Search results for: nitrate toxicity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1287

Search results for: nitrate toxicity

147 Bioefficacy of Ocimum sanctum on Survival, Development and Reproduction of Dengue Vector Aedes aegypti L. (Diptera: Culicidae)

Authors: Mohd Shazad, K. K. Gupta

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Vector borne diseases are a serious global concern. Aedes aegypti, the primary vector for viruses that cause dengue fever, dengue haemorrhagic fever, chikungunya and yellow fever is widespread over large areas of the tropics and subtropics. In last decade, diseases transmitted by Aedes aegypti are of serious concern. In past decade, number of cases of dengue fever, dengue hemorrhagic fever, and chikungunya has increased multifold. Present research work focused on impact of ethanol extract of Ocimum sanctum on dengue vector Aedes aegypti. 0-24 hr. old fourth instar larvae of lab-bred population of Aedes aegypti were exposed to ethanol leaf extract of Ocimum with concentrations ranging from 50 ppm to 400 ppm. Survival and development and the treated larvae and reproductive behaviour of the adults emerged from the treated larvae was evaluated. Our results indicated larvicidal potential of the leaf ethanol extract. The influence of the extract was dose dependent. 77.2% mortality was observed in the larvae exposed to 400 ppm for 24 hr. Treatment at lower concentrations revealed delayed toxicity. The larvae survived after treatment showed severe developmental anomalies. Consequently, there was the significant increase in duration of fourth instar larva. The L4 treated with 400-ppm extract moulted after 4.6 days; this was in sharp contrast to control where the larval period of the fourth instar lasts three days. The treated fourth instar larvae in many cases transformed into larva-pupa intermediates with the combination of larva, pupa characters. The larva-pupa intermediates had reduced life span and failed to moult successfully. The adults emerged from the larvae treated with lower doses had reduced reproductive potential. The females exhibited longer preoviposition period, reduced oviposition rate, abnormal oviposition behaviour and decreased fertility. Our studies indicated the possibility of the presence of JH mimic or JH analogue in the leaf ethanol extract of Ocimum. The present research work explored the potentials of Ocimum sanctum, also known as the queen of herbs, in integrated vector management programme of Aedes aegypti, which is a serious threat to human health.

Keywords: Aedes aegypti, development, mortality, Ocimum sanctum reproduction

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146 The Assessment of Infiltrated Wastewater on the Efficiency of Recovery Reuse and Irrigation Scheme: North Gaza Emergency Sewage Treatment Project as a Case Study

Authors: Yaser S. Kishawi, Sadi R. Ali

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Part of Palestine, Gaza Strip (365 km2 and 1.8 million habitants) is considered a semi-arid zone relies solely on the Coastal Aquifer. The coastal aquifer is only source of water with only 5-10% suitable for human use. This barely covers the domestic and agricultural needs of Gaza Strip. Palestinian Water Authority Strategy is finding non-conventional water resource from treated wastewater to cover agricultural requirements and serve the population. A new WWTP project is to replace the old-overloaded Biet Lahia WWTP. The project consists of three parts; phase A (pressure line and infiltration basins-IBs), phase B (a new WWTP) and phase C (Recovery and Reuse Scheme–RRS– to capture the spreading plume). Currently, only phase A is functioning. Nearly 23 Mm3 of partially treated wastewater were infiltrated into the aquifer. Phase B and phase C witnessed many delays and this forced a reassessment of the RRS original design. An Environmental Management Plan was conducted from Jul 2013 to Jun 2014 on 13 existing monitoring wells surrounding the project location. This is to measure the efficiency of the SAT system and the spread of the contamination plume with relation to the efficiency of the proposed RRS. Along with the proposed location of the 27 recovery wells as part of the proposed RRS. The results of monitored wells were assessed compared with PWA baseline data. This was put into a groundwater model to simulate the plume to propose the best suitable solution to the delays. The redesign mainly manipulated the pumping rate of wells, proposed locations and functioning schedules (including wells groupings). The proposed simulations were examined using visual MODFLOW V4.2 to simulate the results. The results of monitored wells were assessed based on the location of the monitoring wells related to the proposed recovery wells locations (200m, 500m, and 750m away from the IBs). Near the 500m line (the first row of proposed recovery wells), an increase of nitrate (from 30 to 70mg/L) compare to a decrease in Chloride (1500 to below 900mg/L) was found during the monitoring period which indicated an expansion of plume to this distance. On this rate with the required time to construct the recovery scheme, keeping the original design the RRS will fail to capture the plume. Based on that many simulations were conducted leading into three main scenarios. The scenarios manipulated the starting dates, the pumping rate and the locations of recovery wells. A simulation of plume expansion and path-lines were extracted from the model monitoring how to prevent the expansion towards the nearby municipal wells. It was concluded that the location is the most important factor in determining the RRS efficiency. Scenario III was adopted and showed effective results even with a reduced pumping rates. This scenario proposed adding two additional recovery wells in a location beyond the 750m line to compensate the delays and effectively capture the plume. A continuous monitoring program for current and future monitoring wells should be in place to support the proposed scenario and ensure maximum protection.

Keywords: soil aquifer treatment, recovery reuse scheme, infiltration basins, North Gaza

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145 Application of Free Living Nitrogen Fixing Bacteria to Increase Productivity of Potato in Field

Authors: Govinda Pathak

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In modern agriculture, the sustainable enhancement of crop productivity while minimizing environmental impacts remains a paramount challenge. Plant Growth Promoting Rhizobacteria (PGPR) have emerged as a promising solution to address this challenge. The rhizosphere, the dynamic interface between plant roots and soil, hosts intricate microbial interactions crucial for plant health and nutrient acquisition. PGPR, a subset of rhizospheric microorganisms, exhibit multifaceted beneficial effects on plants. Their abilities to stimulate growth, confer stress tolerance, enhance nutrient availability, and suppress pathogens make them invaluable contributors to sustainable agriculture. This work examines the pivotal role of free living nitrogen fixer in optimizing agricultural practices. We delve into the intricate mechanisms underlying PGPR-mediated plant-microbe interactions, encompassing quorum sensing, root exudate modulation, and signaling molecule exchange. Furthermore, we explore the diverse strategies employed by PGPR to enhance plant resilience against abiotic stresses such as drought, salinity, and metal toxicity. Additionally, we highlight the role of PGPR in augmenting nutrient acquisition and soil fertility through mechanisms such as nitrogen fixation, phosphorus solubilization, and mineral mobilization. Furthermore, we discuss the potential of PGPR in minimizing the reliance on chemical fertilizers and pesticides, thereby contributing to environmentally friendly agriculture. However, harnessing the full potential of PGPR requires a comprehensive understanding of their interactions with host plants and the surrounding microbial community. We also address challenges associated with PGPR application, including formulation, compatibility, and field efficacy. As the quest for sustainable agriculture intensifies, harnessing the remarkable attributes of PGPR offers a holistic approach to propel agricultural productivity while maintaining ecological balance. This work underscores the promising prospect of free living nitrogen fixer as a panacea for addressing critical agricultural challenges regarding chemical urea in an era of sustainable and resilient food production.

Keywords: PGPR, nitrogen fixer, quorum sensing, Rhizobacteria, pesticides

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144 Innovative Preparation Techniques: Boosting Oral Bioavailability of Phenylbutyric Acid Through Choline Salt-Based API-Ionic Liquids and Therapeutic Deep Eutectic Systems

Authors: Lin Po-Hsi, Sheu Ming-Thau

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Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.

Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability

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143 Efficacy and Safety of Updated Target Therapies for Treatment of Platinum-Resistant Recurrent Ovarian Cancer

Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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142 Quantum Chemical Prediction of Standard Formation Enthalpies of Uranyl Nitrates and Its Degradation Products

Authors: Mohamad Saab, Florent Real, Francois Virot, Laurent Cantrel, Valerie Vallet

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All spent nuclear fuel reprocessing plants use the PUREX process (Plutonium Uranium Refining by Extraction), which is a liquid-liquid extraction method. The organic extracting solvent is a mixture of tri-n-butyl phosphate (TBP) and hydrocarbon solvent such as hydrogenated tetra-propylene (TPH). By chemical complexation, uranium and plutonium (from spent fuel dissolved in nitric acid solution), are separated from fission products and minor actinides. During a normal extraction operation, uranium is extracted in the organic phase as the UO₂(NO₃)₂(TBP)₂ complex. The TBP solvent can form an explosive mixture called red oil when it comes in contact with nitric acid. The formation of this unstable organic phase originates from the reaction between TBP and its degradation products on the one hand, and nitric acid, its derivatives and heavy metal nitrate complexes on the other hand. The decomposition of the red oil can lead to violent explosive thermal runaway. These hazards are at the origin of several accidents such as the two in the United States in 1953 and 1975 (Savannah River) and, more recently, the one in Russia in 1993 (Tomsk). This raises the question of the exothermicity of reactions that involve TBP and all other degradation products, and calls for a better knowledge of the underlying chemical phenomena. A simulation tool (Alambic) is currently being developed at IRSN that integrates thermal and kinetic functions related to the deterioration of uranyl nitrates in organic and aqueous phases, but not of the n-butyl phosphate. To include them in the modeling scheme, there is an urgent need to obtain the thermodynamic and kinetic functions governing the deterioration processes in liquid phase. However, little is known about the thermodynamic properties, like standard enthalpies of formation, of the n-butyl phosphate molecules and of the UO₂(NO₃)₂(TBP)₂ UO₂(NO₃)₂(HDBP)(TBP) and UO₂(NO₃)₂(HDBP)₂ complexes. In this work, we propose to estimate the thermodynamic properties with Quantum Methods (QM). Thus, in the first part of our project, we focused on the mono, di, and tri-butyl complexes. Quantum chemical calculations have been performed to study several reactions leading to the formation of mono-(H₂MBP), di-(HDBP), and TBP in gas and liquid phases. In the gas phase, the optimal structures of all species were optimized using the B3LYP density functional. Triple-ζ def2-TZVP basis sets were used for all atoms. All geometries were optimized in the gas-phase, and the corresponding harmonic frequencies were used without scaling to compute the vibrational partition functions at 298.15 K and 0.1 Mpa. Accurate single point energies were calculated using the efficient localized LCCSD(T) method to the complete basis set limit. Whenever species in the liquid phase are considered, solvent effects are included with the COSMO-RS continuum model. The standard enthalpies of formation of TBP, HDBP, and H2MBP are finally predicted with an uncertainty of about 15 kJ mol⁻¹. In the second part of this project, we have investigated the fundamental properties of three organic species that mostly contribute to the thermal runaway: UO₂(NO₃)₂(TBP)₂, UO₂(NO₃)₂(HDBP)(TBP), and UO₂(NO₃)₂(HDBP)₂ using the same quantum chemical methods that were used for TBP and its derivatives in both the gas and the liquid phase. We will discuss the structures and thermodynamic properties of all these species.

Keywords: PUREX process, red oils, quantum chemical methods, hydrolysis

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141 The Staphylococcus aureus Exotoxin Recognition Using Nanobiosensor Designed by an Antibody-Attached Nanosilica Method

Authors: Hamed Ahari, Behrouz Akbari Adreghani, Vadood Razavilar, Amirali Anvar, Sima Moradi, Hourieh Shalchi

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Considering the ever increasing population and industrialization of the developmental trend of humankind's life, we are no longer able to detect the toxins produced in food products using the traditional techniques. This is due to the fact that the isolation time for food products is not cost-effective and even in most of the cases, the precision in the practical techniques like the bacterial cultivation and other techniques suffer from operator errors or the errors of the mixtures used. Hence with the advent of nanotechnology, the design of selective and smart sensors is one of the greatest industrial revelations of the quality control of food products that in few minutes time, and with a very high precision can identify the volume and toxicity of the bacteria. Methods and Materials: In this technique, based on the bacterial antibody connection to nanoparticle, a sensor was used. In this part of the research, as the basis for absorption for the recognition of bacterial toxin, medium sized silica nanoparticles of 10 nanometer in form of solid powder were utilized with Notrino brand. Then the suspension produced from agent-linked nanosilica which was connected to bacterial antibody was positioned near the samples of distilled water, which were contaminated with Staphylococcus aureus bacterial toxin with the density of 10-3, so that in case any toxin exists in the sample, a connection between toxin antigen and antibody would be formed. Finally, the light absorption related to the connection of antigen to the particle attached antibody was measured using spectrophotometry. The gene of 23S rRNA that is conserved in all Staphylococcus spp., also used as control. The accuracy of the test was monitored by using serial dilution (l0-6) of overnight cell culture of Staphylococcus spp., bacteria (OD600: 0.02 = 107 cell). It showed that the sensitivity of PCR is 10 bacteria per ml of cells within few hours. Result: The results indicate that the sensor detects up to 10-4 density. Additionally, the sensitivity of the sensors was examined after 60 days, the sensor by the 56 days had confirmatory results and started to decrease after those time periods. Conclusions: Comparing practical nano biosensory to conventional methods like that culture and biotechnology methods(such as polymerase chain reaction) is accuracy, sensitiveness and being unique. In the other way, they reduce the time from the hours to the 30 minutes.

Keywords: exotoxin, nanobiosensor, recognition, Staphylococcus aureus

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140 Internal Mercury Exposure Levels Correlated to DNA Methylation of Imprinting Gene H19 in Human Sperm of Reproductive-Aged Man

Authors: Zhaoxu Lu, Yufeng Ma, Linying Gao, Li Wang, Mei Qiang

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Mercury (Hg) is a well-recognized environmental pollutant known by its toxicity of development and neurotoxicity, which may result in adverse health outcomes. However, the mechanisms underlying the teratogenic effects of Hg are not well understood. Imprinting genes are emerging regulators for fetal development subject to environmental pollutants impacts. In this study, we examined the association between paternal preconception Hg exposures and the alteration of DNA methylation of imprinting genes in human sperm DNA. A total of 618 men aged from 22 to 59 was recruited from the Reproductive Medicine Clinic of Maternal and Child Care Service Center and the Urologic Surgery Clinic of Shanxi Academy of Medical Sciences during April 2015 and March 2016. Demographic information was collected using questionnaires. Urinary Hg concentrations were measured using a fully-automatic double-channel hydride generation atomic fluorescence spectrometer. And methylation status in the DMRs of imprinting genes H19, Meg3 and Peg3 of sperm DNA were examined by bisulfite pyrosequencing in 243 participants. Spearman’s rank and multivariate regression analysis were used for correlation analysis between sperm DNA methylation status of imprinting genes and urinary Hg levels. The median concentration of Hg for participants overall was 9.09μg/l (IQR: 5.54 - 12.52μg/l; range = 0 - 71.35μg/l); no significant difference was found in median concentrations of Hg among various demographic groups (p > 0.05). The proportion of samples that a beyond intoxication criterion (10μg/l) for urinary Hg was 42.6%. Spearman’s rank correlation analysis indicates a negative correlation between urinary Hg concentrations and average DNA methylation levels in the DMRs of imprinted genes H19 (rs=﹣0.330, p = 0.000). However, there was no such a correlation found in genes of Peg3 and Meg3. Further, we analyzed of correlation between methylation level at each CpG site of H19 and Hg level, the results showed that three out of 7 CpG sites on H19 DMR, namely CpG2 (rs =﹣0.138, p = 0.031), CpG4 (rs =﹣0.369, p = 0.000) and CpG6 (rs=﹣0.228, p = 0.000), demonstrated a significant negative correlation between methylation levels and the levels of urinary Hg. After adjusting age, smoking, drinking, intake of aquatic products and education by multivariate regression analysis, the results have shown a similar correlation. In summary, mercury nonoccupational environmental exposure in reproductive-aged men associated with altered DNA methylation outcomes at DMR of imprinting gene H19 in sperm, implicating the susceptibility of the developing sperm for environmental insults.

Keywords: epigenetics, genomic imprinting gene, DNA methylation, mercury, transgenerational effects, sperm

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139 Phytochemical Screening, Proximate Analysis, Lethality Studies and Anti-Tumor Potential of Annona muricata L. (Soursop) Fruit Extract in Rattus novergicus

Authors: O. C. Abbah, O. Obidoa, J. Omale

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Prostate tumor is fast becoming a leading cause of morbidity and mortality in human male adults, with 50 percent of men aged 50 years and above having histological evidence of the benign tumor. The study was set out to undertake phytochemical screening and proximate analysis of the pulp of A. muricata fruit - soursop; to determine the acute toxicity of the fruit pulp extract and its effect on male albino Wistar rats with concurrent induction of experimental benign prostate hyperplasia (BPH). Eighteen rats (average weight of 100g) were used for the lethality studies and were orally administered graded doses of aqueous extracts of the fruit pulp up to 5000 mg/kg body weight. Twenty five rats weighing 150-200g were divided into five groups of five rats each for the tumor studies. The groups included four controls – Hormone control, HC, which took Testosterone, T; and Estradiol, E2 – only, in olive oil as vehicle; Vehicle control, VC; Soursop control, SC, which received the extract only; VS, Vehicle and Soursop – and the Test group, TG (500mg/kg b.w.). All rats were dosed orally. Tumor was induced with exogenous Testosterone propionate: Estradiol valerate at 300µg: 80µg/kg b.w. (respectively) in olive oil, administered subcutaneously in the inguinal region of the rats on alternate days for 21 days. Administration of the fruit pulp at graded doses up to 5000mg/kg resulted in no lethality even after 72 hours. Results from tumor studies revealed that the administration of the fruit extracts significantly (p < 0.05) reduced the relative prostate weight of the TG compared with the HC, with values of 006±0.001 and 0.010±0.003 respectively. Treatment with vehicle, soursop and vehicle with soursop caused no significant (p>0.05) change in prostate size, with their respective relative prostate weights being 0.002±0.001, 0.004±0.002 and 0.002±0.001 compared with TG. Also, treatment with A. muricata fruit extract significantly decreased (p < 0.05) serum prostate specific antigen, PSA, in TG compared with HC, with values 0.055±0.017 and 0.194±0.068 ng/ml respectively. Furthermore, A. muricata administration displayed Testosterone boosting, Estradiol lowering and consequently testosterone-estradiol ratio increasing potential at the end of the 21 days. The preventive property of soursop against experimental BPH was corroborated by histological evidence in this study. The study concludes that A. muricata fruit holds a great potential for benign prostate tumor prevention and, possibly, management.

Keywords: annona muricata, benign prostate tumor, hormone, preventive potential, soursop

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138 Effects of Lime and N100 on the Growth and Phytoextraction Capability of a Willow Variety (S. Viminalis × S. Schwerinii × S. Dasyclados) Grown in Contaminated Soils

Authors: Mir Md. Abdus Salam, Muhammad Mohsin, Pertti Pulkkinen, Paavo Pelkonen, Ari Pappinen

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Soil and water pollution caused by extensive mining practices can adversely affect environmental components, such as humans, animals, and plants. Despite a generally positive contribution to society, mining practices have become a serious threat to biological systems. As metals do not degrade completely, they require immobilization, toxicity reduction, or removal. A greenhouse experiment was conducted to evaluate the effects of lime and N100 (11-amino-1-hydroxyundecylidene) chelate amendment on the growth and phytoextraction potential of the willow variety Klara (S. viminalis × S. schwerinii × S. dasyclados) grown in soils heavily contaminated with copper (Cu). The plants were irrigated with tap or processed water (mine wastewater). The sequential extraction technique and inductively coupled plasma-mass spectrometry (ICP-MS) tool were used to determine the extractable metals and evaluate the fraction of metals in the soil that could be potentially available for plant uptake. The results suggest that the combined effects of the contaminated soil and processed water inhibited growth parameter values. In contrast, the accumulation of Cu in the plant tissues was increased compared to the control. When the soil was supplemented with lime and N100; growth parameter and resistance capacity were significantly higher compared to unamended soil treatments, especially in the contaminated soil treatments. The combined lime- and N100-amended soil treatment produced higher growth rate of biomass, resistance capacity and phytoextraction efficiency levels relative to either the lime-amended or the N100-amended soil treatments. This study provides practical evidence of the efficient chelate-assisted phytoextraction capability of Klara and highlights its potential as a viable and inexpensive novel approach for in-situ remediation of Cu-contaminated soils and mine wastewaters. Abandoned agricultural, industrial and mining sites can also be utilized by a Salix afforestation program without conflict with the production of food crops. This kind of program may create opportunities for bioenergy production and economic development, but contamination levels should be examined before bioenergy products are used.

Keywords: copper, Klara, lime, N100, phytoextraction

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137 Triazenes: Unearthing Their Hidden Arsenal Against Malaria and Microbial Menace

Authors: Frans J. Smit, Wisdom A. Munzeiwa, Hermanus C. M. Vosloo, Lyn-Marie Birkholtz, Richard K. Haynes

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Malaria and antimicrobial infections remain significant global health concerns, necessitating the continuous search for novel therapeutic approaches. This abstract presents an overview of the potential use of triazenes as effective agents against malaria and various antimicrobial pathogens. Triazenes are a class of compounds characterized by a linear arrangement of three nitrogen atoms, rendering them structurally distinct from their cyclic counterparts. This study investigates the efficacy of triazenes against malaria and explores their antimicrobial activity. Preliminary results revealed significant antimalarial activity of the triazenes, as evidenced by in vitro screening against P. falciparum, the causative agent of malaria. Furthermore, the compounds exhibited broad-spectrum antimicrobial activity, indicating their potential as effective antimicrobial agents. These compounds have shown inhibitory effects on various essential enzymes and processes involved in parasite survival, replication, and transmission. The mechanism of action of triazenes against malaria involves interactions with critical molecular targets, such as enzymes involved in the parasite's metabolic pathways and proteins responsible for host cell invasion. The antimicrobial activity of the triazenes against bacteria and fungi was investigated through disc diffusion screening. The antimicrobial efficacy of triazenes has been observed against both Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains, making them potential candidates for combating drug-resistant infections. Furthermore, triazenes possess favourable physicochemical properties, such as good stability, solubility, and low toxicity, which are essential for drug development. The structural versatility of triazenes allows for the modification of their chemical composition to enhance their potency, selectivity, and pharmacokinetic properties. These modifications can be tailored to target specific pathogens, increasing the potential for personalized treatment strategies. In conclusion, this study highlights the potential of triazenes as promising candidates for the development of novel antimalarial and antimicrobial therapeutics. Further investigations are necessary to determine the structure-activity relationships and optimize the pharmacological properties of these compounds. The results warrant additional research, including MIC studies, to further explore the antimicrobial activity of the triazenes. Ultimately, these findings contribute to the development of more effective strategies for combating malaria and microbial infections.

Keywords: malaria, anti-microbials, triazene, resistance

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136 Environmental Impacts of Point and Non-Point Source Pollution in Krishnagiri Reservoir: A Case Study in South India

Authors: N. K. Ambujam, V. Sudha

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Reservoirs are being contaminated all around the world with point source and Non-Point Source (NPS) pollution. The most common NPS pollutants are sediments and nutrients. Krishnagiri Reservoir (KR) has been chosen for the present case study, which is located in the tropical semi-arid climatic zone of Tamil Nadu, South India. It is the main source of surface water in Krishnagiri district to meet the freshwater demands. The reservoir has lost about 40% of its water holding capacity due to sedimentation over the period of 50 years. Hence, from the research and management perspective, there is a need for a sound knowledge on the spatial and seasonal variations of KR water quality. The present study encompasses the specific objectives as (i) to investigate the longitudinal heterogeneity and seasonal variations of physicochemical parameters, nutrients and biological characteristics of KR water and (ii) to examine the extent of degradation of water quality in KR. 15 sampling points were identified by uniform stratified method and a systematic monthly sampling strategy was selected due to high dynamic nature in its hydrological characteristics. The physicochemical parameters, major ions, nutrients and Chlorophyll a (Chl a) were analysed. Trophic status of KR was classified by using Carlson's Trophic State Index (TSI). All statistical analyses were performed by using Statistical Package for Social Sciences programme, version-16.0. Spatial maps were prepared for Chl a using Arc GIS. Observations in KR pointed out that electrical conductivity and major ions are highly variable factors as it receives inflow from the catchment with different land use activities. The study of major ions in KR exhibited different trends in their values and it could be concluded that as the monsoon progresses the major ions in the water decreases or water quality stabilizes. The inflow point of KR showed comparatively higher concentration of nutrients including nitrate, soluble reactive phosphorus (SRP), total phosphors (TP), total suspended phosphorus (TSP) and total dissolved phosphorus (TDP) during monsoon seasons. This evidently showed the input of significant amount of nutrients from the catchment side through agricultural runoff. High concentration of TDP and TSP at the lacustrine zone of the reservoir during summer season evidently revealed that there was a significant release of phosphorus from the bottom sediments. Carlson’s TSI of KR ranged between 81 and 92 during northeast monsoon and summer seasons. High and permanent Cyanobacterial bloom in KR could be mainly due to the internal loading of phosphorus from the bottom sediments. According to Carlson’s TSI classification Krishnagiri reservoir was ranked in the hyper-eutrophic category. This study provides necessary basic data on the spatio-temporal variations of water quality in KR and also proves the impact of point and NPS pollution from the catchment area. High TSI warrants a greater threat for the recovery of internal P loading and hyper-eutrophic condition of KR. Several expensive internal measures for the reduction of internal loading of P were introduced by many scientists. However, the outcome of the present research suggests for the innovative algae harvesting technique for the removal of sediment nutrients.

Keywords: NPS pollution, nutrients, hyper-eutrophication, krishnagiri reservoir

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135 Impact of Water Interventions under WASH Program in the South-west Coastal Region of Bangladesh

Authors: S. M. Ashikur Elahee, Md. Zahidur Rahman, Md. Shofiqur Rahman

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This study evaluated the impact of different water interventions under WASH program on access of household's to safe drinking water. Following survey method, the study was carried out in two Upazila of South-west coastal region of Bangladesh namely Koyra from Khulna and Shymnagar from Satkhira district. Being an explanatory study, a total of 200 household's selected applying random sampling technique were interviewed using a structured interview schedule. The predicted probability suggests that around 62 percent household's are out of year-round access to safe drinking water whereby, only 25 percent household's have access at SPHERE standard (913 Liters/per person/per year). Besides, majority (78 percent) of the household's have not accessed at both indicators simultaneously. The distance from household residence to the water source varies from 0 to 25 kilometer with an average distance of 2.03 kilometers. The study also reveals that the increase in monthly income around BDT 1,000 leads to additional 11 liters (coefficient 0.01 at p < 0.1) consumption of safe drinking water for a person/year. As expected, lining up time has significant negative relationship with dependent variables i.e., for higher lining up time, the probability of getting access for both SPHERE standard and year round access variables becomes lower. According to ordinary least square (OLS) regression results, water consumption decreases at 93 liters for per person/year of a household if one member is added to that household. Regarding water consumption intensity, ordered logistic regression (OLR) model shows that one-minute increase of lining up time for water collection tends to reduce water consumption intensity. On the other hand, as per OLS regression results, for one-minute increase of lining up time, the water consumption decreases by around 8 liters. Considering access to Deep Tube Well (DTW) as a reference dummy, in OLR, the household under Pond Sand Filter (PSF), Shallow Tube Well (STW), Reverse Osmosis (RO) and Rainwater Harvester System (RWHS) are respectively 37 percent, 29 percent, 61 percent and 27 percent less likely to ensure year round access of water consumption. In line of health impact, different type of water born diseases like diarrhea, cholera, and typhoid are common among the coastal community caused by microbial impurities i.e., Bacteria, Protozoa. High turbidity and TDS in pond water caused by reduction of water depth, presence of suspended particle and inorganic salt stimulate the growth of bacteria, protozoa, and algae causes affecting health hazard. Meanwhile, excessive growth of Algae in pond water caused by excessive nitrate in drinking water adversely effects on child health. In lieu of ensuring access at SPHERE standard, we need to increase the number of water interventions at reasonable distance, preferably a half kilometer away from the dwelling place, ensuring community peoples involved with its installation process where collectively owned water intervention is found more effective than privately owned. In addition, a demand-responsive approach to supply of piped water should be adopted to allow consumer demand to guide investment in domestic water supply in future.

Keywords: access, impact, safe drinking water, Sphere standard, water interventions

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134 Analyze the Properties of Different Surgical Sutures

Authors: Doaa H. Elgohary, Tamer F. Khalifa, Mona M. Salem, M. A. Saad, Ehab Haider Sherazy

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Textiles have conquered new areas over the past three decades, including agriculture, transportation, filtration, military, and medicine. The use of textiles in the medical field has increased significantly in recent years and covers almost everything. Medical textiles represent a huge market as they are widely used not only in hospitals, hygiene, and healthcare but also in hotels and other environments where hygiene is required. However, not all fibers are suitable for the manufacture of medical textile products. Some special properties are required for the manufactured materials, e.g. Strength, elasticity, spinnability, etc. In addition to the usual properties of medical fibers, non-toxicity, sterilizability, biocompatibility, biodegradability, good absorbability, softness, and freedom from additives, etc., desirable properties include impurities. Stitching is one of the most common practices in the medical field. as it is a biomaterial device, either natural or synthetic, used to connect blood vessels and connect tissues. In addition to being very strong, suture material should easily dissolve in bodily fluids and lose strength as the tissue gains strength. In this work, a study to select the most used materials for sutures, it was found that silk, VICRYL and polypropylene were the most used materials in varying numbers. The research involved the analysis of 36 samples from three different materials (mostly commonly used), the tests were carried out on 36 imported samples for four different companies. Each company supplied three different materials (silk, VICRYL and polypropylene) with three different gauges (4, 3.5 and 3 metric). The results of the study were tabulated, presented, and discussed. Practical statistical science serves to support the practical analysis of experimental work products and the various relationships between variables to achieve the best sampling performance with the functional purpose generated for it. Analysis of the imported sutures shows that VICRYL sutures had the highest tensile strength, toughness, knot tensile strength and knot toughness, followed by polypropylene and silk. As yarn counts, weight and diameter increase, its tensile strength and toughness increase while its elongation and knot tension decrease. The multifilament yarn construction (silk and VICRYL) scores higher compared to the monofilament construction (polypropylene), resulting in increases in tenacity, toughness, knot tensile strength and knot toughness.

Keywords: biodegradable yarns, braided sutures, irritation, knot tying, medical textiles, surgical sutures, wound healing

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133 Rice Tablet Poisoning in Iran

Authors: Somayeh Khanjani, Samaneh Nabavi, Shirin Jalili

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Aluminum phosphide (ALP) is an inorganic phosphide used to control insects and is a highly effective insecticide and rodenticide used frequently to protect stored grain. Acute poisoning with this compound is common in some countries including India and Iran, and is a serious health problem. In Iran it was known as "rice tablet", for its use to preserve rice. Two kinds of rice tablets one being herbal while other containing 3g aluminum phosphide (AlP) are available for use in Iranian households to protect stored food grains from pests and rodents. The toxicity of Aluminum phosphide is attributed to the liberation of phosphine gas in contact with water or weak acid and is the major cause of poisoning and deaths. Rice tablet (Aluminum Phosphid) poisoning may be associated with serious and sometimes incurable complications. In 61.3% of patients were shown uniform ingestion. Vomiting was the most common symptoms reported by 96.4% patients. Agitation was reported in 36.9% and felling of thirsty in 27.9 %. Although many complications such as Hypotension, Adult Respiratory Distress Syndrome (ARDS), Acute Renal Failure (ARF) AND Multi Organ Failure (MOF) were the common complications observed in these patients, but the most lethal complication was Cardiac Arrhythmias occurred in 36.9% of cases. Abdominal pain in 31.4% of the patients, nausea in 79.4% of the patients and 41.1% of the patients showed metabolic acidosis. Suicidal intention was the most common cause of poisoning leading to deaths in 18.6% of the patients. Aluminum phosphide can cause either elevation, decrease or no change in electrolytes, bicarbonate and blood glucose level. The possible mechanism for changes in blood glucose levels are complex and depend on the balance of factors which increase its concentration and those which reduce it. AlP poisoning has been postulated to stimulate cortisol which leads to increasing blood level of cortisol, also it may cause stimulation of glucagon, and Adrenaline secretion; in addition, it can inhibit insulin synthesis which may lead to hyperglycemia. Another suggested mechanism of hyperglycemia is rennin activity in some cases, an increase in magnesium level of plasma and that of tissues, and high phosphate level. Although hyperglycemia is most frequent in this poisoning and also is known as a marker of poor prognostic, hypoglycemia in aluminum phosphide poisoning is a rare finding which may be so dangerous. Patients showed sever hypotension and sever acidosis in addition to sever hypoglycemia. The presenting features of AlP intoxication are rapid onset of shock, severe metabolic acidosis, cardiac dysrhythmias and adult respiratory distress syndrome (ARDS).

Keywords: aluminum phosphide (ALP), rice tablet, poisoning, phosphine gas

Procedia PDF Downloads 489
132 Hierarchical Zeolites as Potential Carriers of Curcumin

Authors: Ewelina Musielak, Agnieszka Feliczak-Guzik, Izabela Nowak

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Based on the latest data, it is expected that the substances of therapeutic interest used will be as natural as possible. Therefore, active substances with the highest possible efficacy and low toxicity are sought. Among natural substances with therapeutic effects, those of plant origin stand out. Curcumin isolated from the Curcuma longa plant has proven to be particularly important from a medical point of view. Due to its ability to regulate many important transcription factors, cytokines, and protein kinases, curcumin has found use as an anti-inflammatory, antioxidant, antiproliferative, antiangiogenic, and anticancer agent. The unfavorable properties of curcumin, such as low solubility, poor bioavailability, and rapid degradation under neutral or alkaline pH conditions, limit its clinical application. These problems can be solved by combining curcumin with suitable carriers such as hierarchical zeolites. This is a new class of materials that exhibit several advantages. Hierarchical zeolites used as drug carriers enable delayed release of the active ingredient and promote drug transport to the desired tissues and organs. In addition, hierarchical zeolites play an important role in regulating micronutrient levels in the body and have been used successfully in cancer diagnosis and therapy. To apply curcumin to hierarchical zeolites synthesized from commercial FAU zeolite, solutions containing curcumin, carrier and acetone were prepared. The prepared mixtures were then stirred on a magnetic stirrer for 24 h at room temperature. The curcumin-filled hierarchical zeolites were drained into a glass funnel, where they were washed three times with acetone and distilled water, after which the obtained material was air-dried until completely dry. In addition, the effect of piperine addition to zeolite carrier containing a sufficient amount of curcumin was studied. The resulting products were weighed and the percentage of pure curcumin in the hierarchical zeolite was calculated. All the synthesized materials were characterized by several techniques: elemental analysis, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, Fourier transform infrared (FT-IR), N2 adsorption, and X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The aim of the presented study was to improve the biological activity of curcumin by applying it to hierarchical zeolites based on FAU zeolite. The results showed that the loading efficiency of curcumin into hierarchical zeolites based on commercial FAU-type zeolite is enhanced by modifying the zeolite carrier itself. The hierarchical zeolites proved to be very good and efficient carriers of plant-derived active ingredients such as curcumin.

Keywords: carriers of active substances, curcumin, hierarchical zeolites, incorporation

Procedia PDF Downloads 72
131 Identification of Potent and Selective SIRT7 Anti-Cancer Inhibitor via Structure-Based Virtual Screening and Molecular Dynamics Simulation

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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130 Control of Doxorubicin Release Rate from Magnetic PLGA Nanoparticles Using a Non-Permanent Magnetic Field

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

Procedia PDF Downloads 236
129 Taraxacum Officinale (Dandelion) and Its Phytochemical Approach to Malignant Diseases

Authors: Angel Champion

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Chemotherapy and radiation use an acidified approach to induce apoptosis, which only kills mature cancer cells while resulting in gene and cell damage with significant levels of toxicity in tumor-affected tissues and organs. The acid approach, where the cells exterminated are not differentiated, induces the disappearance of white blood cells from the blood. This increases susceptibility to infection in severe forms of cancer spread. However, chemotherapy and radiation cannot kill cancer stem cells that metastasize, being the leading cause of 98% of cancer fatalities. With over 12 million new cancer cases symptomatic each year, including common malignancies such as Hepatocellular Carcinoma (HCC), this study aims to assess the bioactive constituents and phytochemical composition of Taraxacum Officinale (Dandelion). This analysis enables pharmaceutical quality and potency to be applied to studies on cancer cell proliferation and apoptosis. A phytochemical screening is carried out to identify the antioxidant components of Dandelion root, stem, and flower extract. The constituents tested for are phlorotannins, carbohydrates, glycosides, saponins, flavonoids, alkaloids, sterols, triterpenes, and anthraquinone glycosides. To conserve the existing phenolic compounds, a portion of the constituent tests will be examined with an acid, alcohol, or aqueous solvent. As a result, the qualitative and quantitative variations within the Dandelion extract that measure uniform effective potency are vital to the conformity for producing medicinal products. These medicines will be constructed with a consistent, uniform composition that physicians can use to control and effectively eradicate malignant diseases safely. Taraxacum Officinale's phytochemical composition comprises a highly-graded potency due to present bioactive contents that will essentially drive out malignant disease within the human body. Its high potency rate is powerful enough to eliminate both mature cancer cells and cancer stem cells without the cell and gene damage induced by chemotherapy and radiation. Correspondingly, the high margins of cancer mortality on a global scale are mitigated. This remarkable contribution to modern therapeutics will essentially optimize the margins of natural products and their derivatives, which account for 50% of pharmaceuticals in modern therapeutics, while preventing the adverse effects of radiation and chemotherapy drugs.

Keywords: antioxidant, apoptosis, metastasize, phytochemical, proliferation, potency

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128 Selected Macrophyte Populations Promotes Coupled Nitrification and Denitrification Function in Eutrophic Urban Wetland Ecosystem

Authors: Rupak Kumar Sarma, Ratul Saikia

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Macrophytes encompass major functional group in eutrophic wetland ecosystems. As a key functional element of freshwater lakes, they play a crucial role in regulating various wetland biogeochemical cycles, as well as maintain the biodiversity at the ecosystem level. The high carbon-rich underground biomass of macrophyte populations may harbour diverse microbial community having significant potential in maintaining different biogeochemical cycles. The present investigation was designed to study the macrophyte-microbe interaction in coupled nitrification and denitrification, considering Deepor Beel Lake (a Ramsar conservation site) of North East India as a model eutrophic system. Highly eutrophic sites of Deepor Beel were selected based on sediment oxygen demand and inorganic phosphorus and nitrogen (P&N) concentration. Sediment redox potential and depth of the lake was chosen as the benchmark for collecting the plant and sediment samples. The average highest depth in winter (January 2016) and summer (July 2016) were recorded as 20ft (6.096m) and 35ft (10.668m) respectively. Both sampling depth and sampling seasons had the distinct effect on variation in macrophyte community composition. Overall, the dominant macrophytic populations in the lake were Nymphaea alba, Hydrilla verticillata, Utricularia flexuosa, Vallisneria spiralis, Najas indica, Monochoria hastaefolia, Trapa bispinosa, Ipomea fistulosa, Hygrorhiza aristata, Polygonum hydropiper, Eichhornia crassipes and Euryale ferox. There was a distinct correlation in the variation of major sediment physicochemical parameters with change in macrophyte community compositions. Quantitative estimation revealed an almost even accumulation of nitrate and nitrite in the sediment samples dominated by the plant species Eichhornia crassipes, Nymphaea alba, Hydrilla verticillata, Vallisneria spiralis, Euryale ferox and Monochoria hastaefolia, which might have signified a stable nitrification and denitrification process in the sites dominated by the selected aquatic plants. This was further examined by a systematic analysis of microbial populations through culture dependent and independent approach. Culture-dependent bacterial community study revealed the higher population of nitrifiers and denitrifiers in the sediment samples dominated by the six macrophyte species. However, culture-independent study with bacterial 16S rDNA V3-V4 metagenome sequencing revealed the overall similar type of bacterial phylum in all the sediment samples collected during the study. Thus, there might be the possibility of uneven distribution of nitrifying and denitrifying molecular markers among the sediment samples collected during the investigation. The diversity and abundance of the nitrifying and denitrifying molecular markers in the sediment samples are under investigation. Thus, the role of different aquatic plant functional types in microorganism mediated nitrogen cycle coupling could be screened out further from the present initial investigation.

Keywords: denitrification, macrophyte, metagenome, microorganism, nitrification

Procedia PDF Downloads 149
127 Evaluation of Antioxidant and Anticancer Activity of Tinospora cordifolia against Ehrlich Ascites Carcinoma: In Vitro, in vivo and in silico Approach

Authors: Anik Barua, Rabiul Hossain, Labonno Barua, Rashadul Hossain, Nurul Absar

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Background: Globally, the burden of cancer is increasing consistently. Modern cancer therapies include lots of toxicity in the non-targeted organs reducing the life expectancy of the patients. Hence, scientists are trying to seek noble compounds from natural sources to treat cancer. Objectives: The objectives of the present study are to evaluate the phytochemicals, in vitro antioxidants, and in vivo and in silico anticancer study of various solvent fractions of Tinospora cordifolia (Willd.). Methodology: In this experiment, standard quantitative and qualitative assay methods were used to analyze the phytochemicals. The antioxidant activity was measured using the DPPH and ABTS scavenging methods. The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in Swiss albino mice. In-silico ADME/T and molecular docking study were performed to assess the potential of stated phytochemicals against Transcription Factor STAT3b/DNA Complex of adenocarcinoma. Findings: Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, tannins, and carbohydrates. A significant amount of phenolic (20.19±0.3 mg/g GAE) and flavonoids (9.46±0.18 mg/g GAE) were found in methanolic extract in quantitative screening. Tinospora cordifolia methanolic extract showed promising DPPH and ABTS scavenging activity with the IC50 value of 1222.99 µg/mL and 1534.34 µg/mL, respectively, which was concentration dependent. In vivo anticancer activity in EAC cell-bearing mice showed significant (P < 0.05) percent inhibition of cell growth (60.12±1.22) was found at the highest dose compared with standard drug 5-Fluorouracil (81.18±1.28). Forty-two phytochemicals exhibit notable pharmacokinetics properties and passed drug-likeness screening tests in silico. In molecular docking study, (25S)-3Beta-acetoxy-5-alpha-22-beta-spirost-9(11)-en-12-beta-ol showed docking score (-8.5 kJ/mol) with significant non-bonding interactions with target enzyme. Conclusions: The results were found to be significant and confirmed that the methanolic extract of Tinospora cordifolia has remarkable antitumor activity with antioxidant potential. The Tinospora cordifolia methanolic extract may be considered a potent anticancer agent for advanced research.

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

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126 TiO₂ Nanoparticles Induce DNA Damage and Expression of Biomarker of Oxidative Stress on Human Spermatozoa

Authors: Elena Maria Scalisi

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

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

Procedia PDF Downloads 123
125 Zoledronic Acid with Neoadjuvant Chemotherapy in Advanced Breast Cancer Prospective Study 2011–2014

Authors: S. Sakhri

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Background: The use of Zoledronic acid (ZA) is an established place in the treatment of malignant tumors with a predilection for the skeleton of interest (in particular metastasis). Although the main target of Zoledronic acid was osteoclasts, there are preclinical data suggest that Zoledronic acid may have an antitumor effect on cells other than osteoclasts, including tumor cells. Antitumor activity, including the inhibition of tumor cell growth and the induction of apoptosis of tumor cells, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. Methods. From (2012 to 2014), 438 patients were included respondents the inclusion criteria, respectively. This is a prospective study over a 4 year period. Of all patients (N=438), 432 received neoadjuvant chemotherapy with Zoledronic acid. The primary end point was the pathologic complete response in advancer breast cancer stage. The secondary end point is to evaluate Clinical response according to RECIST criteria; estimate the bone density before and at the end of chemotherapy in women with locally advanced breast cancer, Toxicity Evaluation and Overall survival using Kaplan-Meier and log test. Result: The Objective response rate was 97% after (C4) with 3% stabilizations and 99, 3% of which 0.7% C8 after stabilization. The clinical complete response was 28% after C4 respectively, and 46.8% after C8, the pathologic complete response rate was 40.13% according to the classification Sataloff. We observed that the pathologic complete response rate was the most raised in the group including Her2 (luminal Her2 and Her2) the lowest in the triple negative group as classified by Sataloff. We found that the pCR is significantly higher in the age group (35-50 years) with 53.17%. Those who have more than 50 years in 2nd place with 27.7% and the lower in young woman 35 years pCR was 19%, not statistically significant, -The pCR was also in favor of the menopausal group in 51, 4%, and 48, 55% for non-menopausal women. The average duration of overall survival was also significantly in the subgroup (Luminal -Her2, Her2) compared with triple negative. It is 47.18 months in the luminal group vs. 38.95 in the triple negative group. -Was observed in our study a difference in quality of life between (C1) was the admission of the patient, and after (C8), we found an increase in general signs and a deterioration in the psychological state C1, in contrast to the C8 these general signs and mental status improves, up to 12, and 24 months. Conclusion The results of this study suggest that the addition of ZA to néoadjuvant CT has potential anti-cancer benefit in patients (Luminal -Her2, Her2) compared with triple negative with or without menopause status.

Keywords: HER2+, RH+, breast cancer, tyrosine kinase

Procedia PDF Downloads 190
124 Fuzzy Optimization for Identifying Anticancer Targets in Genome-Scale Metabolic Models of Colon Cancer

Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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123 Antimicrobial Activity, Phytochemistry and Toxicity Of Extracts Of Naturally Growing and Cultivated Aloe Turkanensis

Authors: Zachary Muthii Rukenya, James Mbaria, Peter Mbaabu, Kiama Stephen Gitahi, Ronald Onzago

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Aloe turkanensis is one of the widely used medicinal shrub and in Kenya the plant is mainly found in Baringo, Isiolo, Laikipia, Turkana and West Pokot Counties where it is used in ethno-medicine and ethno-veterinary medicine. The Turkana community uses the plant products to manage malaria, wounds, stomach ache, constipation, pain, skin infection, poultry diseases and retained afterbirth in cows. This evaluated the efficacy and safety of the plant obtained from Turkana County, Kenya. Preliminary data on the use of the plant in the county was collected through observation, photographing and interviews. A sample of the whole plant was harvested in Natira sublocation, in ex-Turkana west district in February 2012 after identification by Aloe-working group herbalists who voluntarily provided information on its medicinal uses. Botanical identification was done at Kenya Forest Research Centre in Karura where voucher specimen was deposited. Cold maceration using 70% methanol and distilled water was used for extraction. Bioassays were to determine the effects of the plant extracts on brine shrimp and selected bacterial and fungal cultures. The extracts were tested in-vitro activity against standard cultures of B. cereus (ATCC 11778), S. aureus (ATCC25923), P. aeroginosa (ATCC 27853), E. coli (ATCC 25922) and a human infections clinical isolate of C. albicans. The extracts of Aloe turkanensis inhibited the growth B. cereus (100-200 mg/ml), S. aureus (50-100 mg/ml), P. aeroginosa (200mg/ml), E. coli (400mg/ml) while C. albicans was not affected. The extracts also inhibited the growth of S. aureus and B. cereus with mean diameters of inhibition zones being 19.75±1 mm and 18.5±05 mm reapectively. Phytochemical screening showed the presence of alkaloids, tarpenoids, steroids, quinones, saponins and tannins in the plant extracts. The extract was found to be non-toxic at a concentration of 1000µg/ml with a 100% survival of Brine Shrimp larva. It was concluded that Aloe turkanensis growing the study area has metabolites that inhibit the growth of microorganisms and is however, there is need for further studies to validate the in-vivo bioactivity of the plant and more generate adequate toxicological data.to support conservation, value chain addition of its products and widespread use as a herbal remedy.

Keywords: Aloe turkanensis, bioactivity, cultivated, human infections

Procedia PDF Downloads 298
122 Antiulcer Potential of Heme Oxygenase-1 Inducers

Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

Procedia PDF Downloads 485
121 Radiation Induced DNA Damage and Its Modification by Herbal Preparation of Hippophae rhamnoides L. (SBL-1): An in vitro and in vivo Study in Mice

Authors: Anuranjani Kumar, Madhu Bala

Abstract:

Ionising radiation exposure induces generation of free radicals and the oxidative DNA damage. SBL-1, a radioprotective leaf extract prepared from leaves Hippophae rhamnoides L. (Common name; Seabuckthorn), showed > 90% survival in mice population that was treated with lethal dose (10 Gy) of ⁶⁰Co gamma irradiation. In this study, early effects of pre-treatment with or without SBL-1 in blood peripheral blood lymphocytes (PBMCs) were investigated by cell viability assays (trypan blue and MTT). The quantitative in vitro study of Hoescht/PI staining was performed to check the apoptosis/necrosis in PBMCs irradiated at 2 Gy with or without pretreatment of SBL-1 (at different concentrations) up to 24 and 48h. Comet assay was performed in vivo, to detect the DNA strands breaks and its repair mechanism on peripheral blood lymphocytes at lethal dose (10 Gy). For this study, male mice (wt. 28 ± 2g) were administered radioprotective dose (30mg/kg body weight) of SBL-1, 30 min prior to irradiation. Animals were sacrificed at 24h and 48h. Blood was drawn through cardiac puncture, and blood lymphocytes were separated using histopaque column. Both neutral and alkaline comet assay were performed using standardized technique. In irradiated animals, alkaline comet assay revealed single strand breaks (SSBs) that showed significant (p < 0.05) increase in percent DNA in tail and Olive tail moment (OTM) at 24 h while at 48h the percent DNA in tail further increased significantly (p < 0.02). The double strands breaks (DSBs) increased significantly (p < 0.01) at 48 h in neutral assay, in comparison to untreated control. The animals pre-treated with SBL-1 before irradiation showed significantly (p < 0.05) less DSBs at 48 h treatment in comparison to irradiated group of animals. The SBL-1 alone treated group itself showed no toxicity. The antioxidant potential of SBL-1 were also investigated by in vitro biochemical assays such as DPPH (p < 0.05), ABTS, reducing ability (p < 0.09), hydroxyl radical scavenging (p < 0.05), ferric reducing antioxidant power (FRAP), superoxide radical scavenging activity (p < 0.05), hydrogen peroxide scavenging activity (p < 0.05) etc. SBL-1 showed strong free radical scavenging power that plays important role in the studies of radiation-induced injuries. The SBL-1 treated PBMCs showed significant (p < 0.02) viability in trypan blue assay at 24-hour incubation.

Keywords: radiation, SBL-1, SSBs, DSBs, FRAP, PBMCs

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120 Noninvasive Technique for Measurement of Heartbeat in Zebrafish Embryos Exposed to Electromagnetic Fields at 27 GHz

Authors: Sara Ignoto, Elena M. Scalisi, Carmen Sica, Martina Contino, Greta Ferruggia, Antonio Salvaggio, Santi C. Pavone, Gino Sorbello, Loreto Di Donato, Roberta Pecoraro, Maria V. Brundo

Abstract:

The new fifth generation technology (5G), which should favor high data-rate connections (1Gbps) and latency times lower than the current ones (<1ms), has the characteristic of working on different frequency bands of the radio wave spectrum (700 MHz, 3.6-3.8 GHz and 26.5-27.5 GHz), thus also exploiting higher frequencies than previous mobile radio generations (1G-4G). The higher frequency waves, however, have a lower capacity to propagate in free space and therefore, in order to guarantee the capillary coverage of the territory for high reliability applications, it will be necessary to install a large number of repeaters. Following the introduction of this new technology, there has been growing concern in recent years about the possible harmful effects on human health and several studies were published using several animal models. This study aimed to observe the possible short-term effects induced by 5G-millimeter waves on heartbeat of early life stages of Danio rerio using DanioScope software (Noldus). DanioScope is the complete toolbox for measurements on zebrafish embryos and larvae. The effect of substances can be measured on the developing zebrafish embryo by a range of parameters: earliest activity of the embryo’s tail, activity of the developing heart, speed of blood flowing through the vein, length and diameters of body parts. Activity measurements, cardiovascular data, blood flow data and morphometric parameters can be combined in one single tool. Obtained data are elaborate and provided by the software both numerical as well as graphical. The experiments were performed at 27 GHz by a no commercial high gain pyramidal horn antenna. According to OECD guidelines, exposure to 5G-millimeter waves was tested by fish embryo toxicity test within 96 hours post fertilization, Observations were recorded every 24h, until the end of the short-term test (96h). The results have showed an increase of heartbeat rate on exposed embryos at 48h hpf than control group, but this increase has not been shown at 72-96 h hpf. Nowadays, there is a scant of literature data about this topic, so these results could be useful to approach new studies and also to evaluate potential cardiotoxic effects of mobile radiofrequency.

Keywords: Danio rerio, DanioScope, cardiotoxicity, millimeter waves.

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119 Risk Assessment and Haloacetic Acids Exposure in Drinking Water in Tunja, Colombia

Authors: Bibiana Matilde Bernal Gómez, Manuel Salvador Rodríguez Susa, Mildred Fernanda Lemus Perez

Abstract:

In chlorinated drinking water, Haloacetic acids have been identified and are classified as disinfection byproducts originating from reaction between natural organic matter and/or bromide ions in water sources. These byproducts can be generated through a variety of chemical and pharmaceutical processes. The term ‘Total Haloacetic Acids’ (THAAs) is used to describe the cumulative concentration of dichloroacetic acid, trichloroacetic acid, monochloroacetic acid, monobromoacetic acid, and dibromoacetic acid in water samples, which are usually measured to evaluate water quality. Chronic presence of these acids in drinking water has a risk of cancer in humans. The detection of THAAs for the first time in 15 municipalities of Boyacá was accomplished in 2023. Aim is to describe the correlation between the levels of THAAs and digestive cancer in Tunja, a city in Colombia with higher rates of digestive cancer and to compare the risk across 15 towns, taking into account factors such as water quality. A research project was conducted with the aim of comparing water sources based on the geographical features of the town, describing the disinfection process in 15 municipalities, and exploring physical properties such as water temperature and pH level. The project also involved a study of contact time based on habits documented through a survey, and a comparison of socioeconomic factors and lifestyle, in order to assess the personal risk of exposure. Data on the levels of THAAs were obtained after characterizing the water quality in urban sectors in eight months of 2022. This, based on the protocol described in the Stage 2 DBP of the United States Environmental Protection Agency (USEPA) from 2006, which takes into account the size of the population being supplied. A cancer risk assessment was conducted to evaluate the likelihood of an individual developing cancer due to exposure to pollutants THAAs. The assessment considered exposure methods like oral ingestion, skin absorption, and inhalation. The chronic daily intake (CDI) for these exposure routes was calculated using specific equations. The lifetime cancer risk (LCR) was then determined by adding the cancer risks from the three exposure routes for each HAA. The risk assessment process involved four phases: exposure assessment, toxicity evaluation, data gathering and analysis, and risk definition and management. The results conclude that there is a cumulative higher risk of digestive cancer due to THAAs exposure in drinking water.

Keywords: haloacetic acids, drinking water, water quality, cancer risk assessment

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118 Electrodeposition of Silicon Nanoparticles Using Ionic Liquid for Energy Storage Application

Authors: Anjali Vanpariya, Priyanka Marathey, Sakshum Khanna, Roma Patel, Indrajit Mukhopadhyay

Abstract:

Silicon (Si) is a promising negative electrode material for lithium-ion batteries (LiBs) due to its low cost, non-toxicity, and a high theoretical capacity of 4200 mAhg⁻¹. The primary challenge of the application of Si-based LiBs is large volume expansion (~ 300%) during the charge-discharge process. Incorporation of graphene, carbon nanotubes (CNTs), morphological control, and nanoparticles was utilized as effective strategies to tackle volume expansion issues. However, molten salt methods can resolve the issue, but high-temperature requirement limits its application. For sustainable and practical approach, room temperature (RT) based methods are essentially required. Use of ionic liquids (ILs) for electrodeposition of Si nanostructures can possibly resolve the issue of temperature as well as greener media. In this work, electrodeposition of Si nanoparticles on gold substrate was successfully carried out in the presence of ILs media, 1-butyl-3-methylimidazolium-bis (trifluoromethyl sulfonyl) imide (BMImTf₂N) at room temperature. Cyclic voltammetry (CV) suggests the sequential reduction of Si⁴⁺ to Si²⁺ and then Si nanoparticles (SiNs). The structure and morphology of the electrodeposited SiNs were investigated by FE-SEM and observed interconnected Si nanoparticles of average particle size ⁓100-200 nm. XRD and XPS data confirm the deposition of Si on Au (111). The first discharge-charge capacity of Si anode material has been found to be 1857 and 422 mAhg⁻¹, respectively, at current density 7.8 Ag⁻¹. The irreversible capacity of the first discharge-charge process can be attributed to the solid electrolyte interface (SEI) formation via electrolyte decomposition, and trapped Li⁺ inserted into the inner pores of Si. Pulverization of SiNs results in the creation of a new active site, which facilitates the formation of new SEI in the subsequent cycles leading to fading in a specific capacity. After 20 cycles, charge-discharge profiles have been stabilized, and a reversible capacity of 150 mAhg⁻¹ is retained. Electrochemical impedance spectroscopy (EIS) data shows the decrease in Rct value from 94.7 to 47.6 kΩ after 50 cycles of charge-discharge, which demonstrates the improvements of the interfacial charge transfer kinetics. The decrease in the Warburg impedance after 50 cycles of charge-discharge measurements indicates facile diffusion in fragmented and smaller Si nanoparticles. In summary, Si nanoparticles deposited on gold substrate using ILs as media and characterized well with different analytical techniques. Synthesized material was successfully utilized for LiBs application, which is well supported by CV and EIS data.

Keywords: silicon nanoparticles, ionic liquid, electrodeposition, cyclic voltammetry, Li-ion battery

Procedia PDF Downloads 105