Evaluation of graphical models for multi-group metabolomics data.

Gaussian graphical model is a strong tool for identifying interactions from metabolomics data based on conditional correlation. However, data may be collected from different stages or subgroups of subjects with heterogeneity or hierarchical structure. There are different integrating strategies of graphical models for multi-group data proposed by data scientists. It is challenging to select the methods for metabolism data analysis. This study aimed to evaluate the performance of several different integrating graphical models for multi-group data and provide support for the choice of strategy for similar characteristic data. We compared the performance of seven methods in estimating graph structures through simulation study. We also applied all the methods in breast cancer metabolomics data grouped by stages to illustrate the real data application. The method of Shaddox et al. achieved the highest average area under the receiver operating characteristic curve and area under the precision-recall curve across most scenarios, and it was the only approach with all indicators ranked at the top. Nevertheless, it also cost the most time in all settings. Stochastic search structure learning tends to result in estimates that focus on the precision of identified edges, while BEAM, hierarchical Bayesian approach and birth-death Markov chain Monte Carlo may identify more potential edges. In the real metabolomics data analysis from three stages of breast cancer patients, results were in line with that in simulation study.

Research progress in the development of 3D skin models and their application to in vitro skin irritation testing.

Toxicological assessment of chemicals is crucial for safeguarding human health and the environment. However, traditional animal experiments are associated with ethical, technical, and predictive limitations in assessing the toxicity of chemicals to the skin. With the recent development of bioengineering and tissue engineering, three-dimensional (3D) skin models have been commonly used as an alternative for toxicological studies. The skin consists of the subcutaneous, dermis, and epidermis. All these layers have crucial functions such as physical and biological protection and thermoregulation. The epidermis is the shallowest layer protecting against external substances and media. Because the skin is the first contact point for many substances, this organ is very significant for assessing local toxicity following skin exposure. According to the classification of the United Nations Global Harmonized System, skin irritation is a major potentially hazardous characteristic of chemicals, and this characteristic must be accurately assessed and classified for enhancing chemical safety management and preventing and reducing chemical accidents. This review discusses the research progress of 3D skin models and introduces their application in assessing chemical skin irritation.

Peptide-Functionalized Prussian Blue Nanomaterial for Antioxidant Stress and NIR Photothermal Therapy against Alzheimer's Disease.

Excessive accumulations of reactive oxygen species (ROS) and amyloid-ß (Aß) protein are closely associated with the complex pathogenesis of Alzheimer's disease (AD). Therefore, approaches that synergistically exert elimination of ROS and dissociation of Aß fibrils are effective therapeutic strategies for correcting the AD microenvironment. Herein, a novel near infrared (NIR) responsive Prussian blue-based nanomaterial (PBK NPs) is established with excellent antioxidant activity and photothermal effect. PBK NPs possess similar activities to multiple antioxidant enzymes, including superoxide dismutase, peroxidase, and catalase, which can eliminate massive ROS and relieve oxidative stress. Under the NIR irradiation, PBK NPs can generate local heat to disaggregate Aß fibrils efficiently. By modifying CKLVFFAED peptide, PBK NPs display obvious targeting ability for blood-brain barrier penetration and Aß binding. Furthermore, in vivo studies demonstrate that PBK NPs have outstanding ability to decompose Aß plaques and alleviate neuroinflammation in AD mouse model. Overall, PBK NPs provide evident neuroprotection by reducing ROS levels and regulating Aß deposition, and may accelerate the development of multifunctional nanomaterials for delaying the progression of AD.

Multi-dimensional evaluation of cardiotoxicity in mice following respiratory exposure to polystyrene nanoplastics.

BACKGROUND: Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. RESULTS: Here, we systematically investigated the cardiotoxicity of 40 nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0 µg/day, 16 µg/day, 40 µg/day and 100 µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. CONCLUSION: The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity.

Recent consequences of micro-nanaoplastics (MNPLs) in subcellular/molecular environmental pollution toxicity on human and animals.

Microplastics and Nanoplastics (MNPLs) pollution has been recognized as the important environmental pollution caused by human activities in addition to global warming, ozone layer depletion and ocean acidification. Most of the current studies have focused on the toxic effects caused by plastics and have not actively investigated the mechanisms causing cell death, especially at the subcellular level. The main content of this paper focuses on two aspects, one is a review of the current status of MNPLs contamination and recent advances in toxicological studies, which highlights the possible concentration levels of MNPLs in the environment and the internal exposure of humans. It is also proposed to pay attention to the compound toxicity of MNPLs as carriers of other environmental pollutants and pathogenic factors. Secondly, subcellular toxicity is discussed and the modes of entry and intracellular distribution of smaller-size MNPLs are analyzed, with particular emphasis on the importance of organelle damage to elucidate the mechanism of toxicity. Importantly, MNPLs are a new type of environmental pollutant and researchers need to focus not only on their toxicity, but also work with governments to develop measures to reduce plastic emissions, optimize degradation and control plastic aggression against organisms, especially humans, from multiple perspectives.

Hearing loss and hypertension among noise-exposed workers: a pilot study based on baseline data.

This study aimed to assess the prevalence of noise-induced hearing loss (NIHL) and hypertension, and the association between NIHL and hypertension using occupational physical examination data of 42,588 noise-exposed workers from local enterprises in Yangzhou between 2015 and 2017. The average binaural high-frequency threshold on average (BHFTA), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 23.09 ± 11.32 dB, 126.85 ± 15.94 mm Hg and 79.94 ± 11.61 mm Hg. The prevalence of NIHL and hypertension were 24.38% and 25.40%. An increased risk of NIHL and hypertension was observed in the groups of males, aged >35 years, noise exposure time >5 years, noise exposure level >85 dB(A) and smoking. 32.25% NIHL workers had hypertension. NIHL workers were at higher risk of hypertension (adjusted OR = 1.07, 95%CI = 1.02-1.13). This study shows that the noise-exposed workers have high risk of developing NIHL and hypertension.

LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRNA RPL34-AS1 in the development and progression of ESCC. METHODS: The expression level of RPL34-AS1 in ESCC tissues and cell lines was determined by RT-qPCR. Functional experiments in vitro and in vivo were employed to explore the effects of RPL34-AS1 on tumor growth in ESCC cells. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between RPL34-AS1, miR-575 and ACAA2. RESULTS: RPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. Functionally, upregulation of RPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, invasion and migration in vitro, whereas knockdown of RPL34-AS1 elicited the opposite function. Consistently, overexpression of RPL34-AS1 inhibited tumor growth in vivo. Mechanistically, RPL34-AS1 acted as a competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC. CONCLUSIONS: Our results reveal a role for RPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using RPL34-AS1 as a potential biomarker and an effect target for patients with ESCC.

Metabolomics-based molecular signatures reveal the toxic effect of co-exposure to nitrosamines in drinking water.

Nitrosamines, a group of emerging nitrogenous pollutants, are ubiquitously found in the drinking water system. However, less is known about how systemic biological responses resist or tolerate nitrosamines, especially long-term co-exposure at low concentrations. In this study, untargeted metabolomics was used to investigate the metabolic perturbations in human esophageal epithelial Het-1A cells induced by a mixture of nine common nitrosamines in drinking water at environmentally relevant, human-internal-exposure, and genotoxic concentrations. Generally, the disrupted metabolic spectrum became complicated with nitrosamines dose increasing. Notably, two inflammation-associated pathways, namely, cysteine (Cys) and methionine (MET) metabolism, and nicotinate and nicotinamide metabolism, changed significantly under the action of nitrosamines, even at the environmentally relevant level. Furthermore, targeted metabolomics and molecular biology indicators in cells were identified in mice synchronously. For one thing, the up-regulated Cys and MET metabolism provided methyl donors for histone methylation in the context of pro-inflammatory response. For another, the down-regulated NAD+/NADH ratio inhibited the deacetylation of NF-кB p65 and eventually activated the NF-кB signaling pathway. Taken collectively, the metabolomics molecular signatures were important indicative markers for nitrosamines-induced inflammation. The potential crosstalk between the inflammatory cascade and metabolic regulation also requires further studies. These findings suggest that more attention should be paid to long-term co-exposure at low concentrations in the control of nitrosamines pollution in drinking water. Additionally, this study also highlights a good prospect of the combined metabolomic-molecular biology approach in environmental toxicology.

Copper induces oxidative stress and apoptosis of hippocampal neuron via pCREB/BDNF/ and Nrf2/HO-1/NQO1 pathway.

Disordered copper metabolism has been suggested to occur to several neurological conditions, including Alzheimer's disease and Parkinson's disease. However, the underlying mechanism was still unclear. This might link to copper-induced hippocampal neuronal apoptosis and decrease in neurons viability. Our vitro experiment showed copper exposure induced oxidative stress and promoted apoptosis of HT22 murine hippocampal neuronal cell. Mechanistically, we found copper, on the one hand, prevented phosphorylation of cAMP response element binding protein (CREB) to decrease expression its downstream target protein Brain-derived neurotrophic factor (BDNF), and to decrease mitochondrial membrane potential and Bcl-2/Bax ratio; on the other hand, copper-induced reactive oxygen species (ROS), promoted lipid peroxidation, reduced antioxidant enzyme activity of GSH-Px. Copper-induced oxidative damage further decreased the phosphorylation of CREB, decreased expression of Bcl-2, enhanced expression of Bax, and accelerated the dissociation of keap1-Nrf2 complex, promoted the nuclear translocation of Nrf2, stimulate the expression of antioxidant molecules HO-1 and NQO1. In conclusion, we found copper inhibited pCREB/BDNF signaling pathway by prevent CREB from phosphorylation, further found that oxidative damage not only inhibited neuroprotective signaling pathways and induced apoptosis, but activated antioxidant protection signals Nrf2/HO-1/NQO1 signaling pathway.

Reactive oxygen species-mediated activation of NLRP3 inflammasome associated with pyroptosis in Het-1A cells induced by the co-exposure of nitrosamines.

Nitrosamines were a class of important environmental carcinogens associated with digestive tract neoplasms. As the early toxic effect of nitrosamines, inflammatory response participated in the malignant transformation of cells and promoted the occurrence and development of tumors. However, the role of NLRP3 inflammasome in the nitrosamines-induced inflammatory response was unclear. In this study, the human esophageal epithelial cells (Het-1A) were used to explore potential mechanisms of the activation of NLRP3 inflammasome under co-exposure to nine nitrosamines commonly found in drinking water at the doses of 0, 4, 20, 100, 500, and 2500 ng/mL. The results showed that nitrosamines stimulated activation of the NLRP3 inflammasome and induced cellular oxidative damage in a dose-dependent manner. Pretreatment of reactive oxygen species scavenger N-acetyl-L-cysteine (NAC), particularly mitochondrial reactive oxygen species (mtROS) scavengers Mito-TEMPO, effectively inhibited the activation of NLRP3 inflammasome, suggesting that nitrosamines could mediate the activation of NLRP3 inflammasome via mtROS. Furthermore, we found that nitrosamines co-exposure also promoted cell pyroptosis through the NLRP3/caspase-1/GSDMD pathway, which was demonstrated by adding the caspase-1 inhibitor Z-YVAD-FMK and constructing NLRP3 downregulated Het-1A cell line. This study revealed the underlying mechanism of the activation of NLRP3 inflammasome initiated by nitrosamines co-exposure and provided new perspectives on the toxic effects of nitrosamines.

Let-7e-5p, a promising novel biomarker for benzene toxicity, is involved in benzene-induced hematopoietic toxicity through targeting caspase-3 and p21.

Benzene is a common industrial chemical and environmental pollutant. However, the mechanism of hematotoxicity caused by exposure to low doses of benzene is unknown. Let-7e-5p pathway regulatory networks were constructed by bioinformatics analysis using a benzene-induced aplastic anemia (BIAA) mouse model. The MTT assay, EdU staining, flow cytometric analysis, dual luciferase reporter gene assay, and RIP assay were utilized to evaluate the effects of benzoquinone (1,4-BQ) on let-7e-5p pathway. This study consisted of 159 workers with a history of low-level benzene exposure and 159 workers with no history of benzene exposure. After the confounding factors were identified, the associations between let-7e-5p expression and hematotoxicity were assessed by multiple linear regression. Furthermore, we used four machine learning algorithms (decision trees, neural network, Bayesian network, and support vector machines) to construct a predictive model for detecting benzene-causing hematotoxicity in workers. In this study, compared with respective controls, let-7e-5p expression was decreased in BIAA mice and benzene-exposed workers. After 1,4-BQ exposure, let-7e-5p overexpression negatively regulated caspase-3 and p21 expression, protected cells from apoptosis, and facilitated cell proliferation. RIP assays, and dual luciferase reporter gene assays confirmed that let-7e-5p could target p21 and caspase-3 and regulate the cell cycle and apoptosis. The support vector machines classifier achieved the best prediction of benzene-induced hematotoxicity (prediction accuracy = 88.27, AUC = 0.83) by statistically characterizing the internal dose of benzene exposure and the oxidative stress index, as well as the expression levels of let-7e-5p pathway-related genes in benzene-exposed workers. Let-7e-5p may be a potential therapeutic target of benzene-induced hematotoxicity, provide a basis for evaluating the health hazards of long-term and low-dose benzene exposure in workers, and supply a reference for revising occupational health standards.

Metabolomic transition trajectory and potential mechanisms of N-nitrosomethylbenzylamine induced esophageal squamous cell carcinoma in rats.

Esophageal squamous cell carcinoma (ESCC) is an environment-relevant malignancy with a high mortality. Nitrosamines, a class of nitrogen-containing environmental carcinogens, are widely suggested as a risk factor for ESCC. However, how nitrosamines affect metabolic regulation to promote ESCC tumorigenesis is largely unknown. In this study, the transition trajectory of serum metabolism in the course of ESCC induced by N-nitrosomethylbenzylamine (NMBA) in rats was depicted by an untargeted metabolomic analysis, and the potential molecular mechanisms were revealed. The results showed that the metabolic alteration in rats was slight at the basal cell hyperplasia (BCH) stage, while it became apparent when the esophageal lesion developed into dysplasia (DYS) or more serious conditions. Moreover, serum metabolism of severe dysplasia (S-DYS) showed more similar characteristics to that of carcinoma in situ (CIS) and invasive cancer (IC). Aberrant nicotinate (NA) and nicotinamide (NAM) metabolism, tryptophan (TRP) metabolism, and sphingolipid metabolism could be the key players favoring the malignant transformation of esophageal epithelium induced by NMBA. More particularly, NA and NAM metabolism in the precancerous stages and TRP metabolism in the cancerous stages were demonstrated to replenish NAD+ in different patterns. Furthermore, both the IDO1-KYN-AHR axis mediated by TRP metabolism and the SPHK1-S1P-S1PR1 axis by sphingolipid metabolism provided an impetus to create the pro-inflammatory yet immune-suppressive microenvironment to facilitate the esophageal tumorigenesis and progression. Together, these suggested that NMBA exerted its carcinogenicity via more than one pathway, which may act together to produce combination effects. Targeting these pathways may open up the possibility to attenuate NMBA-induced esophageal carcinogenesis. However, the interconnection between different metabolic pathways needs to be specified further. And the integrative and multi-level systematic research will be conducive to fully understanding the mechanisms of NMBA-induced ESCC.

Removal of microcystins from water and primary treatment technologies - A comprehensive understanding based on bibliometric and content analysis, 1991-2020.

Microcystins are a group of heptapeptide hepatotoxins produced by a variety of algae and are frequently detected in aquatic ecosystems, posing a global threat to ecological stability and human health. However, it is difficult to eliminate them completely and innocuously from water by conventional water treatment processes. This study comprehensively evaluated a total of 821 original articles retrieved from the Web of Science (1991-2020) about the removal of microcystins using bibliometric and content analysis to provide a qualitative and quantitative research landscape and a global view of research hotspots and future research directions. Furthermore, the primary and promising treatment technologies for microcystin pollution were also summarized and discussed. The results indicated an urgent practical demand to remediate microcystin pollution according to the increasing number of publications since 2005. China had the highest number of publications, whereas the United States was the core country in the international collaboration network. The Chinese Academy of Sciences and University of Cincinnati showed their leading positions considering article amounts and academic cooperation. Dionysiou DD contributed the most articles, and Carmichael WW had the highest number of co-citations. Three treatment technologies, including biodegradation, chemical oxidation and adsorption, were the major strategies to remediate the pollution of microcystins in water. In addition, the toxicity of toxins/their metabolites, degradation kinetics, and elimination mechanism were also important research contents. Bacterial degradation, photocatalytic degradation, and multiple-technologies approach have been identified with great potential and should be given more attention in future studies. This work summarizes the current research status on microcystin management, provides a valuable reference for researchers to identify potential opportunities for collaboration in related fields, and guides future research directions to inter-disciplinary and multi-perspective approaches.

Impact of waste of COVID-19 protective equipment on the environment, animals and human health: a review.

During the Corona Virus Disease 2019 (COVID-19) pandemic, protective equipment, such as masks, gloves and shields, has become mandatory to prevent person-to-person transmission of coronavirus. However, the excessive use and abandoned protective equipment is aggravating the world's growing plastic problem. Moreover, above protective equipment can eventually break down into microplastics and enter the environment. Here we review the threat of protective equipment associated plastic and microplastic wastes to environments, animals and human health, and reveal the protective equipment associated microplastic cycle. The major points are the following:1) COVID-19 protective equipment is the emerging source of plastic and microplastic wastes in the environment. 2) protective equipment associated plastic and microplastic wastes are polluting aquatic, terrestrial, and atmospheric environments. 3) Discarded protective equipment can harm animals by entrapment, entanglement and ingestion, and derived microplastics can also cause adverse implications on animals and human health. 4) We also provide several recommendations and future research priority for the sustainable environment. Therefore, much importance should be attached to potential protective equipment associated plastic and microplastic pollution to protect the environment, animals and humans.

Smart Catalyzed Hairpin Assembly-Induced DNAzyme Nanosystem for Intracellular UDG Imaging.

Uracil DNA glycosylase (UDG) is one of the key initiators for the base excision repair pathway. Since abnormal UDG expression is associated with various diseases, sensitive detection of UDG activity is critical for early clinical diagnosis. Here, a smart catalyzed hairpin assembly (CHA)-DNAzyme nanosystem is developed for intracellular UDG imaging by incorporating CHA and DNAzyme onto MnO2 nanosheets. In this strategy, the biodegradable MnO2 nanosheets are employed as nanocarriers for efficiently adsorbing and delivering five DNA probes into cells by endocytosis. Then, the MnO2 nanosheets are degraded by cellular glutathione to release the DNA modules at the same intracellular position. Liberated Mn2+, an indispensable DNAzyme cofactor, was used to promote catalytic cleavage for facilitating the cascade process in cells. Based on the uracil site-recognition and -excision operation of the target UDG, the activated CHA-DNAzyme nanosystem generates lots of DNAzyme-assisted CHA products, turning on the fluorescence resonance energy transfer response. This autocatalytic CHA-DNAzyme nanosystem provides a detectable minimum UDG concentration of 0.23 mU/mL, which is comparable to some reported UDG detection approaches. As a multiple signal amplification strategy, the CHA-DNAzyme nanosystem realizes the UDG imaging in living cells with enhanced sensitivity, indicating great promise in the prediction and diagnosis of early-stage cancer.

Infection with Human Papillomavirus 18 Promotes Alkylating Agent-Induced Malignant Transformation in a Human Esophageal Cell Line.

The relationship between human papillomavirus (HPV) and esophageal cancer (EC) has been controversial, which may be caused by the difference in geographic regions of sample origin. Thus, we conducted a case-control study to find that HPV increased the risk of esophageal cancer, and the HPV18 detection rate is the highest (24.2%) among patients with EC, suggesting that HPV18 could be the most risk subtype of HPV infected. We then identified high-risk HPV18 and N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) to establish a model on the viral etiology cooperating with environmental carcinogens. Het-1A cells containing HPV18 were continuously exposed to MNNG or not; then the morphological phenotype and function assays were performed in 25th passage cells. MNNG promoted the proliferation and invasion abilities and inhibited apoptosis both in Het-1A-HPV18 and control group. However, the Het-1A-HPV18 had a stronger change in phenotypic features and formed more transformed foci in soft agar. Further, Western blot found p53 and p21 were down-regulated, and expression of c-Myc, MMP-2, and MMP-9 and Bcl-2/Bax ratio were up-regulated. Our results revealed that MNNG was easier to induce malignant transformation of Het-1A cells transfected with HPV18. It is good evidence for the close relationship between HPV and the etiology of EC, providing foundation for further study in molecular mechanism and specific intervention targets.

N6-methyladenosine RNA modification and its interaction with regulatory non-coding RNAs in colorectal cancer.

As one of the most common forms of RNA modification, N6-methyladenosine (m6A) RNA modification has attracted increasing research interest in recent years. This reversible RNA modification added a new dimension to the post-transcriptional regulation of gene expression. In colorectal cancer (CRC), the role of m6A modification has been extensively studied, not only on mRNAs but also on non-coding RNAs (ncRNAs). In the present review, we depicted the role of m6A modification in CRC, systematically elaborate the interaction between m6A modification and regulatory ncRNAs in function and mechanism. Moreover, we discussed the potential applications in clinical.

Short-term effect of fine particulate matter and ozone on non-accidental mortality and respiratory mortality in Lishui district, China.

BACKGROUND: In recent years, air pollution has become an imminent problem in China. Few studies have investigated the impact of air pollution on the mortality of the middle-aged and elderly people. Therefore, this study aims to evaluate the impact of PM2.5 (fine particulate matter) and O3 (ozone) on non-accidental mortality and respiratory mortality of the middle-aged and elderly people in Lishui District of Nanjing and provide the evidence for potential prevention and control measures of air pollution. METHOD: Using daily mortality and atmospheric monitoring data from 2015 to 2019, we applied a generalized additive model with time-series analysis to evaluate the association of PM2.5 and O3 exposure with daily non-accidental mortality and respiratory mortality in Lishui District. Using the population attributable fractions to estimate the death burden caused by short-term exposure to O3 and PM2.5。. RESULT: For every 10 µg/m3 increase in PM2.5, non-accidental mortality increased 0.94% with 95% confidence interval (CI) between 0.05 and 1.83%, and PM2.5 had a more profound impact on females than males. For every 10 µg/m3 increase in O3, respiratory mortality increased 1.35% (95% CI: 0.05, 2.66%) and O3 had a more profound impact on males than females. Compared with the single pollutant model, impact of the two-pollutant model on non-accidental mortality and respiratory mortality slightly decreased. In summer and winter as opposed to the other seasons, O3 had a more obvious impact on non-accidental mortality. The population attributable fractions of non-accidental mortality were 0.84% (95% CI:0.00, 1.63%) for PM2.5 and respiratory mortality were 0.14% (95% CI:0.01, 0.26%) for O3. For every 10 µg/m3 decrease in PM2.5, 122 (95% CI: 6, 237) non-accidental deaths could be avoided. For every 10 µg/m3 decrease in O3, 10 (95% CI: 1, 38) respiratory deaths could be avoided. CONCLUSION: PM2.5 and O3 could significantly increase the risk of non-accidental and respiratory mortality in the middle-aged and elderly people in Lishui District of Nanjing. Exposed to air pollutants, men were more susceptible to O3 damage, and women were more susceptible to PM2.5 damage. Reduction of PM2.5 and O3 concentration in the air may have the potential to avoid considerable loss of lives.

Integrating transcriptomics and behavior tests reveals how the C. elegans responds to copper induced aging.

Copper (Cu) pollution in water and agricultural soil has always been a worldwide concern. This research aims to investigate the health effects of copper exposure on Caenorhabditis elegans (C. elegans) under the existing environmental quality standards (1 mg/L and 2 mg/L) via lifespan, reproduction, biological markers and transcriptome analysis. The results showed that copper of these two environmental standards shorten the lifespan of nematodes, reduced the brood size, reduced the frequency of pharyngeal pumps and prolonged defecation time as aging-related behaviors, and increased the levels of aging-related markers ROS, MDA and H2O2. There was a certain effect trend for the two exposure concentrations. Further, the possible molecular mechanism of copper-induced aging and reproductive effects on C. elegans was explored. Differential gene expression analysis was performed, and 2332 genes (567 up- and 1765 down-regulated genes) in the 1 mg/L group, 2449 DEGs (724 up- and 1725 down-regulated genes) in the 2 mg/L group in response to copper treatment. The top 20 regulated genes were vit (vit-1, vit-3, vit-4) genes, col genes (col-35, col-72, col-114, col-123, col-164, col-183, col-185), eea-1, him-18 and grl-20, which suggested that cuticle collagen synthesis and yolk expression were disrupted by copper. Analysis of KEGG pathway showed copper exposure widely affects longevity regulation pathways, thereby promoting aging. In summary, the sequencing results extensively and deeply reveal the health hazards of environmentally relevant doses of copper exposure to C. elegans, and behavioral testing verified that copper promoted aging of C. elegans.

In vitro evaluation of nanoplastics using human lung epithelial cells, microarray analysis and co-culture model.

Nanoplastics, including polystyrene nanoplastics (PS-NPs), are widely existed in the atmosphere, which can be directly and continuously inhaled into the human body, posing a serious threat to the respiratory system. Therefore, it is urgent to estimate the potential pulmonary toxicity of airborne NPs and understand its underlying mechanism. In this research, we used two types of human lung epithelial cells (bronchial epithelium transformed with Ad12-SV40 2B, BEAS-2B) and (human pulmonary alveolar epithelial cells, HPAEpiC) to investigate the association between lung injury and PS-NPs. We found PS-NPs could significantly reduce cell viability in a dose-dependent manner and selected 7.5, 15 and 30 µg/cm2 PS-NPs as the exposure dosage levels. Microarray detection revealed that 770 genes in the 7.5 µg/cm2 group and 1951 genes in the 30 µg/cm2 group were distinctly altered compared to the control group. Function analysis suggested that redox imbalance might play central roles in PS-NPs induced lung injury. Further experiments verified that PS-NPs could break redox equilibrium, induce inflammatory effects, and triggered apoptotic pathways to cause cell death. Importantly, we found that PS-NPs could decrease transepithelial electrical resistance by depleting tight junctional proteins. Result also demonstrated that PS-NPs-treated cells increased matrix metallopeptidase 9 and Surfactant protein A levels, suggesting the exposure of PS-NPs might reduce the repair ability of the lung and cause tissue damage. In conclusion, nanoplastics could induce oxidative stress and inflammatory responses, followed by cell death and epithelial barrier destruction, which might result in tissue damage and lung disease after prolonged exposure.