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The Toxicological Effects of Bifenthrin on Urban Aquatic Fauna and Its Direct and Indirect Effects on Threatened Litoria raniformis Populations
No full textSynthetic pyrethroids generally have low toxicity to mammals but are highly toxic to aquatic macroinvertebrates, fish, and frogs at very low concentrations. Bifenthrin is currently the most common synthetic pyrethroid used for termite control in new housing estates, contaminating Melbourne’s waterbodies and the increasing concentrations of bifenthrin in urban aquatic ecosystems in Melbourne is threatening the local aquatic fauna. Bifenthrin is usually found in high concentrations in sediments, especially in the vicinity of new housing developments where it is widely used as a termite control.
Litoria raniformis (Growling Grass Frog) and Galaxiella pusilla (Dwarf galaxias) are threatened species that inhabit wetlands in the greater Melbourne area. These species could be affected by direct exposure to bifenthrin or indirectly through reduction of their food sources (zooplankton and some macroinvertebrates).
A pilot survey was conducted in the aquatic habitats of 17 waterbodies inhabited by L. raniformis and 14 waterbodies inhabited by G. pusilla in February 2021 to see whether bifenthrin was present in sediments. Bifenthrin was found in 47% and 42% of wetlands inhabited by L. raniformis and G. pusilla respectively. The bifenthrin concentrations were mostly exceeding the toxic value for aquatic fauna (0.011 mg/kg) and the concentrations could be associated with presence of new residential developments in the vicinity of these sites (p = 0.004).
Surveys were conducted in 26 wetlands across the greater Melbourne area over a three-year period (2021, 2022 and 2023) to determine whether bifenthrin concentrations change over time in response to urban development in their catchments. Bifenthrin was detected in 22 (87%), 24 (92%) and 22 (88%) wetlands in 2021, 2022 and 2023 respectively. Zinc (Zn) was detected in high concentrations in older wetlands (>10 years) and Zn concentrations were positively correlated with the age of the wetland. (rs = 0.623, p = 0.003), 2022 – (rs = 0.464, p = 0.017), 2023 – (rs = 0.426, p = 0.034).
Stormwater runoff is a major way of transporting bifenthrin into aquatic habitats. Bifenthrin was detected in surface water samples collected in March 2023 from the wetlands and bifenthrin was detected in 61.5% of surface water samples collected with a positive correlation (p = 0.045) with turbidity. Rainfall also had a positive correlation with the turbidity (p = 0.027).
Zooplankton and macroinvertebrate bioassessments were conducted in the same 26 wetlands where the sediment monitoring was carried out to determine what effects bifenthrin contamination may have on them. Zooplankton sampling was carried out in every season (i.e. 5 sampling events) from October 2021 to March 2023. Macroinvertebrates were sampled in October 2021 (Spring) and May/June 2023 (Autumn).
Zooplankton communities tend to differ greatly in abundance between sites and between seasons. It was observed that by the last sampling event (March 2023), many sites had greatly reduced zooplankton abundance compared to the previous summer in 2022. Heavy rainfall was observed 7-days prior to sampling events in October 2021 (30-55 mm) and September 2022 (22-45 mm), which could be contributing to decreased numbers in those sampling rounds.
The macroinvertebrate composition was similar in all wetlands in spring 2021 and autumn 2022. The dominant taxa were Oligochaeta, Hygrophila, Hypogastropoda and Chironomidae. The sediment-bound bifenthrin had no correlation to macroinvertebrate numbers, but all the animals present were pollutant tolerant families with low SIGNAL biotic index scores. Sensitive taxa were only observed at two wetlands in very low numbers (Hydrobiosidae and Telephlebiidae were found at two sites).
Zooplankton is commonly used in ecotoxicological tests as they are highly sensitive to toxic substances and because they are good indicators of aquatic ecosystem health. The local species Daphnia carinata was used in laboratory tests to determine its sensitivity to bifenthrin. Low concentrations of bifenthrin in surface waters and sediments were toxic to D. carinata. The 48h LC50 for acute exposure was 0.0071 µg/L and the 48h LC50 for sediment was 1.603 mg/kg. Water exposures were more toxic to D. carinata in in concentrations as low as 0.010 µg/L showed significant responses. Therefore, current concentrations within the environment are likely to affect D. carinata and this indicated that the surface water concentrations present in the wetlands would be at concentrations that would potentially be toxic to other zooplankton species as well. This may have a negative effect on higher orders like threatened L. raniformis tadpoles that can rely on these organisms as a source of food.
To determine the effects of direct exposure of bifenthrin on L. raniformis tadpoles, 48-h acute water and sediment toxicity tests were carried out in laboratory conditions. The tadpoles showed signs of stress (swimming on sides, not feeding and not active) in the highest concentration (0.5 µg/L) in water exposures. One-way analysis of variance with Tukey post hoc test conducted showed the highest concentration (0.5 µg/L) being significantly different to the control (33.20±0.2, p=0.016) in development stages after the 48-hr acute water test. The control also had a significantly greater weight compared to the 0.5 µg/L treatment (0.6700±0.1928, p=0.05 Biomarker acetylcholinesterase (AChE) expression did not significantly vary between treatment (p≥0.05).
With the results of this study, it is very clear that bifenthrin is very commonly occurring in Melbourne wetlands and in concentrations above the guideline value (0.011 mg/Kg). Therefore, it should be potentially harming the biota in the wetlands including the zooplankton, macroinvertebrates, and L. raniformis tadpoles. Bifenthrin is certainly contributing to wetland pollution, and it could be having direct and indirect effects on the biota and their communities. Declining populations of zooplankton, macroinvertebrates, and L. raniformis confirms that wetlands are affected by the pollution. More work is needed to identify how communities of aquatic fauna would react to bifenthrin in their habitats. Special attention should be given to threatened L. raniformis tadpoles and its life stages that would mostly be vulnerable to bifenthrin toxicity. Control measures should be identified and applied to bifenthrin usages to protect the aquatic fauna in urban wetlands.</p
Primary school teachers’ beliefs towards a systemic implementation of STEM-related instructional approaches in Saudi Arabia
No full textSaudi Arabia has changed economically and socially in recent decades, education has become increasingly important, with a particular focus on Science and Mathematics, Engineering and Technology (STEM). Thus, a total of 72 STEM centres were established by the Saudi Minister of Education to improve teachers’ skills and raise the quality of education. This study aims to investigate the implementation of STEM approaches by primary schools’ teachers in the Northern Borders Region of Saudi Arabia. This study explores the teachers' PCK, beliefs, and the constraints they encounter by implementing STEM approaches. Data was collected through a mixed methods approach using a survey and interviews. The results of this study indicate that most teachers implemented STEM teaching approaches in their PCK as they believed that they could develop new knowledge and skills necessary to teach their subjects within implemented STEM. Teachers believed they could learn new technologies and use resources necessary to teach their subjects within an implemented STEM system. The main constraints identified by them were a lack of sufficient knowledge about STEM, paucity of internet and related devices, and lack of classroom preparation. The findings also indicate that teachers are genuinely interested in using STEM teaching strategies, but they need to be supported with appropriately designed and delivered training and facilities. These results shed light on teachers' need to refine and update their IT and critical thinking skills. As well as the Saudi Ministry of Education needs to develop both in-service and refresher training and development programs for teachers.</p
Topology optimisation with an adaptive design domain
No full textTopology optimisation has undergone tremendous development in the past decades. In the conventional optimisation techniques, the design space is usually fixed and predefined. In this thesis, a subdomain-based method, named the adaptive design domain (ADD) method, is proposed to optimise structures with an adaptive design space. Through a systematic study, this method is established for both engineering structural design and biomechanical morphogenesis. The thesis consists of four research components. First, the ADD method is developed based on the bi-directional evolutionary structural optimisation (BESO) technique. In the ADD method, the initial design domain is divided into a certain number of subdomains. Different evolution strategies are proposed for updating the design space.
In the second research component, the ADD method is used for engineering structural design. In this application, the evolution of the subdomains depends on their efficiency. Through the automatic, flexible and intelligent adaptation of the design domain, the ADD method is capable of generating diverse high-performance designs with distinctly different topologies. Several represented examples are provided to demonstrate the effectiveness of the ADD method. The results show that, compared with conventional approaches, the ADD method can improve the structural performance substantially by optimising the layout of material while reshaping the design domain. In addition, the loads and boundary conditions can also be simultaneously updated along with the design domain evolution.
In the third research component, the ADD method is used for biomechanical morphogenesis. In past centuries, the growth of plants has attracted extensive attention from scientists. However, there still remains a challenge to quantitatively decipher the biomechanical mechanisms underlying the morphological evolution of plant organs. The ADD method is applied to the simulation of the growth of plant roots. The taproot and the fibrous systems are selected as two typical root systems for the present study. It is found that both systems tend to maximise the transport efficiency of water and nutrients. The evolution of the subdomains depends on the coupling effects of biomechanical and environmental factors. According to the simulations, the lateral roots in the taproot systems develop hierarchically branched layouts from the main roots, while the growth directions of root caps are regulated by geotropism, hydrotropism and growth inertia. The thickness and concentration of roots depend on the growth history, and root hairs are generated to promote water and nutrient absorption. These results are consistent with our experimental observations. This research component not only helps understand the topological formation of root systems, but also provides a quantitative tool for exploring the structure–property–function interrelations of living systems.
In the fourth research component, a subdomain-based parallel strategy is developed to improve the efficiency of the ADD method. In this strategy, matrix calculation is used to calculate weight functions in each subdomain efficiently. Besides, the calculations in multiple subdomains can be executed simultaneously by multiprocessors, which makes the most of the computing resources. This strategy is integrated into an efficient and compact Python code, which can be used for a design domain with an arbitrary shape. Through comparisons with the previous topology optimisation codes, the proposed strategy is shown to have the advantages of higher efficiency, better flexibility and simpler implementation. Therefore, this parallel strategy is used in the second and third components in this thesis.
In summary, this thesis has established an effective, flexible and efficient optimisation method with an adaptive design space. The main contributions of this thesis are outlined below. First, the ADD method is developed based on the BESO technique. Second, the ADD method is successfully implemented into engineering structural designs, where high-performance structures can be achieved. Third, a trans-disciplinary computational framework for plant root growth has been developed based on the ADD method. Various taproot and fibrous root systems can be simulated and the corresponding underlying biomechanisms are revealed. Finally, a simple parallel strategy is developed to improve the efficiency of both the ADD method and general three-dimensional topology optimisation
Liquid metal derived 2D post-transitional metal (In, Sn, Bi) compounds and their sensing properties
No full textAmong the post-transitional metals, 2D liquid metals of indium (In), tin (Sn), and bismuth (Bi) are representatives. These metals have melting points of 156.6℃, 231.93℃, and 271.3℃, respectively, and can be easily heated above their melting points using a laboratory hotplate. Liquid metals have emerged as a promising method for synthesizing semiconductor oxides and sulfides. Various compounds, such as SnS, In2O3, and TeO2, have been synthesized with outstanding properties, including piezoelectricity, photoelectricity, transistors and catalysts. Despite the significant progress made in the application of liquid metals, their potential in gas sensing and piezoelectricity remains largely unexplored, especially in 2D post-transitional metal (In, Sn, Bi) compounds. Therefore, the present study focuses on exploring the properties of 2D post-transitional metal compounds due to their promising potential outcomes. In this PhD thesis, the author establishes a new method to create gas sensor by liquid metal printing, this method can transfer oxide skin of molten indium to substrate in seconds. Various non-stratified 2D materials can be obtained from liquid metal surfaces that are not naturally accessible. Homogenous atomically flat formatted on the interfaces of liquid metals with air produces unprecedented high-quality oxide layers that can be transferred onto desired substrates. The atomically flat and large areas provide large surface-to-volume ratios ideal for sensing applications. Versatile crucial applications of the liquid metal-derived 2D oxides have been realized; however, their gas-sensing properties remain largely underexplored. The cubic In2O3 structure, which is nonlayered, can be formed as an ultrathin layer on the surface of liquid indium during the self-limiting CabreraMott oxidation process in the air. The morphology, crystal structure, and band structure of the harvested 2D In2O3 nanosheets from liquid indium are characterized. Sensing capability toward2 several gases, both inorganic and organic, entailing NO2, O2, NH3, H2, H2S, CO, and Methyl Ethyl Ketone (MEK) are explored. A high ohmic resistance change of 1974% at 10 ppm, fast response, and recovery times are observed for NO2 at an optimum temperature of 200 ℃. The sensing fundamentals are investigated for NO2, and its performances and cross-selectivity to different gases are analysed. The NO2 sensing response from room temperature to 300 ℃ has been measured and discussed, and stability after 24 hours of continuous operation is presented. The results demonstrate liquid metalderived 2D oxides as promising materials for gas sensing applications.
After investigating the 2D indium oxide by liquid metal for gas sensing application, this PhD research is extended to explore other liquid metal oxide compounds which form on the surface of bismuth liquid metals. Atomically thin, mechanically flexible, memory-functional and power-generating crystals play a crucial role in the technological advancement of portable devices. However, the adoption of these crystals in such technologies is impeded by expensive and laborious synthesis methods, as well as the need for large-scale, mechanically stable, and air-stable materials. Here we present an instant-in-air liquid metal printing process utilizing liquid bismuth (Bi), forming naturally occurring, air-stable, atomically thin, mechanically flexible nanogenerators and ferroelectric oxides. Despite the centrosymmetric nature of the monoclinic P21/c system of achieved α-Bi2O3-δ the high kinetics of liquid metal synthesis leads to the formation of vacancies that disrupt the symmetry which was confirmed by density functional theory (DFT) calculations. The polarization switching was measured and utilized for ferroelectric nanopatterning. The exceptional attributes of these atomically thin multifunctional stable oxides, including piezoelectricity, mechanical flexibility, and polarizability, present significant opportunities for developing nano-components that can be seamlessly integrated into a wide range of devices.
In the final parts, the author of this PhD thesis discovered the possibility to doping modification of 2D intrinsic oxide materials which have been synthesised before, gas–liquid reaction phenomena on liquid-metal solvents can be used to form intriguing 2D materials with large lateral dimensions, where the free energies of formation determine the final product. A vast selection of elements can be incorporated into the liquid metal-based nanostructures, offering a versatile platform for fabricating3 novel optoelectronic devices. While conventional doping techniques of semiconductors present several challenges for 2D materials. Liquid metals provide a facile route for obtaining doped 2D semiconductors. In this work, we successfully demonstrate that the doping of 2D SnS can be realized in a glove box containing a diluted H2S gas. Low melting point elements such as Bi and In are alloyed with base liquid Sn in varying concentrations, resulting in the doping of 2D SnS layers incorporating Bi and In sulphides. Optoelectronic properties for photodetectors and piezoelectronics can be tuned through the controlled introduction of selective migration doping. The structural modification of 2D SnS results in a 22.6% enhancement of the d11 piezoelectric coefficient. In addition, photodetector response times have increased by several orders of magnitude. Doping methods using liquid metals have significantly changed the photodiode and piezoelectric device performances, providing a powerful approach to tune optoelectronic device outputs. In conclusion, during the author's PhD research period, several novel discoveries were successfully verified, and new method for synthesizing piezoelectric materials based on liquid metals were proposed. Additionally, numerous devices with extraordinary properties were created. The results of this research have the potential to inspire new directions in various industries, including gas sensing, piezoelectricity, and photoelectricity
Situated encounters with light
No full textThis PhD focusses on light-based art encounters with art that challenge preconception. Offering an understanding of how shifting perceptions in an artwork’s presence can connect visitors with artists in psychologically affecting ways, the research examines how artworks can engage visitors through strange light phenomenon, with an aim to share in the wonder of the material world of light.
Perceptual shift is identified as a situated perspective of art that is unique to bodily experiences of the artwork. Competing perceptual interpretations inhabit some works, as light and image-based observation compete for attention, while others are invested with changeover moments of discovery for gallery visitors to unveil. Through the analysis of these encounters the investigative nature of art is fed back to studio practice. Unexpected interactions between light, heat and tactile materials are used to generate outcomes that are challenging to both artist and visitor.
This research interweaves a critical analysis of artworks, theoretical investigation of situated psychology, neuroscientific studies and studio-based investigations into the materiality of light. This bricoleur’s workshop of theory and practice are woven together in a series of artistic outputs that glow with the knowledge they were made to be investigated, to couple with visitors, sharing the experiential nature of the discoveries made through this project
Ultra-performance polymer and composites in extrusion based additive manufacturing with space applications
No full textRenewed global interest in space exploration will increase demand for compact spacecrafts such as CubeSats. Launch costs are still expensive, at around $20,000/kg to deliver satellites to low earth orbit (LEO). Strategies to reduce launch costs, such as using lightweight materials and optimization of structural topology are of commercial significance and will assist in opening greater access to space. The structure of a CubeSat is currently manufactured from lightweight metals such as Aluminium. A greater strategic use of lower density polymers will reduce mass and result in cost savings. Topology optimization of structures and reduction of joints and fixtures can also result in mass reduction. Advanced manufacturing techniques such as Additive Manufacturing (AM) can allow increased topology optimization due to reduced design constraints compared to traditional manufacturing methods. Material extrusion technologies such as Fused filament fabrication (FFF) is a type of AM which uses thermoplastics as raw material feedstocks. Currently there are limited materials available suitable for FFF that can withstand space environment including extreme temperature fluctuations, high vacuum, UV radiation, galactic cosmic radiation, etc. Out of the ultra-performance polymers used in FFF process, a certain grade of Polyether ketone ketone (PEKK) was appealing due to its thermal, mechanical, outgassing, and chemical resistance properties which ensures its applicability in space environment while offering processability in FFF. While previous studies have exposed ultra-performance polymers to simulated space environment such as thermal cycles, UV radiation, protons and electrons, limited studies have analysed the effects of heavy ions from galactic cosmic rays (GCR) and solar particle events (SPE) on these polymers. As some ultra-performance polymers are already being used to manufacture end-use components for space, it is crucial to gain an understanding about the durability of these polymers when used in space. Initial experiments involved exposing FFF printed and compression moulded samples of PEKK to heavy ion irradiation using particle accelerators at ANSTO, Lucas Heights. Absorbed dose and fluence of particles were determined from literature and SPENVIS simulations. Chemical, surface, and micro mechanical properties of PEKK was studied before and after irradiation to gain an understanding of durability of PEKK when exposed to radiation in space.
Performance of FFF printed parts in space environment can be improved by optimizing FFF process parameters as properties of finished parts are highly dependent on process parameters as observed in previous studies. However, due to costs and printing difficulty associated with ultra-performance polymers, there is a need to use predictive design of experiments (DoE) methods to reduce the experimental runs while optimising process parameters. A comparison between full factorial and Taguchi design of experiments were performed in Chapter 3 where selected process parameters were varied, and mechanical and surface properties were analysed. Due to cost and printing difficulty associated with ultra-performance thermoplastics, an engineering semi-crystalline thermoplastic, Nylon 6/66 was used in Chapter 3. As PEKK and Nylon 6/66 are both semi-crystalline, the idea was to develop fundamental knowledge on relationships between structure-process-property of semi-crystalline polymers in the FFF process that are applicable for PEKK and other ultra-performance semi-crystalline thermoplastics within FFF. Results showed that when responses varied linearly, Taguchi DoE could accurately predict responses while reducing experimental effort by 50%.
Taguchi DoE was thus used in the two subsequent chapters to fully optimize process parameters for PEKK. Tensile properties of PEKK were optimized in Chapter 4 using Taguchi DoE by altering build orientation, number of contours, raster angle, and infill pattern. As number of contours significantly influenced the tensile properties as observed from main effects plots, no. of contours was varied in more levels in the subsequent chapter. Chapter 5 optimized numerous properties such as compressive, flexure, porosity, thermomechanical and dynamic mechanical. Once neat PEKK was fully characterized, properties of PEKK were further improved using additives to achieve multi-functional properties required in space in Chapter 6. Upon reviewing various additives used in the FFF process from literature, Graphene nano platelets, Graphene Oxide and Boron Carbide were used to reinforce the ultra-performance polymer and their thermal, chemical, mechanical, microstructure, and electrical properties were studied. Printability of the composites were confirmed by comparing their rheology with neat PEKK and printable commercial PEKK matrix composites. Small samples were printed using the composite filaments and characterized to identify favourable additives for PEKK in the FFF process. Potential future research opportunities were then identified in the final Chapter
An analytical study on farmland allocation in the conversion from conventional to organic farming
No full textOrganic farming refers to an agricultural system that relies on farm resources and excludes or strictly limits the use of external inputs such as synthetic fertilizers and pesticides. It enhances food quality and public health and contributes to a more sustainable environment. Although there is a growth in certified organic farmland (from 11 to 72.3 million hectares between 1999 and 2019), this constitutes only 1.5 percent of the world's agricultural farmlands in 2019. The main impediment to the conversion to organic farming is the financial difficulties that a farmer experiences in terms of a decrease in production and an increase in farming costs owning to such transitional practices. Furthermore, uncertainty in the yield, weather, and price may intensify the adverse effects of transitional practices.
This study aims to find the optimal cropping pattern and conversion plan to optimise a farmer’s payoff in the conversion to organic farming, with respect to the uncertainty in the crop’s revenue that is drawn by uncertainty in its yield and price. Reviewing the relevant literature, crop production planning has been considered in a wide range of decision-making models in the upstream level of the agricultural supply chain including cropping policy, harvesting operations, capital investments, and pest control strategies. However, there are few studies on farmland allocation while planning conversion from conventional to organic farming, and to the best of my knowledge, this work is the first that focuses on farmland allocation decisions under uncertainty during the conversion period. Also, this is the first study that numerically compares the different approaches in the conversion to organic farming. This thesis proposes three models to seek the optimal farmland allocation in conversion from conventional to organic farming.
To establish the first model, utilizing studies and surveys on organic farming methods, conversion to organic farming, and crop production planning, the technical parameters (including transitional and rotational parameters affecting the farmer’s payoff) are explored and estimated. A multi-period optimisation model in the presence of crop rotation and revenue uncertainty is then developed to sequentially decide on the starting year of conversion and cropping pattern. The multistage stochastic optimization model is approximated with a two-stage stochastic optimization model, and to embed the dynamic nature of sequential decision making a rolling horizon framework is considered for the two-stage stochastic model. The model is calibrated to represent a grower of corn and soybean in Iowa and using a seemingly unrelated regression model, crops’ revenues are simulated and utilized in the numerical experiments. The performance of the farmland allocation model is examined against other policies in the agriculture industry, including monoculture (growing only one crop) and systematic crop rotation in terms of profit shortfall (when obtained profit is less than the acceptable profit), average profit, and the minimum yearly profit. The results are reported and studied to extract insights on the cropping pattern in the conversion to organic farming. This chapter presents the excellence of the developed model in terms of the proposed rotation pattern.
In the second model with the goal of enhancing farmer’s profit shortfall in the conversion period, by adopting gradual conversion (where the farmland is converted to organic farming on a field-by-field basis), this study tries to reduce the adverse effects of transitional farming in comparison with a whole-farmland conversion (the first model). The stochastic multi-period optimisation model is developed into a chance-constrained multi-stage optimisation model to decide on the agricultural method in addition to the cropping pattern. Conducting numerical experiments, the performance of the developed model is examined against different cropping pattern policies in both gradual and whole-farmland conversion approaches and findings are translated into insights. This chapter highlights the improvements in the profit shortfall made by the developed gradual conversion model in the farmland allocation decisions.
Finally, considering the ability of reinforcement learning to overcome the curse of dimensionality in comparison with multi-stage stochastic programming solving methods, required components for reinforcement learning including the set of states, the set of actions, and the reward function are presented to find the optimal farmland allocation policy. The performance of the reinforcement learning method under different designs of reward function is evaluated to provide insights into the conversion planning and application of reinforcement algorithms in farmland allocation decision-making
An investigation on nanocarrier-mediated glucose-responsive delivery of antidiabetic lipophilic molecules
No full textDiabetes mellitus (DM) is a metabolic health burden recognized by high blood glucose levels. International Diabetes Federation reported that the number of patients with DM was approximately 537 million (20−79 years) across the world in 2021, and the predicted number of individuals with DM will be 784 million by 2045. Type 2 diabetes mellitus (T2DM) is defined by impaired glucose metabolism resulting from reduced insulin production and/or decreased insulin sensitivity. T2DM represents approximately 90% of all types of DM. Uncontrolled T2DM can lead to a range of health disorders, including nephropathy, neuropathy, and retinopathy. Diabetic retinopathy (DR) is an inflammatory disease of blood vessels of the eye, the retina in particular and can cause irreversible blindness in patients with DM.
Approximately half of all patients with DM cannot attain the required glycaemic level by using conventional medicines. An alternative strategy is required to overcome this crucial issue. Glucose-responsive delivery of antidiabetic molecules is a promising strategy for maintaining normoglycemia and reducing the risk of hypoglycaemia associated with currently available therapeutic agents. Three key types of glucose-responsive delivery systems are used in antidiabetic drug delivery. These include glucose oxidase (GOx)-based systems, glucose-binding proteins (GBP)-based systems, and phenylboronic acid (PBA)-based systems. A significant portion of the antidiabetic drugs are lipophilic molecules such as sulphonylureas, e.g., Glimepiride, Glipizide, and Glyburide; thiazolidinediones e.g., Rosiglitazone and Pioglitazone; inhibitors of dipeptidyl peptidase-4 (DPP-4), e.g., Alogliptin and Linagliptin, and inhibitors of sodium-glucose cotransporter 2 (SGLT2), e.g., Canagliflozin and Empagliflozin. Various lipid-soluble micronutrients, like vitamin K (VK) and vitamin D (VD) have also shown studies on glucose-sensitive delivery of lipophilic antidiabetic molecules are limited.
Herein, we examine the glucose-responsive delivery of VK and VD by using dextran-capped mesoporous silica nanoparticles (MSN) functionalized with 3-carboxyphenylboronic acid (CPBA) to alleviate hyperglycemia and diabetic retinopathy. Previous studies have found a link between VD and VK deficiencies and the aetiology of diabetes and its complications. Therefore, VD and VK are used as model antidiabetic therapies in this study.
Amine functionalized-MSN were prepared by tetraethyl orthosilicate (TEOS) and (3-aminopropyl)trimethoxysilane (APTES) by using a template N-cetyl-N,N,N-trimethylammonium bromide (CTAB). CPBA functionalization was performed on the surface of MSN (MSN-CPBA). Lipid-soluble VK and VD were loaded in channel-like pores of MSN-CPBA and the pores were capped with dextran. The CPBA-functionalization, physical nature of nanocarriers, shape, internal and surface morphology, size, pore diameter and volume, and nature of surface charge were examined using Alizarin red S test, field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), Fourier transformed infrared (FTIR) spectroscopy, nitrogen adsorption/desorption isotherm, hydrodynamic size distribution and surface charge analyser and thermogravimetric analyser, respectively. The loading and release efficiencies of lipophilic molecules were measured by using reverse-phase (RP)-HPLC. Transmission electron microscopic image analysis revealed an appropriate particle size of 238.6 ± 30.9 nm which was consistent with their hydrodynamic size. The surface charge of VK/VD-loaded dextran-gated MSN-CPBA (MSN-CPBA-VK/VD-Dex) was negative. The VK or VD was loaded inside the pores of MSN-CPBA by physical adsorption, and the loading capacity of MSN-CPBA was 206.7 and 263.6 µg/mg (w/w) in the case of VK and VD, respectively.
The pores of the nanoparticles were capped using dextran via binding with CPBA. Glucose is a 1,2 cis-diol molecule that has a very high affinity towards carboxyphenylboronic acid compared to dextran which triggers the untethering of dextran from MSN allowing the pores to open and release VK or VD. At 24 h, the release of VK was 10.21 and 18.62 µg/mL (∼49.1% and ∼90.2%) in a phosphate-buffered saline (PBS) in exposure to 11 mM and 25 mM of glucose concentration. In contrast, VK release was 1.5 and 0.99 µg/mL in myocytes and hepatocytes, respectively, at the same time point and 25 mM glucose concentration. In cell-free systems, VD release was found to be 10.97 and 19.81 µg/mL (∼16.79% and ∼75 %) against exposure to 11- and 25-mM glucose, respectively. The VD releases were 2.12 and 3.48 μg/mL in myocytes against 11 and 25 mM of glucose exposure, respectively. The result showed that the VD release was faster compared to the VK release. The glucose-responsive delivery of VK was examined in high-fat diet-induced diabetic mice. The levels of Gla-proteins (VK biomarkers) were significantly increased in skeletal muscles and liver of mice with diabetes supplemented with MSN-CPBA-VK-Dex in comparison with mice in the control group, demonstrating the glucose-sensitive release of VK in mice.
VK/VD loaded MSN-CPBA were internalized in two major cell types, which are involved in glucose metabolism, myocytes (C2C12) and hepatocytes (CC1), by using a confocal microscope. The green/red fluorescence was observed inside the cells suggesting the cellular uptake of fluorescent isothiocyanate/ rhodamine B isothiocyanate (FITC/RITC)-labelled MSN-CPBA. The nanoparticle internalizations in myocytes and hepatocytes were confirmed by a Flow cytometric study. Approximately 97% of myocytes and 90 % of hepatocytes engulfed MSN-CPBA-VK-Dex at 2 h. MSN-CPBA-VK/VD-Dex did not show cytotoxic effects in mammalian myocytes, hepatocytes and human retinal epithelial cells cultured in low and high glucose-treated culture medium.
The effect of MSN-CPBA-VK/VD-Dex on glucose uptake was significantly improved in the high glucose (HG)-treated myocytes. The improvement of glucose uptake was mediated by improving the GLUT4 expression in myocytes. The GLUT4 expression was increased by 1.57-fold in HG-induced myocytes supplemented with MSN-CPBA-VK/VD-Dex compared to that in HG-induced myocytes in the control. The in vivo study demonstrated that blood glucose level is markedly decreased in high-fat diet-induced diabetic mice treated with MSN-CPBA-VK-Dex compared to the control. However, VK alone at the same dose present in the nanoparticles did not show a significant hypoglycemic effect in mice with diabetes. The blood glucose levels were 6.5 ± 0.8 and 13.5 ± 4.4 mM in mice with diabetes supplemented with MSN-CPBA-VK-Dex and VK alone, respectively. Histological studies demonstrated that muscle tissues of mice with diabetes showed several complications including muscular focal necrosis, infiltration of lymphocytes, atrophic muscle fibers, and reduced thickness of muscle fibers. The lesions of muscles were mitigated in diabetic mice treated with MSN-CPBA-VK-Dex; however, VK alone could not enable the restoration of pathophysiological alterations. Likewise, liver injuries were alleviated in mice with diabetes treated with MSN-CPBA-VK-Dex, but VK alone was not able to mitigate the pathophysiological changes associated with diabetes, indicating elevated bioavailability of VK in MSN-CPBA-VK-Dex-treated mice with diabetes.
We also investigated the glucose-responsive delivery of VD by using MSN-CPBA to alleviate diabetic retinopathy (DR) in the human retinal pigmented epithelial cell culture model. In patients with diabetes, mitochondrial ROS production is dramatically raised in the retinal epithelium resulting in the destruction of epithelial cells and the occurrence of DR. Treatment with MSN-CPBA-VD-Dex showed remarkable efficiency in reducing oxidative stress in the high glucose (25 mM)-treated adult retinal pigmented epithelial (ARPE-19) cells. In addition, VD-loaded nanoparticles were able to reduce the secretion of proinflammatory, cytokine interleukin 6 (IL-6) in retinal cells exposed to HG. Thus, MSN-CPBA-VD-Dex showed promising results in alleviating diabetic retinopathy by managing oxidative stress and inflammation associated with cellular exposure to high glucose levels.
In conclusion, the MSN-CPBA-based delivery system was able to deliver lipid-soluble molecules, VK and VD, in a glucose-sensitive manner both in vitro and in vivo. MSN-CPBA-VK/VD-Dex demonstrated its hypoglycemic effect in HG-treated myocytes as well as in HFD-induced diabetic mice. In addition, the study revealed MSN-CPBA-VD-Dex was able to reduce oxidative stress via controlling ROS production and secretion of proinflammatory cytokine IL-6 in retinal epithelial cells exposed to HG. Thus, MSN-CPBA-VD-Dex was capable of controlling DR
Immune modulation by rural exposures and allergy protection
No full textBackground: Growing up on traditional farms protects children from the development of asthma and allergies. However, we have identified distinct asthma-protective factors, such as poultry exposure. This study aims to examine the biological effect of
rural exposure in China. Methods: We recruited 67 rural children (7.4 ± 0.9 years) and 79 urban children
(6.8 ± 0.6 years). Depending on the personal history of exposure to domestic poultry
(DP), rural children were further divided into those with DP exposure (DP+, n= 30) and
those without (DP−
, n= 37). Blood samples were collected to assess differential cell
counts and expression of immune-related genes. Dust samples were collected from
poultry stables inside rural households. In vivo activities of nasal administration of DP
dust extracts were tested in an ovalbumin-induced asthma model.
Results: There was a stepwise increase in the percentage of eosinophils (%) from
rural DP+ children (median = 1.65, IQR = [1.28, 3.75]) to rural DP− children (3.40, [1.70,
6.50]; DP+ vs. DP−
, p= .087) and to the highest of their urban counterparts (4.00,
[2.00, 7.25]; urban vs. DP+, p= .017). Similarly, rural children exhibited reduced mRNA
expression of immune markers, both at baseline and following lipopolysaccharide
(LPS) stimulation. Whereas LPS stimulation induced increased secretion of Th1 and proinflammatory cytokines in rural DP+ children compared to rural DP−
children and
urban children. Bronchoalveolar lavage of mice with intranasal instillation of dust
extracts from DP household showed a significant decrease in eosinophils as compared to those of control mice (p< .05). Furthermore, DP dust strongly inhibited gene
expression of Th2 signature cytokines and induced IL-17 expression in the murine
asthma model.
Conclusions: Immune responses of rural children were dampened compared to urban
children and those exposed to DP had further downregulated immune responsiveness. DP dust extracts ameliorated Th2-driven allergic airway inflammation in mice.
Determining active protective components in the rural environment may provide directions for the development of primary prevention of asthma
One-dimensional single atom arrays on ferroelectric nanosheets for enhanced CO2 photoreduction
No full textSingle-atom catalysts show excellent catalytic performance because of their coordination environments and electronic configurations. However, controllable regulation of single-atom permutations still faces challenges. Herein, we demonstrate that a polarization electric field regulates single atom permutations and forms periodic one-dimensional Au single-atom arrays on ferroelectric Bi4Ti3O12 nanosheets. The Au single-atom arrays greatly lower the Gibbs free energy for CO2 conversion via Au-O=C=O-Au dual-site adsorption compared to that for Au-O=C=O single-site adsorption on Au isolated single atoms. Additionally, the Au single-atom arrays suppress the depolarization of Bi4Ti3O12, so it maintains a stronger driving force for separation and transfer of photogenerated charges. Thus, Bi4Ti3O12 with Au single-atom arrays exhibit an efficient CO production rate of 34.15 µmol·g−1·h−1, ∼18 times higher than that of pristine Bi4Ti3O12. More importantly, the polarization electric field proves to be a general tactic for the syntheses of one-dimensional Pt, Ag, Fe, Co and Ni single-atom arrays on the Bi4Ti3O12 surface