PPARα agonist fenofibrate attenuates iron-induced liver injury in mice by modulating the Sirt3 and ß-catenin signaling.

Iron accumulation is frequently associated with chronic liver diseases. However, our knowledge on how iron contributes to the liver injury is limited. Aberrant Wnt/ß-catenin signaling is a hallmark of several hepatic pathologies. We recently reported that peroxisome proliferator-activated receptor α (PPARα) agonist, fenofibrate, prevents iron-induced oxidative stress and ß-catenin signaling by chelating the iron. Sirtuin3 (Sirt3), a type of NAD+-dependent deacetylase, that plays a critical role in metabolic regulation was found to prevent ischemia reperfusion injury (IRI) by normalizing the Wnt/ß-catenin pathway. In the present study, we explored if fenofibrate prevents iron-induced liver injury by regulating the Sirt3 and ß-catenin signaling. In vitro and in vivo iron treatment resulted in the downregulation of PPARα, Sirt3, active ß-catenin, and its downstream target gene c-Myc in the mouse liver. Pharmacological activation of Sirt3, both in vitro and in vivo, by Honokiol (HK), a known activator of Sirt3, abrogated the inhibitory effect of iron overload on active ß-catenin expression and prevented the iron-induced upregulation of α smooth muscle actin (αSMA) and TGFß expression. Intrinsically, PPARα knockout mice showed significant downregulation of hepatic Sirt3 levels. In addition, treatment of iron overload mice with PPARα agonist fenofibrate reduced hepatic iron accumulation and prevented iron-induced downregulation of liver Sirt3 and active ß-catenin, mitigating the progression of fibrosis. Thus, our results establish a novel link between hepatic iron and PPARα, Sirt3, and ß-catenin signaling. Further exploration on the mechanisms by which fenofibrate ameliorates iron-induced liver injury likely has significant therapeutic impact on iron-associated chronic liver diseases.NEW & NOTEWORTHY Hepatic intracellular iron accumulation has been implicated in the pathophysiology of chronic liver diseases. In this study, we identified a novel mechanism involved in the progression of fibrosis. Excess iron accumulation in liver caused downregulation of PPARα-Sirt3-Wnt signaling leading to fibrosis. This work has significant translational potential as PPARα agonist fenofibrate could be an attractive therapeutic drug for the treatment of liver disorders associated with iron overload.

Fenofibrate prevents iron induced activation of canonical Wnt/ß-catenin and oxidative stress signaling in the retina.

Accumulating evidence strongly implicates iron in the pathogenesis of aging and disease. Iron levels have been found to increase with age in both the human and mouse retinas. We and others have shown that retinal diseases such as age-related macular degeneration and diabetic retinopathy are associated with disrupted iron homeostasis, resulting in retinal iron accumulation. In addition, hereditary disorders due to mutation in one of the iron regulatory genes lead to age dependent retinal iron overload and degeneration. However, our knowledge on whether iron toxicity contributes to the retinopathy is limited. Recently, we reported that iron accumulation is associated with the upregulation of retinal and renal renin-angiotensin system (RAS). Evidences indicate that multiple genes/components of the RAS are targets of Wnt/ß-catenin signaling. Interestingly, aberrant activation of Wnt/ß-catenin signaling is observed in several degenerative diseases. In the present study, we explored whether iron accumulation regulates canonical Wnt signaling in the retina. We found that in vitro and in vivo iron treatment resulted in the upregulation of Wnt/ß-catenin signaling and its downstream target genes including renin-angiotensin system in the retina. We confirmed further that iron activates canonical Wnt signaling in the retina using TOPFlash T-cell factor/lymphoid enhancer factor promoter assay and Axin2-LacZ reporter mouse. The presence of an iron chelator or an antioxidant reversed the iron-mediated upregulation of Wnt/ß-catenin signaling in retinal pigment epithelial (RPE) cells. In addition, treatment of RPE cells with peroxisome proliferator-activated receptor (PPAR) α-agonist fenofibrate prevented iron-induced activation of oxidative stress and Wnt/ß-catenin signaling by chelating the iron. The role of fenofibrate, an FDA-approved drug for hyperlipidemia, as an iron chelator has potentially significant therapeutic impact on iron associated degenerative diseases.

Effects of core titanium crystal dimension and crystal phase on ROS generation and tumour accumulation of transferrin coated titanium dioxide nanoaggregates.

Radionuclide-stimulated therapy (RaST), which is enhanced by Cherenkov radiation, has enabled deep tissue stimulation of UV photosensitizers, providing a new path for cancer treatment. Previous reports have shown UV-active titanium dioxide (TiO2) nanoparticles (NPs) modified with transferrin inhibit tumour growth after orthogonal treatment with Cherenkov radiation-emitting radionuclides such as 18F-fluorodeoxyglucose (FDG). However, poor understanding of TiO2 NP parameters on reactive oxygen species (ROS) generation and particle distribution limits effective therapy. Here we sought to delineate the effects of crystal phase and core TiO2 crystal dimension (cTd) on ROS production and particle morphology. We prepared Transferrin (Tf)-TiO2 nanoaggregates (NAGs) using solvothermally synthesized cTd sizes from 5 to 1000 nm diameter and holo- or apo-transferrin. Holo-transferrin was unable to stabilize TiO2 NPs while apo-transferrin stabilized TiO2 into uniform nanoaggregates (NAGs), which were invariant with differing cTd, averaging 116 ± 1.04 nm for cTds below 100 nm. ROS production increased from 5 to 25 nm cTd, attaining a peak at 25 nm before decreasing with larger sizes. The supra-25 nm ROS production decrease was partially driven by a ~1/r 3 surface area decline. Additionally, amorphous TiO2 of equal core size exhibited a 2.6-fold increase in ROS production compared to anatase NAGs, although limited stability halted further use. Although both 5 and 25 nm anatase cTds formed similarly sized NAGs, 5 nm anatase showed a four-fold higher tumour-to-muscle ratio than the 25 nm NPs in tumour-bearing mice, demonstrating the intricate relationships between physical and biological properties of NAGs. The combined in vivo and ROS results demonstrate that anatase crystals and cTd size of 25 nm or less are ideal particle parameters to balance biodistribution with ROS production efficiency.

Osteotropic Radiolabeled Nanophotosensitizer for Imaging and Treating Multiple Myeloma.

Rapid liver and spleen opsonization of systemically administered nanoparticles (NPs) for in vivo applications remains the Achilles' heel of nanomedicine, allowing only a small fraction of the materials to reach the intended target tissue. Although focusing on diseases that reside in the natural disposal organs for nanoparticles is a viable option, it limits the plurality of lesions that could benefit from nanomedical interventions. Here we designed a theranostic nanoplatform consisting of reactive oxygen (ROS)-generating titanium dioxide (TiO2) NPs, coated with a tumor-targeting agent, transferrin (Tf), and radiolabeled with a radionuclide (89Zr) for targeting bone marrow, imaging the distribution of the NPs, and stimulating ROS generation for cell killing. Radiolabeling of TiO2 NPs with 89Zr afforded thermodynamically and kinetically stable chelate-free 89Zr-TiO2-Tf NPs without altering the NP morphology. Treatment of multiple myeloma (MM) cells, a disease of plasma cells originating in the bone marrow, with 89Zr-TiO2-Tf generated cytotoxic ROS to induce cancer cell killing via the apoptosis pathway. Positron emission tomography/X-ray computed tomography (PET/CT) imaging and tissue biodistribution studies revealed that in vivo administration of 89Zr-TiO2-Tf in mice leveraged the osteotropic effect of 89Zr to selectively localize about 70% of the injected radioactivity in mouse bone tissue. A combination of small-animal PET/CT imaging of NP distribution and bioluminescence imaging of cancer progression showed that a single-dose 89Zr-TiO2-Tf treatment in a disseminated MM mouse model completely inhibited cancer growth at euthanasia of untreated mice and at least doubled the survival of treated mice. Treatment of the mice with cold Zr-TiO2-Tf, 89Zr-oxalate, or 89Zr-Tf had no therapeutic benefit compared to untreated controls. This study reveals an effective radionuclide sensitizing nanophototherapy paradigm for the treatment of MM and possibly other bone-associated malignancies.

Electrospray Functionalization of Titanium Dioxide Nanoparticles with Transferrin for Cerenkov Radiation Induced Cancer Therapy.

Titanium dioxide (TiO2) nanoparticles have shown success as photosensitizers in the form of light-based cancer therapy called Cerenkov radiation induced therapy (CRIT). While TiO2 nanoparticles have been reported to be an effective therapeutic agent, there has been little work to control their functionalization and stability in aqueous suspension. In this work, the controlled coating of 25 nm diameter TiO2 nanoparticles with the glycoprotein transferrin (Tf) for application in CRIT was demonstrated using an electrospray system. Monodisperse nanoscale droplets containing TiO2 and Tf were dried during flight, coating the proteins on the surface of the metal oxide nanoparticles. Real-time scanning mobility particle sizing, dynamic light scattering, and transmission electron microscopy show efficient control of the Tf coating thickness when varying the droplet size and the ratio of Tf to TiO2 in the electrospray precursor suspension. Further, the functionality of Tf-coated TiO2 nanoparticles was demonstrated, and these particles were found to have enhanced targeting activity of Tf to the Tf receptor after electrospray processing. The electrospray-coated Tf/TiO2 particles were also found to be more effective at killing the multiple myeloma cell line MM1.S than that of nanoparticles prepared by other reported functionalization methods. In summary, this investigation not only provides a single-step functionalization technique for nanomaterials used in Cerenkov radiation induced therapy but also elucidates an electrospray coating technique for nanomaterials that can be used for a wide range of drug design and delivery purposes.

Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis.

AIM: CaCO3 nanoparticles (nano-CaCO3) can neutralize the acidic pHe of solid tumors, but the lack of intrinsic imaging signal precludes noninvasive monitoring of pH-perturbation in tumor microenvironment. We aim to develop a theranostic version of nano-CaCO3 to noninvasively monitor pH modulation and subsequent tumor response. MATERIALS & METHODS: We synthesized ferromagnetic core coated with CaCO3 (magnetite CaCO3). Magnetic resonance imaging (MRI) was used to determine the biodistribution and pH modulation using murine fibrosarcoma and breast cancer models. RESULTS: Magnetite CaCO3-MRI imaging showed that nano-CaCO3 rapidly raised tumor pHe, followed by excessive tumor-associated acid production after its clearance. Continuous nano-CaCO3 infusion could inhibit metastasis. CONCLUSION: Nano-CaCO3 exposure induces tumor metabolic reprogramming that could account for the failure of previous intermittent pH-modulation strategies to achieve sustainable therapeutic effect.

Investigating the Effects of Stove Emissions on Ocular and Cancer Cells.

More than a third of the world's population relies on solid fuels for cooking and heating, with major health consequences. Although solid fuel combustion emissions are known to increase the prevalence of illnesses such as chronic obstructive pulmonary disease and lung cancer, however, their effect on the eyes is underexplored. This study assesses the acute toxicity of solid fuel combustion emissions on healthy ocular cells and a cancer cell line. Three healthy ocular cell lines (corneal, lens, and retinal epithelial cells) and a cancer cell line (Chinese hamster ovary cells) were exposed to liquid and gas phase emissions from applewood and coal combustion. Following the exposure, real-time cell attachment behavior was monitored for at least 120 hours with electrical cell impedance spectroscopy. The viability of the cells, amount of apoptotic cells, and generation of reactive oxygen species (ROS) were quantified with MTT, ApoTox-Glo, and ROS-Glo H2O2 assays, respectively. The results showed that coal emissions compromised the viability of ocular cells more than applewood emissions. Interestingly, the cancer cells, although their viability was not compromised, generated 1.7 to 2.7 times more ROS than healthy cells. This acute exposure study provides compelling proof that biomass combustion emissions compromise the viability of ocular cells and increase ROS generation. The increased ROS generation was fatal for ocular cells, but it promoted the growth of cancer cells.

NO2 gas sensing performance enhancement based on reduced graphene oxide decorated V2O5 thin films.

Here, we demonstrate improved NO2 gas sensing properties based on reduced graphene oxide (rGO) decorated V2O5 thin film. Excluding the DC sputtering grown V2O5 thin film, rGO was spread over V2O5 thin film by the drop cast method. The formation of several p-n heterojunctions was greatly affected by the current-voltage relation of the rGO-decorated V2O5 thin film due to the p-type and n-type nature of rGO and V2O5, respectively. Initially with rGO decoration on V2O5 thin film, current decreased in comparison to the pristine V2O5 thin film, whereas depositing rGO film on a glass substrate drastically increased current. Among all sensors, only the rGO-decorated V2O5 sensor revealed a maximum NO2 gas sensing response for 100 ppm at 150 °C, and it achieved an approximately 61% higher response than the V2O5 sensor. The elaborate mechanism for an extremely high sensing response is attributed to the formation and modulation of p-n heterojunctions at the interface of rGO and V2O5. In addition, the presence of active sites like oxygenous functional groups on the rGO surface enhanced the sensing response. On that account, sensors based on rGO-decorated V2O5 thin film are highly suitable for the purpose of NO2 gas sensing. They enable the timely detection of the gas, further protecting the ecosystem from its harmful effects.

Investigation of aerosol and gas emissions from a coal-fired power plant under various operating conditions.

The concentrations of fine particles and selected gas pollutants in the flue gas entering the stack were measured under several common operation modes in an operating coal power plant producing electricity. Particle size distributions in a diameter range from 10 nm to 20 µm were measured by a scanning mobility particle sizer (SMPS), and the flue gas temperature and concentrations of CO2 and SO2 were monitored by a continuous emission monitoring system (CEMS). During the test campaign, five plant operating modes were studied: soot blowing, bypass of flue-gas desulfurization (FGD), reheat burner operating at 0% (turned off), 27%, and 42% (normal condition) of its full capacity. For wet and dry aerosols, the measured mode sizes were both around 40 nm, but remarkable differences were observed in the number concentrations (#/cm3, count per square centimeter). A prototype photoionizer enhanced electrostatic precipitator (ESP) showed improved removal efficiency of wet particles at voltages above +11.0 kV. Soot blowing and FGD bypass both increased the total particle number concentration in the flue gas. The temperature was slightly increased by the FGD bypass mode and varied significantly as the rating of reheat burner changed. The variations of CO2 and SO2 emissions showed correlations with the trend of total particle number concentration possibly due to the transitions between gas and particle phases. The results are useful in developing coal-fired power plant operation strategies to control fine particle emissions and developing amine-based CO2 capture technologies without operating and environmental concerns associated with volatile amine emissions.Implications: The measurement of the fine particle size distributions in the exhaust gas under several common operating conditions of a coal-fired power plant revealed different response relations between aerosol number concentration and the operating condition. A photo-ionizer enhanced ESP was demonstrated to capture fine particles with higher efficiency compared to conventional ESPs, and the removal efficiency increased with the applied voltage. The characteristic information of aerosols and main gaseous pollutants in the exhaust gas is extremely important for developing and deploying CO2 scrubbers, whose amine emissions and operating effectiveness depends greatly on the upstream concentrations of fine particles, SO2, from the power plant.

Design of Cerenkov Radiation-Assisted Photoactivation of TiO2 Nanoparticles and Reactive Oxygen Species Generation for Cancer Treatment.

The use of Cerenkov radiation to activate nanoparticles in situ was recently shown to control cancerous tumor growth. Although the methodology has been demonstrated to work, to better understand the mechanistic steps, we developed a mathematic model that integrates Cerenkov physics, light interaction with matter, and photocatalytic reaction engineering. Methods: The model describes a detailed pathway for localized reactive oxygen species (ROS) generation from the Cerenkov radiation-assisted photocatalytic activity of TiO2 The model predictions were verified by comparison to experimental reports in the literature. The model was then used to investigate the effects of various parameters-the size of TiO2 nanoparticles, the concentration of TiO2 nanoparticles, and the activity of the radionuclide 18F-FDG-on the number of photons and ROS generation. Results: The importance of nanoparticle size in ROS generation for cancerous tumor growth control was elucidated, and an optimal size was proposed. Conclusion: The model described here can be used for other radionuclides and nanoparticles and can provide guidance on the concentration and size of TiO2 nanoparticles and the radionuclide activity needed for efficient cancer therapy.

Aerosol-synthesized siliceous nanoparticles: impact of morphology and functionalization on biodistribution.

INTRODUCTION: Siliceous nanoparticles (NPs) have been extensively studied in nanomedicine due to their high biocompatibility and immense biomedical potential. Although numerous technologies have been developed, the synthesis of siliceous NPs for biomedical applications mainly relies on a few core technologies predominantly intended to produce spherical-shaped NPs. METHODS: In this context, the impact of different morphologies of siliceous NPs on biodistribution in vivo is limited. In the present study, we developed a novel technique based on an aerosol silane reactor to produce sintered silicon NPs of similar size but different surface areas due to distinct spherical subunits. Silica-converted particles were functionalized for radiolabeling with copper-64 (64Cu) to systematically analyze their behavior in the passive targeting of A431 tumor xenografts in mice after intravenous injection. RESULTS: While low nonspecific uptake was observed in most organs, the majority of particles were accumulated in the liver, spleen, and lung. Depending on the morphologies and function-alization, significant differences in the uptake profiles of the particles were observed. In terms of tumor uptake, spherical shapes with lower surface areas showed the highest accumulation and tumor-to-blood ratios of all investigated particles. CONCLUSION: This study highlights the importance of shape and fuctionalization of siliceous NPs on organ and tumor accumulation as significant factors for biomedical applications.

SnO2 Nanostructured Thin Films for Room-Temperature Gas Sensing of Volatile Organic Compounds.

We demonstrated room-temperature gas sensing of volatile organic compounds (VOCs) using SnO2 nanostructured thin films grown via the aerosol chemical vapor deposition process at deposition temperatures ranging from 450 to 600 °C. We investigated the film's sensing response to the presence of three classes of VOCs: apolar, monopolar, and biopolar. The synthesis process was optimized, with the most robust response observed for films grown at 550 °C as compared to other temperatures. The role of film morphology, exposed surface planes, and oxygen defects were explored using experimental techniques and theoretical calculations to improve the understanding of the room-temperature gas sensing mechanism, which is proposed to be through the direct adsorption of VOCs on the sensor surface. Overall, the improved understanding of the material characteristics that enable room-temperature sensing gained in this work will be beneficial for the design and application of metal oxide gas sensors at room temperature.

Associations between household air pollution and reduced lung function in women and children in rural southern India.

Half of the world's population still relies on solid fuels to fulfill its energy needs for cooking and space heating, leading to high levels of household air pollution (HAP), adversely affecting human health and the environment. A cross-sectional cohort study was conducted to investigate any associations between: (1) HAP metrics (mass concentration of particulate matter of aerodynamic size less than 2.5 µm (PM2.5 ), lung-deposited surface area (LDSA) and carbon monoxide (CO)); (2) a range of household and socio-demographic characteristics; and (3) lung function for women and children exposed daily to biomass cookstove emissions, in rural southern India. HAP measurements were collected inside the kitchen of 96 households, and pulmonary function tests were performed for the women and child in each enrolled household. Detailed questionnaires captured household characteristics, health histories and various socio-demographic parameters. Simple linear and logistic regression analysis was performed to examine possible associations between the HAP metrics, lung function and all household/socio-demographic variables. Obstructive lung defects (forced vital capacity (FVC) ≥ lower limit of normal (LLN) and forced expiratory volume in 1 second (FEV1 )/FVC < LLN) were found in 8% of mothers and 9% of children, and restrictive defects (FVC < LLN and FEV1 /FVC ≥ LLN) were found in 17% of mothers and 15% of children. A positive association between LDSA, included for the first time in this type of epidemiological study, and lung function was observed, indicating LDSA is a superior metric compared to PM2.5 to assess effects of PM on lung function. HAP demonstrated a moderate association with subnormal lung function in children. The results emphasize the need to look beyond mass-based PM metrics to assess fully the association between HAP and lung function.

Improved Sensitivity with Low Limit of Detection of a Hydrogen Gas Sensor Based on rGO-Loaded Ni-Doped ZnO Nanostructures.

We report enhanced hydrogen-gas-sensing performance of a Ni-doped ZnO sensor decorated with the optimum concentration of reduced graphene oxide (rGO). Ni-doped ZnO nanoplates were grown by radio frequency sputtering, rGO was synthesized by Hummer's method and decorated by the drop cast method of various concentration of rGO (0-1.5 wt %). The current-voltage characteristics of the rGO-loaded sensor are highly influenced by the loading concentration of rGO, where current conduction decreases and sensor resistance increases as the rGO concentration is increased up to 0.75 wt % because of the formation of various Schottky heterojunctions at rGO/ZnO interfaces. With the combined effect of more active site availability and formation of various p-n heterojunctions due to the optimum loading concentration of rGO (0.75 wt %), the sensor shows the maximum sensing response of ∼63.8% for 100 ppm hydrogen at moderate operating temperature (150 °C). The rGO-loaded sensors were able to detect a minimum of 1 ppm hydrogen concentration and showed high selectivity. However, a further increase in the rGO concentration (1.5 wt %) leads to the reduction of the relative response of hydrogen gas, ascribed to the formation of interconnections of rGO between electrodes. Therefore, it reduces the total resistance of the sensor and minimizes the effect of p-n heterojunction on sensor response.

Hyaluronate coating enhances the delivery and biocompatibility of gold nanoparticles.

For targeted delivery with nanoparticles (NPs) as drug carriers, it is imperative that the NPs are internalized into the targeted cell. Surface properties of NPs influence their interactions with cells. We examined the responses of retinal pigment epithelial cells, NIH 3T3 fibroblast cells, and Chinese hamster ovary cells to gold nanoparticles (Au NPs) in their nascent form as well as coated with end-thiolated hyaluronate (HS-HA). The grafting density of HS-HA on Au NPs was calculated based on total organic carbon measurements and thermal gravimetric analysis. We imaged the intracellular NPs by 3D confocal microscopy. We quantified viability and generation of reactive oxygen species (ROS) of the cells to Au NPs and monitored cell-surface attachment via electrical cell-substrate impedance sensing. The results confirmed that receptors on cell surfaces, for HA, are critical in internalizing HS-HA-Au NPs, and HA may mitigate ROS pathways known to lead to cell death. The 50- and 100-nm HS-HA-Au NPs were able to enter the cells; however, their nascent forms could not. This study shows that the delivery of larger Au NPs is enhanced with HS-HA coating and illustrates the potential of HA-coated NPs as a drug delivery agent for inflamed, proliferating, and cancer cells that express CD44 receptors.

Comparing the performance of 3 bioaerosol samplers for influenza virus.

Respiratory viral diseases can be spread when a virus-containing particle (droplet) from one individual is aerosolized and subsequently comes into either direct or indirect contact with another individual. Increasing numbers of studies are examining the occupational risk to healthcare workers due to proximity to patients. Selecting the appropriate air sampling method is a critical factor in assuring the analytical performance characteristics of a clinical study. The objective of this study was to compare the physical collection efficiency and virus collection efficiency of a 5 mL compact SKC BioSampler®, a gelatin filter, and a glass fiber filter, in a laboratory setting. The gelatin filter and the glass fiber filter were housed in a home-made filter holder. Submersion (with vortexing and subsequent centrifugation) was used for the gelatin and glass fiber filters. Swabbing method was also tested to retrieve the viruses from the glass fiber filter. Experiments were conducted using the H1N1 influenza A virus A/Puerto Rico/8/1934 (IAV-PR8), and viral recovery was determined using culture and commercial real-time-PCR (BioFire and Xpert). An atomizer was used to aerosolize a solution of influenza virus in PBS for measurement, and two Scanning Mobility Particle Sizers were used to determine particle size distributions. The SKC BioSampler demonstrated a U-shaped physical collection efficiency, lowest for particles around 30-50 nm, and highest at 10 nm and 300-350 nm within the size range examined. The physical collection efficiency of the gelatin filter was strongly influenced by air flow and time: a stable collection across all particle sizes was only observed at 2 L/min for the 9 min sampling time, otherwise, degradation of the filter was observed. The glass fiber filter demonstrated the highest physical collection efficiency (100% for all sizes) of all tested samplers, however, its overall virus recovery efficiency fared the worst (too low to quantify). The highest viral collection efficiencies for the SKC BioSampler and gelatin filter were 5% and 1.5%, respectively. Overall, the SKC BioSampler outperformed the filters. It is important to consider the total concentration of viruses entering the sampler when interpreting the results.

Cu-chitosan nanoparticle boost defense responses and plant growth in maize (Zea mays L.).

In agriculture, search for biopolymer derived materials are in high demand to replace the synthetic agrochemicals. In the present investigation, the efficacy of Cu-chitosan nanoparticles (NPs) to boost defense responses against Curvularia leaf spot (CLS) disease of maize and plant growth promotry activity were evaluated. Cu-chitosan NPs treated plants showed significant defense response through higher activities of antioxidant (superoxide dismutase and peroxidase) and defense enzymes (polyphenol oxidase and phenylalanine ammonia-lyase). Significant control of CLS disease of maize was recorded at 0.04 to 0.16% of Cu-chitosan NPs treatments in pot and 0.12 to 0.16% of NPs treatments in field condition. Further, NPs treatments exhibited growth promotry effect in terms of plant height, stem diameter, root length, root number and chlorophyll content in pot experiments. In field experiment, plant height, ear length, ear weight/plot, grain yield/plot and 100 grain weight were enhanced in NPs treatments. Disease control and enhancement of plant growth was further enlightened through Cu release profile of Cu-chitosan NPs. This is an important development in agriculture nanomaterial research where biodegradable Cu-chitosan NPs are better compatible with biological control as NPs "mimic" the natural elicitation of the plant defense and antioxidant system for disease protection and sustainable growth.

Organic and inorganic speciation of particulate matter formed during different combustion phases in an improved cookstove.

Residential solid fuel combustion in cookstoves has established health impacts including bladder and lung cancers, cataracts, low birth weight, and pneumonia. The chemical composition of particulate matter (PM) from 4 commonly-used solid fuels (coal, dung, ambient/dry applewood, and oakwood pellets), emitted from a gasifier cookstove, as well as propane, were examined. Temporal changes between the different cookstove burn-phases were also explored. Normalized concentrations of non-refractory PM1, total organics, chloride, ammonium, nitrate, sulfate, and 41 particle-phase polycyclic aromatic hydrocarbons (PAHs) were measured using a High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and a Thermal desorption Aerosol Gas chromatograph (TAG), respectively. Coal demonstrated the highest fraction of organic matter in its particulate emission composition (98%), followed by dung (94%). Coal and dung also demonstrated the highest numbers and concentrations of PAHs. While dry applewood emitted ten times lower organic matter compared to ambient applewood, a higher fraction of these organics was composed of PAHs, especially the more toxic ones such as benzo(a)pyrene (9.63ng/L versus 0.04ng/L), and benzo(b)fluoranthene (31.32ng/L versus 0.19ng/L). Data from the AMS demonstrated no clear trends for any of the combustion fuels over the different combustion phases unlike the previously reported trends observed for the physical characteristics. Of the solid fuels, pellets demonstrated the lowest emissions. Emissions from propane were below the quantification limit of the instruments. This work highlights the benefits of incorporating additional metrics into the cookstove evaluation process, thus enriching the existing PM data inventory.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma.

PURPOSE: Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. METHODS: B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. RESULTS: B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. CONCLUSIONS: B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

Monodispersed calcium carbonate nanoparticles modulate local pH and inhibit tumor growth in vivo.

The acidic extracellular environment of tumors potentiates their aggressiveness and metastasis, but few methods exist to selectively modulate the extracellular pH (pHe) environment of tumors. Transient flushing of biological systems with alkaline fluids or proton pump inhibitors is impractical and nonselective. Here we report a nanoparticles-based strategy to intentionally modulate the pHe in tumors. Biochemical simulations indicate that the dissolution of calcium carbonate nanoparticles (nano-CaCO3) in vivo increases pH asymptotically to 7.4. We developed two independent facile methods to synthesize monodisperse non-doped vaterite nano-CaCO3 with distinct size range between 20 and 300 nm. Using murine models of cancer, we demonstrate that the selective accumulation of nano-CaCO3 in tumors increases tumor pH over time. The associated induction of tumor growth stasis is putatively interpreted as a pHe increase. This study establishes an approach to prepare nano-CaCO3 over a wide particle size range, a formulation that stabilizes the nanomaterials in aqueous solutions, and a pH-sensitive nano-platform capable of modulating the acidic environment of cancer for potential therapeutic benefits.