Integration of fluorescence quenching correction into trihalomethane formation prediction models.

Despite there being numerous models of trihalomethane (THM) formation, they are limited by high estimation errors, which can be close to the regulatory limits for THMs, due to the fluorescence quenching effect. In this research, the estimation error for THM formation was reduced by correcting the quenching effect. The trihalomethane formation potential (THMFP) test was conducted in the presence of chlorine and bromine, individually and in mixtures. The THM precursors used in this study were protein (bovine serum albumin; BSA), amino acids (tryptophan and tyrosine), chlorine, bromine, and Suwannee River natural organic matter (SWNOM). BSA tended to form bromodichloromethane (BDCM) rather than trichloromethane (TCM) during chlorination in the presence of bromide (Br-). In contrast, SWNOM tended to form chlorinated THMs (TCM) rather than brominated THMs (BDCM and dibromochloromethane; DBCM), and no TBMs were formed in these processes. BSA with SWNOM decreased the formation of TCM due to the decrease in the amount of TCM precursor in SWNOM through binding with BSA. The concentration of each THM species was predicted from the fluorescence intensity of peak C, corrected fluorescence intensity of peak T, and Br- concentration. The use of humic-like and corrected protein-like fluorescence in the excitation-emission matrix model for predicting THM species reduced the prediction error. In this research, correction of the fluorescence quenching decreased the mean percentage estimation error for TCM, BDCM, and DBCM from 47%, 35%, and > 100% in classical approaches to 6.6%, 26.9%, and 2.0%, respectively. This study is expected to make contributions in reporting the relationship between the concentration of natural organic matter compositions and the formation of THM species.

Therapeutic HNF4A mRNA attenuates liver fibrosis in a preclinical model.

BACKGROUND & AIMS: Therapeutic targeting of injuries that require transient restoration of proteins by mRNA delivery is an attractive approach that, until recently, has remained poorly explored. In this study, we examined the therapeutic utility of mRNA delivery for liver fibrosis and cirrhosis. Specifically, we aimed to demonstrate the therapeutic efficacy of human hepatocyte nuclear factor alpha (HNF4A) mRNA in mouse models of fibrosis and cirrhosis. METHODS: We investigated restoration of hepatocyte functions by HNF4A mRNA transfection in vitro, and analyzed the attenuation of liver fibrosis and cirrhosis in multiple mouse models, by delivering hepatocyte-targeted biodegradable lipid nanoparticles (LNPs) encapsulating HNF4A mRNA. To identify potential mechanisms of action, we performed microarray-based gene expression profiling, single-cell RNA sequencing, and chromatin immunoprecipitation. We used primary liver cells and human liver buds for additional functional validation. RESULTS: Expression of HNF4A mRNA led to restoration of the metabolic activity of fibrotic primary murine and human hepatocytes in vitro. Repeated in vivo delivery of LNP-encapsulated HNF4A mRNA induced a robust inhibition of fibrogenesis in 4 independent mouse models of hepatotoxin- and cholestasis-induced liver fibrosis. Mechanistically, we discovered that paraoxonase 1 is a direct target of HNF4A and it contributes to HNF4A-mediated attenuation of liver fibrosis via modulation of liver macrophages and hepatic stellate cells. CONCLUSION: Collectively, our findings provide the first direct preclinical evidence of the applicability of HNF4A mRNA therapeutics for the treatment of fibrosis in the liver. LAY SUMMARY: Liver fibrosis and cirrhosis remain unmet medical needs and contribute to high mortality worldwide. Herein, we take advantage of a promising therapeutic approach to treat liver fibrosis and cirrhosis. We demonstrate that restoration of a key gene, HNF4A, via mRNA encapsulated in lipid nanoparticles decreased injury in multiple mouse models of fibrosis and cirrhosis. Our study provides proof-of-concept that mRNA therapy is a promising strategy for reversing liver fibrosis and cirrhosis.

Impact of holding time on toxicity change of urban road dust during runoff process.

During runoff process, the urban road dust (URD) passes through the road-side gutters and detention tanks, where it gets hold for a certain period of time, hours to weeks, before making its way into the water bodies. A part of the water-exchangeable toxicants are leached by the water, and some strongly bound toxicants remain attached to the URD. Toxicity of urban runoff is dependent on holding time, water volume, and the type and composition of the wet road dust (WeRD) and leachate. However, there are no studies that have elucidated the manner in which toxicities of the WeRD and leachate vary during prolonged holding in the runoff processes. The main objectives of this research were to, i) identify the distribution of toxicants in the WeRD and leachate, and ii) evaluate the change in toxicity during prolonged holding. The URD samples that were collected from residential road, arterial road and highways in Tokyo, Japan, were mixed with moderately hard water in varying ratios (1:2 to 1:16) and were held for a certain time (1h to 5days) before centrifuging into the WeRD and leachate. Toxicity test was conducted with ostracod Heterocypris incongruens direct contact test. Toxicity of both the WeRD and leachate from residential area was not significantly greater than the 20% lethal limit. Toxicity of the WeRD from other stations initially decreased, further reached a minimum corresponding to the critical holding time, and it subsequently increased again. Toxicity of the arterial leachate gradually increased, whereas that of the highway leachate gradually decreased during 5days holding. Unionized ammonia and zinc were confirmed as one of the possible toxicants. This study proposes and verifies a model for the toxicity change of the WeRD during prolonged holding.

Carcinogenic profile, toxicity and source apportionment of polycyclic aromatic hydrocarbons accumulated from urban road dust in Tokyo, Japan.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in urban environments. Urban road dust (URD) generated by traffic is an important PAH accumulator. Twelve priority PAHs in < 2000 µm fraction of ten URD samples from Tokyo, Japan were characterized based on profile distributions, carcinogenicity, toxicity, and source apportionment by cluster analysis, biplot and diagnostic ratios. PAH concentrations (mg/kg dry weight) in arterial roads, highways, highway parking, highway drainage pit and residential area URD samples were 2.06-4.24, 0.25-3.37, 3.44, 4.94, and 5.26 respectively, dominated by the ∑4 rings (average 46%) and ∑5 + 6 rings (average 41%) PAHs. Biplot analysis revealed that the antecedent dry weather period, vehicle frequency and organic matter content were the dominant environmental factors governing PAH profiles of different road types. The total amount of carcinogenic PAHs in the residential URD (2.12 mg/kg) was higher than those in the arterial road (0.60-2.00 mg/kg) and highway (0.10-1.84 mg/kg) URD. Toxic equivalent concentrations (TECs) of residential, arterial road and highway URD were 0.54, (0.12-0.57), and (0.02-0.51) mg/kg, respectively. The dominant PAH sources were found to be petrogenic combustion in arterial road and highway URD, and pyrogenic combustion consisting of a mix of biomass, petroleum and traffic-related sources in the residential and highway drainage pit samples. This is also the first study to find that TEC-based toxicity should not be taken as a measure of URD toxicity.

A Total Economic Valuation of Wetland Ecosystem Services: An Evidence from Jagadishpur Ramsar Site, Nepal.

Wetlands are the most productive ecosystem and provide wide arrays of wetland ecosystems (goods and services) to the local communities in particular and global communities in general. However, management of the wetland often does not remain priority and recognized as the unproductive waste land mainly due to poor realization of the economic value of the wetlands. Taking this into account, the study estimated the total economic value of the Jagadishpur Reservoir taking into account direct, indirect, and nonuse value. The study prioritized six major values of the reservoir which include wetland goods consumption, tourism, irrigation, carbon sequestration, biodiversity conservation, and conservation for future use (existence and option value). The study used market and nonmarket based valuation techniques to estimate total economic value of the reservoir. Household survey, focus group discussions, and interaction with the tourism entrepreneurs and district stakeholders were carried out to collect information. The study estimated the total annual economic value of the reservoir as NRs 94.5 million, where option/existence value remains main contributor followed by direct use value such as wetland goods and tourism and indirect use value, for example, carbon sequestration, biodiversity conservation, and irrigation. The study reveals that the local communities gave high importance to the future use value and are willing to make investment for conservation and restoration of reservoir given its conservation significance.

Characterization of toxicants in urban road dust by Toxicity Identification Evaluation using ostracod Heterocypris incongruens direct contact test.

The current study involves characterization of organic compounds, heavy metals, and ammonia as potential toxicants in one arterial road (St. 3) and two highway (St. 7 and 8) urban road dust (URD) collected in Tokyo, Japan. URD toxicity was evaluated by Toxicity Identification Evaluation using the ostracod Heterocypris incongruens direct contact test. URDs were treated with resins (10% XAD-4, 20% SIR-300 and 20% SIR-600) to determine the reduction in mortality after treatment. The mortality of ostracods exposed to St. 3 URD (baseline 80%) was significantly (p<0.05) reduced to 0% and 47% after XAD-4 and SIR-300 treatment respectively. This reduction led us to suspect hydrophobic organic compounds and heavy metals as potential toxicants. Subsequent elution of the recovered XAD-4 with polar (methanol, acetone) and non-polar (dichloromethane) solvents confirmed the dominance of relatively polar hydrophobic organic toxicants. The dissolved concentration of Cu and Zn after SIR-300 treatment exceeded the 50% lethal concentration (LC50) for ostracods, which led us to suspect Cu and Zn as other probable toxicants. The concentration of Zn in a SIR-300 acidic elutriate, recovered after the termination of toxicity test, confirmed Zn as one of the toxicants in St. 3. The baseline mortality (100%) of St. 7 was significantly reduced (23%) by SIR-300 treatment. This indicated the presence of heavy metals as the probable toxicant. However, the concentration of dissolved heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) in the overlying water was below previously reported LC50 values for each metal in St. 7. Recovery of Zn concentrations exceeding the LC50 in the St. 7 SIR-300 elutriate led us to suspect a dietary exposure route of Zn to the ostracod during the direct contact test. The overall results indicate that the toxicant types can vary widely depending on the road sampled.

Toxicity assessment of size-fractionated urban road dust using ostracod Heterocypris incongruens direct contact test.

Urban road dusts (URDs, n=10) were collected from arterial, residential, parking area in highway and highway roads in and around Tokyo, Japan, to characterize toxicity of size-fractions by the ostracod Heterocypris incongruens direct contact test. The URDs were collected with vacuum cleaner and highway sweeping vehicles, dried and size-fractionated before conducting toxicity test. The LC20 and LC50 of URDs varied (v/v) from 1.6 to 49%, and 3.8 to 67% respectively. Cluster analysis of URDs based on the concentration of heavy metal and PAHs standardized with the organic matter content was able to differentiate URDs into two groups, one group of higher toxicity and the other group of medium and lower toxicity. Mortality of ostracod decreased for some of the URDs when holding time of URD-water mixture was changed from 1h to 24h prior to the toxicity test. Fraction of fine particles was not always more toxic than the other fractions of coarse and medium particles. Site specific differences in toxicity of size-fractionated URDs indicated the complexity in defining URD toxicity as there could be co-existence of various non-targeted toxicants.

Wiring-up carbon single wall nanotubes to polycrystalline inorganic semiconductor thin films: low-barrier, copper-free back contact to CdTe solar cells.

We have discovered that films of carbon single wall nanotubes (SWNTs) make excellent back contacts to CdTe devices without any modification to the CdTe surface. Efficiencies of SWNT-contacted devices are slightly higher than otherwise identical devices formed with standard Au/Cu back contacts. The SWNT layer is thermally stable and easily applied with a spray process, and SWNT-contacted devices show no signs of degradation during accelerated life testing.