Cerium oxide nanoparticle conjugation to microRNA-146a mechanism of correction for impaired diabetic wound healing.

Diabetic wounds represent a significant healthcare burden and are characterized by impaired wound healing due to increased oxidative stress and persistent inflammation. We have shown that CNP-miR146a synthesized by the conjugation of cerium oxide nanoparticles (CNP) to microRNA (miR)-146a improves diabetic wound healing. CNP are divalent metal oxides that act as free radical scavenger, while miR146a inhibits the pro-inflammatory NFκB pathway, so CNP-miR146a has a synergistic role in modulating both oxidative stress and inflammation. In this study, we define the mechanism(s) by which CNP-miR146a improves diabetic wound healing by examining immunohistochemical and gene expression analysis of markers of inflammation, oxidative stress, fibrosis, and angiogenesis. We have found that intradermal injection of CNP-miR146a increases wound collagen, enhances angiogenesis, and lowers inflammation and oxidative stress, ultimately promoting faster closure of diabetic wounds.

Lung function improves after delayed treatment with CNP-miR146a following acute lung injury.

Acute respiratory distress syndrome (ARDS) is a highly morbid pulmonary disease characterized by hypoxic respiratory failure. Its pathogenesis is characterized by unrestrained oxidative stress and inflammation, with long-term sequelae of pulmonary fibrosis and diminished lung function. Unfortunately, prior therapeutic ARDS trials have failed and therapy is limited to supportive measures. Free radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA-146a (miR146a), termed CNP-miR146a, have been shown to prevent acute lung injury in a pre-clinical model. In this study, we evaluated the potential of delayed treatment with CNP-miR146a at three or seven days after injury to rescue the lung from acute injury. We found that intratracheal CNP-miR146a administered three days after injury lowers pulmonary leukocyte infiltration, reduce inflammation and oxidative stress, lower pro-fibrotic gene expression and collagen deposition in the lung, and ultimately improve pulmonary function.

Predicting sustainable arsenic mitigation using machine learning techniques.

This study evaluates state-of-the-art machine learning models in predicting the most sustainable arsenic mitigation preference. A Gaussian distribution-based Naïve Bayes (NB) classifier scored the highest Area Under the Curve (AUC) of the Receiver Operating Characteristic curve (0.82), followed by Nu Support Vector Classification (0.80), and K-Neighbors (0.79). Ensemble classifiers scored higher than 70% AUC, with Random Forest being the top performer (0.77), and Decision Tree model ranked fourth with an AUC of 0.77. The multilayer perceptron model also achieved high performance (AUC=0.75). Most linear classifiers underperformed, with the Ridge classifier at the top (AUC=0.73) and perceptron at the bottom (AUC=0.57). A Bernoulli distribution-based Naïve Bayes classifier was the poorest model (AUC=0.50). The Gaussian NB was also the most robust ML model with the slightest variation of Kappa score on training (0.58) and test data (0.64). The results suggest that nonlinear or ensemble classifiers could more accurately understand the complex relationships of socio-environmental data and help develop accurate and robust prediction models of sustainable arsenic mitigation. Furthermore, Gaussian NB is the best option when data is scarce.

ß-Sitosterol & quercetin enhances brain development in iodine deficient rat models.

BACKGROUND: Recently thyroid hormone studies on brain growth, development and activity are regaining popularity. Thyroid hormones have long been believed to play critical role in mammalian brain growth and maturation regulating facets of neuronal cell growth, proliferation and differentiation and further signaling and glial cell differentiation. Deficiency of these hormones in mother leads to mental retardation in the subsequent offspring's. METHODS: In this presented study, brain development of iodine deficient rat models created through deficiency in feeding, mating and further selection. Young adult female wistar rats were induced with iodine deficiency and then mated with healthy male rats. These pregnant hypothyroid induced females were treated with ß-sitosterol (150 mg/kg/day) and quercetin (150 mg/kg/day) alone and in combination for whole gestation period. Analysis were dealt with the genetic and histological studies of the pups brain. PCR based RNA analysis was also carried out. Histology was done using eosin and hematoxylin. RESULTS: Positive impacts of the ß-sitosterol and quercetin on the iodine deficient brain were observed upon histological and PCR analysis. Altogether, the analysis proves that combined doses of ß-sitosterol and quercetin for normal brain development in iodine deficient infants hence can be potentially applied as therapeutics in iodine deficiency circumstances.

Strain-specific differences in muscle Ca2+ transport and mitochondrial electron transport chain proteins between FVB/N and C57BL/6J mice.

Genetically engineered mouse models have been used to determine the role of sarcolipin (SLN) in muscle. However, a few studies had difficulty in detecting SLN in FBV/N mice and questioned its relevance to muscle metabolism. It is known that genetic alteration of proteins in different inbred mice strains produces dissimilar functional outcomes. Therefore, here we compared the expression of SLN and key proteins involved in Ca2+ handling and mitochondrial metabolism between FVB/N and C57BL/6J mouse strains. Data suggest that SLN expression is less abundant in the skeletal muscles of FVB/N mice than in the C57BL/6J strain. The expression of Ca2+ transporters in the mitochondrial membranes was also lower in FVB/N than in C57BL/6J mice. Similarly, electron transport chain proteins in the mitochondria were less abundant in FVB/N mice, which may contribute to differences in energy metabolism. Future studies using different mouse strains should take these differences into account when interpreting their data.

Cerium oxide nanoparticle delivery of microRNA-146a for local treatment of acute lung injury.

Acute respiratory distress syndrome (ARDS) is a devastating pulmonary disease with significant in-hospital mortality and is the leading cause of death in COVID-19 patients. Excessive leukocyte recruitment, unregulated inflammation, and resultant fibrosis contribute to poor ARDS outcomes. Nanoparticle technology with cerium oxide nanoparticles (CNP) offers a mechanism by which unstable therapeutics such as the anti-inflammatory microRNA-146a can be locally delivered to the injured lung without systemic uptake. In this study, we evaluated the potential of the radical scavenging CNP conjugated to microRNA-146a (termed CNP-miR146a) in preventing acute lung injury (ALI) following exposure to bleomycin. We have found that intratracheal delivery of CNP-miR146a increases pulmonary levels of miR146a without systemic increases, and prevents ALI by altering leukocyte recruitment, reducing inflammation and oxidative stress, and decreasing collagen deposition, ultimately improving pulmonary biomechanics.

Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice.

Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) (i.e. uncoupling protein 1 (UCP1)-based) and skeletal muscle (i.e. sarcolipin (SLN)-based) thermogenesis processes play important roles in temperature homeostasis, but their relative contributions differ from small to large mammals. In this study, we investigated the functional interplay between skeletal muscle- and BAT-based thermogenesis under mild versus severe cold adaptation by employing UCP1-/- and SLN-/- mice. Interestingly, adaptation of SLN-/- mice to mild cold conditions (16 °C) significantly increased UCP1 expression, suggesting increased reliance on BAT-based thermogenesis. This was also evident from structural alterations in BAT morphology, including mitochondrial architecture, increased expression of electron transport chain proteins, and depletion of fat droplets. Similarly, UCP1-/- mice adapted to mild cold up-regulated muscle-based thermogenesis, indicated by increases in muscle succinate dehydrogenase activity, SLN expression, mitochondrial content, and neovascularization, compared with WT mice. These results further confirm that SLN-based thermogenesis is a key player in muscle non-shivering thermogenesis (NST) and can compensate for loss of BAT activity. We also present evidence that the increased reliance on BAT-based NST depends on increased autonomic input, as indicated by abundant levels of tyrosine hydroxylase and neuropeptide Y. Our findings demonstrate that both BAT and muscle-based NST are equally recruited during mild and severe cold adaptation and that loss of heat production from one thermogenic pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic processes.

Developing robust arsenic awareness prediction models using machine learning algorithms.

Arsenic awareness plays a vital role in ensuring the sustainability of arsenic mitigation technologies. Thus far, however, few studies have dealt with the sustainability of such technologies and its associated socioeconomic dimensions. As a result, arsenic awareness prediction has not yet been fully conceptualized. Accordingly, this study evaluated arsenic awareness among arsenic-affected communities in rural India, using a structured questionnaire to record socioeconomic, demographic, and other sociobehavioral factors with an eye to assessing their association with and influence on arsenic awareness. First a logistic regression model was applied and its results compared with those produced by six state-of-the-art machine-learning algorithms (Support Vector Machine [SVM], Kernel-SVM, Decision Tree [DT], k-Nearest Neighbor [k-NN], Naïve Bayes [NB], and Random Forests [RF]) as measured by their accuracy at predicting arsenic awareness. Most (63%) of the surveyed population was found to be arsenic-aware. Significant arsenic awareness predictors were divided into three types: (1) socioeconomic factors: caste, education level, and occupation; (2) water and sanitation behavior factors: number of family members involved in water collection, distance traveled and time spent for water collection, places for defecation, and materials used for handwashing after defecation; and (3) social capital and trust factors: presence of anganwadi and people's trust in other community members, NGOs, and private agencies. Moreover, individuals' having higher social network positively contributed to arsenic awareness in the communities. Results indicated that both the SVM and the RF algorithms outperformed at overall prediction of arsenic awareness-a nonlinear classification problem. Lower-caste, less educated, and unemployed members of the population were found to be the most vulnerable, requiring immediate arsenic mitigation. To this end, local social institutions and NGOs could play a crucial role in arsenic awareness and outreach programs. Use of SVM or RF or a combination of the two, together with use of a larger sample size, could enhance the accuracy of arsenic awareness prediction.

Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function.

Skeletal muscle has been suggested as a site of nonshivering thermogenesis (NST) besides brown adipose tissue (BAT). Studies in birds, which do not contain BAT, have demonstrated the importance of skeletal muscle-based NST. However, muscle-based NST in mammals remains poorly characterized. We recently reported that sarco/endoplasmic reticulum Ca(2+) cycling and that its regulation by SLN can be the basis for muscle NST. Because of the dominant role of BAT-mediated thermogenesis in rodents, the role of muscle-based NST is less obvious. In this study, we investigated whether muscle will become an important site of NST when BAT function is conditionally minimized in mice. We surgically removed interscapular BAT (iBAT, which constitutes ∼70% of total BAT) and exposed the mice to prolonged cold (4 °C) for 9 days. The iBAT-ablated mice were able to maintain optimal body temperature (∼35-37 °C) during the entire period of cold exposure. After 4 days in the cold, both sham controls and iBAT-ablated mice stopped shivering and resumed routine physical activity, indicating that they are cold-adapted. The iBAT-ablated mice showed higher oxygen consumption and decreased body weight and fat mass, suggesting an increased energy cost of cold adaptation. The skeletal muscles in these mice underwent extensive remodeling of both the sarcoplasmic reticulum and mitochondria, including alteration in the expression of key components of Ca(2+) handling and mitochondrial metabolism. These changes, along with increased sarcolipin expression, provide evidence for the recruitment of NST in skeletal muscle. These studies collectively suggest that skeletal muscle becomes the major site of NST when BAT activity is minimized.

Procerain B, a cysteine protease from Calotropis procera, requires N-terminus pro-region for activity: cDNA cloning and expression with pro-sequence.

We have previously reported isolation and characterization of a novel plant cysteine protease, Procerain B, from the latex of Calotropis procera. Our initial attempts for active recombinant Procerain B in Escherichiacoli expression system was not successful. The reason for inactive enzyme production was attributed to the absence of 5' pro-region in the Procerain B cDNA that may be involved in proper folding and production of mature active protein. The current manuscript reports the cloning of full length Procerain B for the production of the active protein. The complete cDNA sequence of Procerain B with pro-region sequence was obtained by using RNA ligase mediated rapid amplification of 5' cDNA ends (RLM-RACE). The N-terminus pro-sequence region consists of 127 amino acids and characterized as the member of inhibitory I29 family. Further the three dimensional structure of full length Procerain B was modelled by homology modelling using X-ray crystal structure of procaricain (PDB ID: 1PCI). N-terminus pro-sequence of full length Procerain B runs along the active site cleft. Full length Procerain B was expressed in prokaryotic system and activated in vitro at pH 4.0. This is the first study reporting the production of active recombinant cysteine protease from C.procera.

Investigating temperature variability on antioxidative behavior of synthesized cerium oxide nanoparticle for potential biomedical application.

Cerium oxide nanoparticles (CNP) have garnered significant attention due to their versatile redox properties and wound-healing applications. The antioxidative nature of CNP is due to its ability to be oxidized and reduced, followed by the capture or release of oxygen which is used for scavenging reactive oxygen species (ROS). Herein, CNP is produced through a wet chemistry approach and its tunable redox property is tested across a range of temperatures. The synthesized CNP was observed to reveal the signature peak at 245 nm indicating a high Ce+3/Ce+4 ratio. Towards evaluating the redox antioxidative behavior, CNPs were subjected to a comprehensive analysis for superoxide dismutase mimetic analysis with riboflavin-mediated nitroblue tetrazolium scavenging assay. The results demonstrated that the redox activity of cerium oxide nanoparticles was strongly influenced by the different temperature ranges. Superoxide dismutase mimetic activity was observed to be reduced with a decrease in temperature as we moved from 4°C (80% activity) to -80°C (47% activity) at 1 mM conc of CNP. Similarly, the SOD mimetic activity increased with an increase in temperature from 40°C (72% activity) to 70°C (94% activity). Further, CNP was found to inhibit E. coli (gram+ve) and Enterobacter (gram-ve) beyond 70% simultaneously at 1 mM conc, indicating its potential application as a remarkable antimicrobial agent. CNP also inhibited the alpha-amylase activity up to the 60% at 1 mM conc suggesting its potential application in antidiabetic wound healing therapy. Overall, the CNP finds its application in mitigating the oxidative stress-related disorder exhibited by its high antioxidative, antimicrobial, and antidiabetic behavior.

Influence of differential arsenic exposure on cellular redox homeostasis of exposed rural women of West Bengal.

The metalloid arsenic (As) induces oxidative stress is a well-known fact. However, the extent of variation of oxidative stress according to different exposure levels of As in groundwater and the mechanism responsible for As mediated oxidative stress is yet to be elucidated in a human population of West Bengal. In the present study, we have investigated the impact of low level (> 10 ≤ 50 µg/L) and high-level groundwater As (> 50 µg/L) on cellular redox status, DNA damage, and repair mechanisms in chronically exposed rural women of West Bengal. Prediction models of ordinary least square regression of nail As, forced vital capacity (FVC) %, and that of forced expiratory volume during the first one second (FEV1) % deciphered that accumulation of As in nails may predict hemoglobin deficiency. Moreover, consumption of As-laced water tends to decrease FEV1% and FVC%. A strong positive correlation was observed between water and nail As level and reactive oxygen species (ROS) generation. ROS, perturbed nuclear factor erythroid 2-related factor 2(Nrf2)/ Kelch-like ECH-associated protein 1 (Keap1) redox regulation, compromised antioxidant defense machinery-superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione transferase (GST), induced DNA damage, and suppressed DNA repair proteins-poly ADP ribose polymerase1(PARP1)/ X-ray repair cross-complementing protein 1(XRCC1)/ 8-oxoguanine glycosylase (OGG1) in a dose-dependent manner. All the low and high As areas had very high cancer risk values for the exposed population. It has been predicted that if the As level in the drinking water of a 40-year adult increases by 2 ug/L, the likelihood of the cancer risk will increase by 10%, keeping the body weight and amount of water intake constant. Thus, long-term exposure to either low or high As is seriously affecting the lives of asymptomatic women who are vulnerable to developing carcinogenic changes after a period of latency.

Ameliorating hydroxychloroquine induced retinal toxicity through cerium oxide nanoparticle treatments.

The present study investigated the potential protective effects of cerium oxide nanoparticles (CNP) on human retinal pigment epithelium (ARPE-19) cells damaged by hydroxychloroquine (HCQ). Toxicity of HCQ on the ARPE-19 cells was explored with a dose response trial. CNP rescue both a pre-treatment protocol, where CNP were applied 24 hours prior to HCQ application and a simultaneous treatment protocol where both CNP and HCQ were applied together, were used. In the dose response trial, 250 µM HCQ showed 51.84% cell viability after 24 hours and 32.75% after 48 hours time period. This was selected as model HCQ dose for rescue trials. The simultaneous treatment trials did not show a significant increase in viability compared to model toxic dose. The CNP pre-treatment trials showed a significant increase in cellular viability compared to model toxic dose with 68.03% ± 3.27 viability (p = 4.56E-05) at 24 hours and 51.85% ± 4.96 (p = 1.18E-05) at 48 hours time period. CNP pre-treatment showed significant protection of cells from HCQ induced toxicity. The difference in efficacy of simultaneous and pre-treatment is hypothesized to lie in the cellular localization of CNP. Furthermore, including the reactive oxygen species (ROS) scavenging properties of CNP seems to be responsible for protection, the effect of CNP on autophagosome and lysosome colocalization are also hypothesized to play a significant role.

ALD based nanostructured zinc oxide coated antiviral silk fabric.

The COVID-19 pandemic has underscored the importance of research and development in maintaining public health. Facing unprecedented challenges, the scientific community developed antiviral drugs, virucides, and vaccines to combat the infection within the past two years. However, an ever-increasing list of highly infectious SARS-CoV-2 variants (gamma, delta, omicron, and now ba.2 stealth) has exacerbated the problem: again raising the issues of infection prevention strategies and the efficacy of personal protective equipment (PPE). Against this backdrop, we report an antimicrobial fabric for PPE applications. We have fabricated a nanofibrous silk-PEO material using electrospinning followed by zinc oxide thin film deposition by employing the atomic layer deposition technique. The composite fabric has shown 85% more antibacterial activity than the control fabric and was found to possess substantial superoxide dismutase-mimetic activity. The composite was further subjected to antiviral testing using two different respiratory tract viruses: coronavirus (OC43: enveloped) and rhinovirus (RV14: non-enveloped). We report a 95% reduction in infectious virus for both OC43 and RV14 from an initial load of ∼1 × 105 (sample size: 6 mm dia. disk), after 1 h of white light illumination. Furthermore, with 2 h of illumination, ∼99% reduction in viral infectivity was observed for RV14. High activity in a relatively small area of fabric (3.5 × 103 viral units per mm2) makes this antiviral fabric ideal for application in masks/PPE, with an enhanced ability to prevent antimicrobial infection overall.

Cerium oxide nanomaterial with dual antioxidative scavenging potential: Synthesis and characterization.

Many studies have linked reactive oxygen species (ROS) to various diseases. Biomedical research has therefore sought a way to control and regulate ROS produced in biological systems. In recent years, cerium oxide nanoparticles (nanoceria, CNPs) have been pursued due to their ability to act as regenerative ROS scavengers. In particular, they are shown to have either superoxide dismutase (SOD) or catalase mimetic (CAT) potential depending on the ratio of Ce3+/Ce4+ valence states. Moreover, it has been demonstrated that SOD mimetic activity can be diminished by the presence of phosphate, which can be a problem given that many biological systems operate in a phosphate-rich environment. Herein, we report a CNP formulation with both SOD and catalase mimetic activity that is preserved in a phosphate-rich media. Characterization demonstrated a highly dispersed, stable solution of uniform-sized, spherical-elliptical shaped CNP of 12 ± 2 nm, as determined through dynamic light scattering, zeta potential, and transmission electron microscopy. Mixed valence states of Ce ions were observed via UV/Visible spectroscopy and XPS (Ce3+/Ce4+ > 1) (Ce3+∼ 62%). X-ray diffraction and XPS confirmed the presence of oxygen-deficient cerium oxide (CeO2-x) particles. Finally, the CNP demonstrated very good biocompatibility and efficient reduction of hydrogen peroxide under in-vitro conditions.

Characterization of a nitric oxide (NO) donor molecule and cerium oxide nanoparticle (CNP) interactions and their synergistic antimicrobial potential for biomedical applications.

HYPOTHESIS: Broad-spectrum antimicrobials are needed to mitigate the complicated nature of antibiotic-resistant infections. It is imperative to formulate new antimicrobials by combining agents with different mechanisms and broader microbial targets. A combined antimicrobial solution could be a highly critical step towards developing a strategy to prevent polymicrobial infections. Herein, we have investigated the interaction and antimicrobial potential of a solution that contains cerium oxide nanoparticles (CNP) and a nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP). It is hypothesized that these two agents induce synergistic effects and would provide broad antimicrobial effects since CNP is known to be an effective antifungal agent while NO released by SNAP is known to be a potent bactericidal agent. EXPERIMENTS: Different concentrations of SNAP and CNP were combined in a solution and tested for colloidal stability, NO release, mammalian cell cytotoxicity, and antimicrobial efficacy against Staphylococcus aureus, Escherichia coli, and Candida albicans, accounting for Gram-positive bacteria, Gram-negative bacteria, and fungi, respectively. FINDINGS: SNAP and CNP combined in equimolar solution of 3 mM were found to be highly virulent for all microbes tested compared to higher amounts of the treatments required individually. These results hold a promising outlook toward the development of broad-spectrum antimicrobial coatings and films with the potential to prevent polymicrobial infections and further enhance biomedical device usage and applications.

Engineered nanoceria modulate neutrophil oxidative response to low doses of UV-B radiation through the inhibition of reactive oxygen species production.

To avoid aging and ultraviolet mediated skin disease the cell repair machinery must work properly. Neutrophils, also known as polymorphonuclear leukocytes, are the first and most abundant cell types which infiltrate sites of irradiation and play an important role in restoring the microenvironment homeostasis. However, the infiltration of neutrophils in ultraviolet-B (UV-B) irradiated skin might also contribute to the pathophysiology of skin disease. The polymorphonuclear leukocytes activation induced by UV-B exposure may lead to prolonged, sustained NADPH oxidase activation followed by an increase in reactive oxygen species (ROS) production. Our previous work showed that cerium oxide nanoparticles can protect L929 fibroblasts from ultraviolet-B induced damage. Herein, we further our investigation of engineered cerium oxide nanoparticles (CNP) in conferring radiation protection specifically in modulation of neutrophils' oxidative response under low dose of UV-B radiation. Our data showed that even low doses of UV-B radiation activate neutrophils' oxidative response and that the antioxidant, ROS-sensitive redox activities of engineered CNPs are able to inhibit the effects of NADPH oxidase activation while conferring catalase and superoxide dismutase mimetic activity. Further, our investigations revealed similar levels of total ROS scavenging for both CNP formulations, despite substantial differences in cerium redox states and specific enzyme-mimetic reaction activity. We therefore determine that CNP activity in mitigating the effects of neutrophils' oxidative response, through the decrease of ROS and of cell damage such as chromatin condensation, suggests potential utility as a radio-protectant/therapeutic against UV-B damage.

COVID-19: A master stroke of Nature.

This article presents the status of countries affected by COVID-19 (as of mid-May 2020) and their preparedness to combat the after-effects of the pandemic. The report also provides an analysis of how human behavior may have triggered such a global pandemic and why humans need to consider living sustainably to make our future world livable for all. COVID-19 originated in the city of Wuhan, China in December 2019. As of mid-May, it has spread to 213 countries and territories worldwide. The World Health Organization has declared COVID-19 a global pandemic, with a death toll of over 300,000 to date. The U.S. is currently the most impacted country. Collaborative efforts of scientists and politicians across the world will be needed to better plan and utilize global health resources to combat this global pandemic. Machine learning-based prediction models could also help by identifying potential COVID-19-prone areas and individuals. The cause of the emergence of COVID-19 is still a matter of research; however, one consistent theme is humanity's unsustainable behavior. By sustainably interacting with nature, humans may have avoided this pandemic. If unsustainable human practices are not controlled through education, awareness, behavioral change, as well as sustainable policy creation and enforcement, there could be several such pandemics in our future.

Ceria Nanoparticles Mitigate the Iron Oxidative Toxicity of Human Retinal Pigment Epithelium.

Oxidative injury is implicated in retinal damage observed in age-related macular degeneration (AMD), as well as other degenerative conditions. Abnormally elevated levels of iron accumulation within the retinal pigment epithelium have been detected in eyes with AMD, and it is suspected to play a role in the pathogenesis through the production of reactive oxygen species (ROS). Ceria nanoparticles (CNP) have the ability to scavenge ROS. This study sought to evaluate the ability of CNP to mitigate iron-induced oxidative stress and assess cell viability in the human ARPE-19 cell line in vitro. Cell viability was measured by an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and compared between experimental groups undergoing 48-hr exposure to a ferrous iron solution with and without 24-hr CNP pre-treatment. The CNP effect on ROS formation was evaluated additionally by H2DCFDA (2,7-dichlorodihydrofluorescein diacetate) fluorescent probe assay and superoxide dismutase assay. CNP demonstrated a three-fold increase in cell viability and a reduction in ROS generation. The results show a promising treatment modality for diseases causing oxidative damage in the eye.

Exposure to nanoceria impacts larval survival, life history traits and fecundity of Aedes aegypti.

Effectively controlling vector mosquito populations while avoiding the development of resistance remains a prevalent and increasing obstacle to integrated vector management. Although, metallic nanoparticles have previously shown promise in controlling larval populations via mechanisms which are less likely to spur resistance, the impacts of such particles on life history traits and fecundity of mosquitoes are understudied. Herein, we investigate the chemically well-defined cerium oxide nanoparticles (CNPs) and silver-doped nanoceria (AgCNPs) for larvicidal potential and effects on life history traits and fecundity of Aedes (Ae.) aegypti mosquitoes. When 3rd instar larvae were exposed to nanoceria in absence of larval food, the mortality count disclosed significant activity of AgCNPs over CNPs (57.8±3.68% and 17.2±2.81% lethality, respectively) and a comparable activity to Ag+ controls (62.8±3.60% lethality). The surviving larvae showed altered life history traits (e.g., reduced egg hatch proportion and varied sex ratios), indicating activities of these nanoceria beyond just that of a larvicide. In a separate set of experiments, impacts on oocyte growth and egg generation resulting from nanoceria-laced blood meals were studied using confocal fluorescence microscopy revealing oocytes growth-arrest at 16-24h after feeding with AgCNP-blood meals in some mosquitoes, thereby significantly reducing average egg clutch. AgCNPs caused ~60% mortality in 3rd instar larvae when larval food was absent, while CNPs yielded only ~20% mortality which contrasts with a previous report on green-synthesized nanoceria and highlights the level of detail required to accurately report and interpret such studies. Additionally, AgCNPs are estimated to contain much less silver (0.22 parts per billion, ppb) than the amount of Ag+ needed to achieve comparable larvicidal activity (2.7 parts per million, ppm), potentially making these nanoceria ecofriendly. Finally, this work is the first study to demonstrate the until-now-unappreciated impacts of nanoceria on life history traits and interference with mosquito egg development.