Search results for: proline accumulation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 971

Search results for: proline accumulation

821 Exploring the Strategy to Identify Seed-Specific Acyl-Hydrolases from Arabidopsis thaliana by Activity-Based Protein Profiling

Authors: M. Latha, Achintya K. Dolui, P. Vijayaraj

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Vegetable oils mainly triacylglycerol (TAG) are an essential nutrient in the human diet as well as one of the major global commodity. There is a pressing need to enhance the yield of oil production to meet the world’s growing demand. Oil content is controlled by the balance between synthesis and breakdown in the cells. Several studies have established to increase the oil content by the overexpression of oil biosynthetic enzymes. Interestingly the significant oil accumulation was observed with impaired TAG hydrolysis. Unfortunately, the structural, as well as the biochemical properties of the lipase enzymes, is widely unknown, and so far, no candidate gene was identified in seeds except sugar-dependent1 (SDP1). Evidence has shown that SDP1directly responsible for initiation of oil breakdown in the seeds during germination. The present study is the identification of seed-specific acyl-hydrolases by activity based proteome profiling (ABPP) using Arabidopsis thaliana as a model system. The ABPP reveals that around 8 to 10 proteins having the serine hydrolase domain and are expressed during germination of Arabidopsis seed. The N-term sequencing, as well as LC-MS/MS analysis, was performed for the differentially expressed protein during germination. The coding region of the identified proteins was cloned, and lipases activity was assessed with purified recombinant protein. The enzyme assay was performed against various lipid substrates, and we have observed the acylhydrolase activity towards lysophosphatidylcholine and monoacylglycerol. Further, the functional characteristic of the identified protein will reveal the physiological significance the enzyme in oil accumulation.

Keywords: lipase, lipids, vegetable oil, triacylglycerol

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820 Design, Synthesis, and Evaluation of Small Peptides for Managing Inflammation: Inhibition to Substrate Approach

Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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819 Effect of Vesicular Arbuscular mycorrhiza on Phytoremedial Potential and Physiological Changes in Solanum melongena Plants Grown under Heavy Metal Stress

Authors: Ritu Chaturvedi, Mayank Varun, M. S. Paul

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Heavy metal contamination of soil is a growing area of concern since the soil is the matrix that supports flora and impacts humans directly. Phytoremediation of contaminated sites is gaining popularity due to its cost effectiveness and solar driven nature. Some hyperaccumulators have been identified for their potential. Metal-accumulating plants have various mechanisms to cope up with stress and one of them is increasing antioxidative capacity. The aim of this research is to assess the effect of Vesicular arbuscular mycorrhiza (VAM) application on the phytoremedial potential of Solanum melongena (Eggplant) and level of photosynthetic pigments along with antioxidative enzymes. Results showed that VAM application increased shoot length, root proliferation pattern of plants. The level of photosynthetic pigments, proline, SOD, CAT, APX altered significantly in response to heavy metal treatment. In conclusion, VAM increased the uptake of heavy metals which lead to the activation of the defense system in plants for scavenging free radicals.

Keywords: heavy metal, phytoextraction, phytostabilization, reactive oxygen species

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818 Effectiveness of Multi-Business Core Development Policy in Tokyo Metropolitan Area

Authors: Takashi Nakamura

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In the Tokyo metropolitan area, traffic congestion and long commute times are caused by overconcentration in the central area. To resolve these problems, a core business city development policy was adopted in 1988. The core business cities, which include Yokohama, Chiba, Saitama, Tachikawa, and others, have designated business facilities accumulation districts where assistance measures are applied. Focusing on Yokohama city, this study investigates the trends in the number of offices, employees, and commuters at 2001 and 2012 Economic Census, as well as the average commute time in the Tokyo metropolitan area from 2005 to 2015 Metropolitan Transportation Census. Surveys were administered in 2001 and 2012 Economic Census to participants who worked in Yokohama, according to their distribution in the city's 1,757 subregions. Four main findings emerged: (1) The number of offices increased in Yokohama when the number of offices decreased in the Tokyo metropolitan area overall. Additionally, the number of employees at Yokohama increased. (2) The number of commuters to Tokyo's central area increased from Saitama prefecture, Tokyo Tama area, and Tokyo central area. However, it decreased from other areas. (3) The average commute time in the Tokyo metropolitan area was 67.7 minutes in 2015, a slight decrease from 2005 and 2010. (4) The number of employees at business facilities accumulation districts in Yokohama city increased greatly.

Keywords: core business city development policy, commute time, number of employees, Yokohama city, distribution of employees

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817 Production of Mycelial Biomass, Exopolysaccharide, and Enzyme during Solid-State Fermentation of Plant Raw Materials by Medicinal Mushrooms

Authors: Tamar Khardziani, Violeta Berikashvili, Amrosi Chkuaseli, Vladimir Elisashvili

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The main objectives of this proposal are to develop low-cost, innovative, and competitive technologies for the production of mycelial biomass of medicinal mushrooms as a natural food supplement for poultry. To fulfill this task, industrial strains of Lentinus edodes, Ganoderma lucidum, and Pleurotus ostreatus were used in this study. The solid-state fermentation (SSF) of wheat grains, wheat bran, and soy flour was performed in flasks and bags. Among nine mushroom strains, P. ostreatus 2191 appeared to be the most productive in protein biomass accumulation in the SSF of wheat bran. All mushrooms produced exopolysaccharide with the highest yield of 5-8 mg/mL depending on fungal strain and growth substrate. Supplementation of medium with 1% glycerol and 2-4% peptone favored mushroom growth and protein accumulation. Among inorganic nitrogen sources, KNO₃ also provided high biomass and protein production. The SSF of all growth substrates was accompanied by the secretion of cellulase and xylanase activities. The highest CMCase activity (12-13 U/g) was revealed in the cultivation of P. ostreatus 2191 using wheat bran as a growth substrate and ammonium sulfate or yeast extract as a nitrogen source, whereas the highest xylanase activity was detected in the fermentation of soy flour supplemented with peptone. Acknowledgments: This work was supported by the Shota Rustaveli National Science Foundation of Georgia (Grant number STEM-22-2077).

Keywords: mushrooms, plant raw materials, fermentation, biomass protein, cellulase

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816 Antioxidant Characteristics of Serbian Conifers

Authors: Dubravka Štajner, Boris M. Popović, Saša Orlović, Ružica Ždero, Milan Popović, Aleksandra Popović

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Many plants possess antioxidant ingredients that provides efficacy by additive or synergistic activities. Present article highlights an antioxidant capacity of Serbian conifer plants. Antioxidant activities of the crude extracts were assessed using different assays. In this study, quantities of phenolic compounds (total phenols, flavonoids, tannins and proanthocyanidins), contents of photosynthetic pigments (chlorophyll a and b and carotenoids), soluble proteins and proline were examined. MDA quantities and ability of extracts to remove reactive nitrogen and oxygen species (RNOS) were also investigated. Furthermore, antioxidant activities of extracts against DPPH∙, ferric reducing antioxidant power, permanganate reducing antioxidant capacity were also determined. According to almost all used assays, antioxidant and scavenging capacities of silver fir (Abies alba Mill.), and Douglas fir (Pseudotsuga menziesii) were superior compared to spruce. Presented results implicated that leaves of Douglas fir and silver fir possessed outstanding antioxidant characteristics that could diminish damage caused by oxygen radicals which are responsible for many of the bodily changes and susceptibility to different diseases.

Keywords: conifers, antioxidant activity, reducing power, lipid peroxidation

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815 Polymer Nanocoatings With Enhanced Self-Cleaning and Icephobic Properties

Authors: Bartlomiej Przybyszewski, Rafal Kozera, Katarzyna Zolynska, Anna Boczkowska, Daria Pakula

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The build-up and accumulation of dirt, ice, and snow on structural elements and vehicles is an unfavorable phenomenon, leading to economic losses and often also posing a threat to people. This problem occurs wherever the use of polymer coatings has become a standard, among others in photovoltaic farms, aviation, wind energy, and civil engineering. The accumulated pollution on the photovoltaic modules can reduce their efficiency by several percent, and snow stops power production. Accumulated ice on the blades of wind turbines or the wings of airplanes and drones disrupts the airflow by changing their shape, leading to increased drag and reduced efficiency. This results in costly maintenance and repairs. The goal of the work is to reduce or completely eliminate the accumulation of dirt, snow, and ice build-up on polymer coatings by achieving self-cleaning and icephobic properties. It is done by the use of a multi-step surface modification of the polymer nanocoatings. For this purpose, two methods of surface structuring and the preceding volumetric modification of the chemical composition with proprietary organosilicon compounds and/or mineral additives were used. To characterize the surface topography of the modified coatings, light profilometry was utilized. Measurements of the wettability parameters (static contact angle and contact angle hysteresis) on the investigated surfaces allowed to identify their wetting behavior and determine relation between hydrophobic and anti-icing properties. Ice adhesion strength was measured to assess coatings' anti-icing behavior.

Keywords: anti-icing properties, self-cleaning, polymer coatings, icephobic coatings

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814 Magnesium Foliar Application and Phosphorien Soil Inoculation Positively Affect Pisum sativum L. Plants Grown on Sandy Calcareous Soil

Authors: Saad M. Howladar, Ashraf Sh. Osman, Mostafa M. Rady, Hassan S. Al-Zahrani

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The effects of soil inoculation with phosphorien-containing Phosphate-Dissolving Bacteria (PDB) and/or magnesium (Mg) foliar application at the rates of 0, 0.5 and 1mM on growth, green pod and seed yields, and chemical constituents of Pisum sativum L. grown on a sandy calcareous soil were investigated. Results indicated that PDB and/or Mg significantly increased shoot length, number of branches plant–1, total leaf area plant–1 and canopy dry weight plant–1, leaf contents of pigments, soluble sugars, free proline, nitrogen, phosphorus, potassium, magnesium, and calcium, and Ca/Na ratio, while leaf Na content was reduced. PDB and/or Mg also increased green pod and seed yields. We concluded that PDB and Mg have pronounced positive effects on Pisum sativum L. plants grown on sandy calcareous soil. PDB and Mg, therefore, have the potential to be applied for various crops to overcome the adverse effects of the newly-reclaimed sandy calcareous soils.

Keywords: bio-p-fertilizer, mg foliar application, newly-reclaimed soils, Pisum sativum L.

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813 Fatigue Life Prediction under Variable Loading Based a Non-Linear Energy Model

Authors: Aid Abdelkrim

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A method of fatigue damage accumulation based upon application of energy parameters of the fatigue process is proposed in the paper. Using this model is simple, it has no parameter to be determined, it requires only the knowledge of the curve W–N (W: strain energy density N: number of cycles at failure) determined from the experimental Wöhler curve. To examine the performance of nonlinear models proposed in the estimation of fatigue damage and fatigue life of components under random loading, a batch of specimens made of 6082 T 6 aluminium alloy has been studied and some of the results are reported in the present paper. The paper describes an algorithm and suggests a fatigue cumulative damage model, especially when random loading is considered. This work contains the results of uni-axial random load fatigue tests with different mean and amplitude values performed on 6082T6 aluminium alloy specimens. The proposed model has been formulated to take into account the damage evolution at different load levels and it allows the effect of the loading sequence to be included by means of a recurrence formula derived for multilevel loading, considering complex load sequences. It is concluded that a ‘damaged stress interaction damage rule’ proposed here allows a better fatigue damage prediction than the widely used Palmgren–Miner rule, and a formula derived in random fatigue could be used to predict the fatigue damage and fatigue lifetime very easily. The results obtained by the model are compared with the experimental results and those calculated by the most fatigue damage model used in fatigue (Miner’s model). The comparison shows that the proposed model, presents a good estimation of the experimental results. Moreover, the error is minimized in comparison to the Miner’s model.

Keywords: damage accumulation, energy model, damage indicator, variable loading, random loading

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812 Comparison of an Upflow Anaerobic Sludge Blanket and an Anaerobic Filter for Treating Wheat Straw Wash Water

Authors: Syazwani Idrus, Charles Banks, Sonia Heaven

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The effect of osmotic stress was carried out to determine the ability for biogas production in two types of digesters; anaerobic sludge blanket and anaerobic filters in treating wheat straw washed water. Two anaerobic filters (AF1 and 2) and two UASB reactors (U1 and 2) with working volumes of 1.5 L were employed at mesophilic temperatures (37°C). Digesters AF1 and two were seeded with an inoculum which had previously been fed on with a synthetic wastewater includingSodium Chloride and Potassium Chloride. Digesters U1 and two were seeded with 1 kg wet weight of granular sludge which had previously been treating paper mill effluent. During the first 48 days, all digesters were successfully acclimated with synthetic wastewater (SW) to organic loading rate (OLR) of 6 g COD l^-1 day-1. Specific methane production (SMP) of 0.333 l CH4 g-1 COD). The feed was then changed to wash water from a washing operation to reduce the salt content of wheat straw (wheat straw wash water, WSW) at the same OLR. SMP fell sharply in all reactors to less than 0.1 l CH4 g^-1 COD, with the AF affected more than the UASB. The OLR was reduced to 2.5 g COD l^-1 day^-1 to allow adaptation to WSW, and both the UASB and the AF reactors achieved an SMP of 0.21 l CH4 g^-1 COD added at 82% of COD removal. This study also revealed the accumulation of potassium (K) inside the UASB granules to a concentration of 4.5 mg K g^-1 wet weight of granular sludge. The phenomenon of lower SMP and accumulation of K indicates the effect of osmotic stress when fed on WSW. This finding is consistent with the theory that methanogenic organisms operate a Potassium pump to maintain ionic equilibrium, and as this is an energy-driven process, it will, therefore, reduce the overall methane yield.

Keywords: wheat straw wash water, upflow anaerobic sludge blanket, anaerobic filter, specific methane production, osmotic stress

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811 Impact of Anthropogenic Activities on Soil Quality Using the Land Snail Cantareus apertus as Bioindicator of Heavy Metals Accumulation in The Bejaia Region (Northeastern Algeria)

Authors: Benbelil-Tafoughalt Saida, Tababouchet Meriem

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The main goal of this study was to investigate the impact of anthropogenic activities on soil quality using the land snail Cantareusapertus as a bioindicator of heavy metal accumulation. Concentrations of cadmium, copper, and zinc were measured in various body organs, viz: viscera and foot of the land snail Cantareusapertus. The snails were collected from two different sites in the Bejaia region (Northeastern Algeria), exposed to different sources of contamination by trace metals. The first sampling site is an urban areas, and the second is characterized by heavy industry, a potential source of soil pollution via heavy metal contamination. The concentrations of heavy metal in all viscera and foot samples were measured using an atomic absorption spectrophotometer. Bioconcentration of the trace metals Cu, Zn, and Cd varied between the viscera and the foot with the viscera having the highest concentration (µgg-1) of all metals than the foots; Cu, 2.03 – 5.8 (Viscera), 0.05 – 3.30 (Foot), Zn, 23.64 – 45.02 (Viscera), 1.87 – 15.15 (Foot) and Cd, 0.36 – 15.26 (Viscera), 0.18 – 13.73 (Foot), which suggest that ingestion may be the main uptake route of these essential metals. On the other hand, the levels of heavy metals varied significantly among the sampling area (P<0.001). in fact, in the foots as well as in the viscera, the concentrations of all studied metals is significantly higher in the snails sampled from sites closest to potential sources of pollution compared to those collected from urban areas characterized by moderate pollution.

Keywords: anthropogenic activities, Bioconcentration, Cantareus apertus, trace metals

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810 Study of Heat Transfer through the Ground and its Accumulation Properties to Increase the Energy Efficiency of Underground Buildings

Authors: Sandeep Bandarwadkar, Tadas Zdankus

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To maintain a comfortable indoor temperature for its residents in the colder season, heating a building is necessary. Due to the expansion in the construction sectors, the consumption of heating energy is increasing. According to Eurostat data, in the European Union, the share of energy consumption of heating energy for space and cooling in residential buildings was around 63% in 2019. These figures indicate that heating energy still accounts for a significant portion of total energy consumption in Europe. Innovation is crucial to reduce energy consumption in buildings and achieve greater energy efficiency and sustainability. It can bring about new solutions that are smarter and more natural energy generation to reduce greenhouse gas emissions. The ground can serve as an effective and sustainable heat accumulator for heating and cooling. The temperature of the ground is higher than that of the ambient air in the colder period and lower in the warmer period. The building deep in the soil could use less thermal energy compared to the above-ground buildings that provide the same amount of thermal comfort. The temperature difference between the soil and the air inside the building decreases as the temperature of the soil increases. In progress, this process generates the condition that acts against heat loss. However, heat dissipates further to the consecutive layers and reaches thermal equilibrium. The charging of the ground by heat and its dissipation through the adjacent soil layers was investigated experimentally. The results of this research showed that 9% of the energy savings in partially underground buildings and 44.4% in completely underground buildings were derived from heating the space. Heat loss to the ground is treated as a charge of the soil by thermal energy. The dependence of the intensity of the charge on time was analysed and presented.

Keywords: heat transfer, accumulation of heat, underground building, soil charge

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809 Potential of Castor Bean (Ricinus Communis L.) for Phytoremediation of Soils Contaminated with Heavy Metals

Authors: Violina Angelova, Mariana Perifanova-Nemska, Krasimir Ivanov

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The aim of this research was to investigate the potential for the use of Ricinus communis L. (castor oil plant) to remediate metal-polluted sites. This study was performed in industrially polluted soils containing high concentrations of Zn, Pb and Cd, situated at different distances (0.3, 2.0 and 15.0 km) from the source of pollution - the Non-Ferrous Metal Works near Plovdiv, Bulgaria. On reaching commercial ripeness, the castor oil plants were gathered and the contents of heavy metals in their different parts – roots, stems, leaves and seeds, were determined after dry ashing. Physico-chemical characterization, total, DTPA extractable and water-soluble metals in rhizospheric soil samples were carried. Translocation factors (TFs) were also determined. The quantitative measurements were carried out with ICP. A soxhlet extraction was used for the extraction of the oil, using hexane as solvent. The oil was recovered by simple distillation of the solvent. The residual oil obtained was investigated for physicochemical parameters and fatty acid composition. Bioaccumulation factor and translocation factor values (BAF and TF > 1) were greater than one suggesting efficient accumulation in the shoot. The castor oil plant may be preferred as a good candidate for phytoremediation (phytoextraction). These results indicate that R. communis has good potential for removing Pb from contaminated soils attributed to its fast growth, high biomass, strong absorption and accumulation for Pb. The concentrations of heavy metals in the oil were low as seed coats accumulated the highest concentrations of Cd and Pb. In addition, the result of the fatty acid composition analysis confirms the oil to be of good quality and can be used for industrial purposes such as cosmetics, soaps and paint.

Keywords: castor bean, heavy metals, phytoremediation, polluted soils

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808 A Vaccination Program to Control an Outbreak of Acute Hepatitis A among MSM in Taiwan, 2016

Authors: Ying-Jung Hsieh, Angela S. Huang, Chu-Ming Chiu, Yu-Min Chou, Chin-Hui Yang

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Background and Objectives: Hepatitis A is primarily acquired by the fecal-oral route through person-to-person contact or ingestion of contaminated food or water. During 2010 to 2014, an average of 83 cases of locally-acquired disease was reported to Taiwan’s notifiable disease system. Taiwan Centers for Disease Control (TCDC) identified an outbreak of acute hepatitis A which began in June 2015. Of the 126 cases reported in 2015, 103 (82%) cases were reported during June–December and 95 cases (92%) of them were male. The average age of all male cases was 31 years (median, 29 years; range, 15–76 years). Among the 95 male cases, 49 (52%) were also infected with HIV, and all reported to have had sex with other men. To control this outbreak, TCDC launched a free hepatitis A vaccination program in January 2016 for close contacts of confirmed hepatitis A cases, including family members, sexual partners, and household contacts. Effect of the vaccination program was evaluated. Methods: All cases of hepatitis A reported to the National Notifiable Disease Surveillance System were included. A case of hepatitis A was defined as a locally-acquired disease in a person who had acute clinical symptoms include fever, malaise, loss of appetite, nausea or abdominal discomfort compatible with hepatitis, and tested positive for anti-HAV IgM during June 2015 to June 2016 in Taiwan. The rate of case accumulation was calculated using a simple regression model. Results: During January–June 2016, there were 466 cases of hepatitis A reported; of the 243 (52%) who were also infected with HIV, 232 (95%) had a history of having sex with men. Of the 346 cases that were followed up, 259 (75%) provided information on contacts but only 14 (5%) of them provided the name of their sexual partners. Among the 602 contacts reported, 349 (58%) were family members, 14 (2%) were sexual partners, and 239 (40%) were other household contacts. Among the 602 contacts eligible for free hepatitis A vaccination, 440 (73%) received the vaccine. There were 87 (25%) cases that refused to disclose their close contacts. The average case accumulation rate during January–June 2016 was 21.7 cases per month, which was 6.8 times compared to the average case accumulation rate during June–December 2015 of 3.2 cases per month. Conclusions: Despite vaccination program aimed to provide free hepatitis A vaccine to close contacts of hepatitis A patients, the outbreak continued and even gained momentum in transmission. Refusal by hepatitis A patients to provide names of their close contacts and rejection of contacts to take the hepatitis A vaccine may have contributed to the poor effect of the program. Targeted vaccination efforts of all MSM may be needed to control the outbreak among this population in the short term. In the long term, universal vaccination program is needed to prevent the infection of hepatitis A.

Keywords: hepatitis A, HIV, men who have sex with men, vaccination

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807 Optimizing Nitrogen Fertilizer Application in Rice Cultivation: A Decision Model for Top and Ear Dressing Dosages

Authors: Ya-Li Tsai

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Nitrogen is a vital element crucial for crop growth, significantly influencing crop yield. In rice cultivation, farmers often apply substantial nitrogen fertilizer to maximize yields. However, excessive nitrogen application increases the risk of lodging and pest infestation, leading to yield losses. Additionally, conventional flooded irrigation methods consume significant water resources, necessitating precise agricultural and intelligent water management systems. In this study, it leveraged physiological data and field images captured by unmanned aerial vehicles, considering fertilizer treatment and irrigation as key factors. Statistical models incorporating rice physiological data, yield, and vegetation indices from image data were developed. Missing physiological data were addressed using multiple imputation and regression methods, and regression models were established using principal component analysis and stepwise regression. Target nitrogen accumulation at key growth stages was identified to optimize fertilizer application, with the difference between actual and target nitrogen accumulation guiding recommendations for ear dressing dosage. Field experiments conducted in 2022 validated the recommended ear dressing dosage, demonstrating no significant difference in final yield compared to traditional fertilizer levels under alternate wetting and drying irrigation. These findings highlight the efficacy of applying recommended dosages based on fertilizer decision models, offering the potential for reduced fertilizer use while maintaining yield in rice cultivation.

Keywords: intelligent fertilizer management, nitrogen top and ear dressing fertilizer, rice, yield optimization

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806 Study of the Possibility of Adsorption of Heavy Metal Ions on the Surface of Engineered Nanoparticles

Authors: Antonina A. Shumakova, Sergey A. Khotimchenko

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The relevance of research is associated, on the one hand, with an ever-increasing volume of production and the expansion of the scope of application of engineered nanomaterials (ENMs), and on the other hand, with the lack of sufficient scientific information on the nature of the interactions of nanoparticles (NPs) with components of biogenic and abiogenic origin. In particular, studying the effect of ENMs (TiO2 NPs, SiO2 NPs, Al2O3 NPs, fullerenol) on the toxicometric characteristics of common contaminants such as lead and cadmium is an important hygienic task, given the high probability of their joint presence in food products. Data were obtained characterizing a multidirectional change in the toxicity of model toxicants when they are co-administered with various types of ENMs. One explanation for this fact is the difference in the adsorption capacity of ENMs, which was further studied in in vitro studies. For this, a method was proposed based on in vitro modeling of conditions simulating the environment of the small intestine. It should be noted that the obtained data are in good agreement with the results of in vivo experiments: - with the combined administration of lead and TiO2 NPs, there were no significant changes in the accumulation of lead in rat liver; in other organs (kidneys, spleen, testes and brain), the lead content was lower than in animals of the control group; - studying the combined effect of lead and Al2O3 NPs, a multiple and significant increase in the accumulation of lead in rat liver was observed with an increase in the dose of Al2O3 NPs. For other organs, the introduction of various doses of Al2O3 NPs did not significantly affect the bioaccumulation of lead; - with the combined administration of lead and SiO2 NPs in different doses, there was no increase in lead accumulation in all studied organs. Based on the data obtained, it can be assumed that at least three scenarios of the combined effects of ENMs and chemical contaminants on the body: - ENMs quite firmly bind contaminants in the gastrointestinal tract and such a complex becomes inaccessible (or inaccessible) for absorption; in this case, it can be expected that the toxicity of both ENMs and contaminants will decrease; - the complex formed in the gastrointestinal tract has partial solubility and can penetrate biological membranes and / or physiological barriers of the body; in this case, ENMs can play the role of a kind of conductor for contaminants and, thus, their penetration into the internal environment of the body increases, thereby increasing the toxicity of contaminants; - ENMs and contaminants do not interact with each other in any way, therefore the toxicity of each of them is determined only by its quantity and does not depend on the quantity of another component. Authors hypothesized that the degree of adsorption of various elements on the surface of ENMs may be a unique characteristic of their action, allowing a more accurate understanding of the processes occurring in a living organism.

Keywords: absorption, cadmium, engineered nanomaterials, lead

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805 Examining Postcolonial Corporate Power Structures through the Lens of Development Induced Projects in Africa

Authors: Omogboyega Abe

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This paper examines the relationships between socio-economic inequalities of power, race, wealth engendered by corporate structure, and domination in postcolonial Africa. The paper further considers how land as an epitome of property and power for the locals paved the way for capitalist accumulation and control in the hands of transnational corporations. European colonization of Africa was contingent on settler colonialism, where properties, including land, were re-modified as extractive resources for primitive accumulation. In developing Africa's extractive resources, transnational corporations (TNCs) usurped states' structures and domination over native land. The usurpation/corporate capture that exists to date has led to remonstrations and arguably a counter-productive approach to development projects. In some communities, the mention of extractive companies triggers resentment. The paradigm of state capture and state autonomy is simply inadequate to either describe or resolve the play of forces or actors responsible for severe corporate-induced human rights violations in emerging markets. Moreover, even if the deadly working conditions are conceived as some regulatory failure, it is tough to tell whose failure. The analysis in this paper is that the complexity and ambiguity evidenced by the multiple regimes and political and economic forces shaping production, consumption, and distribution of socio-economic variables are not exceptional in emerging markets. Instead, the varied experience in developing countries provides a window for seeing what we face in understanding and theorizing the structure and operation of the global economic and regulatory order in general.

Keywords: colonial, emerging markets, business, human rights, corporation

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804 Nitrogen-Fixing Rhizobacteria (Rhizobium mililoti 2011) Enhances the Tolerance and the Accumulation of Cadmium in Medicago sativa

Authors: Tahar Ghnaya, Majda Mnasri, Hanen Zaier, Rim Ghabriche, Chedly Abdelly

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It is known that the symbiotic association between plant and microorganisms are beneficial for plant growth and resistance to metal stress. Hence, it was demonstrated that Arbuscular mycorrhizal fungi have a positive effect on host plants growing in metal polluted soils. Legume plants are those which normally associate to rhizobacteria in order to fix atmospheric nitrogen. The aim of this work was to evaluate the effect this type of symbiosis on the tolerance and the accumulation of Cd. We chose Medicago sativa, as a modal for host legume plants and Rhizobium mililoti 2011 as rhizobial strain. Inoculated and non-inoculated plants of M. sativa were submitted during three month to 0, 50, and 100 mgCd/kg dry soil. Results showed that the presence of Cd in the medium induced, in both inoculated and non-inoculated plants, a chlorosis and necrosis. However, these symptoms were more pronounced in non-inoculated plants. The beneficial effect of inoculation of M. sativa with R. meliloti, on plant growth was confirmed by the measurement of biomass production which showed that the symbiotic association between host plant and rhizobacteria alleviates significantly Cd effect on biomass production, so inoculated plants produced more dry weight as compared to non-inoculated ones in the presence of all Cd tretments. On the other hand, under symbiosis conditions, Cd was more accumulated in different plant organs. Hence, in these plants, shoot Cd concentration reached 425 and it was 280 µg/gDW in non-inoculated ones in the presence of 100 ppm Cd. This result suggests that symbiosis enhances the absorption and translocation of Cd in this plant. In nodules and roots, we detected the highest Cd concentrations, demonstrating that these organs are able to concentrate Cd in their tissues. These data confirm that M. sataiva, cultivated in symbiosis with Rhizobium mililoti could be used in phytoextraction of Cd from contaminated soils.

Keywords: Cd, phytoremediation, Medicago sativa, Arbuscular mycorrhizal

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803 Dietary Risk Assessment of Green Leafy Vegetables (GLV) Due to Heavy Metals from Selected Mining Areas

Authors: Simon Mensah Ofosu

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Illicit surface mining activities pollutes agricultural lands and water bodies and results in accumulation of heavy metals in vegetables cultivated in such areas. Heavy metal (HM) accumulation in vegetables is a serious food safety issues due to the adverse effects of metal toxicities, hence the need to investigate the levels of these metals in cultivated vegetables in the eastern region. Cocoyam leaves, cabbage and cucumber were sampled from selected farms in mining areas (Atiwa District) and non -mining areas (Yilo Krobo and East Akim District) of the region for the study. Levels of Cadmium, Lead, Mercury and Arsenic were investigated in the vegetables with Atomic Absorption Spectrometer, and the results statistically analyzed with Microsoft Office Excel (2013) Spread Sheet and ANOVA. Cadmium (Cd) and arsenic (As) were the highest and least concentrated HM in the vegetables sampled, respectively. The mean concentrations of Cd and Pb in cabbage (0.564 mg/kg, 0.470 mg/kg), cucumber (0.389 mg/kg, 0.190 mg/kg), cocoyam leaves (0.410 mg/kg, 0.256 mg/kg) respectively from the mining areas exceeded the permissible limits set by Joint FAO/WHO. The mean concentrations of the metals in vegetables from the mining and non-mining areas varied significantly (P<0.05). The Target Hazard Quotient (THQ) was used to assess the health risk posed to the human population via vegetable consumption. The THQ values of cadmium, mercury, and lead in adults and children through vegetable consumption in the mining areas were greater than 1 (THQ >1). This indicates the potential health risk that the children and adults may be facing. The THQ values of adults and children in the non-mining areas were less than the safe limit of 1 (THQ<1), hence no significant health risk posed to the population from such areas.

Keywords: food safety, risk assessment, illicit mining, public health, contaminated vegetables

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802 Stressful Life Events and Their Influence on Childhood Obesity and Emotional Well-Being: Cross-Sectional Study

Authors: M. Rojo, M. Blanco, T. Lacruz, S. Solano, L. Beltran, M. Graell, A. R. Sepulveda.

Abstract:

There is an association between an early accumulation of Stressful Life Events (SLE) during childhood and various physical and psychological health complications. However, there are only a few studies on this topic in children and adolescents with overweight or obesity. The general aim of the study was to evaluate the accumulation and type of SLE in 200 children from 8 to 12 years old and analyze the relationship with their emotional well-being and weight status (obesity, overweight and normal weight). The children and their families completed an interview. The evaluated variables that are included in this study are sociodemographic measures, medical/psychological history, anthropometric measures (BMI, z-BMI), and psychological variables (children's clinical interview K-SADS-PL(Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime Version) and battery of questionnaires). Results: Children with overweight and obesity accumulate more stressful events from an early age and have a significantly higher percentage of psychiatric diagnoses, compared to their peers with normal weight. Presenting a child psychiatric disorder is related to greater z-BMI and the total number of SLE (p < 0.001). A higher z-BMI is also related to a greater number of stressful events during childhood. There is also a positive and significant relationship between the total number of SLE and worse emotional well-being (higher levels of anxious and depressive symptoms and low self-esteem of children) (p < 0.01). Conclusion: Children with overweight and obesity grow up in a family, school, and social context where more stressors are accumulated. This is also directly associated with worse emotional well-being. It is necessary to implement multidisciplinary prevention and intervention strategies in different changes (school, family, and health). This study is included in a project funded by the Ministry of Innovation and Science (PSI2011-23127).

Keywords: childhood obesity, emotional well-being, psychopathology, stressful life events

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801 Manganese Contamination Exacerbates Reproductive Stress in a Suicidally-Breeding Marsupial

Authors: Ami Fadhillah Amir Abdul Nasir, Amanda C. Niehaus, Skye F. Cameron, Frank A. Von Hippel, John Postlethwait​, Robbie S. Wilson

Abstract:

For suicidal breeders, the physiological stresses and energetic costs of breeding are fatal. Environmental stressors such as pollution should compound these costs, yet suicidal breeding is so rare among mammals that this is unknown. Here, we explored the consequences of metal contamination to the health, aging and performance of endangered, suicidally-breeding northern quolls (Dasyurus hallucatus) living near an active manganese mine on Groote Eylandt, Northern Territory, Australia. We found respirable manganese dust at levels exceeding international recommendations even 20km from mining sites and substantial accumulation of manganese within quolls’ hair, testes, and in two brain regions—the neocortex and cerebellum, responsible for sensory perception and motor function, respectively. Though quolls did not differ in sprint speeds, motor skill, or manoeuvrability, those with higher accumulation of manganese crashed at lower speeds during manoeuvrability tests, indicating a potential effect on sight or cognition. Immune function and telomere length declined over the breeding season, as expected with ageing, but manganese contamination exacerbated immune declines and suppressed cortisol. Unexpectedly, male quolls with higher levels of manganese had longer telomeres, supporting evidence of unusual telomere dynamics among Dasyurids—though whether this affects their lifespan is unknown. We posit that sublethal contamination via pollution, mining, or urbanisation imposes physiological costs on wildlife that may diminish reproductive success or survival.

Keywords: ecotoxicology, heavy metal, manganese, telomere length, cortisol, locomotor

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800 Macronutrient Accumulation and Partitioning for Six Wheat Genotypes Grown at Contrasting Nitrogen Supply

Authors: E. Chakwizira, D. J. Moot, M. Andrews, E. Teixeira

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Partitioning of macro-nutrients in wheat (Triticum aestivum L.) plant organs have not been extensively studied, particularly for modern genotypes grown under contrasting N supply. Nutrient accumulation and partitioning of phosphorus, potassium, calcium, magnesium and sulphur (P, K, Ca, Mg and S) were determined for six wheat genotypes [12S2-2021, 12S3-3019, 13S3-2026, Discovery, Duchess and Reliance] grown with (200 kg/ha) or without (0 kg/ha) nitrogen (N), in a fully irrigated field experiment in 2017-18 season at Lincoln, New Zealand. Data were collected at three growth stages (GS): tillering (GS21), anthesis (GS60) and grain maturity (GS92). Grain yield varied with both N and genotype; from 6-7.5 t/ha for the 0 kg N/ha crops and 8.1-9.3 t/ha for the 200 kg N/ha treatments. Plant nutrient uptake at maturity responded to both N supply and genotype for all nutrients, except S which did not differ among the genotypes. For example, total P uptake averaged 13.5 (12.4-14.3) kg/ha for the 0 kg N/ha treatments and 17.8 (15.1-19.7) kg/ha when 200 kg N/ha was applied. Similarly, K uptake increased from an average of 23 (21.6-25.3) for the 0 kg N/ha treatments to 34.3 (32.4-40.8) kg/ha when 200 kg N/ha was applied. Similar trends were observed for Ca and Mg. The S content only responded to N supply but not to genotype, increasing from 7.9 kg/ha for the 0 kg N treatments to 12.8 kg/ha when 200 kg N was applied. Relative nutrient content at anthesis compared with those at maturity were 30% for P, 100% for both K and Ca and 34% of Mg. Sulphur content at anthesis decreased 29% with N supply and was highest for genotypes 12S2-2021 compared with the other five genotype. At grain maturity, the ratio of nutrients in grain to total plant nutrient, defined as the nutrient harvest index (NHI) varied with both N supply and genotype. Averaged across treatments, the NHI was 0.96 for P, 0.53 for K, 0.58 for Ca, 0.90 for Mg and 0.85 for S. These results suggest that Ca and K should be provided earlier in the season as there is limited or no uptake after anthesis. These results also show that Ca and K are important for structural functions, while P, Mg and S are remobilised to the grains and become important for quality.

Keywords: anthesis, genotype, nutrient harvests index, NHI, Triticum aestivum L.

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799 Biologically Synthesised Silver Nanoparticles Induces Autophagy and JNK Signaling as a Pro-Survival Response by Abrogating Reactive Oxygen Species Accumulation in Cancer Cells

Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

Abstract:

Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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798 Allelopathic Effect of Duranta Repens on Salinity-Stressed Solanum Lycopersicum Seedlings

Authors: Olusola Nafisat Omoniyi

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Aqueous extract of Duranta repens leaves was investigated for its allelopathic effect on Solanum lycopersicum Seedlings germinated and grown under salinity condition. The study was carried out using both laboratory petri dish and pot assays to simulate the plant’s natural environmental conditions. The experiment consisted of 5 groups (1-5), each containing 5 replicates (of 10 seeds). Group 1 was treated with distilled water; Group 2 was treated with 5 mM NaCl; Group 3 was treated with the Extract, Group 4 was treated with a mixture of 5 mM NaCl and the Extract (2:1 v/v), and Group 5 was treated with a mixture of 5 mM NaCl and the Extract (1:2 v/v). The results showed that treatment with NaCl caused significant reductions in germination, growth parameters (plumule and radicle lengths), and chlorophyll concentration of S. lycopersicum seedlings when compared to those treated with D. rupens aqueous leaf extract. Salinity also caused an increase in malondialdehyde and proline concentrations and lowered the activity of superoxide dismutase. However, in the presence of the extract, the adverse effects of the NaCl were attenuated, implying that the extract improved tolerance of S. lycopersicum seedlings. In conclusion, the findings of this study show that the extract is very important in the optimal growth of the plant in saline soil, which has become useful for the management of soil salinity problems.

Keywords: agriculture, allelopathic, salinity, soil, tomato, production, photosynthesis

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797 Enhancement of Growth and Lipid Accumulation in Microalgae with Aggregation Induced Emission-Based Photosensitiser

Authors: Sharmin Ferdewsi Rakhi, A. H. M. Mohsinul Reza, Brynley Davies, Jianzhong Wang, Youhong Tang, Jian Qin

Abstract:

Mass production of microalgae has become a focus of research owing to their promising aspects for sustainable food, biofunctional compounds, and biofuel feedstock. However, low lipid content with optimum algal biomass is still a challenge that must be resolved for commercial use. This research aims to determine the effects of light spectral shift and reactive oxygen species (ROS) on growth and lipid biosynthesis in a green microalga, Chlamydomonas reinhardtii. Aggregation Induced Emission (AIE)-based photosensitisers, CN-TPAQ-PF6 ([C₃₂H₂₃N₄]+) with high ROS productivity, was introduced into the algal culture media separately for effective conversion of the green-yellow-light to the red spectra. The intense photon energy and high-photon flux density in the photosystems and ROS supplementation induced photosynthesis and lipid biogenesis. In comparison to the control, maximum algal growth (0.15 g/l) was achieved at 2 µM CN-TPAQ-PF6 exposure. A significant increase in total lipid accumulation (146.87 mg/g dry biomass) with high proportion of 10-Heptadecanoic acid (C17:1) linolenic acid (C18:2), α-linolenic acid (C18:3) was observed. The elevated level of cellular NADP/NADPH triggered the Acetyl-Co-A production in lipid biogenesis cascade. Furthermore, MTT analysis suggested that this nanomaterial is highly biocompatible on HaCat cell lines with 100% cell viability. This study reveals that the AIE-based approach can strongly impact algal biofactory development for sustainable food, healthy lipids and eco-friendly biofuel.

Keywords: microalgae, photosensitiser, lipid, biomass, aggregation-induced-emission, reactive oxygen species

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796 Physicochemical, Heavy Metals Analysis of Some Multi-Floral Algerian Honeys

Authors: Assia Amri, Naima Layachi, Ali Ladjama

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The characterization of some Algerian honey was carried out on the basis of their physico-chemical properties: moisture,hydroxy methyl furfural, diastase activity, pH,free, total and lactonic acidity, electrical conductivity, minerals and proline content. Studied samples are found to be low in moisture and therefore safe from fermentation, low in HMF level and high in diastase activity. Additionally the diastase activity and the HMF content are widely recognized parameters indicating the freshness of honey. Phenolic compounds present in honey are classified into two groups - simple phenols and polyphenols. The simple phenols in honey are various phenol acids, but polyphenols are various flavonoids and flavonides. The aim of our work was to determine antioxidant properties of various Algerian honey samples–the total phenol content, total flavonoids content, as well as honey anti radical activity.The quality of honey samples differs on account of various factors such as season, packaging and processing conditions, floral source, geographical origin and storage period. It is important that precautions should be taken to ensure standardization and rationalization of beekeeping techniques, manufacturing procedures and storing processes to improve honey quality.

Keywords: honey, physico-chemical characterization, phenolic coumpound, HMF, diastase activity

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795 Enhancing Mitochondrial Activity and Metabolism in Aging Female Germ Cells: Synergistic Effects of Dual ROCK and ROS Inhibition

Authors: Kuan-Hao Tsui, Li-Te Lin, Chia-Jung Li

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The combination of Y-27632 and Vitamin C significantly enhances the quality of aging germ cells by reducing reactive oxygen species (ROS) production, restoring mitochondrial membrane potential balance, and promoting mitochondrial fusion. The age-related decline in oocyte quality contributes to reduced fertility, increased aneuploidy, and diminished embryo quality, with mitochondrial dysfunction in both oocytes and granulosa cells being a key factor in this decline. Experiments on aging germ cells investigated the effects of the Y-27632 and Vitamin C combination. In vivo studies involved aged mice to assess oocyte maturation and ROS accumulation during culture. The assessment included mitochondrial activity, ROS levels, mitochondrial membrane potential, and mitochondrial dynamics. Cellular energy metabolism and ATP production were also measured. The combination treatment effectively addressed mitochondrial dysfunction and regulated cellular energy metabolism, promoting oxygen respiration and increasing ATP production. In aged mice, this supplement treatment enhanced in vitro oocyte maturation and prevented ROS accumulation in aging oocytes during culture. While these findings are promising, further research is needed to explore the long-term effects and potential side effects of the Y-27632 and Vitamin C combination. Additionally, translating these findings to human subjects requires careful consideration. Overall, the study suggests that the Y-27632 and Vitamin C combination could be a promising intervention to mitigate aging-related dysfunction in germ cells, potentially enhancing oocyte quality, particularly in the context of in vitro fertilization.

Keywords: ovarian aging, supplements, ROS, mitochondria

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794 Shale Gas Accumulation of Over-Mature Cambrian Niutitang Formation Shale in Structure-Complicated Area, Southeastern Margin of Upper Yangtze, China

Authors: Chao Yang, Jinchuan Zhang, Yongqiang Xiong

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The Lower Cambrian Niutitang Formation shale (NFS) deposited in the marine deep-shelf environment in Southeast Upper Yangtze (SUY), possess excellent source rock basis for shale gas generation, however, it is currently challenged by being over-mature with strong tectonic deformations, leading to much uncertainty of gas-bearing potential. With emphasis on the shale gas enrichment of the NFS, analyses were made based on the regional gas-bearing differences obtained from field gas-desorption testing of 18 geological survey wells across the study area. Results show that the NFS bears low gas content of 0.2-2.5 m³/t, and the eastern region of SUY is higher than the western region in gas content. Moreover, the methane fraction also presents the similar regional differentiation with the western region less than 10 vol.% while the eastern region generally more than 70 vol.%. Through the analysis of geological theory, the following conclusions are drawn: Depositional environment determines the gas-enriching zones. In the western region, the Dengying Formation underlying the NFS in unconformity contact was mainly plateau facies dolomite with caves and thereby bears poor gas-sealing ability. Whereas the Laobao Formation underling the NFS in eastern region was a set of siliceous rocks of shelf-slope facies, which can effectively prevent the shale gas from escaping away from the NFS. The tectonic conditions control the gas-enriching bands in the SUY, which is located in the fold zones formed by the thrust of the Southern China plate towards to the Sichuan Basin. Compared with the western region located in the trough-like folds, the eastern region at the fold-thrust belts was uplifted early and deformed weakly, resulting in the relatively less mature level and relatively slight tectonic deformation of the NFS. Faults determine whether shale gas can be accumulated in large scale. Four deep and large normal faults in the study area cut through the Niutitang Formation to the Sinian strata, directly causing a large spillover of natural gas in the adjacent areas. For the secondary faults developed within the shale formation, the reverse faults generally have a positive influence on the shale accumulation while the normal faults perform the opposite influence. Overall, shale gas enrichment targets of the NFS, are the areas with certain thickness of siliceous rocks at the basement of the Niutitang Formation, and near the margin of the paleouplift with less developed faults. These findings provide direction for shale gas exploration in South China, and also provide references for the areas with similar geological conditions all over the world.

Keywords: over-mature marine shale, shale gas accumulation, structure-complicated area, Southeast Upper Yangtze

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793 Mannose-Functionalized Lipopolysaccharide Nanoparticles for Macrophage-Targeted Dual Delivery of Rifampicin and Isoniazid

Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

Abstract:

Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

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792 Mechanism of Modeling the Level of Bcr-Abl Oncoprotein by Ubiquitin-Proteasome System in Chronic Myeloid Leukemia

Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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