Enhanced Sensitivity of A549 Cells to Doxorubicin with WS2 and WSe2 Nanosheets via the Induction of Autophagy.

The excellent physicochemical properties of two-dimensional transition-metal dichalcogenides (2D TMDCs) such as WS2 and WSe2 provide potential benefits for biomedical applications, such as drug delivery, photothermal therapy, and bioimaging. WS2 and WSe2 have recently been used as chemosensitizers; however, the detailed molecular basis underlying WS2- and WSe2-induced sensitization remains elusive. Our recent findings showed that 2D TMDCs with different thicknesses and different element compositions induced autophagy in normal human bronchial epithelial cells and mouse alveolar macrophages at sublethal concentrations. Here, we explored the mechanism by which WS2 and WSe2 act as sensitizers to increase lung cancer cell susceptibility to chemotherapeutic agents. The results showed that WS2 and WSe2 enhanced autophagy flux in A549 lung cancer cells at sublethal concentrations without causing significant cell death. Through the autophagy-specific RT2 Profiler PCR Array, we identified the genes significantly affected by WS2 and WSe2 treatment. Furthermore, the key genes that play central roles in regulating autophagy were identified by constructing a molecular interaction network. A mechanism investigation uncovered that WS2 and WSe2 activated autophagy-related signaling pathways by interacting with different cell surface proteins or cytoplasmic proteins. By utilizing this mechanism, the efficacy of the chemotherapeutic agent doxorubicin was enhanced by WS2 and WSe2 pre-treatment in A549 lung cancer cells. This study revealed a feature of WS2 and WSe2 in cancer therapy, in which they eliminate the resistance of A549 lung cancer cells against doxorubicin, at least partially, by inducing autophagy.

Fe-Co Co-Doped 1D@2D Carbon-Based Composite as an Efficient Catalyst for Zn-Air Batteries.

A Fe-Co dual-metal co-doped N containing the carbon composite (FeCo-HNC) was prepared by adjusting the ratio of iron to cobalt as well as the pyrolysis temperature with the assistance of functionalized silica template. Fe1Co-HNC, which was formed with 1D carbon nanotubes and 2D carbon nanosheets including a rich mesoporous structure, exhibited outstanding oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activities. The ORR half-wave potential is 0.86 V (vs. reversible hydrogen electrode, RHE), and the OER overpotential is 0.76 V at 10 mA cm-2 with the Fe1Co-HNC catalyst. It also displayed superior performance in zinc-air batteries. This method provides a promising strategy for the fabrication of efficient transition metal-based carbon catalysts.

Nanoplastic Exposure at Environmental Concentrations Disrupts Hepatic Lipid Metabolism through Oxidative Stress Induction and Endoplasmic Reticulum Homeostasis Perturbation.

In this study, we investigated the mechanism underlying the perturbation of hepatic lipid metabolism in response to micro/nanoplastic (MP/NP) exposure at environmentally relevant concentrations. Polystyrene (PS) MPs/NPs with different sizes (0.1, 0.5, and 5.0 µm) were studied for their effects on the homeostasis and function of Nile tilapia (Oreochromis niloticus) liver. Results showed that PS MPs/NPs were readily internalized and accumulated in various internal organs/tissues, especially in fish liver and muscle. Smaller-sized NPs caused more severe toxicity than larger MPs, including hepatic steatosis, inflammatory response, and disturbed liver function. Mechanistically, PS NPs with a particle size of 100 nm perturbed protein homeostasis in the endoplasmic reticulum (ER) by inhibiting the expression of chaperone proteins and genes involved in ER-associated degradation. This led to the activation of the PERK-eIF2α pathway, which caused dysfunction of hepatic lipid metabolism. Induction of oxidative stress and activation of the Nrf2/Keap1 pathway were also involved in the PS NP-induced hepatic lipid accumulation. These findings highlight the potential adverse effects of environmental MPs/NPs on aquatic organisms, raising concerns about their ecotoxicity and food safety.

Zn2+ loading as a critical contributor to the circ_0008553-mediated oxidative stress and inflammation in response to PM2.5 exposures.

Inflammation is a major adverse outcome induced by inhaled particulate matter with a diameter of ≤ 2.5 µm (PM2.5), and a critical trigger of most PM2.5 exposure-associated diseases. However, the key molecular events regulating the PM2.5-induced airway inflammation are yet to be elucidated. Considering the critical role of circular RNAs (circRNAs) in regulating inflammation, we predicted 11 circRNAs that may be involved in the PM2.5-induced airway inflammation using three previously reported miRNAs through the starBase website. A novel circRNA circ_0008553 was identified to be responsible for the PM2.5-activated inflammatory response in human bronchial epithelial cells (16HBE) via inducing oxidative stress. Using a combinatorial model PM2.5 library, we found that the synergistic effect of the insoluble core and loaded Zn2+ ions at environmentally relevant concentrations was the major contributor to the upregulation of circ_0008553 and subsequent induction of oxidative stress and inflammation in response to PM2.5 exposures. Our findings provided new insight into the intervention of PM2.5-induced adverse outcomes.

UVA-LED-Assisted Activation of the Ferrate(VI) Process for Enhanced Micropollutant Degradation: Important Role of Ferrate(IV) and Ferrate(V).

This paper investigated ultraviolet A light-emitting diode (UVA-LED) irradiation to activate Fe(VI) for the degradation of micropollutants (e.g., sulfamethoxazole (SMX), enrofloxacin, and trimethoprim). UVA-LED/Fe(VI) could significantly promote the degradation of micropollutants, with rates that were 2.6-7.2-fold faster than for Fe(VI) alone. Comparatively, UVA-LED alone hardly degraded selected micropollutants. The degradation performance was further evaluated in SMX degradation via different wavelengths (365-405 nm), light intensity, and pH. Increased wavelengths led to linearly decreased SMX degradation rates because Fe(VI) has a lower molar absorption coefficient at higher wavelengths. Higher light intensity caused faster SMX degradation, owing to the enhanced level of reactive species by stronger photolysis of Fe(VI). Significantly, SMX degradation was gradually suppressed from pH 7.0 to 9.0 due to the changing speciation of Fe(VI). Scavenging and probing experiments for identifying oxidative species indicated that high-valent iron species (Fe(V)/Fe(IV)) were responsible for the enhanced degradation. A kinetic model involving target compound (TC) degradation by Fe(VI), Fe(V), and Fe(IV) was employed to fit the TC degradation kinetics by UVA-LED/Fe(VI). The fitted results revealed that Fe(IV) and Fe(V) primarily contributed to TC degradation in this system. In addition, transformation products of SMX degradation by Fe(VI) and UVA-LED/Fe(VI) were identified and the possible pathways included hydroxylation, self-coupling, bond cleavage, and oxidation reactions. Removal of SMX in real water also showed remarkable promotion by UVA-LED/Fe(VI). Overall, these findings could shed light on the understanding and application of UVA-LED/Fe(VI) for eliminating micropollutants in water treatments.

Enhanced Permanganate Activation under UVA-LED Irradiation: Unraveled Mechanism Involving Manganese Species and Hydroxyl Radical.

Permanganate [Mn(VII)] has gained broad attention in water treatment. However, its limited reactivity toward some refractory micropollutants hinders its application for micropollutant degradation. Herein, we introduced UVA-LED photolysis of Mn(VII) (UVA-LED/Mn(VII)) to degrade micropollutants (diclofenac (DCF), 4-chlorophenol (4-CP), atrazine, and nitrobenzene) by selecting DCF and 4-CP as target micropollutants. The effects of operating conditions (e.g., light intensity, radiation wavelengths, pH, and water constituents) on DCF and 4-CP degradation as well as the underlying mechanisms were systematically studied. The degradation rates of DCF and 4-CP linearly decreased with increasing radiation wavelengths (from 365 to 405 nm), likely due to the decreased molar absorption coefficients and quantum yields of Mn(VII). Reactive manganese species (RMnS), including Mn(V), Mn(III), and HO•, were generated in the UVA-LED/Mn(VII) process. Mn(V) and HO• were responsible for DCF degradation, while Mn(III), HO•, and likely Mn(V) accounted for 4-CP degradation. Competitive kinetic results revealed that contributions of RMnS and HO• decreased with increasing radiation wavelengths, wherein RMnS played the dominant role. Increasing pH displayed opposite effects on DCF and 4-CP degradation with higher degradation efficiency obtained at acidic pH for the former one but alkaline pH for the latter one. The presence of water background ions (e.g., Cl-, HCO3-, and Ca2+) barely influenced DCF and 4-CP degradation. Finally, in comparison with Mn(VII) alone, enhanced degradation of DCF and 4-CP by UVA-LED/Mn(VII) was observed in real waters. This work advances the understanding of the photochemistry of manganese species in micropollutant degradation and facilitates Mn(VII) oxidation in practical application.

Biotransformation of bisphenol F by white-rot fungus Phanerochaete sordida YK-624 under non-ligninolytic condition.

Environmental bisphenol F (BPF) has a cyclic endocrine disruption effect, seriously threatening animal and human health. It is frequently detected in environmental samples worldwide. For BPF remediation, biological methods are more environmentally friendly than physicochemical methods. White-rot fungi have been increasingly studied due to their potential capability to degrade environmental pollutants. Phanerochaete sordida YK-624 has been shown to degrade BPF by ligninolytic enzymes under ligninolytic conditions. In the present study, degradation of BPF under non-ligninolytic conditions (no production of ligninolytic enzymes) was investigated. Our results showed that BPF could be completely removed after 7-d incubation. A metabolite of BPF, 4,4'-dihydroxybenzophenone (DHBP) was identified by mass spectrometry and nuclear magnetic resonance, and DHBP was further degraded by this fungus to form 4-hydroxyphenyl 4-hydroxybenzoate (HPHB). DHBP and HPHB were the intermediate metabolites of BPF and would be further degraded by P. sordida YK-624. We also found that cytochrome P450s played an important role in BPF degradation. Additionally, transcriptomic analysis further supported the involvement of these enzymes in the action of BPF degradation. Therefore, BPF is transformed to DHBP and then to HPHB likely oxidized by cytochrome P450s in P. sordida YK-624. Furthermore, the toxicological studies demonstrated that the order of endocrine-disrupting activity for BPF and its metabolites was HPHB > BPF > DHBP. KEY POINTS: • White-rot fungus Phanerochaete sordida YK-624 could degrade BPF. • Cytochrome P450s were involved in the BPF degradation. • The order of endocrine disrupting activity was: HPHB > BPF > DHBP.

Lead Exposure Causes Spinal Curvature during Embryonic Development in Zebrafish.

Lead (Pb) is an important raw material for modern industrial production, they enter the aquatic environment in several ways and cause serious harm to aquatic ecosystems. Lead ions (Pb2+) are highly toxic and can accumulate continuously in organisms. In addition to causing biological deaths, it can also cause neurological damage in vertebrates. Our experiment found that Pb2+ caused decreased survival, delayed hatching, decreased frequency of voluntary movements at 24 hpf, increased heart rate at 48 hpf and increased malformation rate in zebrafish embryos. Among them, the morphology of spinal malformations varied, with 0.4 mg/L Pb2+ causing a dorsal bending of the spine of 72 hpf zebrafish and a ventral bending in 120 hpf zebrafish. It was detected that spinal malformations were mainly caused by Pb2+-induced endoplasmic reticulum stress and apoptosis. The genetic changes in somatic segment development which disrupted developmental polarity as well as osteogenesis, resulting in uneven myotomal development. In contrast, calcium ions can rescue the series of responses induced by lead exposure and reduce the occurrence of spinal curvature. This article proposes new findings of lead pollution toxicity in zebrafish.

A Universal Biofilm Reactor Sensor for the Determination of Biochemical Oxygen Demand of Different Water Areas.

In this study, we developed a simple strategy to prepare a biofilm reactor (BFR) sensor for the universal biochemical oxygen demand (BOD) determination. The microorganisms in fresh water were domesticated by artificial seawater with different salinity gradients successively to prepare the BFR sensor. The prepared BFR sensor exhibits an efficient ability to degrade a variety of organic substances. The linear range of BOD determination by the BFR sensor is 1.0-10.0 mg/L-1 with a correlation coefficient of 0.9951. The detection limit is 0.30 mg/L according to three times of signal-to-noise ratio. What is more, the BFR sensor displayed excellent performances for the BOD determination of different water samples, including both fresh water and seawater. The 16S-rRNA gene sequencing technology was used to analyze the microbial species before and after the domestication. The results show that it is a general approach for the rapid BOD determination in different water samples.

Carbon-nanotube-entangled Co,N-codoped carbon nanocomposite for oxygen reduction reaction.

The design of highly efficient and stable electrocatalysts for oxygen reduction reaction (ORR) is still a great challenge. Herein, we prepared Co,N-codoped carbon nanocomposites (Co@NC-ZM) with entangled carbon nanotubes. The large Brunauer-Emmett-Teller surface area (604.7 m2 g-1), rich mesoporous feature, Co,N doping and synergetic effect between various species of Co@NC-ZM can expose more active sites and facilitate conductivity and mass transport. Benefiting from the above unique advantages, Co@NC-ZM exhibits excellent ORR performance with more positive onset potential (0.96 V) and half-wave potential (0.83 V) than those of commercial Pt/C (0.96 and 0.81 V, correspondingly). This work provides a new strategy for further exploring efficient non-precious-metal-based catalysts for ORR.

Elucidation of the Critical Role of Core Materials in PM2.5-Induced Cytotoxicity by Interrogating Silica- and Carbon-Based Model PM2.5 Particle Libraries.

An insoluble core with adsorbed pollutants constitutes the most toxic part of PM2.5 particles. However, the toxicological difference between carbon and silica cores remains unknown. Here, we employed 32-membered carbon- and silica-based model PM2.5 libraries that each was loaded with four toxic airborne pollutants including Cr(VI), As(III), Pb2+, and BaP in all possible combinations to explore their contributions to cytotoxicity in normal human bronchial cells. The following three crucial findings were revealed: (1) more adsorption of polar pollutants in a silica core (such as Cr(VI), As(III), and Pb2+) and nonpolar ones in a carbon core (such as BaP); (2) about 41% more cell uptake of carbon- than silica-based particles; and (3) about 59% less toxicity in silica- than carbon-based particles when pollutants other than Cr(VI) were loaded. This was reversed after Cr(VI) loading (silica particles were 56% more toxic). The difference maker is that compared to stable silica, carbon particles reduce Cr(VI) to less toxic Cr(III). Our findings highlight the different roles of carbon and silica cores in inducing health risks of PM2.5 particles.

Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles.

Non-alcoholic fatty liver disease (NAFLD), mainly characterized by the accumulation of excess fat in hepatocytes, is the most prevalent liver disorder afflicting ~25% of adults worldwide. In vivo studies have shown that adult rodents with NAFLD were more sensitive to metallic nanoparticles (MNPs) than healthy MNPs. However, due to the complex interactions between various cell types in a fatty liver, it has become a major challenge to reveal the toxic effects of MNPs to specific types of liver cells such as steatotic hepatocytes. In this study, we reported the susceptibility of steatotic hepatocytes in cytotoxicity and the induction of oxidative stress to direct exposures to MNPs with different components (silver, ZrO2, and TiO2 NPs) and sizes (20-30 nm and 125 nm) in an oleic acid (OA) -induced steatotic HepG2 (sHepG2) cell model. Furthermore, the inhibitory potential of MNPs against the process of fatty acid oxidation (FAO) were obvious in sHepG2 cells, even at extremely low doses of 2 or 4 µg/mL, which was not observed in non-steatotic HepG2 (nHepG2) cells. Further experiments on the differential cell uptake of MNPs in nHepG2 and sHepG2 cells demonstrated that the susceptibility of steatotic hepatocytes to MNP exposures was in association with the higher cellular accumulation of MNPs. Overall, our study demonstrated that it is necessary and urgent to take the intracellular exposure dose into consideration when assessing the potential toxicity of environmentally exposed MNPs.

Crossing Biological Barriers by Engineered Nanoparticles.

Engineered nanoparticles (ENPs) may cause toxicity if they cross various biological barriers and are accumulated in vital organs. Which factors affect barrier crossing efficiency of ENPs are crucial to understand. Here, we present strong data showing that various nanoparticles crossed biological barriers to enter vital animal organs and cause toxicity. We also point out that physicochemical properties of ENPs, modifications of ENPs in biofluid, and physiological and pathological conditions of the body all affect barrier crossing efficiency. We also summarized our limited understanding of the related mechanisms. On the basis of this summary, major research gaps and direction of further efforts are then discussed.

Fe/N-doped hollow porous carbon spheres for oxygen reduction reaction.

Herein, we design a dual-template-assisted pyrolysis method to prepare ultra-small Fe3O4 nanoparticles anchored on Fe/N-doped hollow porous carbon spheres (0.010-Fe/NHPCS-800) for oxygen reduction reaction (ORR). The synthesized SiO2 nanospheres, which are selected as the hard template, contribute to forming macroporous structure. Pluronic ® F127 is employed to fabricate mesopores through high-temperature pyrolysis as a soft template. In this way, the 0.010-Fe/NHPCS-800 architecture represents an ordered hierarchically porous property with a large BET surface area (1812 m2 g-1), which can facilitate the mass transport of reactants and increase the electrochemically active area. The Fe3O4 nanoparticles wrapped by graphitic carbon layers provide more active sites, and the synergistic interaction between Fe3O4 nanoparticles and doping N has a positive effect on ORR performance. The 0.010-Fe/NHPCS-800 catalyst outperforms the most effective ORR activities among a series of Fe/NHPCS samples with onset potential of 0.95 V (versus reversible hydrogen potential) and half-wave potential of 0.81 V, which is almost the same as the commercial Pt/C (0.96 and 0.81 V, correspondingly) in 0.10 M KOH. However, both the stability and durability of 0.010-Fe/NHPCS-800 surpass those of commercial Pt/C. Given all these advantages, 0.010-Fe/NHPCS-800 is a promising candidate to take the place of Pt-based electrocatalysts for ORR in the future.

Oral Co-Exposures to zinc oxide nanoparticles and CdCl2 induced maternal-fetal pollutant transfer and embryotoxicity by damaging placental barriers.

Synergistic toxicity from multiple environmental pollutants poses greater threat to humans, especially to susceptible pregnant population. Here we evaluated combined toxicity from environment pollutants zinc oxide nanoparticles (ZnO NPs) and cadmium chloride (CdCl2) using two pregnant mice models established by oral administration during peri-implantation or organogenesis period. We found that exposures to combined pollutants only at organogenesis stage induced higher fetal deformity rate compared to co-exposures at peri-implantation stage. We further discovered that surface charge of ZnO NPs were modified after Cd2+ adsorption and the resulting nanoadducts caused more severe damages in placental barriers by causing shed endothelial cells and decreased expressions of tight junction proteins ZO1, occludin, claudin-4 and claudin-8. These cellular and molecular events enhanced maternal-fetal transfer of both pollutants and aggravated embryotoxicity. Our findings help elucidate synergistic embryotoxicity by nanoparticle/pollutant adducts and establish proper safety criteria for pregnant population in an era that nanotechnology-based products are widely used.

miR-21 and miR-19b delivered by hMSC-derived EVs regulate the apoptosis and differentiation of neurons in patients with spinal cord injury.

BACKGROUND: In this study, we aimed to evaluate the therapeutic effects of extracellular vesicles (EVs), which were collected from differentiated PC12 cells and mesenchymal cells (MSCs), on the treatment of spinal cord injury (SCI). In addition, we aimed to identify miRNAs related to the inhibitory effect of EVs against cell apoptosis. METHODS: Electron microscopy was used to observe the distributions of EVs in the samples. Real-time PCR, western blot, thiazolyl blue tetrazolium bromide (MTT) assay, and flow cytometry were performed to establish the molecular signaling pathway underlying the effect of EVs in SCI. In addition, a Basso-Beattie-Bresnahan (BBB) score system, Nissl staining, immunohistochemistry assay, and TdT-mediated dUTP nick-end labeling (TUNEL) assay were conducted to validate the molecular signaling pathway established above. RESULTS: The expression of miR-21 and miR-19b was upregulated in EVs isolated from induced PC12 cells and MSCs, along with decreased expression of phosphatase and tensin homolog (PTEN) messenger RNA (mRNA)/protein and a lower level of cell apoptosis. The transfection of miR-21/miR-19b precursors into the cells also exhibited an inhibitory effect on cell apoptosis. In addition, in-silicon analysis and luciferase assays validated the role of PTEN as a virtual target of miR-21/miR-19b. Finally, the BBB scores and Nissl staining also validated the therapeutic effects of EVs derived from differentiated P12 cells/MSCs in SCI rats. Accordingly, the negative correlations between miR-21/miR-19b and PTEN mRNA/protein were implicated in the post-SCI recovery. CONCLUSIONS: The increased levels of miR-21/miR-19b in the EVs derived from differentiated PC12 cells and MSCs suppresses the apoptosis of neuron cells by downregulating the expression of PTEN.

Cobalt sulfide/N,S-codoped defect-rich carbon nanotubes hybrid as an excellent bi-functional oxygen electrocatalyst.

The design of high-efficient and durable bi-functional oxygen electrocatalysts is still a great challenge. In this work, novel Co9S8 nanoparticles/N,S-codoped defect-rich carbon nanotubes (Co9S8/N,S-CNTs) were fabricated by an ingenious template method. CdS nanowires, as a sacrificial template, can be removed simultaneously during the carbonization process without additional post-treatments. The large BET surface area (661.2 m2 g-1) and pore volume (1.49 cm3 g-1) of Co9S8/N,S-CNTs could largely enhance the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities by facilitating the mass transportation and exposing more active sites. The abundant defects produced by the evaporation of Cd and S doping could provide more active sites for ORR and OER. Coupling with Co9S8, Co9S8/N,S-CNTs possesses more defects in the carbon skeleton, better electron conductivity, and larger effective electrochemical area. Co9S8/N,S-CNTs not only performs excellent ORR activity with a half-wave potential of 0.821 V but also owns RuO2-like OER activity in alkaline solution. The potential difference (ΔE) between ORR and OER is as low as 0.78 V in 0.10 M KOH. The excellent bi-functional performance enables the potential to be utilized in fuel cells and metal-air batteries.

New insights into the effect of pH on the mechanism of ofloxacin electrochemical detection in aqueous solution.

Antibiotic contamination in water has become an increasingly serious problem that poses a potentially huge threat to human health. Ofloxacin (OFL) is a typical broad-spectrum quinolone antibiotic and is frequently detected in a wide variety of aquatic environments. Given its frequent contamination, the need for new electrochemical sensors to quickly and efficiently detect OFL in aquatic environments has attracted increasing attention. Solution pH is an important factor affecting the performance of electrochemical sensors. This work investigates OFL detection using graphene/glassy carbon electrodes (Gr/GCE) in phosphate-buffered saline across a range of pH (3-8). The molecular polarity analysis method was first used to reveal interactions between target contaminants and the electrode interface. The electrode properties and the polarity of OFL were studied using SEM, XPS, FT-IR spectrometry, zeta potentiometry and modelling calculation of molecular properties. Our results showed that OFL interacts with the surface of Gr/GCE via both hydrogen bonding and coulomb electrostatic forces. The electrical signal decreased more quickly in an alkaline than acidic environment, which was due to the differences between coulomb electrostatic and hydrogen bonding forces. These results also showed variations in the OFL peak current response under different pH conditions. Collectively, these findings provide a better foundation for the rapid identification of the optimal pH environment for the electrical analysis of contaminants like antibiotics in an aquatic environment.

Size-dependent maternal-fetal transfer and fetal developmental toxicity of ZnO nanoparticles after oral exposures in pregnant mice.

The widespread application of nanomaterial-based products has caused safety concerns worldwide, especially for susceptible pregnant population. Here, we revealed the effect of the size of ZnO nanoparticles (ZnO NPs) on placental and fetal developmental toxicities. We found that smaller ZnO NPs (13 nm) were able to cross both the intestinal barrier and the placental barrier to reach the fetus after oral exposure and caused fetal developmental toxicity. However, larger ZnO NPs (57 nm) and bulk ZnO particles were not able to cross these barriers and exert effects. We also discovered that the organogenesis period (GD7-GD16) was more vulnerable to such toxicity compared with the peri-implantation period (GD1-GD10) of pregnancy. This new understanding that smaller nanoparticles may pass through multiple biological barriers to induce toxicity in susceptible populations is crucial for the safeguarding of humans from the widespread application of nanoproducts. The discovery that the organogenesis stage in pregnancy is more vulnerable to nanotoxicity than the peri-implantation stage is provides valuable guidance for an improved protection strategy.

Cr(VI)/Pb2+ are responsible for PM2.5-induced cytotoxicity in A549 cells while pulmonary surfactant alleviates such toxicity.

The composition of PM2.5 is extremely complicated, making the causes of PM2.5-induced toxicity hard to understand. To identify the major toxic components of PM2.5 particles, we used reductionism approach, synthesized and investigated a model PM2.5 library containing 24 carbon nanoparticles with adsorbed pollutants including Cr(VI), Pb2+, As(III) and BaP either individually or in combinations. Our data showed that major physicochemical characteristics of model PM2.5 library members were similar to PM2.5 particles from Guangzhou city (PM2.5-GZ). Cytotoxicity of lung cells (A549) was increasing as the member of adsorbed pollutants at environment relevant concentrations. Using these model particles, we identified that co-existence of Cr(VI) and Pb2+ components contributed to the PM2.5-induced cytotoxicity in A549 cells. Besides, pulmonary surfactant reduced the PM2.5-induced cytotoxicity in A549 cells probably via enhancing cell autophagy. The findings from this study suggest that systematic investigation using model PM2.5 particle library helps identify key toxic pollutants in otherwise very complex PM2.5 particles and facilitate our understanding of the underlying biological mechanisms.