. Pyrazole derivatives have been successfully synthesized by simple and facile method and studied for their antibacterial activity. These compounds were prepared from pyrazolic difunctional compounds as starting materials, by reaction with salicylic acid, paracetamol and thiosemicarbazide respectively. Structure of all the prepared compounds confirmation were proved using (FT-IR), (1H-NMR) and (13C-NMR) spectra in addition to melting points. The screening of the antimicrobial activity of the pyrazolic derivatives was examined against different microorganisms in the present study. They were screened for their antimicrobial activities against gram positive bacteria, gram negative bacteria and Candida albicans. The synthesized compounds were found to exhibit high antibacterial and antifungal efficiency against several tested bacterial strains, using agar diffusion method and filter paper disc-diffusion method. Ampicillin was used as positive control for all strains except Candida albicans for which Nystatin was used. The obtained results reveal that the antibacterial activity of some pyrazolic derivatives is comparable to that observed for the control samples (Ampicilin and Nystatin), suggesting a strong antibacterial activity. The analysis of these results shows that synthesized products react on the surfaces cell walls that are disrupted. When these products are in contact with the bacteria, they damage the membrane, leading to the perturbation of different cellular processes and then leakage of cytoplasm, resulting in the death of the cells. The results will be presented in details. The obtained products constitute effective antibacterial agents and important compounds for biological systems.

Keywords: salicylic acid, antimicrobial activities, antioxidant activity, paracetamol, pyrazole, thiosemicarbazide

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Authors: Ouzid Yasmina, Aiche-Iratni Ghenima, Harchaoui Lina, Saadoun Noria, Houali Karim

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Medicinal plants are an important source of bioactive molecules with biological activities such as anticancer, antioxidant, anti-inflammatory, antibacterial, antimitotic.... These molecules include alkaloids, polyphenols and terpenes. The latter can be extracted by different solvents, namely: water, ethanol, methanol, butanol, acetone... This is why it seemed interesting to us to evaluate in vitro the antimitotic and genotoxic effect of these secondary metabolites contained in the aqueous extract of the leaves of Peganum harmala L. by the Allium cepa L. test on meristematic cells by calculating the mitotic parameters (The mitotic index, the aberration index and the limit value of cytotoxicity).A spectrophotometric determination of secondary metabolites, namely alkaloids and flavonoids in the aqueous extract of this essence, was performed. As a result, the alkaloid content is estimated to be 28.42 μg EC/mg extract, and the flavonoid content is 12.52 μg EQ/mg extract. The determination of the mitotic index revealed disturbances in cell division with a highly significant difference between the negative control (distilled water) and the different samples (aqueous extracts, colchicine and quecetin). The exposure of meristematic cells to our samples resulted in a large number of chromosomal, nuclear and cellular aberrations with an aberration index reaching 16.21±1.28% for the 4mg/ml aqueous extract and 11.71±3.32% for the 10mg/ml aqueous extract. The limit value of cytotoxicity revealed that our samples are sublethal on Allium cepa L. meristematic cells.

Keywords: allium cepa l., antimitotic and genotoxic effect, aqueous leaf extract, laghouat (algeria), peganum harmala l., secondary metabolites

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Authors: S. M. M. Syairah, M. H. Rajikin, A. R. Sharaniza

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Several embryonic cellular mechanism including cell cycle, growth and apoptosis are regulated by phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The goal of present study is to determine the effects of annatto (Bixa orellana)-derived δ-tocotrienol (δ-TCT) on the regulations of PI3K/Akt genes in murine morula. Twenty four 6-8 week old (23-25g) female balb/c mice were randomly divided into four groups (G1-G4; n=6). Those groups were subjected to the following treatments for 7 consecutive days: G1 (control) received tocopherol stripped corn oil, G2 was given 60 mg/kg/day of δ-TCT mixture (contains 90% delta & 10% gamma isomers), G3 was given 60 mg/kg/day of pure δ-TCT (>98% purity) and G4 received 60 mg/kg/day α-TOC. On Day 8, females were superovulated with 5 IU Pregnant Mare’s Serum Gonadotropin (PMSG) for 48 hours followed with 5 IU human Chorionic Gonadotropin (hCG) before mated with males at the ratio of 1:1. Females were sacrificed by cervical dislocation for embryo collection 48 hours post-coitum. About fifty morula from each group were used in the gene expression analyses using Affymetrix QuantiGene Plex 2.0 Assay. Present data showed a significant increase (p<0.05) in the average number (mean + SEM) of morula produced in G2 (26.0 + 0.45), G3 (23.0 + 0.63) and G4 (25.0 + 0.73) compared to control group (G1 – 16.0 + 0.63). This is parallel with the high expression of PDK1 gene with increase of 2.75-fold (G2), 3.07-fold (G3) and 3.59-fold (G4) compared to G1 (1.78-fold). From the present data, it can be concluded that supplementation with δ-TCT(s) and α-TOC induced high expression of PDK1 in G2-G4 which enhanced the PI3K/Akt signaling activity, resulting in the increased number of morula.

Keywords: delta-tocotrienol, embryonic development, nicotine, vitamin E

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Authors: Kim Byeong-Gon, Lee Pureun-Haneul, Hong Jisu, Jang An-Soo

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Background: Diesel exhaust particles (DEPs) lead to trigger airway hyperresponsiveness (AHR) and airway dysfunction or inflammation in respiratory systems. Whether tight junction protein changes can contribute to development or exacerbations of airway diseases remain to be clarified. Objective: The aim of this study was to observe the effect of DEP on tight junction proteins in one airway both nose and lung in a mouse model. Methods: Mice were treated with saline (Sham) and exposed to 100 μg/m³ DEPs 1 hour a day for 5 days a week for 4 weeks and 8 weeks in a closed-system chamber attached to a ultrasonic nebulizer. Airway hyperresponsiveness (AHR) was measured and bronchoalveolar lavage (BAL) fluid, nasal lavage (NAL) fluid, lung and nasal tissue was collected. The effects of DEP on tight junction proteins were estimated using western blot, immunohistochemical in lung and nasal tissue. Results: Airway hyperresponsiveness and number of inflammatory cells were higher in DEP exposure group than in control group, and were higher in 4 and 8 weeks model than in control group. The expression of tight junction proteins CLND4, -5, and -17 in both lung and nasal tissue were significantly increased in DEP exposure group than in the control group. Conclusion: These results suggesting that CLDN4, -5 and -17 may be involved in the airway both nose and lung, suggesting that air pollutants cause to disruption of epithelial and endothelial cell barriers. Acknowledgment: This research was supported by Korea Ministry of Environment (MOE) as 'The Environmental Health Action Program' (2016001360009) and Soonchunhyang University Research Fund.

Keywords: diesel exhaust particles, air pollutant, tight junction, Claudin, Airway inflammation

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Authors: Yanping Liao, Congcong He, Ruigang Zhao

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The application of magnetocardiography signals to detect cardiac electrical function is a new technology developed in recent years. The magnetocardiography signal is detected with Superconducting Quantum Interference Devices (SQUID) and has considerable advantages over electrocardiography (ECG). It is difficult to extract Magnetocardiography (MCG) signal which is buried in the noise, which is a critical issue to be resolved in cardiac monitoring system and MCG applications. In order to remove the severe background noise, the Total Variation (TV) regularization method is proposed to denoise MCG signal. The approach transforms the denoising problem into a minimization optimization problem and the Majorization-minimization algorithm is applied to iteratively solve the minimization problem. However, traditional TV regularization method tends to cause step effect and lacks constraint adaptability. In this paper, an improved TV regularization method for denoising MCG signal is proposed to improve the denoising precision. The improvement of this method is mainly divided into three parts. First, high-order TV is applied to reduce the step effect, and the corresponding second derivative matrix is used to substitute the first order. Then, the positions of the non-zero elements in the second order derivative matrix are determined based on the peak positions that are detected by the detection window. Finally, adaptive constraint parameters are defined to eliminate noises and preserve signal peak characteristics. Theoretical analysis and experimental results show that this algorithm can effectively improve the output signal-to-noise ratio and has superior performance.

Keywords: constraint parameters, derivative matrix, magnetocardiography, regular term, total variation

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Authors: M. Zareh, H. Mohammadi, B. Naser

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Atherosclerotic plaque rupture is the main trigger of heart attack and brain stroke which are the leading cause of death in developed countries. Better understanding of rupture-prone plaque can help clinicians detect vulnerable plaques- rupture prone or instable plaques- and apply immediate medical treatment to prevent these life-threatening cardiovascular events. Therefore, there are plenty of studies addressing disclosure of vulnerable plaques properties. Necrotic core and fibrous tissue are two major tissues constituting atherosclerotic plaque; using histopathological and numerical approaches, many studies have demonstrated that plaque rupture is strongly associated with a large necrotic core and a thin fibrous cap, two morphological characteristic which can be acquired by two-dimensional imaging of atherosclerotic plaque present in coronary and carotid arteries. Plaque rupture is widely considered as a mechanical failure inside plaque tissue; this failure occurs when the stress within plaque excesses the strength of tissue material; hence, finite element method, a strong numerical approach, has been extensively applied to estimate stress distribution within plaques with different compositions which is then used for assessment of various vulnerability characteristics including plaque morphology, material properties and blood pressure. This study aims to evaluate significance of three-dimensional morphology on vulnerability degree of atherosclerotic plaque. To reach this end, different two-dimensional geometrical models of atherosclerotic plaques are considered based on available data and named Main 2D Models (M2M). Then, for each of these M2Ms, two three-dimensional idealistic models are created. These two 3D models represent two possible three-dimensional morphologies which might exist for a plaque with similar 2D morphology to one of M2Ms. Finite element method is employed to estimate stress, von-Mises stress, within each 3D models. Results indicate that for each M2Ms stress can significantly varies due to possible 3D morphological changes in that plaque. Also, our results show that an atherosclerotic plaque with thick cap may experience rupture if it has a critical 3D morphology. This study highlights the effect of 3D geometry of plaque on its instability degree and suggests that 3D morphology of plaque might be necessary to more effectively and accurately assess atherosclerotic plaque vulnerability.

Keywords: atherosclerotic plaque, plaque rupture, finite element method, 3D model

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Authors: Miranda Lin

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This project examined the impact of a globally focused service-learning project implemented in a multicultural education course in a Midwestern university. This project facilitated critical self-reflection and build cross-cultural competence while nurturing a partnership with two schools that serve students with disabilities in Vietnam. Through a service-learning project, pre-service teachers connected via Skype with the principals/teachers at schools in Vietnam to identify and subsequently develop needed instructional materials for students with mild, moderate, and severe disabilities. Qualitative data sources include students’ intercultural competence self-reflection survey (pre-test and post-test), reflections, discussions, service project, and lesson plans. Literature Review- Global service-learning is a teaching strategy that encompasses service experiences both in the local community and abroad. Drawing on elements of global learning and international service-learning, global service-learning experiences are guided by a framework that is designed to support global learning outcomes and involve direct engagement with difference. By engaging in real-world challenges, global service-learning experiences can support the achievement of learning outcomes such as civic. Knowledge and intercultural knowledge and competence. Intercultural competence development is considered essential for cooperative and reciprocal engagement with community partners.Method- Participants (n=27*) were mostly elementary and early childhood pre-service teachers who were enrolled in a multicultural education course. All but one was female. Among the pre-service teachers, one Asian American, two Latinas, and the rest were White. Two pre-service teachers identified themselves as from the low socioeconomic families and the rest were from the middle to upper middle class.The global service-learning project was implemented in the spring of 2018. Two Vietnamese schools that served students with disabilities agreed to be the global service-learning sites. Both schools were located in an urban city.Systematic collection of data coincided with the course schedule as follows: an initial intercultural competence self-reflection survey completed in week one, guided reflections submitted in week 1, 9, and 16, written lesson plans and supporting materials for the service project submitted in week 16, and a final intercultural competence self-reflection survey completed in week 16. Significance-This global service-learning project has helped participants meet Merryfield’s goals in various degrees. They 1) learned knowledge and skills in the basics of instructional planning, 2) used a variety of instructional methods that encourage active learning, meet the different learning styles of students, and are congruent with content and educational goals, 3) gained the awareness and support of their students as individuals and as learners, 4) developed questioning techniques that build higher-level thinking skills, and 5) made progress in critically reflecting on and improving their own teaching and learning as a professional educator as a result of this project.

Keywords: global service-learning, teacher education, intercultural competence, diversity

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Authors: Chi-Ching Lee, Po-Jung Huang, Kuo-Yang Huang, Petrus Tang

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Background: Recent advances in high-throughput research technologies such as new-generation sequencing and multi-dimensional liquid chromatography makes it possible to dissect the complete transcriptome and proteome in a single run for the first time. However, it is almost impossible for many laboratories to handle and analysis these “BIG” data without the support from a bioinformatics team. We aimed to provide a web-based analysis platform for users with only limited knowledge on bio-computing to study the functional genomics and proteomics. Method: We use NCI-60 as an example dataset to demonstrate the power of the web-based analysis platform and data delivering system: C-eXpress takes a simple text file that contain the standard NCBI gene or protein ID and expression levels (rpkm or fold) as input file to generate a distribution map of gene/protein expression levels in a heatmap diagram organized by color gradients. The diagram is hyper-linked to a dynamic html table that allows the users to filter the datasets based on various gene features. A dynamic summary chart is generated automatically after each filtering process. Results: We implemented an integrated database that contain pre-defined annotations such as gene/protein properties (ID, name, length, MW, pI); pathways based on KEGG and GO biological process; subcellular localization based on GO cellular component; functional classification based on GO molecular function, kinase, peptidase and transporter. Multiple ways of sorting of column and rows is also provided for comparative analysis and visualization of multiple samples.

Keywords: cancer, visualization, database, functional annotation

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Authors: A. Flammini, R. Morbidelli, C. Saltalippi

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The increase of air surface temperature at global scale is a fact, with values around 0.85 ºC since the late nineteen century, as well as a significant change in main features of rainfall regime. Nevertheless, the detected climatic changes are not equally distributed all over the world, but exhibit specific characteristics in different regions. Therefore, studying the evolution of climatic indices in different geographical areas with a prefixed standard approach becomes very useful in order to analyze the existence of climatic trend and compare results. In this work, a methodology to investigate the climatic change and its effects on a wide set of climatic indices is proposed and applied at regional scale in the case study of a Mediterranean area, Umbria region in Italy. From data of the available temperature stations, nine temperature indices have been obtained and the existence of trends has been checked by applying the non-parametric Mann-Kendall test, while the non-parametric Pettitt test and the parametric Standard Normal Homogeneity Test (SNHT) have been applied to detect the presence of break points. In addition, aimed to characterize the rainfall regime, data from 11 rainfall stations have been used and a trend analysis has been performed on cumulative annual rainfall depth, daily rainfall, rainy days, and dry periods length. The results show a general increase in any temperature indices, even if with a trend pattern dependent of indices and stations, and a general decrease of cumulative annual rainfall and average daily rainfall, with a time rainfall distribution over the year different from the past.

Keywords: climatic change, temperature, rainfall regime, trend analysis

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Authors: T. D. Ibragimov, A. R. Imamaliyev, G. M. Bayramov

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Influence of barium titanate particles on electro-optic properties of liquid crystal 4-cyano-4′-pentylbiphenyl (5CB) with positive dielectric anisotropy and the liquid crystalline (LC) mixture Н-37 consisting of 4-methoxybezylidene-4'–butylaniline and 4-ethoxybezylidene-4'–butylaniline with negative dielectric anisotropy was investigated. It was shown that a presence of particles inside 5СВ and H-37 decreased the clearing temperature from 35.2 °С to 32.5°С and from 61.2 oC to 60.1oC, correspondingly. The threshold voltage of the Fredericksz effect became 0.3 V for the BaTiO3-5CB colloid while the beginning of this effect of the pure 5СВ was observed at 2.1 V. Threshold voltage of the Fredericksz effect increased from 2.8 V to up 3.1 V at additive of particles into H-37. A rise time of the BaTiO3-5CB colloid improved while a decay time worsened in comparison with the pure 5CB at all applied voltages. The inverse trends were observed for the H-37 matrix, namely, a rise time worsened and a decay time improved. Among other things, the effect of fast light modulation was studied at application of the rectangular impulse with direct bias to an electro-optical cell with the BaTiO3 particles+5CB and the pure 5CB. At this case, a rise time of the composite worsened, a decay time improved in comparison with the pure 5CB. The pecularities of electrohydrodynamic instability (EHDI) formation was also investigated into the composite with the H-37 matrix. It was found that the voltage of the EHDI formation decreased, a rise time increased and a decay time decreased in comparison with the pure H-37. First of all, experimental results are explained by appearance of local electric fields near the polarized ferroelectric particles at application of external electric field and an existence of the additional obstacles (particles) for movement of ions.

Keywords: liquid crystal, ferroelectric particles, composite, electro-optics

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Authors: J. Pazourek, K. Šmejkal, P. Kollár, J. Rajchard, J. Šinko, Z. Balounová, E. Vlková, H. Salmonová

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Pectinatella magnifica (Leidy, 1851) is an invasive freshwater animal that lives in colonies. A colony of Pectinatella magnifica (a gelatinous blob) can be up to several feet in diameter large and under favorable conditions it exhibits an extreme growth rate. Recently European countries around rivers of Elbe, Oder, Danube, Rhine and Vltava have confirmed invasion of Pectinatella magnifica, including freshwater reservoirs in South Bohemia (Czech Republic). Our project (Czech Science Foundation, GAČR P503/12/0337) is focused onto biology and chemistry of Pectinatella magnifica. We monitor the organism occurrence in selected South Bohemia ponds and sandpits during the last years, collecting information about physical properties of surrounding water, and sampling the colonies for various analyses (classification, maps of secondary metabolites, toxicity tests). Because the gelatinous matrix is during the colony lifetime also a host for algae, bacteria and cyanobacteria (co-habitants), in this contribution, we also applied a high performance liquid chromatography (HPLC) method for determination of potentially present cyanobacterial toxins (microcystin-LR, microcystin-RR, nodularin). Results from the last 3-year monitoring show that these toxins are under limit of detection (LOD), so that they do not represent a danger yet. The final goal of our study is to assess toxicity risks related to fresh water resources invaded by Pectinatella magnifica, and to understand the process of invasion, which can enable to control it.

Keywords: cyanobacteria, fresh water resources, Pectinatella magnifica invasion, toxicity monitoring

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Authors: Xu Yifei, Le Yining, Yang Qingluan, Tu Yanjie

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Objective: This study aims to investigate the distribution features of Traditional Chinese Medicine (TCM) syndromes and syndrome elements in Epstein-Barr virus-associated diseases and then explores the relations between TCM syndromes or syndrome elements and laboratory indicators of Epstein-Barr virus-associated diseases. Methods: A cross-sectional study of 70 patients with EBV infection was described. We assessed the diagnostic information and laboratory indicators of these patients from Huashan Hospital Affiliated to Fudan University between November 2017 and July 2019. The disease diagnosis and syndrome differentiation were based on the diagnostic criteria of EBV-associated diseases and the theory of TCM respectively. Confidence correlation analysis, logistic regression analysis, cluster analysis, and the Sankey diagram were used to analyze the correlation between the data. Results: The differentiation of the 4 primary TCM syndromes in the collected patients was correlated with the indexes of immune function, liver function, inflammation, and anemia, especially the relationship between Qifen syndrome and high lactic acid dehydrogenase level. The common 11 TCM syndrome elements were associated with the increased CD3+ T cell rate, low hemoglobin level, high procalcitonin level, high lactic acid dehydrogenase level, and low albumin level. Conclusion: The changes in immune function indexes, procalcitonin, and liver function-related indexes in patients with EBV-associated diseases were consistent with the evolution law of TCM syndromes. This study provides a reference for judging the pathological stages of these kinds of diseases, predicting their prognosis, and guiding subsequent treatment strategies based on TCM syndrome type.

Keywords: EBV-associated diseases, traditional Chinese medicine syndrome, syndrome element, diagnostics

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Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

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Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

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In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

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Authors: Hossein Tavallali, Mohammad Ali Karimi, Gohar Deilamy-Rad

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The proposed method for speciation, preconcentration and determination of Fe(II) and Fe(III) in pharmaceutical products was developed using of alumina-coated magnetite nanoparticles (Fe₃O₄/Al₂O₃ NPs) as solid phase extraction (SPE) sorbent in magnetic mixed hemimicell solid phase extraction (MMHSPE) technique followed by flame atomic absorption spectrometry analysis. The procedure is based on complexation of Fe(II) with 1, 10-phenanthroline (OP) as complexing reagent for Fe(II) that immobilized on the modified Fe₃O₄/Al₂O₃ NPs. The extraction and concentration process for pharmaceutical sample was carried out in a single step by mixing the extraction solvent, magnetic adsorbents under ultrasonic action. Then, the adsorbents were isolated from the complicated matrix easily with an external magnetic field. Fe(III) ions determined after facility reduced to Fe(II) by added a proper reduction agent to sample solutions. Compared with traditional methods, the MMHSPE method simplified the operation procedure and reduced the analysis time. Various influencing parameters on the speciation and preconcentration of trace iron, such as pH, sample volume, amount of sorbent, type and concentration of eluent, were studied. Under the optimized operating conditions, the preconcentration factor of the modified nano magnetite for Fe(II) 167 sample was obtained. The detection limits and linear range of this method for iron were 1.0 and 9.0 - 175 ng.mL⁻¹, respectively. Also the relative standard deviation for five replicate determinations of 30.00 ng.mL^-1 Fe²⁺ was 2.3%.

Keywords: Alumina-Coated magnetite nanoparticles, Magnetic Mixed Hemimicell Solid-Phase Extraction, Fe(ΙΙ) and Fe(ΙΙΙ), pharmaceutical sample

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Authors: Amos Sunday Onikanni, Bashir Lawal, Babatunji Emmanuel Oyinloye, Gomaa Mostafa-Hedeab, Mohammed Alorabi, Simona Cavalu, Augustine O. Olusola, Chih-Hao Wang, Gaber El-Saber Batiha

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The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in a significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ-induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 β/Na+-K+-ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescent leaves could be considered a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Keywords: diabetes mellitus, neuroprotective, antioxidant, pro-inflammatory cytokines

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