Safety evaluation of PEGylated MNPs and p-PEGylated MNPs in SD rats.

Polyethylene glycol-coated magnetic nanoparticles (PEGylated MNPs) have demonstrated prominent advantages in cancer diagnosis and hyperthermia therapy. However, there is currently lack of standard mode and sufficient toxicity data for determining the delayed risk of PEGylated MNPs. Nevertheless, the toxicity potentials, especially those associated with the oxidative stress, were ubiquitously reported. In this study, PEGylated MNPs and p-PEGylated MNPs were administrated to SD (Sprague Dawley) rats by single intravenously injection, and various toxicity indicators were monitored till 56 days post-administration for a comprehensive toxicity evaluation. We revealed that both nanoparticles could be rapidly cleared from plasma and enter tissues, such as, liver, kidneys and spleen, and p-PEGylated MNP is less prone to be accumulated in the tissues, indicating a lower toxicity risk. PEGylated MNPs were more likely to up-regulate the expression levels of Th2 type cytokines and trigger inflammatory pathways, but no related pathological change was found. Both MNPs are not mutagenic, while recoverable mild DNA damage associated with the presence of nanoparticles might also be observed. This study demonstrated a research approach for the non-clinical safety evaluation of nanoparticles. It also provided comprehensive valuable safety data for PEGylated and p-PEGylated MNPs, for promoting the clinical application and bio-medical translation of such MNPs with PEG modifications in the cancer diagnosis and therapy.

A novel mRNA rabies vaccine as a promising candidate for rabies post-exposure prophylaxis protects animals from different rabies viruses.

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.

Tracking Carbon Flows in China's Iron and Steel Industry.

Accurately tracking carbon flows is the first step toward reducing the climate impacts of the iron and steel industry (ISI), which is still lacking in China. In this study, we track carbon flows from coal/mineral mines to end steel users by coupling the cross-process material and energy flow model, point-based emission inventory, and interprovincial trade matrices. In 2020, ISI emitted 2288 Tg of CO2 equivalent (CO2eq, including CH4 and CO2), 96% of which came from energy use and 4% from raw material decomposition. Often overlooked off-gas use and CH4 leakage in coal mines account for 25% of life-cycle emissions. Due to limited scrap resources and a high proportion of pig iron feed, the life-cycle emission intensity of the electric arc furnace (EAF) (1.15 t CO2eq/t steel) is slightly lower than the basic oxygen furnace (BOF) (1.58 t CO2eq/t steel) in China. In addition, over 49% of producer-based emissions are driven by interprovincial coal/coke/steel trade. In particular, nearly all user-based emissions in Zhejiang and Beijing are transferred to steelmaking bases. Therefore, we highlight the need for life-cycle and spatial shifts in user-side carbon management.

Evaluation of the health risk using multi-pollutant air quality health index: case study in Tianjin, China.

Introduction: Air pollution imposes a significant burden on public health. Compared with the popular air quality index (AQI), the air quality health index (AQHI) provides a more comprehensive approach to measuring mixtures of air pollutants and is suitable for overall assessments of the short-term health effects of such mixtures. Methods: We established an AQHI and cumulative risk index (CRI)-AQHI for Tianjin using single-and multi-pollutant models, respectively, as well as environmental, meteorological, and daily mortality data of residents in Tianjin between 2018 and 2020. Results and discussion: Compared with the AQI, the AQHI and CRI-AQHI established herein correlated more closely with the exposure-response relationships of the total mortality effects on residents. For each increase in the interquartile range of the AQHI, CRI-AQHI and AQI, the total daily mortality rates increased by 2.06, 1.69 and 0.62%, respectively. The AQHI and CRI-AQHI predicted daily mortality rate of residents more effectively than the AQI, and the correlations of AQHI and CRI-AQHI with health were similar. Our AQHI of Tianjin was used to establish specific (S)-AQHIs for different disease groups. The results showed that all measured air pollutants had the greatest impact on the health of persons with chronic respiratory diseases, followed by lung cancer, and cardiovascular and cerebrovascular diseases. The AQHI of Tianjin established in this study was accurate and dependable for assessing short-term health risks of air pollution in Tianjin, and the established S-AQHI can be used to separately assess health risks among different disease groups.

Determination of 25 quaternary ammonium compounds in sludge by liquid chromatography-mass spectrometry.

With the pandemic of COVID-19, the application of quaternary ammonium compounds (QACs), which can be used in SARS-CoV-2 disinfection products, has increased substantially. QACs cumulated in sewer system are ultimately deposited and enriched in sludge. QACs in the environment can adversely affect human health and the environment. In this study, a liquid chromatography-mass spectrometry method was established for the simultaneous determination of 25 QACs in sludge samples. Ultrasonic extraction and filtration of the samples was performed using a 50 mM hydrochloric acid-methanol solution. The samples were separated by liquid chromatography and detected in multiple reaction monitoring mode. The matrix effects of the sludge on the 25 QACs ranged from - 25.5% to 7.2%. All substances showed good linearity in the range of 0.5-100 ng/mL, with all determination coefficients (R2) greater than 0.999. The method detection limits (MDLs) were 9.0 ng/g for alkyltrimethylammonium chloride (ATMAC), 3.0 ng/g for benzylalkyldimethylammonium chloride (BAC), and 3.0 ng/g for dialkyldimethylammonium chloride (DADMAC). The spiked recovery rates were in the range of 74-107%, while the relative standard deviations were in the range of 0.8-20.6%. Considering its sensitivity, accuracy, and easy operation, the proposed method in this study was used to determine 22 sludge samples collected from a comprehensive wastewater treatment plant. The results showed that the concentrations of ΣATMACs, ΣBACs, and ΣDADMACs were 19.684, 3.199, and 8.344 µg/g, respectively. The main components included ATMAC-C16, ATMAC-C18, ATMAC-C20, ATMAC-C22, BAC-C12, and DADMAC-C18:C18, with concentrations exceeding 1.0 µg/g. The concentration relationships of different components in the congeners showed that some components were of similar origin.

Refined assessment and decomposition analysis of carbon emissions in high-energy intensive industrial sectors in China.

Carbon emissions from high-energy intensive industrial sectors are the focus of this study due to the huge energy consumption of these sectors. A refined carbon emission inventory of Chinese high-energy intensive industrial sectors in 2020 was first developed at the point source level. The results showed that coal-fired power plants (CFPPs) were the leading contributors to carbon emissions, followed by iron and steel smelting (ISS) and cement production (CMP). Provinces with high carbon emission intensity were mainly concentrated in the north and northeast coasts, while exhibiting a developed economic level and a concentration of heavy industries. Additionally, the growth in China's industrial carbon emissions from 1995 to 2020 can be divided into three phases. The largest decrease in emission intensity was observed in Central, Southwest, North, and East China. Furthermore, the economic structure remained the dominant driver of carbon emissions from the 10th to 13th Five-Year Plan (FYP), playing a positive promotional role. The contribution of economic structure, energy intensity, and energy structure to carbon emissions varied substantially by region and period. With the proposal of sustainable development and energy conservation in China, the influence of economic structure on the carbon emissions of industrial sectors has gradually weakened since the 11th FYP. The reduction in industrial carbon emissions in China under three scenarios could reach up to 46.6 % from 2030 to 2050. The results indicate that industrial carbon emission control in China needs to be integrated into the refined control pathway for conventional air pollutants, considering the spatial variability of industrial carbon emissions in China.

Application of loofah and insects in a bio-trickling filter to relieve clogging.

Bio-trickling filters (BTFs) use an inert filler to purify pollutants making them prone to clogging due to bacterial accumulation. To investigate the performance of a non-inert filler in BTF and its cooperation with insects to relieve clogging, a vertical BTF was constructed with a loofah/Pall ring/polydimethylsiloxane composite filler and selected bacteria to purify toluene. The BTF was started up within 17 d and restarted within 3 d after starvation for 12-16 d. Its average removal efficiency was >90% at steady state. The maximum elimination capacity of 86.4 g·(m3·h)-1 was obtained at a volume capacity of 96.2 g·(m3·h)-1. The introduction of holometabolous insects (Clogmia albipunctata) rapidly removed the biofilm and accelerated the degradation of the loofah, which alleviated clogging. Furthermore, confocal laser scanning microscope (CLSM) observations showed that the biofilm polysaccharides were difficult to remove, while lipids were readily lost. Analysis of microbial diversity over time and space revealed that the dominant bacterium, Comamonas, was replaced by diverse microflora with no obvious dominant genus. Insect introduction and loofah migration had little effect on the evolution of microflora. This study provides a promising approach to operating BTFs with less clogging.

Selection of Payloads for Antibody-Drug Conjugates Targeting Ubiquitously Expressed Tumor-Associated Antigens: a Case Study.

The main objective of this work was to demonstrate which kind of payload is the suitable choice for antibody-drug conjugates directed to widely expressed tumor-associated antigen. Trop-2 is overexpressed in various solid tumors, but it is also present on the epithelium of several normal tissues. A well-designed anti-Trop-2 ADC demands a good balance of efficacy and toxicity. In this research, MMAE, SN-38, and DXd were selected as candidates for payloads of the anti-Trop-2 mAb SY02. The antitumor activities and safety profiles of these ADCs were investigated to compare the therapeutic windows. Robust in vitro cytotoxicity was observed on human pancreatic cancer cell CFPAC-1 and breast cancer cell MDA-MB-468 with IC50 generally in the subnanomolar range. Consistent with in vitro assay, SY02-DXd and SY02-SN-38 demonstrated superior efficacy in CFPAC-1 xenograft models with TGI rates of 98.2% and 87.3%, respectively. However, SY02-MMAE could hardly inhibit the tumor growth. Subsequently, antitumor activities of these ADCs were further compared in MDA-MB-468 xenograft model. Complete tumor regression was observed in SY02-DXd and SY02-MMAE groups, indicating their potent antitumor activities. In an exploratory safety and pharmacokinetic study, SY02-DXd demonstrated the best safety profile with minimal adverse events in cynomolgus monkeys, while SY02-MMAE exhibited severe on-target skin toxicity which caused death. In conclusion, SY02-DXd demonstrated superior efficacy and safety with the widest therapeutic window. Based on the efficacy and safety results, moderate cytotoxic payloads would be ideal choices for ADCs targeting ubiquitously expressed antigens.

Unit-based emissions and environmental impacts of industrial condensable particulate matter in China in 2020.

The emission of condensable particulate matter (CPM) and its environmental impacts are arousing concern in China with the effective control of filter particulate matter (FPM). This study established an up-to-date and unit-based CPM emission inventory for industrial sectors and systematically evaluated the effects of CPM on primary and secondary PM2.5 in China. In 2020, the national CPM emissions total for industrial sectors was estimated to be 0.98 Tg with uncertainty from -49% to 66%, including 0.62 Tg of organic CPM (CPMorg) and 0.36 Tg of inorganic CPM (CPMin). Totals of 62%, 23% and 8% CPM were emitted from coal-fired power plants, coal-fired industrial boilers and sinter plants, respectively. By filling CPM emissions in PM2.5 simulation, the normalized mean bias (NMB) of model to observation was improved from -27% to -14% in East, North and Central China. The 4 µg/m3 PM2.5 concentration was attributed to CPM emissions in this region, accounting for 10% of observations. On "polluted" days (PM2.5>75 µg/m3), industrial CPM emissions can contribute 7 µg/m3 PM2.5 in North China. Therefore, China should focus on controlling CPM from coal combustion to ensure continuous air quality improvement.

An Innovative Site-Specific Anti-HER2 Antibody-Drug Conjugate with High Homogeneity and Improved Therapeutic Index.

Purpose: Antibody-drug conjugates (ADCs) have emerged as a potent cancer therapeutic option in recent years. DP303c is a HER2-targeting ADC with a cleavable linker-MMAE payload. The current study aimed to evaluate the therapeutic potentials of DP303c in vitro as well as in vivo. Materials and Methods: Size exclusion chromatography (SEC), reverse-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to analyze the physicochemical characterization of DP303c. An enzyme-linked immunosorbent assay (ELISA), a cell-based assay, and bio-layer interferometry (BLI) were used to evaluate DP303c's affinity with HER2 and Fc receptors. A confocal laser scanning microscopy was used to observe the internalization of DP303c. Antibody-dependent cell-mediated cytotoxicity (ADCC) and cytotoxicity assays were used to investigate the activity of DP303c in vitro. The antitumor activity of DP303c was assessed in vivo in the HER2-positive cell-derived xenograft model. Results: DP303c was a site-specific anti-HER2 antibody-drug conjugate with a monomethyl auristatin E (MMAE) with an average drug-to-antibody ratio (DAR) of 2.0. DP303c showed a high affinity with HER2 and could be effectively internalized. In vitro and in vivo, DP303c showed stronger antitumor activity as compared to trastuzumab-DM1 (T-DM1) in a series of HER2-positive cancer cells and cell-derived xenograft (CDX) models, especially in the lower HER2-expressing cells. DP303c also exhibited high serum stability and a good PK profile. Conclusion: DP303c was a steady and homogenous DAR 2 ADC that was predicted to deliver MMAE inhibitor to tumor cells. DP303c demonstrated remarkable anticancer efficacy against T-DM1 in xenograft models. DP303c was a strong candidate for the treatment of patients with HER2-positive cancer.

Exposure to the real ambient air pollutants alters the composition of nasal mucosa bacteria in the rat model.

Studies have indicated that ambient pollutant exposure correlates with nasal disease, in which nasal mucosa microbiota play a crucial role. However, the association between exposure to real-ambient air pollutants and the composition of nasal mucosa microbiota has not been well studied. This study aimed to explore the composition of nasal mucosa microbiota after exposure to real-ambient air pollutants with a special system. We monitored PM2.5, O3, etc. in the system and confirmed PM2.5 and O3 were the main pollutants. SD rats were exposed to the system for 16 weeks in summer or 22 weeks in autumn-winter. The concentrations of PM2.5 were 24.00 µg/m3 in the Summer stage and 22.21 µg/m3 in the autumn-winter stage. The O3 concentrations were 25.46 and 13.55 µg/m3, respectively. Exposure altered bacterial beta diversity in the summer stage. There were 4 and 3 different bacteria at the king, order, family and genus levels between the two groups at the two stages, respectively. The abundance of opportunistic pathogens changed, Pseudomonas decreased in summer stage, and Bifidobacterium increased in the autumn-winter stage. The influence of the season on the nasal mucosa microbiota was analyzed. The alpha diversity of the autumn-winter stage was higher than that of the summer stage. LEfSe analysis revealed 34 differential bacterial taxa at the king, order, family and genus level in the two control groups and 31 of the two exposure groups, which were not the same as the bacteria between the control groups and exposure groups. We found that PM2.5 combined with O3 exposure was associated with the composition of the nasal mucosa microbiota and the abundance of opportunistic pathogens, in which season likely impacted the microbiota.

A novel mRNA vaccine, SYS6006, against SARS-CoV-2.

The development of vaccines that can efficiently prevent the infection of SARS-CoV-2 is necessary to fight the COVID-19 epidemic. mRNA vaccine has been proven to induce strong humoral and cellular immunity against SARS-CoV-2. Here, we studied the immunogenicity and protection efficacy of a novel mRNA vaccine SYS6006. High expression of mRNA molecules in 293T cells was detected. The initial and boost immunization with a 21-day interval was determined as an optimal strategy for SYS6006. Two rounds of immunization with SYS6006 were able to induce the neutralizing antibodies against the SARS-CoV-2 wild-type (WT) strain, and Delta and Omicron BA.2 variants in mice or non-human primates (NHPs). A3rd round of vaccination could further enhance the titers of neutralization against Delta and Omicron variants. In vitro ELISpot assay showed that SYS6006 could induce memory B cell and T cell immunities specifically against SARS-CoV-2 in mice. FACS analysis indicated that SYS6006 successfully induced SARS-CoV-2-specific activation of T follicular helper cell (Tfh) and Th1 cell, and did not induce CD4+Th2 response in NHPs. SYS6006 vaccine could significantly reduce the viral RNA loads and prevent lung lesions in Delta variant infected hACE2 transgenic mice. Therefore, SYS6006 could provide significant immune protection against SARS-CoV-2.

The Bio-Persistence of Reversible Inflammatory, Histological Changes and Metabolic Profile Alterations in Rat Livers after Silver/Gold Nanorod Administration.

As a widely applied nanomaterial, silver nanomaterials (AgNMs) have increased public concern about their potential adverse biological effects. However, there are few related researches on the long-term toxicity, especially on the reversibility of AgNMs in vivo. In the current study, this issue was tackled by exploring liver damage after an intravenous injection of silver nanorods with golden cores (Au@AgNRs) and its potential recovery in a relatively long term (8 w). After the administration of Au@AgNRs into rats, Ag was found to be rapidly cleared from blood within 10 min and mainly accumulated in liver as well as spleen until 8 w. All detected parameters almost displayed a two-stage response to Au@AgNRs administration, including biological markers, histological changes and metabolic variations. For the short-term (2 w) responses, some toxicological parameters (hematological changes, cytokines, liver damages etc.) significantly changed compared to control and AuNRs group. However, after a 6-week recovery, all abovementioned changes mostly returned to the normal levels in the Au@AgNRs group. These indicated that after a lengthy period, acute bioeffects elicited by AgNMs could be followed by the adaptive recovery, which will provide a novel and valuable toxicity mechanism of AgNMs for potential biomedical applications of AgNMs.

Chemical Composition and Source Apportionment of Wintertime Airborne PM2.5 in Changchun, Northeastern China.

This study presents field observations and laboratory analyses of wintertime airborne particulate matter (PM2.5) and its chemical components in the Changchun metropolitan area, the geographical center of northeastern China. Twenty-four hour PM2.5 filter samples were collected from 23 December 2011 to 31 January 2012 at four sites in the types of traffic, residential, campus, and a near-city rural village, respectively. Daily PM2.5 concentrations ranged from 49 to 466 µg m-3, with an arithmetic average of 143 µg m-3. Laboratory analyses showed that among all measured chemical species, mineral dust contributed the largest proportion (20.7%) to the total PM2.5 mass, followed by secondary inorganic aerosols (SIA, including SO42-, NO3- and NH4+), which constituted 18.8% of PM2.5 mass. Another notable feature of PM2.5 chemical composition was high halogen (Cl- and F-) loadings at all sites, which was likely due to emissions from coal combustion, plastic manufacturing, and glass melting. Among the four sampling sites, the suburban site exhibited the highest PM2.5 levels and extremely high Cl- and F- loadings due to residential wood burning and nearby industrial facilities lacking effective emission controls. Our results report one of the earliest observations of PM2.5 composition in this region, providing a baseline of aerosol profiles of aerosol before PM2.5 was routinely measured by environmental protection agencies in China, which could be useful for assessing long-term trends of air quality and effectiveness of mitigation measures.

[Source Profiles and Impact of VOCs Based on Production Processes in Foundry Industries].

The characteristics of the VOCs species in foundry industries based on the production processes were analyzed through gas chromatography-mass spectrometry (GC-MS) after sampling the emissions of VOCs in 9 typical foundry enterprises using air packages and absorption tubes. The source profiles of the VOCs species in foundry industries based on production processes were established for the first time in China. In addition, the emission characteristics of VOCs and the contribution of VOCs emitted by various production processes to ozone generation were also studied. The results showed that the characteristic components of the VOCs in foundry industries were predominantly aromatic hydrocarbons, halogenated hydrocarbons, and oxygenated hydrocarbons. The average concentrations were 50.9%, 20.8%, and 12.6%, respectively. In general, aromatic hydrocarbons, such as toluene, benzene, and m/p-xylene; halogenated hydrocarbons, such as trichloroethylene and dichloromethane; oxygenated hydrocarbons, such as acetone, ethyl acetate, cyclopentanone, and some alkanes, were the primary VOCs species of the foundry industries. The emission characteristics of different production processes were related to the solvents and surface treating agents used by each process. The results also demonstrated that painting was the largest contributor of VOCs concentrations among all the production processes, followed by the modeling procedure and the silica sol and pouring processes. The OFP values for the different production processes ranged from 0.29-96.09 mg·m-3. Painting was the largest contributor to OFP, followed by the modeling procedure and the melting and pouring processes. Aromatic hydrocarbons and oxygenated hydrocarbons were the dominant contributors to OFP, and 1,3,5-trimethylbenzene, 1,2,4-trimethylbenzene, toluene, and m/p-xylene were the main active components in the foundry industry, with a total contribution to the ozone generation potential of nearly 60%. It is suggested that the painting process should be prioritized regarding control measures to reduce its emissions and impact, while the waste gas from the modeling procedure and the melting and pouring processes should be collected efficiently and treated properly before being discharged to the environment.

Roles of ROS and cell cycle arrest in the genotoxicity induced by gold nanorod core/silver shell nanostructure.

To understand the genotoxicity induced in the liver by silver nanoparticles (AgNPs) and silver ions, an engineered gold nanorod core/silver shell nanostructure (Au@Ag NR) and humanized hepatocyte HepaRG cells were used in this study. The involvement of oxidative stress and cell cycle arrest in the DNA and chromosome damage induced by 0.4-20 µg mL-1 Au@Ag NR were investigated by comet assay, γ-H2AX assay and micronucleus test. Further, the distribution of Au@Ag NR was analyzed. Our results demonstrated that both Ag+ and Au@Ag NR led to DNA cleavage and chromosome damage (clastogenicity) in HepaRG cells and that the Au@Ag NR retained in the nucleus may further release Ag+, aggravating the damages, which are mainly caused by cell cycle arrest and ROS formation. The results reveal the correlation between the intracellular accumulation, Ag+ ion release and the potential genotoxicity of AgNPs.

Investigation of the impact of PM2.5 on the ciliary motion of human nasal epithelial cells.

Nasal epithelium provides a physical barrier to potentially harmful stimuli. Cilia, which is on the apical side of the human nasal epithelial cells (HNEpCs), plays a critical role in removing inhaled harmful matter. Ciliary beat frequency (CBF) and ciliary beat pattern (CBP) are the two important indicators for ciliary beat function. However, impacts of the fine particulate matter (PM2.5) on CBF and CBP are still unknown. We aimed to evaluate the impact of PM2.5 on the ciliary beat function of the HNEpCs and its potential mechanisms. After exposed to PM2.5 for 12 h, cilia of HNEpCs were in disordered arrangement. The ciliary coverage rate was decreased after PM2.5 exposure of a series of concentration, while the proportion of basal cells was continuously increased and could be observed on the apical side of the HNEpCs which is hardly be observed without PM2.5 exposure. PM2.5 increased the CBF after 12 h exposure, while 24 h exposure increased the CBF at the relative lower dosage groups and then made a decrease at relative higher dosage groups. CBF were classified into two different types, which had different changes following PM2.5 exposure. CBP showed significant changes characterized as the increased dyskinesia index. Total levels of cellular ATP and the mitochondrial membrane potential were decreased following 12 h exposure of PM2.5, while no change was found in O2 consumption. In conclusion, PM2.5 impact the ciliary beat function of HNEpCs, and the mitochondrial dysfunction might play an important role in it.

High level of source-specific particulate matter air pollution associated with cardiac arrhythmias.

Epidemiological evidence linking source-specific ambient particulate matter with aerodynamic diameter <2.5 µm (PM2.5) and cardiac arrhythmias is limited. In this study, we investigated the impact of source-specific PM2.5 on cardiac arrhythmias in a panel of forty-five healthy adults living in Beijing, China, between 2015 and 2016. Repeated measures of 24-hour electrocardiograms were conducted during clinical visits, and daily counts of four arrhythmia events including supraventricular premature beat (SVPB), atrial tachycardia (AT), premature ventricular contraction (PVC) and ventricular tachycardia (VT) were recorded. One hundred forty-seven constituents in PM2.5 were analyzed for collected particulate samples, in which fifty-six of them above laboratory detection limits were selected for source apportionment analysis using positive matrix factorization. The average contributions of identified five major sources to PM2.5 were 45.9% from secondary nitrate/sulfate, 18.0% from coal combustion, 16.9% from crustal soil, 13.8% from biomass burning, and 5.4% from cooking. Generalized estimating equation models were used to estimate relative risks (RR) of arrhythmias in association with interquartile-range (IQR) increases in PM2.5 constituents and specific sources. Total PM2.5 mass as well as several combustion related constituents were found of significant impacts on increased risks of arrhythmia events. Among the identified sources of PM2.5, coal burning has been found the major source that associated with increased risks of SVPB, PVC and VT with RR of 1.19 [95% confidence intervals (CI): 1.04, 1.36] to 1.64 (95% CI: 1.35, 2.00). PM2.5 from combustion related secondary nitrate/sulfate was also found of significant impact on SVPB and AT, followed by PM2.5 from biomass burning and crustal soil. Our results indicated that PM2.5 from anthropogenic activity related sources were most responsible for increased risks of arrhythmia events. Our findings enhance the understanding of increased risks of arrhythmias from exposure to PM2.5, and provide evidence on source-specific PM control priorities.

Single-Dosed Genotoxicity Study of Gold Nanorod Core/Silver Shell Nanostructures by Pig-a, Micronucleus, and Comet Assays.

As an increasing number of nanoproducts enter our daily life, their potential health risks have caused widespread concerns and have also promoted studies of nanotoxicity. Among these investigations, the genotoxicity of nanomaterials has attracted more attention. Engineered silver nanorod with gold core and silver shell (Au@Ag NR) was used in this study to investigate the possible genotoxicity and genotoxicity patterns in peripheral lymphocytes and hepatocytes introduced by released Ag+ and the nanoparticle itself by integrating the Pig-a gene, micronucleus, and comet assays. Most of the Au@Ag NR was rapidly cleared from the circulatory system of Sprague Dawley rats, and a small amount of Au@Ag NR was retained in the liver for at least 14 days. Our data confirmed that clastogenicity was the primary genotoxicity type induced by Au@Ag NR, and both NR particles containing Ag and the released Ag+ contribute to genotoxicity. Au@Ag NR was shown to be a clastogen through the introduction of increased %Tail DNA in peripheral lymphocytes (5.82%±0.25%) and hepatocytes (4.83%±0.17%) and promotion of the formation of micronuclei in hepatocytes (1.12%±0.13%) 3 days and 14 days after dosing, respectively (P < 0.05), which could be a result of both Ag+ and Ag shell of the Au@Ag NR. However, Au@Ag NR was not shown to be a mutagen, as the average RBCCD59- count was not changed significantly as compared with control. These data suggest the importance of adopting appropriate genotoxicity testing strategies in identifying the genotoxicity of nanoparticles in vivo.

Silver Nanoparticle Exposure Induces Neurotoxicity in the Rat Hippocampus Without Increasing the Blood-Brain Barrier Permeability.

Silver nanoparticles (Ag-NPs) can enter the brain and subsequently induce neurotoxicity. However, the toxicity of Ag-NPs on the blood-brain barrier (BBB) and the underlying mechanism(s) of action on the hippocampus in vivo are not well understood. To investigate Ag-NP suspension (Ag-NPS)-induced toxicity on the BBB and neurons, Sprague-Dawley rats were randomly divided into 3 groups, and Ag-NPS, Ag-ion, and 5% sucrose solution (vehicle control) were administrated intravenously, respectively. After 24 h exposure to Ag-NPS, the BBB permeability was not significantly changed. However, the Ag concentrations in the brain tissues were only detected in the Ag-NPS group. Gene expression results indicated that the expression of Claudin 4 (tight junction protein) was significantly decreased. Furthermore, astrocyte foot swelling, neuron shrinkage and Ag-NP like particles were observed under transmission electron microscopy. Global gene expression analysis showed that 502 genes were up-regulated and 703 genes were down-regulated in the hippocampi treated with Ag-NPS. In the Ag-NPS-treated group, 78 biological functions were changed based on gene ontology (GO) and 34 signaling pathways were significantly changed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, which were associated with the neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, calcium signaling pathway and MAPK signaling pathway. In comparison, 27 GO and 9 KEGG pathways were changed in the released Ag-ion-treated group. Ag-NPS decreased C1qtnf3 expression and increased Adra1d expression to affect MAPK signaling pathway, which promoted inflammation and apoptosis in the hippocampus. Moreover, Ag-NPS significantly increased Spp1, Cacna1s and Tacr3 mRNAs expression, which may result in intracellular calcium increasing and initiate cell death. Furthermore, Ag-NPS affected calcium signaling pathway and neuroactive ligand-receptor (Grin2a, Drd2, and Adra1d), which are crucial in diverse cellular functions in the brain including cognition and neurodevelopment. These results draw our attention to the importance of Ag-NP-induced toxicity in the rat hippocampus and provide a better understanding of its toxicological mechanisms in vivo.