Development of finely tuned liposome nanoplatform for macrophage depletion.

BACKGROUND: Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes. RESULTS: We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®. CONCLUSION: The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent.

Uric acid regulates α-synuclein transmission in Parkinsonian models.

Ample evidence demonstrates that α-synuclein (α-syn) has a critical role in the pathogenesis of Parkinson's disease (PD) with evidence indicating that its propagation from one area of the brain to others may be the primary mechanism for disease progression. Uric acid (UA), a natural antioxidant, has been proposed as a potential disease modifying candidate in PD. In the present study, we investigated whether UA treatment modulates cell-to-cell transmission of extracellular α-syn and protects dopaminergic neurons in the α-syn-enriched model. In a cellular model, UA treatment decreased internalized cytosolic α-syn levels and neuron-to-neuron transmission of α-syn in donor-acceptor cell models by modulating dynamin-mediated and clathrin-mediated endocytosis. Moreover, UA elevation in α-syn-inoculated mice inhibited propagation of extracellular α-syn which decreased expression of phosphorylated α-syn in the dopaminergic neurons of the substantia nigra leading to their increased survival. UA treatment did not lead to change in markers related with autophagolysosomal and microglial activity under the same experimental conditions. These findings suggest UA may control the pathological conditions of PD via additive mechanisms which modulate the propagation of α-syn.

Mutant PIK3CA as a negative predictive biomarker for treatment with a highly selective PIM1 inhibitor in human colon cancer.

Significant improvement in targeted therapy for colorectal cancer (CRC) has occurred over the past few decades since the approval of the EGFR inhibitor cetuximab. However, cetuximab is used only for patients possessing the wild-type oncogene KRAS, NRAS, and BRAF, and even most of these eventually acquire therapeutic resistance, via activation of parallel oncogenic pathways such as RAS-MAPK or PI3K/Akt/mTOR. The two aforementioned pathways also contribute to the development of therapeutic resistance in CRC patients, due to compensatory and feedback mechanisms. Therefore, combination drug therapies (versus monotherapy) targeting these multiple pathways may be necessary for further efficacy against CRC. In this study, we identified PIK3CA mutant (PIK3CA MT) as a determinant of resistance to SMI-4a, a highly selective PIM1 kinase inhibitor, in CRC cell lines. In CRC cell lines, SMI-4a showed its effect only in PIK3CA wild type (PIK3CA WT) cell lines, while PIK3CA MT cells did not respond to SMI-4a in cell death assays. In vivo xenograft and PDX experiments confirmed that PIK3CA MT is responsible for the resistance to SMI-4a. Inhibition of PIK3CA MT by PI3K inhibitors restored SMI-4a sensitivity in PIK3CA MT CRC cell lines. Taken together, these results demonstrate that sensitivity to SMI-4a is determined by the PIK3CA genotype and that co-targeting of PI3K and PIM1 in PIK3CA MT CRC patients could be a promising and novel therapeutic approach for refractory CRC patients.

Priming mesenchymal stem cells with α-synuclein enhances neuroprotective properties through induction of autophagy in Parkinsonian models.

BACKGROUND: Mesenchymal stem cells (MSCs) may be one of candidates for disease-modifying therapy in Parkinsonian diseases. As knowledge regarding the therapeutic properties of MSCs accumulates, some obstacles still remain to be overcome, especially, successful clinical translation requires the development of culture systems that mimic the natural MSC niche, while allowing clinical-scale cell expansion without compromising quality and function of the cells. In recent years, priming approaches using bioactive peptide or complement components have been investigated to enhance the therapeutic potential of MSCs. METHODS: We investigated an innovative priming strategy by conditioning the MSCs with α-synuclein (α-syn). To induce priming, MSCs were treated with different concentrations of α-syn and various time course. We evaluated whether α-syn enhances stemness properties of MSCs and priming MSCs with α-syn would modulate autophagy-related gene expression profiles. RESULTS: Treatment of naïve MSCs with α-syn upregulated transcriptional factors responsible for regulation of stemness, which was associated with the elevated expression of genes involved in glycolysis and cell re-programming. Primed MSCs with α-syn enhanced the expression of autophagy-regulating miRNA, and exosomes derived from primed MSCs were packed with autophagy-associated miRNA. In α-syn-overexpressing neuronal cells, primed MSCs with α-syn enhanced neuronal viability relative to naïve MSCs, through the induction of autophagy and lysosome activity. Animal study using an α-syn-overexpressing mice showed that the pro-survival effect of MSCs on dopaminergic neurons was more prominent in primed MSC-treated mice compared with that in naïve MSC-treated mice. CONCLUSIONS: The present data suggest that MSC priming with α-syn exerts neuroprotective effects through augmented stemness and possibly the enhancement of autophagy-mediated α-syn modulation in Parkinsonian models.

Uric Acid Enhances Neurogenesis in a Parkinsonian Model by Remodeling Mitochondria.

Background: Adult neurogenesis is the process of generating new neurons to enter neural circuits and differentiate into functional neurons. However, it is significantly reduced in Parkinson's disease (PD). Uric acid (UA), a natural antioxidant, has neuroprotective properties in patients with PD. This study aimed to investigate whether UA would enhance neurogenesis in PD. Methods: We evaluated whether elevating serum UA levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mouse model would restore neurogenesis in the subventricular zone (SVZ). For a cellular model, we primary cultured neural precursor cells (NPCs) from post-natal day 1 rat and evaluated whether UA treatment promoted cell proliferation against 1-methyl-4-phenylpyridinium (MPP+). Results: Uric acid enhanced neurogenesis in both in vivo and in vitro parkinsonian model. UA-elevating therapy significantly increased the number of bromodeoxyuridine (BrdU)-positive cells in the SVZ of PD animals as compared to PD mice with normal UA levels. In a cellular model, UA treatment increased the expression of Ki-67. In the process of modulating neurogenesis, UA elevation up-regulated the expression of mitochondrial fusion markers. Conclusion: In MPTP-induced parkinsonian model, UA probably enhanced neurogenesis via regulating mitochondrial dynamics, promoting fusion machinery, and inhibiting fission process.

1,2,3-benzotriazole adversely affects early-life stage of Oryzias latipes.

1,2,3-benzotriazole (BT) is used in large amounts around the world and is one of the substances derived from household chemicals that are of concern for risk when discharged to aquatic environments. Therefore, several studies have been conducted on the aquatic toxicity effects of BT, but the chronic impact assessment studies to evaluate the developmental effects on the early-life stage of fish are insufficient. In this study, the acute toxicity test and subchronic toxicity test (fish, early-life stage toxicity test, ELS test) using embryos of Japanese medaka (Oryzias latipes) were performed to evaluate the acute toxicity, developmental toxicity, growth (indicated by total length and weight at the end of the test), and histopathological effect of BT. In the short-term toxicity test on embryo and sac-fry stage, toxicity value was calculated to be 41 mg/L (NOEC). Based on this value, the exposure concentration of the ELS test was determined as 0.04, 0.4, 4 and 40 mg/L, and total exposure duration was 42 days. At the highest concentration group (40 mg/L), failure of swim bladder inflation and decrease of survival and size (total length and weight) were observed. Moreover, in the histopathological analysis, abnormal findings were detected in swim bladders from the 40 mg/L group such as inflammation and tumor changes. On the other hands, condition index (weight-length relationships, CI) was statistically significantly lower in all exposed groups compared to the control group. NOEC for the survival of BT was calculated to be 4 mg/L. LOEC for CI was 0.04 mg/L, which means BT inhibited weight gain relative to its length on larvae of medaka.

Effect of benzotriazole on oxidative stress response and transcriptional gene expression in Oryzias latipes and Danio rerio embryo.

Emerging contaminants (EC) such as benzotriazole are being released into the environment in various ways, therefore it is necessary to understand how organisms are affected by EC. In this study, we exposed medaka (Oryzias latipes) and zebrafish (Danio rerio) during their embryonic period (1 day after hatching) to benzotriazole to investigate its effects on oxidative stress (ROS, GSH, GST, SOD, CAT and MDA) and changes in gene expression patterns. In both medaka and zebrafish, the influence of oxidative stress was confirmed through an increased MDA level and changes in the ROS and GSH levels. Antioxidant enzymes such as GST, CAT, and SOD were affected by benzotriazole; however, medaka and zebrafish showed different patterns in the effects by benzotriazole. Results of oxidative stress genes expression showed that medaka had either no influence or had a decrease in the gene expression profile, whereas zebrafish had a statistically significant increase in the expression of some genes. The cyp1a gene expression was increased in both species. However, vtg gene expression was increased only in zebrafish but decreased in medaka, indicating no estrogenic effects in medaka. Apoptosis genes showed changes in expression in both the species but was these changes were not dose-dependent. However, zebrafish caspase-9 gene expression was increased in all of the exposed groups, suggesting the effects on the intrinsic pathway associated with caspase-9. In conclusion, the results indicate that the toxic effects of benzotriazole differ at various levels in the two small fish medaka and zebrafish embryos.

Memantine exerts neuroprotective effects by modulating α-synuclein transmission in a parkinsonian model.

Ample evidence has demonstrated that α-Synuclein can propagate from one area of the brain to others via cell-to-cell transmission, which might be the underlying mechanism for pathological propagation and the disease progression of Parkinson's disease (PD). Recent reports have demonstrated cell surface receptor-mediated cell-to-cell transmission of α-synuclein. Memantine decreased the levels of internalized cytosolic α-synuclein and led to attenuation in α-synuclein-induced cell death. Specifically, memantine attenuated α-synuclein-induced expression of clathrin and EEA1, and increased expression of NR2A subunits. Moreover, memantine inhibited propagation of extracellular α-synuclein and thus, decreased the expression of the phosphorylated form of α-synuclein in dopaminergic neurons of the substantia nigra, which was accompanied by increased survival of dopaminergic neurons with functional improvement of motor deficits. The present study demonstrated that memantine modulates extracellular α-synuclein propagation by inhibiting interactions between α-synuclein and NR2A subunits, which leads to neuroprotective effects on nigral dopaminergic neurons against α-synuclein-enriched conditions. The repositioning use of memantine in α-synuclein propagation needs to be further evaluated in patients with α-synucleinopathies as an effective therapeutic approach.

Regulation of influenza A virus mRNA splicing by CLK1.

Influenza A virus carries eight negative single-stranded RNAs and uses spliced mRNAs to increase the number of proteins produced from them. Several genome-wide screens for essential host factors for influenza A virus replication revealed a necessity for splicing and splicing-related factors, including Cdc-like kinase 1 (CLK1). This CLK family kinase plays a role in alternative splicing regulation through phosphorylation of serine-arginine rich (SR) proteins. To examine the influence that modulation of splicing regulation has on influenza infection, we analyzed the effect of CLK1 knockdown and inhibition. CLK1 knockdown in A549 cells reduced influenza A/WSN/33 virus replication and increased the level of splicing of segment 7, which encodes the viral M1 and M2 proteins. CLK1-/- mice infected with influenza A/England/195/2009 (H1N1pdm09) virus supported lower levels of virus replication than wild-type mice. Screening of newly developed CLK inhibitors revealed several compounds that have an effect on the level of splicing of influenza A gene segment M in different models and decrease influenza A/WSN/33 virus replication in A549 cells. The promising inhibitor KH-CB19, an indole-based enaminonitrile with unique binding mode for CLK1, and its even more selective analogue NIH39 showed high specificity towards CLK1 and had a similar effect on influenza mRNA splicing regulation. Taken together, our findings indicate that targeting host factors that regulate splicing of influenza mRNAs may represent a novel therapeutic approach.

n-Butyl acrylate-induced antioxidant system alteration through two generations in Oryzias latipes.

n-Butyl acrylate (nBA) is one of acrylate esters which has been applied to diverse industrial fields. For unveiling of xeno-estrogenic effects and oxidative stress induction by nBA under two-generational exposure regimen (17 weeks), the biomarkers relevant to an estrogenic effect and oxidative stress were analyzed. Acute toxicity value of nBA in Oryzias latipes was 7.2 mg/L (96 h-LC50). Over exposure time, the significant transcriptional change of cytochrome P450 19A (CYP19A) and vitellogenin 1/2 (VTG1/2) was not observed (one-way ANOVA, P < 0.05), meaning no estrogenic effect of nBA. Significant reduction of glutathione (GSH) content was observed in F0 male and female fish, while in F1 male, the content was increased (P < 0.05). Catalase (CAT) activity of male fish showed the significant decrease in both F0 and F1 fish, showing multi-generational suppressing effect of nBA on CAT activity. But in case of reactive oxygen species (ROS), expression level and glutathione S-transferase (GST) activity were not modulated in response to nBA. These findings suggest that nBA could affect an antioxidant system alteration through GSH depletion and inhibition of CAT activity which could be transferred to the next generation, whereas xeno-estrogenic effect would be questionable.

Metformin-induced endocrine disruption and oxidative stress of Oryzias latipes on two-generational condition.

Metformin has been treated for diabetes (type 2). Nowadays, this compound is frequently found in ambient water, influent/effluent of a wastewater treatment plant. To evaluate the metformin aquatic toxicity under a multi-generational exposure regimen, we exposed Oryzias latipes to metformin for two generations (133 d) and investigated its adverse effects. In the F0 generation, metformin significantly elevated gene expression for cytochrome P450 19a (CYP19a) and estrogen receptor α (ERα) in male fish; in female fish, the treatment decreased gene expression of vitellogenin (VTG2) and ERß1, suggesting endocrine disruption (one-way ANOVA, p < 0.05). Intersex occurrence of F0 female fish were found in a concentration-dependent manner, whereas no significant changes in fecundity and hatching rate were observed (p < 0.05). Metformin increased the reactive oxygen species (ROS) content, and decreased the glutathione (GSH) content in F0 male fish compared with those of the control (one-way ANOVA, p > 0.05). In F0 female fish, metformin increased catalase activity compared with that of the control (p > 0.05). The results demonstrated that metformin leads to oxidative stress and two-generation endocrine disruption in O. latipes. These results may be useful for better understanding metformin toxicity mechanism.

The occurrence and distribution of hexabromocyclododecanes in freshwater systems, focusing on tissue-specific bioaccumulation in crucian carp.

The occurrence and distribution of hexabromocyclododecanes (HBCDs) were investigated in freshwater, sediment, and selected crucian carp (Carassius carassius) tissues (muscle, liver, egg, and blood) to evaluate the potential for HBCDs bioaccumulation. The HBCDs concentration ranged from not detected to 0.35ng/L in freshwater, and from 0.037 to 35.4ng/g-dw in sediment. The highest HBCDs concentration was detected in crucian carp liver (5.14±8.15ng/g-ww), followed by egg (3.88±10.1ng/g-ww), blood (0.61±0.63ng/mL), and muscle (0.38±0.70ng/g-ww). In all crucian carp tissues, α-HBCD was the predominant stereoisomer, and the fraction of α-HBCD as a proportion of the total HBCDs in liver tissue (96%) was higher than that in egg tissue (79%). There was a positive correlation between the HBCDs concentration in crucian carp muscle and body size (p<0.01, Spearman). The biota-sediment accumulation factor (BSAF) (0.14) and bioconcentration factor (BCF) (137,000L/kg) values were estimated in crucian carp muscle using field-based data.

PFOA-induced metabolism disturbance and multi-generational reproductive toxicity in Oryzias latipes.

The aims of this study were to examine multi-generational reproductive toxicity and metabolism disturbances in Oryzias latipes exposed to 0.3, 3, and 30mg/L PFOA for 259-day. The highest concentration of PFOA suppressed fecundity over three generations from F0 to F2 and sac-fry survival rate in F2 generation, indicating that PFOA resulted in multi-generational reproductive toxicity (p<0.05). Histologically, in F1 and F2 generations, O. latipes exposed to 30mg/L PFOA revealed accelerated gonad development, and the atrophy and degeneration of thyroid follicular cell. Glucose content showed the highest increase in both genders in all metabolites. However, alanine, glutamine, threonine, and lactate content, which are converted into glucose showed decline tendency, suggesting that PFOA led to gluconeogenesis. Change of osmolyte content affecting osmosis such as a decrease of male myo-inositol (m-Ino), an increase of female trimethylamine N-oxide (TMAO) and an increase of male dimethylamine (DMA) suggest that PFOA might affect osmoregulation of O. latipes. Oxaloacetate of male fish and succinate of female fish showed significant alterations, indicating that PFOA may affect energy metabolism differently by sex. These findings will help elucidate the toxicity of PFOA in diverse biological responses including metabolism change.

Accelerated ecotoxicity of photoreactive nanoparticles on Moina macrocopa.

Zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO2 NPs) are well known as photoreactive nanoparticles (NPs). Various phototoxicities of ZnO NPs and TiO2 NPs were reported on several organisms. It was still necessary to evaluate the toxicity of photoreactive ZnO NPs and TiO2 NPs due to species-specific effects under various irradiation conditions. We compared the acute toxicity of Moina macrocopa under visible, ultraviolet (UV) A, and B irradiations, according to the Organization for Economic Cooperation and Development guidelines for the testing of chemicals (Test No. 202). The sensitivity of ZnO NPs for M. macrocopa was UVB>UVA>visible light irradiation. There were no significant lethal and immobile effects of TiO2 NPs on juveniles under all irradiations and in the tested concentrations of TiO2 NPs. Photoreactive NPs have a potential and accelerated toxicity on organisms in the ambient environments.

Multi-generational xenoestrogenic effects of Perfluoroalkyl acids (PFAAs) mixture on Oryzias latipes using a flow-through exposure system.

To elucidate the multi-generational estrogenic potential of Perfluoroalkyl acids (PFAAs) mixture, vitellogenin (VTG) expression, growth indices, histological alteration, fecundity, hatching rate, larval survival rate, and sex ratio of Japanese medaka (Oryzias latipes) were investigated by exposing the fish to a mixture of perfluorooctane sulfonate (PFOS), perfluroroctanoic acid (PFOA), perfluorobutane sulfonate (PFBS), and perfluorononanoic acid (PFNA) for three generations (238 days). Mixture composition is in the ratio of 1:1:1:1. In addition, whole body burden for each PFAA was analyzed. According to the results, concentrated levels of the PFAAs in both F1 and F2 generation O. latipes were ordered PFOS > PFNA > PFOA > PFBS at both low concentration (0.5 µg/L) and high concentration (5 µg/L), whereas a significant difference in whole body burden based on sex or generation was not detected. Significant induction of VTG expression in F2 and the decline of the gonad somatic index (GSI) in F1 were observed following PFAAs mixture exposure (p < 0.05, one-way ANOVA). Furthermore, suppression level of reproduction rate relative to the control increased as generation was transferred to the next in response to PFAAs mixture or 17 ß-estradiol exposure, with the inhibition of hatchability observed in the F1 generation. The PFAA high concentration caused significant alteration of F1 generation sex ratio, suggesting the adverse effect of PFAA in population level (Chi-square test, P > 0.05). Overall, this study demonstrated that PFAA mixture could have the potential of multi-generational endocrine disruptors in O. latipes.

Shape-Dependent Relaxivity of Nanoparticle-Based T1 Magnetic Resonance Imaging Contrast Agents.

Gold nanostars functionalized with Gd(III) have shown significant promise as contrast agents for magnetic resonance imaging (MRI) because of their anisotropic, branched shape. However, the size and shape polydispersity of as-synthesized gold nanostars have precluded efforts to develop a rigorous relationship between the gold nanostar structure (e.g., number of branches) and relaxivity of surface-bound Gd(III). This paper describes the use of a centrifugal separation method that can produce structurally refined populations of gold nanostars and is compatible with Gd(III) functionalization. Combined transmission electron microscopy and relaxivity analyses revealed that the increased number of nanostar branches was correlated with enhanced relaxivity. By identifying the underlying relaxivity mechanisms for Gd(III)-functionalized gold nanostars, we can inform the design of high-performance MRI contrast agents.

Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells.

Sulindac has anti-neoplastic properties against colorectal cancers; however, its use as a chemopreventive agent has been limited due to toxicity and efficacy concerns. Combinatorial treatment of colorectal cancers has been attempted to maximize anti-cancer efficacy with minimal side effects by administrating NSAIDs in combination with other inhibitory compounds or drugs such as l-ascorbic acid (vitamin C), which is known to exhibit cytotoxicity towards various cancer cells at high concentrations. In this study, we evaluated a combinatorial strategy utilizing sulindac and vitamin C. The death of HCT116 cells upon combination therapy occurred via a p53-mediated mechanism. The combination therapeutic resistance developed in isogenic p53 null HCT116 cells and siRNA-mediated p53 knockdown HCT116 cells, but the exogenous expression of p53 in p53 null isogenic cells resulted in the induction of cell death. In addition, we investigated an increased level of intracellular ROS (reactive oxygen species), which was preceded by p53 activation. The expression level of PUMA (p53-upregulated modulator of apoptosis), but not Bim, was significantly increased in HCT116 cells in response to the combination treatment. Taken together, our results demonstrate that combination therapy with sulindac and vitamin C could be a novel anti-cancer therapeutic strategy for p53 wild type colon cancers.

L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells.

Colon cancer patients with mutant KRAS are resistant to cetuximab, an antibody directed against the epidermal growth factor receptor, which is an effective clinical therapy for patients with wild-type KRAS. Numerous combinatorial therapies have been tested to overcome the resistance to cetuximab. However, no combinations have been found that can be used as effective therapeutic strategies. In this study, we demonstrate that L-ascorbic acid partners with cetuximab to induce killing effects, which are influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human colon cancer cells with a mutant KRAS. L-Ascorbic acid treatment of human colon cancer cells that express a mutant KRAS differentially and synergistically induced cell death with cetuximab in a SVCT-2-dependent manner. The ectopic expression of SVCT-2 induced sensitivity to L-ascorbic acid treatment in human colon cancer cells that do not express SVCT-2, whereas the knockdown of endogenous SVCT-2 induced resistance to L-ascorbic acid treatment in SVCT-2-positive cells. Moreover, tumor regression via the administration of L-ascorbic acid and cetuximab in mice bearing tumor cell xenografts corresponded to SVCT-2 protein levels. Interestingly, cell death induced by the combination of L-ascorbic acid and cetuximab resulted in both apoptotic and necrotic cell death. These cell death mechanisms were related to a disruption of the ERK pathway and were represented by the impaired activation of RAFs and the activation of the ASK-1-p38 pathway. Taken together, these results suggest that resistance to cetuximab in human colon cancer patients with a mutant KRAS can be bypassed by L-ascorbic acid in an SVCT-2-dependent manner. Furthermore, SVCT-2 in mutant KRAS colon cancer may act as a potent marker for potentiating L-ascorbic acid co-treatment with cetuximab.

Formations of calcium carbonate minerals by bacteria and its multiple applications.

Biomineralization is a naturally occurring process in living organisms. In this review, we discuss microbially induced calcium carbonate precipitation (MICP) in detail. In the MICP process, urease plays a major role in urea hydrolysis by a wide variety of microorganisms capable of producing high levels of urease. We also elaborate on the different polymorphs and the role of calcium in the formation of calcite crystal structures using various calcium sources. Additionally, the environmental factors affecting the production of urease and carbonate precipitation are discussed. This MICP is a promising, eco-friendly alternative approach to conventional and current remediation technologies to solve environmental problems in multidisciplinary fields. Multiple applications of MICP such as removal of heavy metals and radionuclides, improve the quality of construction materials and sequestration of atmospheric CO2 are discussed. In addition, we discuss other applications such as removal of calcium ions, PCBs and use of filler in rubber and plastics and fluorescent particles in stationary ink and stationary markers. MICP technology has become an efficient aspect of multidisciplinary fields. This report not only highlights the major strengths of MICP, but also discusses the limitations to application of this technology on a commercial scale.

Continuous ultraviolet irradiation increases the adverse effects of photoreactive nanoparticles on the early development of Oryzias latipes.

The present study investigated the toxicity of photoreactive nanoparticles (NPs) on the development of Oryzias latipes. Buoyant fish embryos are potentially vulnerable to sunlight-derived ultraviolet (UV) irradiation. Zinc oxide (ZnO) NPs in surface water easily absorb UV irradiation from transmitted solar light. In the present study, O. latipes were exposed to ZnO NPs under irradiation with UV or visible light. The ZnO NPs exhibited considerable toxicity toward embryos and sac fry following UV irradiation, and these toxic effects resulted in increased mortality and abnormalities. The UV irradiation induced more serious effects on embryos than did visible light irradiation, and embryonic exposure resulted in irreversible developmental impairment or death of sac fry. The adverse effects of ZnO NPs may result from Zn ions released from photoreactive ZnO NPs. The present study demonstrates photo-dependent developmental impairment of O. latipes embryos as a result of exposure to ZnO NPs. The results demonstrate that the toxicity of photoreactive ZnO NPs could vary under environmentally relevant UV irradiation. These data could serve as a guide for evaluation of the toxicity of photo-activated NPs in natural surface waters and could be useful for the ecological risk assessment of photoreactive NPs.