Carbon dots (CDs) are photoluminescent nanomaterials with wide-ranging applications. Despite their photoactivity, it remains unknown whether CDs degrade under illumination and whether such ...photodegradation poses any cytotoxic effects. Here, we show laboratory-synthesized CDs irradiated with light degrade into molecules that are toxic to both normal (HEK-293) and cancerous (HeLa and HepG2) human cells. Eight days of irradiation photolyzes 28.6-59.8% of the CDs to <3 kilo Dalton molecules, 1431 of which are detected by high-throughput, non-target high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Molecular network and community analysis further reveal 499 cytotoxicity-related molecules, 212 of which contain polyethylene glycol, glucose, or benzene-related structures. Photo-induced production of hydroxyl and alkyl radicals play important roles in CD degradation as affected by temperature, pH, light intensity and wavelength. Commercial CDs show similar photodegraded products and cytotoxicity profiles, demonstrating that photodegradation-induced cytotoxicity is likely common to CDs regardless of their chemical composition. Our results highlight the importance of light in cytocompatibility studies of CDs.
This review evaluates the three dynamic models (biokinetic model: BK, physiologically based pharmacokinetic model: PBPK, and toxicokinetic-toxicodynamic model: TKTD) in our understanding of the key ...questions in metal ecotoxicology in aquatic systems, i.e., bioaccumulation, transport and toxicity. All the models rely on the first-order kinetics principle of metal uptake and elimination. The BK model basically treats organisms as a single compartment, and is both physiologically and geochemically based. With a good understanding of each kinetic parameter, bioaccumulation of metals in any aquatic organisms can be studied holistically and mechanistically. Modeling efforts are not merely restrained from the prediction of metal accumulation in the tissues, but instead provide the direction of the key processes that need to be addressed. PBPK is more physiologically based since it mainly addresses the transportation, transformation and distribution of metals in the organisms. It can be treated conceptually as a multi-compartmental kinetic model, whereas the physiology is driving the development of any good PBPK model which is no generic for aquatic animals and contaminants. There are now increasingly applications of the PBPK modeling specifically in metal studies, which reveal many important processes that are impossible to be teased out by direct experimental measurements without adequate modeling. TKTD models further focus on metal toxicity in addition to metal bioaccumulation. The TK part links exposure and bioaccumulation, while the TD part links bioaccumulation and toxic effects. The separation of TK and TD makes it possible to model processes, e.g., toxicity modification by environmental factors, interaction between different metals, at both the toxicokinetic and toxicodynamic levels. TKTD models provide a framework for making full use of metal toxicity data, and thus provide more information for environmental risk assessments. Overall, the three models reviewed here will continue to provide guiding principles in our further studies of metal bioaccumulation and toxicity in aquatic organisms.
•Three models of metal bioaccumulation in aquatic animals are reviewed.•Modeling provide the direction of the key processes that need to be addressed.•A greater effort is needed to understand the ecotoxicological significance of the key parameters in the model.
Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported ...that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear.
We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing.
We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models.
Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.
The ubiquity of microplastics in the environment has attracted much attention on their risks. Though newly produced plastics were considered inert to aqueous metals, a few studies suggest aged ...microplastics can accumulate metals. Still, knowledge gap exists on the comparability of metal accumulation in field condition and that acquired in controlled laboratory settings. Accordingly, we comparatively assessed the field accumulation and laboratory adsorption of metals on aged microplastics in coastal waters. Microplastics of different polymeric types were aged for 8 weeks at three coastal sites with different contamination levels. Microplastics accumulated metals to substantial concentrations during ageing (median concentrations, μg g−1: Fe = 950, Mn = 94, Zn = 19, Cu = 2.8, Ni = 1.7, Pb = 1.6, and Cd = 0.005). Adsorption capacity of (aged) microplastics was evaluated in laboratory using a stable isotope tracer method. At environmentally realistic concentrations (μg L−1, 114Cd = 1.7, 65Cu = 4.4, 62Ni = 5.4, 206Pb = 0.5, and 68Zn = 13), the median concentrations of newly adsorbed isotopes on the aged microplastics were 0.01, 1.4, 0.07, 0.56, and 1.1 μg g−1, respectively, one to two orders of magnitude higher than those adsorbed on pristine microplastics. However, the composition pattern of metals accumulated on aged microplastics differed from the composition of metals newly adsorbed in laboratory: the prior one reflected the contamination status of ageing sites and varied by polymeric types; whereas the laboratory newly adsorbed metals on aged microplastics were uniformly correlated to particulate Fe and Mn concentrations, suggesting Fe and Mn mineral coatings mediated the ensuing metal adsorption. Such discrepancy unveiled the complexity of metal accumulation behavior in the real environment and highlighted that cares should be taken when translating laboratory findings to risk assessment of metal contaminated microplastics in the real environment.
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•Ageing in coastal waters elevates metal adsorption capacity of microplastics.•Metals accumulated in the field reflect metal contamination of the ageing sites.•Metals accumulated in the field are affected by polymeric types.•Lab adsorption of metals on aged microplastics is mediated by Fe/Mn oxide coatings.
Salinity has considerable effects on the toxicity of metals in estuarine waters. The effects of salinity are manifold, making it difficult to summarize for risk assessments. In this study, we ...separated and quantified the multiple effects of salinity on cadmium (Cd) in a toxicokinetic–toxicodynamic framework. The estuarine clam, Potamocorbula laevis, was used as a model organism. Cd bioaccumulation was measured using a stable-isotope-tracer technique; in parallel, toxicity tests were conducted. With the increase of salinity from 5 to 30, Cd uptake decreased monotonically. In contrast, the intrinsic sensitivity of organisms, measured by the toxicodynamic parameters, reached its minimum at intermediate salinities (i.e., 10 to 20). The overall salinity effects were dominated by the effects on Cd bioaccumulation; therefore, Cd toxicity decreased monotonically with the increases of salinity. The model developed in this study could provide predictions of no-effect concentration (1.7 to 34.9 μg L–1, end point mortality) and the median lethal concentration (LC50) of Cd at different salinities. In conclusion, we developed a framework for quantifying the multiple effects of salinity and a method for estimating no-effect concentration from acute toxicity tests, which can be used for better assessments of metal risks in estuarine waters.
In coastal waters, particulate metals constitute a substantial fraction of the total metals; however, the prevalent water quality criteria are primarily based on dissolved metals, seemingly ...neglecting the contribution of particulate metals. Here we developed a method to quantify the toxicity risk of particulate metals, and proposed a way to calculate modifying factors (MFs) for setting site-specific criteria in turbid waters. Specifically, we used a side-by-side experimental design to study copper (Cu) bioaccumulation and toxicity in an estuarine clam, Potamocorbula laevis, under the exposure to “dissolved only” and “dissolved + particulate” 65Cu. A toxicokinetic-toxicodynamic model (TK-TD) was used to quantify the processes of Cu uptake, ingestion, assimilation, egestion, and elimination, and to relate mortality risk to tissue Cu. We find that particulate Cu contributes 40–67% of the Cu bioaccumulation when the suspended particulate matter (SPM) ranges from 12 to 229 mg L–1. The Cu-bearing SPM also increases the sensitivity of organisms to internalized Cu by decreasing the internal threshold concentration (C IT) from 141 to 76.8 μg g–1. MFs were derived based on the TK-TD model to consider the contribution of particulate Cu (in the studied SPM range) for increasing Cu bioaccumulation (MF = 1.3–2.2) and toxicity (MF = 2.3–3.9). Water quality criteria derived from dissolved metal exposure need to be lowered by dividing by an MF to provide adequate protection. Overall, the method we developed provides a scientifically sound framework to manage the risks of metals in turbid waters.
The citizen-science-based environmental survey can benefit from the smartphone technology used in chemical and biological sensing of a wide range of analytes. Quantification by smartphone-based ...colorimetric assays is being increasingly reported, however, most of the quantification uses empirical formula or complex exhaustive methods. In this study, a versatile and robust algorithm is proposed to overcome these limitations. A model is established to simulate and analyze the conversion process from the camera's spectral information into RGB (Red, Green, Blue) color information. Moreover, the feasibility of the algorithm for the quantification of different analytes is also explored. Based on this algorithm, a versatile smartphone-based environmental analyzer (vSEA) is built and its reliability, versatility, and analytical performance are comprehensively optimized. The good linearity (R2 ≥ 0.9954) and precision (relative standard deviations < 5.3%) indicates that the vSEA is accurate enough to quantify the nutrients in most natural waters. Furthermore, the vSEA is used for the field measurement of five important nutrients, and the results show no significant difference compared to conventional methods. The vSEA offers a simpler and easier method for the on-site measurement of nutrients in natural water bodies, which can aid in the emergency monitoring of aqueous ecosystems and the performance of citizen-science-based research.
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•A universal and practical algorithm for smartphone-based colorimetric detection•A model for simulating and conversion process from camera's spectral information into RGB•A versatile smartphone-based environmental analyzer (vSEA) for on-site detection•Field detection of five nutrients with excellent accuracy
Interindividual variabilities in metal bioaccumulation confound our interpretation of the biomonitoring data. Measuring metal toxicokinetics in organism “individuals” may provide insights into the ...processes underlying the variabilities. Therefore, we developed a double stable isotope method that can simultaneously measure uptake and elimination of metals in individual organisms and thus the distribution of the toxicokinetic parameters. Specifically, we exposed organisms to both isotopes (113Cd and 114Cd; Cd = cadmium) during the first stage and to only one isotope (114Cd) during the second stage. Metal uptake and elimination rate constants (i.e., k u and k e) were simultaneously estimated from the content of the two isotopes measured in each organism at the end of the second stage. We applied the method to investigate the interindividual variability in Cd concentrations caused by body size in two marine mussel species. Cd concentrations are higher in larger Xenostrobus atratus but lower in smaller Perna viridis. Size-dependent Cd uptake is found to be responsible for size effects on Cd concentrations in the mussels and the interspecies differences in the relationship between Cd concentration and body size. Specifically, Cd k u increases with size in X. atratus (0.057–0.297 L g–1 d–1) but decreases with size in P. viridis (0.155–0.351 L g–1 d–1). In contrast, Cd k e is not influenced by body size (X. atratus: 0.002–0.060 d–1; P. viridis: 0.008–0.060 d–1). Overall, we extended the applicability of the stable isotope methods to measure metal toxicokinetics in “individual” organisms, providing a readily available tool for investigating problems related to metal bioaccumulation.
The applicability of the biotic ligand model (BLM) was tested with respect to the biouptake of the lanthanide Sm by the freshwater green alga, Chlamydomonas reinhardtii. In the absence of organic ...ligands, Sm uptake was well described by the Michaelis-Menten equation, consistent with the BLM assumption of single transporter, with the maximum influx rate (Jmax) of 1.5 × 10−14 mol cm−2 s−1 and a binding constant (KSm) of 107.0 M−1. The addition of organic ligands (i.e., malic acid, diglycolic acid and citric acid) decreased Sm influx rates, however, the decreases were much less than that predicted by the BLM, possibly due to the direct contribution of the Sm complexes. Competition effects of two major cations (Ca2+ and Mg2+) and three lanthanide cations (La3+, Ce3+ and Eu3+) were successfully modeled by the BLM, with binding constants corresponding to KCa = 104.0 M−1, KMg = 102.7 M−1, KLa = 106.8 M−1, KCe = 106.9 M−1 and KEu = 107.0 M−1. The binding constants and Jmax were very similar among the four investigated lanthanides and varied progressively with atomic number; therefore, the results obtained in the present study can probably be extrapolated to other rare earth metals.
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•A biotic ligand model is developed for quantifying Sm biouptake by a green alga.•Lanthanides have similar affinity constants for binding to transport sites.•Different lanthanides probably share the same transport site into the alga.•Organic complexes of Sm are likely bioavailable to the alga.
In estuaries, salinity fluctuates rapidly and continuously, greatly affecting the bioavailability and thus toxicity of contaminants, especially metals, causing difficulties in deriving site-specific ...water quality criteria. We developed a method for predicting the toxicity of the metal cadmium (Cd) in estuarine waters of any salinity fluctuation scenario. Cd bioaccumulation and toxicity were measured in an estuarine clam Potamocorbula laevis under stable salinities (salinity = 5, 15, 25) and fluctuating salinities (5–25), using the toxicokinetic–toxicodynamic (TK–TD) framework. Cd bioaccumulation decreases with increasing salinity; whereas intrinsic Cd sensitivity of organisms reaches the minimum at an intermediate salinity around 20. At each specific Cd level, interpolating TK–TD parameters measured at the stable salinities well predicts the Cd bioaccumulation and toxicity under fluctuating salinities. To extend the model for various Cd levels, the biotic ligand model (BLM) was integrated into the TK–TD framework. The BLM-based TK–TD model was successfully applied to scenarios of simulated and monitored salinity fluctuations in estuarine waters, for which the median lethal concentrations and no-effect concentrations (2.0–3.1 μg L–1) of Cd were derived. Overall, we integrated the BLM and TK–TD models and provided a useful tool for predicting metal risks and deriving criteria values for salinity-fluctuating estuarine waters.
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