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As modal parameters are the essential features of structural operational condition, the automated structural modal identification technique is currently driving a strong interest in the field of vibration-based structural health monitoring (SHM). This task is highly judgmental, with user expertise playing an important role as to which estimated mode is being selected. To simplify the identification procedure and improve the identification accuracy, this paper presents an innovative stabilization diagram for operational modal analysis (OMA) based on Natural excitation technique (NExT)/eigensytem realization algorithm (ERA) and hierarchical cluster analysis. It consists of three key steps: (1) Physical modes are filtered preliminarily by a novel distance index based on output matrix from Consistent Mode Indicator (CMI_O); (2) Hierarchical clustering analysis is developed for automatic interpretation of the traditional stabilization diagram; (3) Thompson-Tau technique and a regrouping procedure are introduced for further screening outliers to improving the identification accuracy. Numerically generated data, experimental data obtained from a four-layer structure in the lab and field monitored data from a super high-rise structure are used to verify the applicability and reliability of the proposed method. The results show that the proposed method is able to identify physical modes in high accuracy even with noise interference, enabling the detection of good flexibility and practicability. Furthermore, none of user-defined parameter and less expert experience is demanded for the improved method.

To accurately understand the biological pollution level and toxicity of polydisperse nanoplastics, an effective solution is presented to separate polydisperse nanoplastics and detect their size, mass and number concentration in a biological matrix by asymmetrical flow field fractionation coupled with a diode array detector and a multiangle light scattering detector.

Background This study discusses the effectiveness of artificial intelligence in one-to-one psychological intervention system for middle school students. The purpose of this study is to determine whether middle school students have enough trust in AI machines, to explore their internal psychology, and to evaluate the intervention effect of AI in middle school students' one-to-one psychological intervention system. Subjects and Methods 76 eighth grade students from two parallel classes in the same grade were randomly assigned to the same teacher. The research tools used include two sets of autonomic nerve detectors produced by South Korean medicore company and two sets of self-developed artificial intelligence one-to-one psychological intervention systems, including two artificial intelligence robots Xiaoxin and two emotional bracelets. 36 students in the intervention group received one-on-one intervention of artificial intelligence robot Xiaoxin, and t-test was conducted on physical stress, psychological stress, stress index, sympathetic nerve activity, stress resistance and average heart rate. Test participants can effectively alleviate psychological stress and prevent depression. The data showed that the DASS-21 comprehensive score of subjects participating in the test was 1.7 times that of subjects not participating in the test. In contrast, without participation, they are more likely to show depression, anxiety and stress, and tend to be passive in simple coping styles. The improved method can effectively alleviate the psychological pressure of employees and improve the ability to actively deal with pressure. Results Except for the four indexes of nerve stress and sympathetic nerve activity, P < 0.001. After the intervention, the average heart rate, physical stress and stress index decreased significantly, while the anti stress ability increased significantly. Statistical analysis shows that the one-to-one intervention of artificial intelligence robot Xiaoxin can effectively alleviate students' physical stress and stress index, and improve students' stress resistance. The intermediary effect analysis of emotional arousal found that the direct effect of anger on MCT fluency was significant, B = 3.80, P < 0.001, CI = [1.99, 5.62], and the indirect effect of arousal on MCT fluency was significant, B = 0.58, CI = [0.08, 1.66]; The direct effect of anger on MCT anger was significant, B = 6.08, P < 0.001, CI = [3.26, 8.89], and the indirect effect of arousal on MCT anger was significant, B = 0.80, CI = [0.08, 2.41]; The direct effect of anger on MCT harmfulness was significant, B = 0.42, P = 0.004, CI = [0.14, 0.69], and the indirect effect of arousal on MCT harmfulness was not significant, B = 0.03, CI = [− 0.03, 0.18]. The direct effect of anger on aut fluency was significant, B = 2.58, P = 0.032, CI = [0.23, 4.92], and the indirect effect of arousal on aut fluency was significant, B = 1.22, CI = [0.27, 2.62]); The direct effect of anger on aut novelty was significant, B = 4.60, P = 0.008, CI = [1.23, 7.96], and the indirect effect of arousal on aut novelty was significant, B = 1.79, CI = [0.42, 3.91] (see Figure 4D). The above results show that emotional arousal plays a partial mediating role in the influence of anger on the fluency and novelty of malicious creativity and general creativity, but it has no mediating role in the influence of anger on the harmfulness of malicious creativity. Conclusion Artificial intelligence one-to-one psychological intervention system is effective. Among the 38 students in the intervention group, this shows that most students have a high sense of trust in the artificial intelligence robot Xiaoxin. This sense of trust is enough to make the artificial intelligence one-to-one psychological intervention system play the role of psychological intervention. We should fully understand the important position of artificial intelligence robot in emotional factors, actively improve its role psychological ability, pay special attention to its impact on life attitude and healthy behavior, and be a healthy self-manager, coordinator and collaborator. According to the psychological characteristics of these groups, we should actively and flexibly organize colorful activities, strive to create a relaxed and harmonious living atmosphere, create a friendly and mutually beneficial emotional artificial intelligence relationship, encourage and guide these groups, adjust their psychology to the best state, and promote the healthy development of their good cognition and life.

Background Quantum dots (QDs) have gained increased attention for their extensive biomedical and electronic products applications. Due to the high priority of QDs in contacting the circulatory system, understanding the hemocompatibility of QDs is one of the most important aspects for their biosafety evaluation. Thus far, the effect of QDs on coagulation balance haven’t been fully understood, and limited studies also have yet elucidated the potential mechanism from the perspective of interaction of QDs with coagulation-related proteins. Results QDs induced the derangement of coagulation balance by prolonging the activated partial thromboplastin time and prothrombin time as well as changing the expression levels of coagulation and fibrinolytic factors. The contact of QDs with PTM (prothrombin), PLG (plasminogen) and FIB (fibrinogen) which are primary coagulation-related proteins in the coagulation and fibrinolysis systems formed QDs-protein conjugates through hydrogen-bonding and hydrophobic interaction. The affinity of proteins with QDs followed the order of PTM > PLG > FIB, and was larger with CdTe/ZnS QDs than CdTe QDs. Binding with QDs not only induced static fluorescence quenching of PTM, PLG and FIB, but also altered their conformational structures. The binding of QDs to the active sites of PTM, PLG and FIB may promote the activation of proteins, thus interfering the hemostasis and fibrinolysis processes. Conclusions The interactions of QDs with PTM, PLG and FIB may be key contributors for interference of coagulation balance, that is helpful to achieve a reliable and comprehensive evaluation on the potential biological influence of QDs from the molecular level.

Monitoring the level of exchangeable copper (CuEXC) and ceruloplasmin (Cp) in serum is of great significance for Wilson’s disease (WD). In this work, a facile one-step competitive immunoassay for rapid and simultaneous detection of CuEXC and Cp has been developed based on antigens coated magnetic nanoparticles (immuno-MNPs) and antibodies functionalized quantum dots (QDs-Abs). Just by mixing immuno-MNPs, with diluted serum and QDs-Abs together, the antigens on immuno-MNPs compete with the target in serum and bind to QDs-Abs, thereby causing the changes in fluorescence intensity of QDs. Under selected conditions, this one-step method exhibited excellent precision and selectivity with the measured limit of detection of 0.2 nM and 7.0 μg/L for CuEXC and Cp, respectively. Most importantly, this method was successfully applied to detect CuEXC and Cp without the usual time-consuming pretreatment. The results showed no significant difference (P>0.01) from those of ICP-AES and ELISA; moreover, CuEXC significantly decreased to a normal level after the treatment of preliminarily diagnosed WD patients, while the changes of Cp level is not significant (P > 0.01). Therefore, the proposed one-step competitive immunoassay has great potential applications in the rapid laboratory diagnosis of WD with distinct advantages over the existing methods in terms of multi-target, accuracy, facile, fast and cost-effectiveness.

Perioperative neurocognitive dysfunction (PND) is a prevalent neurological complication after anesthesia and surgery. Ginkgolide B (GB) has been suggested to improve lipopolysaccharide‑induced learning and memory impairment. The present study aimed to investigate whether GB serves a protective role against PND by inhibiting inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Abdominal surgery was performed on 10‑ to 12‑week‑old male C57BL/6 mice under isoflurane anesthesia. Prior to surgery, 1400W (a specific iNOS inhibitor) and GB were administered via intraperitoneal injection. Open field and fear conditioning tests were conducted to assess cognitive function on postoperative days 1 and 3. Biochemical assays were performed to evaluate alterations in NO, malondialdehyde (MDA) and superoxide dismutase (SOD) levels. Western blotting was performed to measure iNOS expression in the hippocampus on postoperative day 1. In addition, hematoxylin and eosin staining was performed to detect the neuronal morphology in the hippocampus. Following treatment with 1400W or GB, surgery‑induced cognitive dysfunction was improved. Compared with the control group, the surgery group exhibited significant overproduction of iNOS and MDA in the hippocampus on postoperative day 1. Higher levels of NO were also detected in the hippocampus and prefrontal cortex of the surgery group on postoperative day 1. Furthermore, pretreatment with 1400W or GB significantly inhibited the surgery‑induced elevation of NO and MDA in brain tissues. Moreover, GB pretreatment significantly inhibited surgery‑induced downregulation of SOD and upregulation of iNOS. Surgery‑induced increases in neuronal loss and the Bax/Bcl‑2 ratio in the hippocampus were significantly inhibited by pretreatment with GB. Collectively, the results of the present study demonstrated that the therapeutic effects of GB on PND were associated with inhibition of iNOS‑induced NO production, increased SOD, and the alleviation of neuronal loss and apoptosis.

At present, PM

Objective: Quantum dots (QDs) has widely applied in the field of science, whose potential toxic effect has increasingly become a focus concern we need pay attention to in public health. The purpose of this article was to explore the toxicity mechanism with oxidative damage from treatment with QDs at the molecular level through a gene microarray. Methods: Mice were administered aqueously synthesized cadmium telluride QDs (CdTe aqQDs) via intravenous tail injection of a 2 µmol/kg solution (based on the molar mass of Cd), and their kidneys were collected at 1 day in strict accordance with the programs used for treated mice. We determined the hierarchical clustering of expression ratios, enriched gene ontology (GO) terms and signaling pathways through gene microarray analysis and bioinformatics analysis in kidney tissue and screened the key enzyme genes, which were verified by real-time quantitative polymerase chain reaction (real-time qPCR). Results: Compared to control group, 459 lncRNAs (197 down-regulated and 262 up-regulated) and 256 mRNAs (103 down-regulated and 153 up-regulated) were differentially expressed. According to biological processes in enriched GO terms, the response to a redox state played a significant role in the biological processes involved altered genes. Pathway analysis showed that the signaling pathways that involved cytochrome P450 (CYP450) enzymes had a close relationship with QDs. Among these signaling pathways, gene expression profiling revealed that selected differentially expressed mRNAs (CYP19A1, CYP1B1, CYP11A1, CYP11B2, and CYP17A1 in the kidney and CYP19A1 and CYP1B1 in the liver) were validated by real-time qPCR, resulting in expression levels of CYP11A1, CYP11B2 and CYP17A1 in the kidney and CYP19A1 and CYP1B1 in the liver that were significantly increased, however in expression levels of CYP19A1 and CYP1B1 compared with control group in the kidney, there was no significant difference. Conclusions: Our results provide a foundation for and potential insight into the role of CYP450-related genes in QD-induced oxidative stress. QDs may produce a great deal of reactive oxygen species (ROS) by promoting high expression of CYP450 enzymes and accumulating steroid hormones, which may be an important toxicity mechanism for mediating oxidative stress and tissue damage.

Monitoring copper (Cu) species in bio-samples is critical for the investigation and auxiliary diagnosis of Cu-metabolism disorders. Herein, a target-triggered DNAzyme walker, consisting of Carboxyfluorescein (FAM)-labeled substrates of the Cu-DNAzyme (Cu-Sub) coated gold nanoparticles (AuNPs) (AuNPs@FAM-Cu-Sub track) and the enzyme chain of the Cu-DNAzyme (Cu-Enzy) functionalized magnetic beads (MBs@Cu-Enzy 3D walking unit), was designed for the sensitive detection of copper species. Upon addition of copper ion (Cu2+), DNAzyme was activated and triggered the walking process, thereby releasing FAM-labeled fragments and recovering fluorescence. When compared with free-running Cu-Enzy or co-conjugated Cu-Enzy on AuNPs walking units, the MBs@Cu-Enzy walking unit exhibited a higher cleavage efficiency, shorter detection time (40 min), and a lower limit of detection (LOD = 3 nM). This improved performance was mainly attributed to multivalent interactions between the 3D track and the 3D walking unit which dramatically increased the affinity and cleavage efficiency. Importantly, good accuracy was observed for copper species analysis in clinical serum samples (n = 130), relative to other instrumentation, inductively coupled plasma atomic emission spectrometry (ICP-AES) (P > 0.01). The serum detection data indicated that total, exchangeable and relative exchangeable Cu variables could serve as potential indicators for the auxiliary diagnosis of Cu-related disorders. Thus, our target-triggered DNAzyme walker provides improved technical support for the in-depth study of clinical Cu metabolic-related diseases.

Convenient and rapid detection of Cu2+ in serum has important clinical significance for related diseases. Herein, a ratiometric detection of Cu2+ based on specific short peptide (SPGH)-assisted enhanced chemiluminescence resonance energy transfer (CRET) has been constructed. An interesting phenomenon that tetra-peptide with the sequence of Ser-Pro-Gly-His (SPGH) was able to specifically and remarkably enhance the catalytic performance of Cu2+ has been discovered, the enhancement mechanism is mainly due to the significant increasing generation of Cu2+-induced hydroxyl radical after addition of SPGH. The chemiluminescence (CL) of the luminol-H2O2 system was efficiently catalyzed by the formed Cu(SPGH)2 complex, which acts as an internal light source to triggers on the fluorescence of QDs via CRET, allowing the ratiometric detection of Cu2+ within 15 min with improved selectivity and sensitivity. The relative standard deviation was lower than 6.38 % due to the ratiometric signal improving its anti-interference ability. Importantly, it is feasible to detect total Cu in human serum, and the results were consistent with that of ICP-AES (r = 0.9321, n=55). The reliable, rapid, yet simple ratiometric detection of Cu2+ in serum based on SPGH-assisted enhanced CRET provides a promising potential alternative method for Cu2+ detection in clinical application.

At present, PM2.5 exposure has been considered as a major risk factor for cardiovascular disease. Most studies have focused on the toxic mechanism of PM2.5 in direct contact with cells or biomolecules, only few studies have reported the toxic mechanism of PM2.5 mediated by intercellular communication. Extracellular vesicles are the main carriers of intercellular communication and signal transduction in vivo, and play a vital role in the occurrence and development of cardiovascular disease. Therefore, the present research aimed to determine whether platelets-derived extracellular vesicles (P-EVs) secreted from PM2.5-exposed platelets are transferred into the human umbilical vein endothelial cells (HUVECs) and mediated the PM2.5-induced vascular endothelial injury by affecting normal cellular function. The result showed that P-EVs secreted from PM2.5-exposed platelets significantly reduced the proliferation promoting effect of normal P-EVs on vascular endothelium by decreasing the effective factors promoting vascular endothelial growth. Meanwhile, the levels of intercellular adhesion molecules, proinflammatory factors (ICAM-1, IL-6, and TNF-α) and the ROS level of HUVECs were markedly elevated. In addition, the apoptotic rate was increased via up-regulating the protein level of cytochrome-C(Cyt C), Bax, cleaved caspase-3 and down-regulating Bcl-2 in HUVECs, indicating that mitochondrial apoptotic pathway was activated by P-EVs secreted from PM2.5-exposed platelets. Further, the expression level of P-EVs targeted miRNAs in HUVECs was altered, indicating that miRNAs released from P-EVs were transferred to HUVECs and regulated the cellular function, while PM2.5 could inhibit this regulatory effect. In summary, these results demonstrate that the P-EVs secreted from PM2.5-exposed platelets can enter the HUVECs, which mediate the PM2.5-induced vascular endothelial injury. These findings provide a new perspective and theoretical basis for further exploring the mechanism of cardiovascular damage caused by PM2.5 exposure.

Environmental particulate matter, especially ultrafine particles (100 nm in diameter), can damage the endothelium and favor cardiovascular disease in the general population. With the wide application of nanomaterials, exposure to nanoscale particles (nanoparticles) in the environment is increasing. Systematic study of the interaction of nanoparticles with plasma proteins is critically important for understanding the cardiovascular toxicity of nanomaterials. We combined kinetics and thermodynamics information from surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) and conformational data from fluorescence spectroscopy and circular dichroism (CD) to explore the binding mechanism between cadmium telluride quantum dots (CdTe QDs) and plasma proteins. Special attention was paid to the interaction between CdTe QDs and coagulation-related proteins and the effects of CdTe QDs on protein conformation. The results showed that the binding affinities of CdTe QDs and plasma proteins depend on the nature of the protein and follow the order of fibrinogen (FIB)plasminogen (PLG)thrombin (TM)metallothionein-II (MT-II)human serum albumin (HSA). The interaction was primarily attributed to hydrophobic forces and the spontaneity of the occurrence of the interaction, and the protein secondary structures of FIB and PLG were changed significantly. The information gained in this study might shed light on the potential toxicity of QDs to the cardiovascular system.

In view of the significance and urgency of the speciation analysis of quantum dots (QDs) and their degradation products for clarifying their degradation rules and toxicity mechanisms, a method for the identification and quantification of CdTe QDs and corresponding ionic species in complex matrices was developed using capillary zone electrophoresis (CZE) coupled to inductively coupled plasma-mass spectrometry (ICP-MS). The quality assessment of commercial CdTe QDs and serum pharmacokinetics of synthesized CdTe QDs in rats were successfully undertaken using the developed CZE-ICP-MS method.

A facile and sensitive method with a tunable dynamic range has been proposed for the detection of Cu2+ based on the self-cleavage of Cu2+-specific DNAzyme and the Cu2+-based inhibition of HRP activity, and this method was applied to evaluate the copper species in healthy people and WD patients.

Jilong Wang,1,2,* Hubo Sun,1,2,* Peijun Meng,1,2 Mengmeng Wang,1,2 Mi Tian,3 Yamin Xiong,1,2 Xueying Zhang,1,2 Peili Huang1,2 1School of Public Health, Capital Medical University, 2Beijing Key Laboratory of Environmental Toxicology, 3Medical Experiment and Test Center, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Although quantum dot (QD)-induced toxicity occurs due to free radicals, generation of oxidative stress mediated by reactive oxygen species (ROS) formation is considered an important mechanism. However, free radical mechanisms are essentially difficult to elucidate at the molecular level because most biologically relevant free radicals are highly reactive and short-lived, making them difficult to directly detect, especially in vivo. Antioxidants play an important role in preventing or, in most cases, limiting the damage caused by ROS. Healthy people and animals possess many endogenous antioxidative substances that scavenge free radicals in vivo to maintain the redox balance and genome integrity. The antioxidant capacity of an organism is highly important but seldom studied. In this study, the dose and time effects of CdTe QDs on the antioxidant capacities of the liver and kidneys were investigated in mice using the electron paramagnetic resonance (EPR) spin-trapping technique. We found that the liver and kidneys of healthy mice contain specific antioxidant capacities that scavenge ·OH and ·O2-. Furthermore, oxidative stress markers (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], glutathione [GSH] and malondialdehyde [MDA]) were examined. In dose course studies, the free radical scavenging efficiencies of the liver and kidneys were found to gradually decrease with increasing concentration of CdTe QD exposure. The activities and levels of SOD, CAT, GPx and MDA were observed to increase in treated groups, whereas those of GSH were reduced. The time course studies revealed that the QD-induced antioxidant efficiency reduction was time dependent with GSH decrease and could recover after a period of time. These experimental results offer new information on QD toxicity in vivo. Specifically, CdTe QDs can deplete GSH to reduce the elimination ability of the liver and kidneys for ·OH and ·O2-, thus inducing oxidative damage to tissues. Keywords: quantum dot, antioxidative capacity, free radical elimination, hydroxyl radical, superoxide anion radical, spin-trapping&nbsp

Amorphous silica nanoparticles are widely applied in many fields. But the adverse effects of silica nanoparticle exposure were unclear. The present study investigated the cytotoxicity and mitochondrial damage of silica nanoparticles exposure in hepatocellular carcinoma cell line (HepG2). The cells were treated with 43 nm non-modified amorphous silica nanoparticles which dispersed in serum-free DMEM at concentrations of 0, 25, 50, 100 and 200 μg/mL for 3 and 24 h. The results showed that the silica nanoparticles could lead to increasing cellular reactive oxygen species (ROS) production for 3 and 24 h exposure. Moreover, the oxidative stress induced by the particles could play an important role of the mitochondrial membrane damage and the cell apoptosis. It indicated that apoptosis through mitochondrial pathway mediated by oxidative stress was a potential mechanism of cytotoxicity induced by silica nanoparticles. The particles could enter the cells through different pathways and dispersed in cytoplasm and deposited inside mitochondria. Mitochondria were the major organelles for the cytotoxicity of silica nanoparticles exposure. Mitochondrial damage was related to the oxidative stress and the direct injurious effect of nanoparticles. It can be considered as the potential mechanism for the cytotoxic effects of amorphous silica nanoparticles.

Polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DP) are two kinds of widely used organic flame retardants, and PBDE and DP residues have been found in both environment and biota. A method for the determination of 8 PBDEs and 2 DPs in fish and fish oil supplements was developed using auto gel permeation chromatography (GPC) coupled with gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS) in the selected ion-monitoring (SIM) mode on a 15 m capillary column. The sample added with BDE-77 and 13C12-BDE-209 as the internal standards was extracted using a Soxhlet extractor, and further purified by auto GPC and a multilayer silica gel column. The sample preparation procedure was optimized, and the characteristic ions and fragmentations of the analytes in NCI/MS were studied. The limits of detection (LODs, S/N = 3) ranged from 2.2 to 39.8 ng/kg. The average recoveries were between 71.1% and 121.4% at two spiked levels of 2 and 20 ng/g for both BDE-209 and DP and 0.2 and 2 ng/g for others with the relative standard deviations between 2.96% and 13.31%. The developed method has been successfully applied in the determination of PBDEs and DPs in several fish and fish oil supplements samples. The total PBDEs found ranged from 2.18 to 15.93 ng/g, and DP was not found. This method was validated to be accurate and sensitive for the trace analysis of PBDEs and DPs in the samples with fat.

Water-soluble quantum dots (QDs) have shown potential as tumor diagnostic agents. However, little is known about their biological behaviors in vivo. Male ICR mice were intravenously given a single dose (2.5 μmol kg−1 body weight) of water-soluble cadmium–telluride (CdTe) QDs (the QDs are approximately 4 nm in diameter and have maximal emission at 630 nm). Inductively coupled plasma mass spectrometry (ICP-MS) was used for measuring the kinetic action of 111Cd and 125Te for 7 days. The plasma kinetics of Cd and Te followed a two-compartment model, in which Cd exhibited greater apparent volume of distribution, greater clearance, faster distribution half-life, and significantly slower elimination half-life compared to Te. Contrary to its relatively transient fate in the plasma, high levels of Cd persisted in the liver and kidneys. Te accumulated primarily in the spleen. The different plasma kinetics and distribution patterns of Cd and Te imply that CdTe QDs have been part of the degradation or aggregation in vivo.

Manganese (Mn) toxicity is most often found in mining and welding industry workers. Accumulation of manganese in the brain can result in a syndrome similar to that of Parkinson's disease. Observations on former Mn-alloy workers suggested that residual effects could last for years after exposure. The objective of this study was to assess effects of Mn in the liver of rats following subacute or subchronic exposure and after recovery. Male Sprague-Dawley rats were exposed to manganese chloride (MnCl(2)) for 30 days, 90 days, or for 90 days followed by a 30-day post-exposure recovery period. Results showed that MnCl(2) exposure resulted in liver injury in rats and the extent of injury correlated positively with exposure time. The effect in mitochondria was stronger than in the membrane or nucleus. Most of the changes in these biomarkers recovered when manganese exposure ceased.

A novel block ionomer complex micelles as drug carrier is developed utilizing self-assemble of poly(ethylene glycol)-block-poly(acrylic acid) (PEG-b-PAA) and cadmium chloride. This micelles are characterized to be have good bio-compatibility, hydrophilicity, passive targeting and sustained slow release property which shows great potential for liver cancer therapy. Block ionomer complex micelles based on PEG-b-PAA and cadmium chloride can self-assemble in distilled water, and Cd 2� agent is entrapped into the core stabilized by PEG shells. Results showed the block ionomer complex micelles to be spherically shaped. Cadmium was incorporated easily into the ionic core with remarkably high efficiency (34.25% weight (wt)/wt). The cadmium-loaded polymeric micelles exhibited sustained and slow release behavior of cadmium and a potent cytotoxicity against SMMC-7721 in vitro. This novel block ionomer complex micelles with cores of metal antitumor drug indicates to be potential carriers for effective drug delivery.

A rapid and sensitive immunoassays of mercury (Hg) in biological samples was developed using quantum dots (QDs) and magnetic beads (MBs) as fluorescent and separated probes, respectively. A monoclonal antibody (mAb) that recognizes an Hg detection antigen (BSA-DTPA-Hg) complex was produced by the injection of BALB/c mice with an Hg immunizing antigen (KLH-DTPA-Hg). Then the ascites monoclonal antibodies were purified. The Hg monoclonal antibody (Hg-mAb) is conjugated with MBs to separate Hg from biological samples, and the other antibody, which is associated with QDs, is used to detect the fluorescence. The Hg in biological samples can be quantified using the relationship between the QDs fluorescence intensity and the concentration of Hg in biological samples following magnetic separation. In this method, the detection linear range is 1-1000ng/mL, and the minimum detection limit is 1ng/mL. The standard addition recovery rate was 94.70-101.18%. The relative standard deviation values were 2.76-7.56%. Furthermore, the Hg concentration can be detected in less than 30min, the significant interference of other heavy metals can be avoided, and the simultaneous testing of 96 samples can be performed. These results indicate that the method could be used for rapid monitoring Hg in the body.

Background Given that the effects of ultrafine fractions (

To observed the chromosome oberration of CHL cells induced by CdTe QDs.The chromosome oberration test of Chinese hamster lung (CHL) cell was conducted in CdTe QDs at the concentrations of 1.6, 3.2, 6.3, 12.6 and 25.2 microl/ml, under the metabolic (+S9) and non-metabolic (-S9) activation systems.The chromosome oberration rate of 12.6 and 25.2 microl/ml CdTe QDs groups were significantly higher than the control groups (P0.01) Under the condition of metabolic activation. Main types of chromosomal aberrations was broken, fragmented and exchange.It was suggested that CdTe QDs could induce the effects of chromosome oberration under the metabolic activation systems (+S9).

Quantum dots (QDs) have widely been used in biomedical and biotechnological applications. However, few studies focus on the assessing toxicity of QDs exposure in vivo. In this study, zebrafish embryos were treated with CdTe QDs (4 nm) during 4–96 h post-fertilization (hpf). Mortality, hatching rate, malformation, heart rate, and QDs uptake were detected. We also measured the larval behavior to analyze whether QDs had persistent effects on larvae locomotor activity at 144 hpf. The results showed that as the exposure dosages increased, the hatching rate and heart rate of zebrafish embryos were decreased, while the mortality increased. Exposure to QDs caused embryonic malformations, including head malformation, pericardial edema, yolk sac edema, bent spine, and yolk not depleted. QDs fluorescence was mainly localized in the intestines region. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lowest dose (2.5 nM QDs) produced substantial hyperactivity while the higher doses groups (5, 10, and 20 nM QDs) elicited remarkably hypoactivity in dark periods. In summary, the data of this article indicated that QDs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior.

To investigate oxidative damage effects induced by CdTe quantum dots (QDs) in mice liver.40 ICR mice were randomly divided into 5 groups, one control group (normal saline), four CdTe QDs (exposed by intravenous injection of 0.2 ml CdTe QDs at the concentration of 0, 0.5, 5, 50 and 500 nmol/ml respectively). All mice were decapitated 24h after the injection. Concentration of MDA and the activities of SOD, CAT, 8-OHdG expression were examined by immunohistochemistry and hepatocellular apoptosis was measured with TUNEL resperctively.The results showed in 500 nmol/ml CdTe QDs group, MDA concentration in the liver tissue were significantly higher than those of control group (P0.05). The activities of SOD in 50 and 500 nmol/ml and CAT in 5, 50 and 500 nmol/ml CdTe QDs groups were significantly lower than those of control group (P0.01). Positive staining for 8-OHdG appeared in 50 and 500 nmol/ml CdTe QDs groups and the apoptosis of liver cells was observed in 500 nmol/ml CdTe QDs group by TUNEL technique.It was suggested that CdTe QDs at certain doses could induce oxidative damage effects of the mice liver in the condition of this experiment.

Silica nanoparticles have become promising carriers for drug delivery or gene therapy. Endothelial cells could be directly exposed to silica nanoparticles by intravenous administration. However, the underlying toxic effect mechanisms of silica nanoparticles on endothelial cells are still poorly understood. In order to clarify the cytotoxicity of endothelial cells induced by silica nanoparticles and its mechanisms, cellular morphology, cell viability and lactate dehydrogenase (LDH) release were observed in human umbilical vein endothelial cells (HUVECs) as assessing cytotoxicity, resulted in a dose- and time- dependent manner. Silica nanoparticles-induced reactive oxygen species (ROS) generation caused oxidative damage followed by the production of malondialdehyde (MDA) as well as the inhibition of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Both necrosis and apoptosis were increased significantly after 24 h exposure. The mitochondrial membrane potential (MMP) decreased obviously in a dose-dependent manner. The degree of DNA damage including the percentage of tail DNA, tail length and Olive tail moment (OTM) were markedly aggravated. Silica nanoparticles also induced G2/M arrest through the upregulation of Chk1 and the downregulation of Cdc25C, cyclin B1/Cdc2. In summary, our data indicated that the toxic effect mechanisms of silica nanoparticles on endothelial cells was through DNA damage response (DDR) via Chk1-dependent G2/M checkpoint signaling pathway, suggesting that exposure to silica nanoparticles could be a potential hazards for the development of cardiovascular diseases.

Mengmeng Wang,1,2,* Jilong Wang,1,2,* Hubo Sun,1,2 Sihai Han,3 Shuai Feng,1 Lu Shi,1 Peijun Meng,1,2 Jiayi Li,1,2 Peili Huang,1,2 Zhiwei Sun1,2 1Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 3College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, People’s Republic of China *These authors contributed equally tothis work Abstract: A complete understanding of the toxicological behavior of quantum dots (QDs) in vivo is of great importance and a prerequisite for their application in humans. In contrast with the numerous cytotoxicity studies investigating QDs, only a few in vivo studies of QDs have been reported, and the issue remains controversial. Our study aimed to understand QD-mediated toxicity across different time points and to explore the roles of free cadmium ions (Cd2+) and hydroxyl radicals (·OH) in tissue damage. Male ICR mice were administered a single intravenous dose (1.5 µmol/kg) of CdTe QDs, and liver and kidney function and morphology were subsequently examined at 1, 7, 14, and 28 days. Furthermore, ·OH production in the tissue was quantified by trapping ·OH with salicylic acid (SA) as 2,3-dihydroxybenzoic acid (DHBA) and detecting it using a high-performance liquid chromatography fluorescence method. We used the induction of tissue metallothionein levels and 2,3-DHBA:SA ratios as markers for elevated Cd2+ from the degradation of QDs and ·OH generation in the tissue, respectively. Our experimental results revealed that the QD-induced histopathological changes were time-dependent with elevated Cd2+ and ·OH, and could recover after a period of time. The Cd2+ and ·OH exhibited delayed effects in terms of histopathological abnormalities. Histological assessments performed at multiple time points might facilitate the evaluation of the biological safety of QDs. Keywords: quantum dot, cadmium ion, metallothionein, hydroxyl radical, toxicity

Nanotechnology has been increasingly applied to various fields, such as biology, chemistry, physics, medicine and engineering. However, a major concern that has been the topic in nanoscience is whether exposure of humans to engineered nanoparticles might cause toxic effects. In the present in vitro study, the influence of silica nanoparticles on fibronectin-mediated cellular response was assessed in normal human keratinocytes. Our results demonstrated that silica nanoparticles but not silica microparticles significantly suppressed cell adhesion and migration to fibronectin. This phenomenon was not observed in cell response to Poly-L-Lysine, which mediates cell adhesion and migration in a way different from that of fibronectin. Moreover, it seemed that this suppression was not due to cytotoxic effects induced by silica nanoparticles. Subsequently, we also showed that silica nanoparticles impaired the fibronectin-induced activation of FAK and its downstream PI3K, AKT and Src. Taken together, our data suggests that silica nanoparticles may negatively modulate cell response to fibronectin.

To investigate the effects of CdTe QDs (cadmium telluride quantum dots) on oxidative stress and DNA damage of liver cells in mice.Thirty ICR male mice were randomly divided into 5 groups: one negative control (normal saline) group. Three CdTe QDs groups (exposed by intravenous injection of 0.2 ml of CdTe QDs at the concentration of 3.75, 37.5 and 375 nmol/ml respectively) for electron paramagnetic resonance (EPR) test, and another positive control group (exposed by intravenous injection of 0.2 ml of cyclophosphamide 20 mg/ml) for single cell gel electrophoresis (SCGE) test. All mice were decapitated 24h after the injection, free radicals and DNA damage of liver cells were detected by EPR and SCGE.The levels of oxygen free radicals detected by EPR were increased with the increase of CdTe QDs. The tail length, olive tail moment, tail DNA (%) and the ratio of tail/head examined by SCGE were also increased with the increase of the dosage of CdTe QDs (P0.01).CdTe QDs could induce oxidative stress and DNA damage of liver cells in mice with a dose-effect relationship.

Polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DP) are two kinds of widely used organic flame retardants, and PBDE and DP residues have been found in both environment and biota. A method for the determination of 8 PBDEs and 2 DPs in fish and fish oil supplements was developed using auto gel permeation chromatography (GPC) coupled with gas chromatography-negative chemical ionization/mass spectrometry (GC-NCI/MS) in the selected ion-monitoring (SIM) mode on a 15 m capillary column. The sample added with BDE-77 and 13C12-BDE-209 as the internal standards was extracted using a Soxhlet extractor, and further purified by auto GPC and a multilayer silica gel column. The sample preparation procedure was optimized, and the characteristic ions and fragmentations of the analytes in NCI/MS were studied. The limits of detection (LODs, S/N = 3) ranged from 2.2 to 39.8 ng/kg. The average recoveries were between 71.1% and 121.4% at two spiked levels of 2 and 20 ng/g for both BDE-209 and DP and 0.2 and 2 ng/g for others with the relative standard deviations between 2.96% and 13.31%. The developed method has been successfully applied in the determination of PBDEs and DPs in several fish and fish oil supplements samples. The total PBDEs found ranged from 2.18 to 15.93 ng/g, and DP was not found. This method was validated to be accurate and sensitive for the trace analysis of PBDEs and DPs in the samples with fat.

A novel block ionomer complex micelles as drug carrier is developed utilizing self-assemble of poly(ethylene glycol)-block-poly(acrylic acid) (PEG-b-PAA) and cadmium chloride. This micelles are characterized to be have good bio-compatibility, hydrophilicity, passive targeting and sustained slow release property which shows great potential for liver cancer therapy. Block ionomer complex micelles based on PEG-b-PAA and cadmium chloride can self-assemble in distilled water, and Cd(²+) agent is entrapped into the core stabilized by PEG shells. Results showed the block ionomer complex micelles to be spherically shaped. Cadmium was incorporated easily into the ionic core with remarkably high efficiency (34.25% weight (wt)/wt). The cadmium-loaded polymeric micelles exhibited sustained and slow release behavior of cadmium and a potent cytotoxicity against SMMC-7721 in vitro. This novel block ionomer complex micelles with cores of metal antitumor drug indicates to be potential carriers for effective drug delivery.

Toxicity due to overexposure to manganese (Mn) is becoming increasingly prevalent. Mn-induced neurodegenerative toxicity has been demonstrated, but little is known concerning the adverse effects of the element on the liver. Under physiological conditions, manganese primarily exists as divalent manganese (Mn(2+)) and trivalent manganese (Mn(3+)). The present study was designed to evaluate and compare the effects of Mn(2+) and Mn(3+) on oxidative hepatic damage, membrane fluidity and histopathological changes in rats. Rats exposed to Mn(2+) or Mn(3+) (2.0mg Mn/kg body weight) showed significant inhibition of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as well as decreased levels of glutathione (GSH) and increased levels of malondialdehyde (MDA) in liver tissues. We also showed a significant inhibition of SOD activity and increased MDA levels in hepatocyte nuclei. We also observed reduced Na(+),K(+)-ATPase activity, increased MDA levels and decreased plasma membrane fluidity, which was accompanied by an increase of fluorescence anisotropy (r) values, in hepatic plasma membranes. In addition, Mn(2+) and Mn(3+) both caused histopathological changes, such as mononuclear cell infiltration, congestion, enlargement of the veins and sinusoids, hepatocellular damage, necrotic changes, mitochondrial hyperplasia, swelling and vacuolization, as determined by light and electron microscopy. Taken together, these data suggest that both Mn(2+) and Mn(3+) inhibit the normal physiological functioning of the liver. Under the experimental conditions used, the adverse effects of Mn(2+) were more severe than those of Mn(3+).

The aim of this study was to investigate the contents of lanthanum (La), cerium (Ce), and neodymium (Nd) that accumulate in nuclei and mitochondria isolated from the liver and their corresponding potential oxidative damage effects on nuclei and mitochondria. Five-week-old male imprinting control region (ICR) mice were exposed to chlorides of La, Ce, or Nd by oral gavage with one of three doses: 10, 20, or 40 mg/kgBW/day for 6 weeks. The concentrations of administered elements in hepatocyte nuclei and mitochondria were determined with inductively coupled plasma-mass (ICP-MS) spectrometry. The accumulation of La, Ce, and Nd in hepatocyte nuclei and mitochondria gradually increased in a dose-dependent manner with exposure to the elements, although the concentrations of La, Ce, and Nd in hepatocyte mitochondria were lower than those in their counterpart nuclei. In hepatocyte nuclei, superoxide dismutase (SOD) and catalase (CAT) activities decreased, whereas glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) levels increased. In hepatocyte mitochondria, SOD, CAT, and GPx activities and GSH levels were significantly decreased, and MDA levels were significantly increased. These results suggest that La, Ce, and Nd presumably enter hepatocytes and mainly accumulate in the nuclei and induce oxidative damage in hepatic nuclei and mitochondria.

To compare the effects of extracts from leaves of Ginkgo biloba L. (EGB761), ginkgo flavonoids (GF) and ginkgo terpenlactones (GT) on the oxidation of human plasma low density lipoproteins (LDL) induced by Fe2+ or Cu2+.LDL was pretreated with EGB761, GF and GT, then was oxidized by CuSO4 or FeSO4 6 micromol/L for 4 h. Fluorescence Spectroscopy methods were adopted to determine the contents of lipofusion (LF), malondialdehyde (MDA) and vitamin E (VitE) of LDL oxidized by Fe2+ or Cu2+ and protected by EGB761, GF or GT.After the oxidation of LDL induced by Fe2+ or Cu2+, VitE was exhausted, while MDA and LF were markedly increased. EGB761, GF and GT prevented the decrease of VitE and increases of MDA and LF in the ox-LDL. The inhibitory effect was GFEGB761GT.GF played the main role in anti-oxidation.

To study the effects of Ginkgo biloba L leave on oxidation of human low density lipoproteins (LDL) induced by Fe2+ or Cu2+ in vitro.LDL was oxidized by Fe2+ or Cu2+ for 1, 2, 4, 6h, while it was protected by extracts from leaves of Ginkgo biloba L. ( EGB761), ginkgo flavonids(GF) and ginkgo terpenlactones (GT). Lipofusion (LF), malondialdehyde (MDA) and vitamin E (VitE) were measured as the index of the oxidation of LDL by means of Fluorescence spectroscopy methods.Each extract can inhibit the oxidation of LDL, the inhibition of each extract is increasing during the first 4 hours and subsequently decrease, after 6 hours all the inhibitor have almost lost their ability on antioxidation.EGB761, GF and GT are effective antioxidant and the anti-oxidation vary with time.

Wen Wang,1–3,* Yang Li,1–3,* Xiaomei Liu,3 Minghua Jin,3 Haiying Du,3 Ying Liu,3 Peili Huang,1,2 Xianqing Zhou,1,2 Lan Yuan,4 Zhiwei Sun1–3 1School of Public Health, Capital Medical University, Beijing, 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 3School of Public Health, Jilin University, Changchun, Jilin, 4Medical and Healthy Analysis Centre, Peking University, Beijing, People's Republic of China *These authors contributed equally to this work Abstract: Silica nanoparticles (SNPs) are one of the most important nanomaterials, and have been widely used in a variety of fields. Therefore, their effects on human health and the environment have been addressed in a number of studies. In this work, the effects of amorphous SNPs were investigated with regard to multinucleation in L-02 human hepatic cells. Our results show that L-02 cells had an abnormally high incidence of multinucleation upon exposure to silica, that increased in a dose-dependent manner. Propidium iodide staining showed that multinucleated cells were arrested in G2/M phase of the cell cycle. Increased multinucleation in L-02 cells was associated with increased generation of cellular reactive oxygen species and mitochondrial damage on flow cytometry and confocal microscopy, which might have led to failure of cytokinesis in these cells. Further, SNPs inhibited cell growth and induced apoptosis in exposed cells. Taken together, our findings demonstrate that multinucleation in L-02 human hepatic cells might be a failure to undergo cytokinesis or cell fusion in response to SNPs, and the increase in cellular reactive oxygen species could be responsible for the apoptosis seen in both mononuclear cells and multinucleated cells. Keywords: silica nanoparticles, human hepatic cell L-02, multinucleation, cell cycle, cell dysfunction, apoptosis