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Fine particulate matter (PM2.5 )-induced detrimental cardiovascular effects have been widely concerned, especially for endothelial cells, which is the first barrier of the cardiovascular system. Among potential mechanisms involved, reactive oxidative species take up a crucial part. However, source of oxidative stress and its relationship with inflammatory response have been rarely studied in PM2.5 -induced endothelial injury. Here, as a key oxidase that catalyzes redox reactions, NADPH oxidase (NOX) was investigated. Human umbilical vein endothelial cells (EA.hy926) were exposed to Standard Reference Material 1648a of urban PM2.5 for 24 h, which resulted in NOX-sourced oxidative stress, endothelial dysfunction, and inflammation induction. These are manifested by the up-regulation of NOX, increase of superoxide anion and hydrogen peroxide, elevated endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) level, reduced nitric oxide (NO) production, and down-regulation of phosphorylation of endothelial NO synthase (eNOS) with increased levels of inducible NO synthase, as well as the imbalance between tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1), and changes in the levels of pro-inflammatory and anti-inflammatory factors. However, administration of NOX1/4 inhibitor GKT137831 alleviated PM2.5 -induced elevated endothelial dysfunction biomarkers (NO, ET-1, ADMA, iNOS, and tPA/PAI-1), inflammatory factors (IL-1β, IL-10, and IL-18), and adhesion molecules (ICAM-1, VCAM-1, and P-selectin) and also passivated NOX-dependent AKT and eNOS phosphorylation that involved in endothelial activation. In summary, PM2.5 -induced NOX up-regulation is the source of ROS in EA.hy926, which activated AKT/eNOS/NO signal response leading to endothelial dysfunction and inflammatory damage in EA.hy926 cells.

Silver nanoparticles (AgNPs) are widely used in various fields such as industry, agriculture, and medical care because of their excellent broad-spectrum antibacterial activity. However, their extensive use has raised concerns about their health risks. Liver is one of the main target organs for the accumulation and action of AgNPs. Therefore, evaluating the toxic effects of AgNPs on liver cells and its mechanisms of action is crucial for the safe application of AgNPs. In the study, polyvinylpyrrolidone (PVP)-coated AgNPs were characterized. The human hepatoma cell line (HepG2) and the normal hepatic cell line (L02) were exposed to different concentrations of AgNPs (20-160 μg/mL) and pretreated with the addition of N-acetylcysteine (NAC) or by Nrf2 siRNA transfection. NAC was able to inhibit the concentration-dependent increase in the level of apoptosis induced by AgNPs in HepG2 cells and L02 cells. Interestingly, HepG2 cells were more sensitive to AgNPs than L02 cells, and this may be related to the different ROS generation and responses to AgNPs by cancer cells and normal cells. In addition, NAC also alleviated the imbalance of antioxidant system and cell cycle arrest, which may be related to AgNPs-induced DNA damage and autophagy. The knockdown of nuclear factor erythroid-derived factor 2-related factor (Nrf2) found that AgNPs-induced ROS and apoptosis levels were further upregulated, but the cell cycle arrest was alleviated. On the whole, Nrf2 exerts a protective role in AgNPs-induced hepatotoxicity. This study complements the hepatotoxicity mechanisms of AgNPs and provides data for a future exploration of AgNPs-related anti-hepatocellular carcinoma drugs.

Along with the rapid development of nanotechnology, the bio-safety assessment of nanotechnology products, including nanomaterials, becomes more and more important. Nematode Caenorhabditis elegans (C. elegans) is a valuable model organism that has been widely used in the field of biology because of their excellent advantages, including low cost, small size, short life span, and highly conservative genomes with vertebral animals. In recent years, the number of nanotoxicological researches using C. elegans is persistently growing. According to these available studies, this review classified the adverse effects of nanomaterials in C. elegans into systematic, cellular and molecular toxicity, and focused on summarizing and analyzing the underlying mechanisms of metal, metal oxide and non-metallic nanomaterials causing toxic effects in C. elegans. The findings in this review provided an insight in further studies on assessing bio-safety of nanomaterials in the ecosystem using C. elegans. This article is protected by copyright. All rights reserved.

Silver nanoparticles (AgNPs) have become widespread in the environment with increasing industrial applications. But the studies about their potential health risks are far from enough, especially in neurotoxic effects. This study aimed to investigate the neurotoxic effects of longer-term exposure (prolonged exposure for 48 h and chronic exposure for 6 days) of 20nm AgNPs with/without polyvinylpyrrolidone (PVP) coating at low concentrations (0.01-10 mg·L-1 ) to Caenorhabditis elegans. The results suggested that exposure to AgNPs induced damage to nematode survival, with the longest and relative average life span reduced. Exposure to AgNPs caused neurotoxicity on locomotion behaviors (head thrashes, body bends, pharyngeal pumping frequency, and defecation interval) and sensory perception behaviors (chemotaxis assay and thermotaxis assay), as well as impaired dopaminergic, GABAergic, and cholinergic neurons, except for glutamatergic, based on the alters fluorescence intensity, in a dose- and time-dependent manner. Further investigations suggested that the low-dose AgNPs (0.01-0.1 mg·L-1 ) exposure raises receptors of GABAergic and dopamine in C. elegans at the genetic level, whereas opposite results were observed at higher doses (1-10 mg·L-1 ), which implied that AgNPs could cause neurotoxicity by impairing neurotransmitter delivery. The PVP-AgNPs could cause a higher fatality rate and neurotoxicity at the same dose. Notably, AgNPs did not cause any deleterious effect on nematodes at the lowest dose of 0.01 mg·L-1 . In general, these results suggested that AgNPs possess the neurotoxic potential in C. elegans and provided useful information to understand the neurotoxicity of AgNPs, which would offer an inspiring perspective on the safe application.

Daunorubicin is a common antineoplastic agent used for the treatment of lymphoma and acute leukemia. Here, we report an 808 nm-excited, citric acid coated, core–shell upconversion fluorescent sensor for daunorubicin (DAU) detection in aqueous solutions. The designed Nd3+ doped core–shell structure significantly raises the upconversion fluorescence intensity, while the presence of citric acid ligands helps to reduce the surface quenching effect exerted by water and improve the dispersibility. The upconversion fluorescence of nanoparticles is efficiently quenched in the presence of DAU via a fluorescence resonance energy transfer mechanism. The dynamic quenching constant was 1.58 × 104 M−1. The fluorescence intensity ratio showed a good linear response to DAU concentration in the range of 0.1 μM to 70 μM with a detection limit of 0.06 μM. The sensing method was simple, rapid, and low-cost and was further applied to determine the levels of DAU in urine with spike recoveries from 97.3% to 101.5%. The proposed fluorescent sensor holds great potential for in vivo imaging and detection of DAU.

Background Along with the wild applications of nitrogen-doped graphene quantum dots (N-GQDs) in the fields of biomedicine and neuroscience, their increasing exposure to the public and potential biosafety problem has gained more and more attention. Unfortunately, the understanding of adverse effects of N-GQDs in the central nervous system (CNS), considered as an important target of nanomaterials, is still limited. Results After we found that N-GQDs caused cell death, neuroinflammation and microglial activation in the hippocampus of mice through the ferroptosis pathway, microglia was used to assess the molecular mechanisms of N-GQDs inducing ferroptosis because it could be the primary target damaged by N-GQDs in the CNS. The microarray data suggested the participation of calcium signaling pathway in the ferroptosis induced by N-GQDs. In microglial BV2 cells, when the calcium content above the homeostatic level caused by N-GQDs was reversed, the number of cell death, ferroptosis alternations and excessive inflammatory cytokines release were all alleviated. Two calcium channels of L-type voltage-gated calcium channels (L-VGCCs) in plasma membrane and ryanodine receptor (RyR) in endoplasmic reticulum (ER) took part in N-GQDs inducing cytosolic calcium overload. L-VGCCs and RyR calcium channels were also involved in promoting the excess iron influx and triggering ER stress response, respectively, which both exert excessive ROS generation and result in the ferroptosis and inflammation in BV2 cells. Conclusion N-GQDs exposure caused ferroptosis and inflammatory responses in hippocampus of mice and cultured microglia through activating two calcium channels to disrupt intracellular calcium homeostasis. The findings not only posted an alert for biomedical applications of N-GQDs, but also highlighted an insight into mechanism researches of GQDs inducing multiple types of cell death in brain tumor therapy in the future. Graphical abstract

Available safety evaluations regarding mesoporous silica nanoparticles (mSiNPs) are based on the assumption of a relatively high exposure concentration, which makes the findings less valuable in a realistic environment. In this study, we employed Caenorhabditis elegans (C. elegans) as a model to assess the neuronal damage caused by mSiNPs at the predicted environmentally relevant concentrations. After nematodes were acute and prolonged exposed to mSiNPs at concentrations over 300 μg/L, locomotion degeneration, shrinking behavior, and abnormal foraging behavior were observed, which were associated with the deficits in the development of GABAergic neurons, including D-type and RME motor neurons. Furthermore, the oxidative stress evidenced by excessive ROS generation might contribute to the mechanism of mSiNPs damaging neurons. Although the neurotoxicity of mSiNPs was weaker than (nonmesoporous) SiNPs, it is still necessary for researchers to pay attention to the adverse effects caused by mSiNPs in the environmental animals, especially with the rapid increase in mSiNPs application. Considering the conserved property of GABAergic neurons during evolution, these findings will shed light on our understanding of the potential eco-risks of NPs to the nervous system of other animal models.

the Artificial intelligence (AI) has gradually changed from frontier technology to practical application with the continuous progress of deep learning technology in recent years. In this paper, the Random forest (RF) algorithm is adopted to preprocess and optimize the feature subset of ICU data sets. Then these optimized feature subsets are used as input of Long shortterm memory (LSTM) deep learning model, and the early disease prediction of ICU inpatients is carried out by the method of neural network deep learning. Experiments show that this prediction method has higher prediction accuracy compared with other machine learning and deep learning models.

Silver nanoparticles (AgNPs) have been incorporated in many consumer and biomedical products. Serious concerns have been expressed about the environmental and public health risks caused by nanoparticles. In previous studies, we found that AgNPs induced microglia polarization of the inflammatory phenotype. Autophagy was a critical for AgNPs-induced neuroinflammation. In the present study, we evaluated in detail the effects of AgNPs in different stages of the autophagy process, and we found that AgNPs induced neuroinflammatory responses and autophagic flux blockage both in the mouse brain and BV2 cells. AgNPs inhibited autophagosome-lysosome fusion and impaired the lysosomal functions by reducing the levels of lysosomal-associated membrane proteins, promoting lysosome membrane permeability and altering the lysosomal acidic microenvironment. These changes resulted in the defects in autophagic substrate clearance and subsequently led neuroinflammation. In addition, the elevation of autophagy could prevent the neuroinflammation induced by AgNPs. As a result, AgNPs hindered autophagic flux by inhibiting autophagosome fusion with lysosomes, thus aggravating the AgNPs-induced neurotoxicity. These findings will provide new insights to investigate the molecular mechanisms of neurotoxicity caused by AgNPs.

Silver selenide quantum dots (Ag

Fine particulate matter (PM

Silver nanoparticles (AgNPs) could accumulate in the central nervous system (CNS) and induce neurotoxicity for their widespread use in industry and medicine. Mitochondria are vulnerable to toxicity of AgNPs, however, their role in the neurotoxicity remains unclear. This study aimed to evaluate AgNPs-induced synaptic degeneration in mouse hippocampal neurons (at a dose of 12-120 mg/kg BW via intravenous injection), and to further investigate mechanism of mitophagy, mitochondrial biogenesis process in the neurotoxicity. The results indicated that AgNPs accumulated in mouse hippocampal neurons and induced neurological deficits of learning and memory, which involved in synaptic degeneration accompanied with mitochondrial damage. Mechanistically, AgNPs exposure increased protein expression of PTEN-induced kinase 1 (PINK1), Parkin and inhibited peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) protein expression, caused disturbed mitophagy and mitochondrial biogenesis. AgNPs also induced synaptic damage by increasing the protein expression of synaptophysin and decreasing PSD95, MAP2 protein expression. AgNPs exposure even promoted protein expression of amyloid precursor protein (APP) using in amyloid-β (Aβ) cleavage. Furthermore, AgNPs induced hippocampal neuronal synaptic degeneration, mitophagy and mitochondrial biogenesis is dependent on particle-specific AgNPs rather than released silver ions. Our research could provide insights into the regulatory mechanisms of AgNPs-induced neurotoxicity. This study will shed the light of neurotoxicological evaluation of nanoparticles and possible early warning of biomedical applications.

Previous studies have revealed that the liver is the main target organ of deposition for engineered nanoparticles. The hepatotoxicity of silver nanoparticles (AgNPs), the widely used antimicrobial nanoparticles, has been of great interest. However, little is known about the regulatory mechanism of the mitochondria in AgNP-induced hepatotoxicity. In the present study, we found that AgNPs, rather than silver ions, induced mitochondrial dynamics disorders, oxidative stress, and mitochondria-dependent hepatocyte apoptosis in mice. Using human hepatocellular carcinoma (HepG2) cells, we confirmed that the interaction between dynamin-related protein 1 (DRP1)-dependent mitochondrial fission and oxidative stress promoted mitochondrial damage and mitochondria-dependent apoptosis induced by AgNPs, as determined by the elimination of DRP1 or addition of N-acetylcysteine (NAC). Interestingly, the crosstalk between DRP1-dependent mitochondrial fission and oxidative stress also activated mitophagy and autophagy flux blocking. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) gene silencing contributed to the aggravation of mitochondrial damage, oxidative stress, and apoptosis. These results revealed that the interplay between mitochondrial fission and oxidative stress induced mitophagy defects and triggered AgNP-induced mitochondria-dependent apoptosis in liver cells both in vivo and in vitro. Our findings provide a perspective for the mechanism of hepatotoxicity induced by exposure to metal NPs.

Despite the potential of cadmium telluride quantum dots (CdTe QDs) in bioimaging and drug delivery, their toxic effects have been documented. It is known that the immunotoxicity of CdTe QDs targeting macrophages is one of their adverse effects, and the protein corona (PC) will affect the biological effects of QDs. In order to prove whether the PC-CdTe QDs complexes could alleviate the toxicity of CdTe QDs without weakening their luminescence, we investigated the impact of protein corona formed in fetal bovine serum (FBS) on the cytotoxicity of CdTe QDs to mitochondria. RAW264.7 cells were used as the model to compare the effects of CdTe QDs and PC-CdTe QDs complexes on the structure, function, quantity, morphology, and mitochondrial quality control of mitochondria. As result, the protein corona form in FBS alleviated the inhibition of CdTe QDs on mitochondrial activity, the damage to mitochondrial membrane, the increase of ROS, and the reduction of ATP content. Also, CdTe QDs increased the number of mitochondria in macrophages, while the complexes did not. In line with this, the morphology of mitochondrial network in macrophages which were exposed to CdTe QDs and PC-CdTe QDs complexes was different. CdTe QDs transformed the network into fragments, punctuations, and short rods, while PC-CdTe QDs complexes made the mitochondrial network highly branched, which was related to the imbalance of mitochondrial fission and fusion. Mechanically, CdTe QDs facilitated mitochondrial fission and inhibited mitochondrial fusion, while protein corona reversed the phenomenon caused by QDs. Besides mitochondrial dynamics, mitochondrial biogenesis and mitophagy were also affected. CdTe QDs increased the expression of mitochondrial biogenesis signaling molecules including PGC-1α, NRF-1 and TFAM, while PC-CdTe QDs complexes played the opposite role. With regard to mitophagy, they both showed promoting effect. In conclusion, the formation of protein corona alleviated the toxic effects of CdTe QDs on the mitochondria in macrophages and affected mitochondrial quality control. Under the premise of ensuring the fluorescence properties of CdTe QDs, these findings provided useful insight into reducing the toxicity of CdTe QDs from two perspectives: protein corona and mitochondria, and shared valuable information for the safe use of QDs.

The resource management of virtualisation system is a core issue in the field of cloud computing. For achieving the goal of efficient manage system resource without performance loss in clouding environment, the authors propose an optimal load balancing controller to assign the resource to different virtual machines, which run on a single physical server. Here, the authors focus on dynamical web workloads that the system resource management problem can be formulated as a dynamical optimisation problem. In the face of dynamical and robust workloads, the authors present an alternative approach based on the constrained boundary linear quadratic control (cBLQC) method, the optimal resource allocation scheme is solved by minimising the quadratic cost function with constrains on the system input and output. Different with existing works that assume a particular distribution for system noise or ignore the noise directly, the authors loosen the restrictions on system noise, which simply assume that system noise belongs with some reasonable norm-bounded set. Experiments on the Xen-based platform with a set of workload patterns show that the efficiency of authors’ method in terms of control precision and stability.

There are generally zero drift, sensitivity drift and nonlinear error in silicon piezoresistive pressure sensors due to the inherent characteristics of semiconductor materials. It is necessary to compensate and correct the errors produced so as to meet the requirements of measurement accuracy. In order to further improve the compensation precision, based on the research of various basic software compensation methods, a surface fitting compensation algorithm based on least square method is designed, and the software is implemented on the Visual Basic platform. The experimental results show that the zero drift, sensitivity drift and nonlinear error is effectively eliminated, and the output precision of the sensor is greatly improved.

The number of biosafety evaluation studies of nanoparticles (NPs) using different biological models is increasing with the rapid development of nanotechnology. Thus far, nematode Caenorhabditis elegans (C. elegans), as a complete model organism, has become an important in vivo alternative assay system to assess the risk of NPs, especially at the environmental level. According to results of qualitative and quantitative analyses, it can be concluded that studies of nanoscientific research using C. elegans is persistently growing. However, the comprehensive conclusion and analysis of toxic effects of NPs in C. elegans are limited and chaotic. This review focused on the effects, especially sublethal ones, induced by NPs in C. elegans, including the development, intestinal function, immune response, neuronal function, and reproduction, as well as the underlying mechanisms of NPs causing these effects, including oxidative stress and alterations of several signaling pathways. Furthermore, we presented some factors that influence the toxic effects of NPs in C. elegans. The advantages and limitations of using nematodes in the nanotoxicology study were also discussed. Finally, we predicted that the application of C. elegans to assess long-term impacts of metal oxide NPs in the ecosystem would become a vital part of the nanoscientific research field, which provided an insight for further study.

Recently, the use of silica nanoparticles (SiO2-NPs) and mesoporous silica nanoparticles (mSiO2-NPs) in the biomedical field, such as biosensors, drug deliveries and bioactivator carriers, is increasing due to their special physiochemical properties. However, the biosafety assessment of them is far lagging behind their rapid application. In this study, we observed that both SiO2-NPs and mSiO2-NPs with certain exposed doses decreased the cell viability while increased the apoptosis rates in the human pulmonary alveolar epithelial cells (HPAEpiC). Generally, mSiO2-NPs presented less toxic effects than SiO2-NPs with same treated dose, which assures the positive application prospect of mSiO2-NPs in the area of biomedicine. Since both SiO2-NPs could be taken into cells and accumulated in the endoplasmic reticulum (ER), which resulted in pathologically morphological changes and subcellular organelle damages, we hypothesized that the ER stress response could be involved in the NPs-induced apoptosis. The findings suggested that SiO2-NPs and mSiO2-NPs exposure increased the expression levels of two ER stress markers, e.g. BiP and CHOP, which could be inhibited by the ER stress inhibitor 4-PBA, following with decreased apoptosis rates in HPAEpiC. Even though it is still unclear of the direct target of NPs causing ER stress response following with cell apoptosis, our findings provide a novel insight for researchers to explore the toxic mechanisms of SiO2-NPs and mSiO2-NPs in order to reduce the adverse effects of them.

PM2.5 has implications in cardiovascular adverse events, but the underlying mechanisms are still obscure. The aim of this study is to evaluate miRNA expression in endothelial cells in response to two realistic doses of PM2.5 and to identify the possible gene targets of deregulated miRNAs through microarray profiling and computational technology. As a result, there are 18 differentially expressed miRNAs between 2.5 μg/cm2 group and the control, of which 11 miRNAs are up-regulated and 7 miRNAs are down-regulated. Relative to the control group, 40 miRNAs are significantly changed in 10 μg/cm2 group with 21 miRNAs being upregulated and 19 miRNAs being downregulated. Interestingly, when two PM2.5-treated groups respectively compared with the control, the expressed trends of 12 miRNAs in 2.5 μg/cm2 group are the same as those in 10 μg/cm2 group, with 8 being upregulated and 4 miRNAs being simultaneously downregulated. Gene ontology (GO) analysis shows that the crucial functional categories of miRNA-targeted genes incorporate transcription-related process and intracellular signal transduction. Pathway analysis reveals that endocytosis, FoxO signaling pathway and PI3K-Akt signaling pathway are involved in the PM2.5-caused cardiotoxicity. Further confirmation by RT-qPCR indicates that PM2.5 could induce the down-regulation of hsa-miR-128-3p, hsa-miR-96-5p, hsa-miR-28-5p, hsa-miR-4478 and hsa-miR-6808-5p, which are in accordance with the results of array data. With the comprehensive analysis of mRNAs and miRNAs, a great number of pairs have been identified, suggesting abnormally expressed miRNAs have functions in the cardiotoxicity of PM2.5, and the function may be achieved through the post-transcriptional regulation of certain genes on the related pathways.

Epidemiological studies and experimental research have illustrated that PM2.5 has an association with cardiovascular adverse events. However, the underlying mechanisms are still unknown. Long non-coding RNAs (lncRNAs) have been proposed to take part in diverse diseases. To comprehensively gain insight into the molecular toxicity of PM2.5, expression patterns are analyzed in EA.hy926 cell line through RNAs microarray. A total of 356 lncRNA transcripts are dysregulated in 2.5 μg/cm2 group, and there are 1283 lncRNAs differentially expressed in 10 μg/cm2 group. From functional analysis, several lncRNAs may be implicated in the bio-pathways of phagosome, TNF signaling pathway, chemokine signaling pathway and gap junction. Moreover, certain lncRNAs participate in the toxicity of PM2.5 through cis- and/or trans-regulation of their co-expressed genes. Therefore, lncRNAs may be used as new candidate biomarkers and potentially preventive targets in cardiotoxicity of PM2.5. Our study indicates that not limited to transcriptional regulation, post-transcriptional regulation plays a pivotal role in PM2.5-caused toxicity.

Silver selenide quantum dots (Ag2Se QDs) provide bright prospects for the application of QDs in the field of biomedicine because they contain low-toxic compounds and show great advantages in the imaging of deep tissues and tiny vascular structures. However, the biosafety of these novel QDs has not been thoroughly evaluated, especially in one main target for toxicity-the central nervous system (CNS). Our previous studies have suggested severe inflammatory responses to cadmium-containing QDs in the hippocampus, which gives us a hint regarding the risk assessment of Ag2Se QDs. In this study, microglial activation followed by enhanced levels of pro-inflammatory cytokines was observed in the hippocampus of mice intravenously injected with Ag2Se QDs. When using the microglial BV2 cells to investigate the underlying mechanisms, we found that the NLRP3 inflammasome activation was involved in the IL-1β-mediated inflammation induced by Ag2Se QDs. On the one hand, Ag2Se QD-activated NF-κB participated in the NLRP3 inflammasome priming and assembly as well as the pro-IL-1β upregulation. On the other hand, Ag2Se QD-induced ROS generation, particularly mtROS, triggered the NLRP3 inflammasome activation and resulted in active caspase-1 to process pro-IL-1β into mature IL-1β release. These findings not only indicated that it is important to evaluate the biosafety of novel QDs, even those containing low-toxic compounds, but also provided an unbiased and mechanism-based risk assessment of similar nanoparticles.

Cabled underwater information networks (CUINs) have evolved over the last decade to provide abundant power and broad bandwidth communication to enable marine science. To ensure reliable operation of the CUINs, the technology for high-impedance fault diagnosis and isolation with high reliability and accuracy is essential. In this paper, we review diagnosis and location methods as applied to a constant voltage ring and the tree topology network. A high-impedance fault diagnosis method based on the variation of the sampling voltage in the primary nodes (PNs) for a constant current remote power supply system is proposed. The methods for analyzing the fault voltage with using power monitoring and control system (PMACS) and communications monitoring, control system (CMACS), and hybrid detection with alternating current and direct current are used for research the high-impedance fault location based on the designed fault isolation circuit. In particular, a verification scheme for high-impedance fault location is designed for the CUINs based on the classical mesh topology. Furthermore, high-impedance faults of nodes and submarine cable sections in the trunk cable are simulated, and the variations of leakage voltage are analyzed. By researching the change of leakage voltage before and after the fault occurs, the feasibility and practicability of the diagnosis and location scheme are verified.

In recent years, the cardiovascular toxicity of urban fine particulate matter (PM

Graphene quantum dots (GQDs), as a novel graphene-based nanoparticle, presented a bright prospect in fields of biomedicine due to their excellent optical property. However, the biosafety assessment of GQDs is far behind their rapid development, which could restrict their wilder applications. This study focused on the potential adverse effects of two kinds of promising GQDs, i.e. nitrogen-doping graphene quantum dots (N-GQDs) and amino-modified graphene quantum dot (A-GQDs) on primary target organs of GNMs, including lung, liver and kidney. The intranasal instillation used here was to imitate the respiratory exposure of GQDs that is a commonly exposure route of GQDs in the environment. Although no severe damages associated with general health occurred in mice treated with GQDs, the fibrosis evidenced by statistically significant increases in the area of collagen I and TGF-ß1 and p-Smad3 expressions were observed in the lung, liver and kidney tissues. Interestingly, the fibrotic effect induced by GQDs could be effectively alleviated by a ferroptosis-specific inhibitor, which demonstrated a close relationship of fibrosis and ferroptosis. This study not only provides new insights on the toxicity mechanisms of GQDs, but also offers some efficient ways to control toxicity of GQDs, like dosage threshold and small molecular drugs.

Microglial cells are resident immune cells in the central nervous system. Activation of microglia as induced by CdTe quantum dots (QDs) can trigger damage to neurons. To quantify the intracellular QDs, we monitored the intracellular Cd concentration in the QD-exposed mouse microglial cells (BV-2 cell line). The extent of cell injury at different times correlated with the Cd concentration in cells at that time. In addition to Cd ion detection, we also monitored the intracellular fluorescence of the QDs. More QDs accumulated in the nucleus than in the cytoplasm. Comet assays confirmed that QDs induce DNA damage. However, DNA cannot interact with QDs, so the DNA damage was not caused by CdTe QDs adducts to DNA but by the increase of the Cd ion concentration and the secondary oxidative damage. In addition to DNA damage, biofilm injury and endogenous reduced glutathione depletion were also apparent in QD-exposed BV-2 cells. These changes can be prevented or even reversed by exogenous reduced glutathione administration.

As the release of silver nanoparticles (AgNPs) in the environment continues to increase, great concerns have been raised about their potential toxicity to humans. It is urgent to assess the possible toxicity of AgNPs to the immune cells of the central nervous system due to the continuous accumulation of AgNPs in the brain. This study aimed to evaluate the neurotoxicity of AgNPs and the regulatory mechanism of autophagy in AgNPs-induced inflammation by using mouse microglia BV2 cell lines. AgNPs decreased the microglia cell activity in a concentration and time-dependent manner. The exposure of BV2 cells to AgNPs at a non-cytotoxic level of 5 μg/mL resulted in increase of pro-inflammatory cytokines and decrease of mRNA expression of anti-inflammatory cytokines. AgNPs exposure increased M1 markers of iNOS expression and decreased the expression of M2 markers of CD206 in a time-dependent manner. Meanwhile, the expression of inflammatory proteins IL-1β and NF-κB increased significantly. Additionally, AgNPs induced an increase in autophagosome and upregulation of LC3II, Beclin1, and p62 expression levels. Pretreatment by an autophagy inhibitor, 3-Methyladenine, caused more AgNPs-treated microglia to polarized into pro-inflammatory phenotypes. Inhibition of autophagy also increased the expression of inflammation-associated mRNA and proteins in BV2 cells. These results indicated that AgNPs could induce pro-inflammatory phenotypic polarization of microglia and the autophagy could play a key regulatory role in the pro-inflammatory phenotypic polarization of microglia induced by AgNPs.

Cr(VI) reduction to Cr(III) has been demonstrated to be an effective method for Cr(VI) detoxification. Herein, we fabricated polyaniline (PANI) nanorod forests-modified Carbon fiber felt (CFF) as CFF-PANI cathode in a Flow-through electrode system (FES) with the counter CFF anode for enhancing Cr(VI) reduction. The CFF-PANI was synthetized via in-situ polymerization under different aniline concentration to investigate the effect of PANI nano-structures on Cr(VI) reduction. It was revealed that BET and electrochemical surface area of PANI nanorods significantly affected the Cr(VI) reduction, and CFF-PANI cathode with the largest BET and electrochemical surface area exhibited ∼ 45% higher Cr(VI) removal and ∼ 35% lower specific energy consumption than the CFF cathode. A decrease-then-stable Cr(VI) removal was observed within 120 min operation time, which was attributed to the electro-adsorption of Cr(VI) species on CFF anode. In-situ sampling experiments revealed that the electrochemical oxidation on CFF anode inhibited the Cr(VI) electro-adsorption, and at applied voltage above 0.7 V, the Cr(VI) reduction on cathode was the main mechanism for Cr(VI) removal. The operation of FES at 0.8 V had the lowest specific energy consumption (48.5 Wh/mol) and maintained ∼ 95% energy efficiency for Cr(VI) reduction with minor competitive reduction of H2O or O2 species. The results suggested that CFF-PANI can be a promising cathode for Cr(VI) reduction from aqueous solutions.

Available safety evaluations regarding mesoporous silica nanoparticles (mSiNPs) are based on the assumption of a relatively high exposure concentration, which makes the findings less valuable in a realistic environment. In this study, we employed

CdTe quantum dots (QDs) are still widely considered as excellent fluorescent probes because of their far more superior optical performance and fluorescence efficiency than non‑cadmium QDs. Thus, it is important to find ways to control their toxicity. In this study, CdTe QDs and CdTe@ZnS QDs both could cause IL-1s-mediated inflammation following with pyroptosis in BV2 cells, but the toxic effects caused by CdTe@ZnS QDs was weaker than CdTe QDs, which demonstrated the partial protection of ZnS shell. When investigating the molecular mechanisms of QDs causing the inflammatory injury, the findings suggested that cadmium-containing QDs exposure activated NF-κB that participated in the NLRP3 inflammasome priming and pro-IL-1s expression. After that, QDs-induced excessive ROS generation triggered the NLRP3 inflammasome activation and resulted in active caspase-1 to process pro-IL-1s into mature IL-1s release and inflammatory cell death, i.e. pyroptosis. Fortunately, the inhibitions of caspase-1, NF-κB and ROS or knocking down of NLRP3 all effectively attenuated the increases in the IL-1s secretion and cell death caused by QDs in BV2 cells. This study provided two methods to alleviate the toxicity of cadmium-containing QDs, in which one is to encapsulate bare-core QDs with a shell and the other is to inhibit their toxic pathways. Since the latter way is more effective than the former one, it is significant to evaluate QDs through a mechanism-based risk assessment to identify controllable toxic targets.

Epidemiological studies have illustrated that PM2.5 is closely related to cardiovascular disease (CVD), but underlying toxicological mechanisms are not yet clear. The main purpose of this study is to disclose the potential biological mechanisms responsible for PM2.5-dependent adverse cardiovascular outcomes through the appliance of genome-wide transcription microarray. From results, compared with the control group, there are 97 genes significantly altered in 2.5 μg/cm2 PM2.5 treated group and 440 differentially expressed genes in 10 μg/cm2 group. Of note, when 2.5 μg/cm2 and 10 μg/cm2 group were respectively compared with the control group, 46 significantly altered genes showed a consistent tendency in two treated groups, of which 31 genes were upregulated while 15 genes were meanwhile downregulated. Based on Gene Ontology (GO) annotation, altered genes are mainly gathered in functions of cellular processes and immune regulation. Pathway analysis indicated that TNF signaling pathway, NOD-like receptor (NLRs) signaling pathway, MAPK signaling pathway and gap junction are vital pathways involved in PM2.5-induced toxicity in EA.hy926. Moreover, results from RT-qPCR further corroborated that changed genes are implicated in oxidative stress, inflammation and metabolic disorder. In addition, metabolism of xenobiotics by cytochrome P450 pathway is the critical pathway which may serve as a target to prevent PM2.5-induced CVD. To sum up, our effort provides a fundamental data for further studies regarding mechanisms of PM2.5-induced cardiovascular toxicity on the basis of genome-wide screening.

Recently, the increasing number of bio-safety assessments on cadmium-containing quantum dots (QDs) suggested that they could lead to detrimental effects on the central nervous system (CNS) of living organisms, but the underlying action mechanisms are still rarely reported. In this study, whole-transcriptome sequencing was performed to analyze the changes in genome-wide gene expression pattern of rat hippocampus after treatments of cadmium telluride (CdTe) QDs with two sizes to understand better the mechanisms of CdTe QDs causing toxic effects in the CNS. We identified 2095 differentially expressed genes (DEGs). Fifty-five DEGs were between the control and 2.2 nm CdTe QDs, 1180 were between the control and 3.5 nm CdTe QDs and 860 were between the two kinds of CdTe QDs. It seemed that the 3.5 nm CdTe QD exposure might elicit severe effects in the rat hippocampus than 2.2 nm CdTe QDs at the transcriptome level. After bioinformatics analysis, we found that most DEG-enriched Gene Ontology subcategories and Kyoto Encyclopedia of Genes and Genomes pathways were related with the immune system process. For example, the Gene Ontology subcategories included immune response, inflammatory response and T-cell proliferation; Kyoto Encyclopedia of Genes and Genomes pathways included NOD/Toll-like receptor signaling pathway, nuclear factor-κB signaling pathway, tumor necrosis factor signaling pathway, natural killer cell-mediated cytotoxicity and T/B-cell receptor signaling pathway. The traditional toxicological examinations confirmed the systemic immune response and CNS inflammation in rats exposed to CdTe QDs. This transcriptome analysis not only revealed the probably molecular mechanisms of CdTe QDs causing neurotoxicity, but also provided references for the further related studies.

The stress wave sensor detect and process the electronic signal of friction, mechanical shock and dynamic load on equipment moving parts, the stress wave analysis are fulfilled by using the time domain and frequency domain feature extraction software, Polynomial neural network (PNN) and data fusion technology. The equipment status are quantitatively analyzed, the equipment fault are accurately predicted. Compared with the current adopted other analysis technologies, the system can monitor the operation condition of the equipment better in real-time, predict the fault earlier. The production safety is guaranteed, the equipment maintenance cost is reduced, and the production efficiency is improved.

The split-radix fast Fourier transform (SRFFT) is attractive for low-power FFT processors as it has the lowest numbers of multiplication operations among all FFT algorithms. FFT algorithms differ from one another by the location of the twiddle factor. The irregular locations of the twiddle factors in the SRFFT lead to complex address generators for the memory containing the twiddle factors. This paper proposes a novel twiddle factor addressing architecture for the split-radix FFT processor, which can effectively reduce its power consumption. This is then used to design a simple memory address generator and a low-power pipelined SRFFT. The proposed algorithm is used to implement a 1024-point pipelined circuit. Post-layout simulation shows that the proposed 1024-point design achieves over 24% and 14.7% lower power consumption for the multiplications and ROM, respectively, compared to a traditional radix-2 single delay feedback (SDF) FFT architecture.

Nanotechnology had matured significantly during the last two decades as it has transitioned from bench top science to applied technology. Even though the issue of safety of nanotechnology has been raised nearly one decade ago, the rapid progress in development and use of nanomaterials has not yet been matched by toxicological investigations. Many recent studies have simply outlined the toxic effects of nanoparticles (NPs), but few have systematically addressed their potentially adverse biological effects on target organs. Some animal models have shown that NPs could be accumulated in various organs. These accumulations can access the vasculature and target other organs, resulting in a potential health risks. After the brief description of current knowledge on the wide applications of several common NPs, their applications and the toxicokinetics, this review focused on effects of NPs on organ functions and mammal health after acute or chronic exposure, and potential mechanisms of action. Due to their physical properties, the liver, kidneys and lung are the main target organs of NPs. Most of NPs show slight toxicity when exposed to animals, while certain toxic effects like oxidative stress generation, inflammation and DNA damage are commonly observed. The severity of NPs toxicity is dependent upon several factors, including exposure dose and administration, NPs chemistry, size, shape, agglomeration state, and electromagnetic properties, which could provide useful information necessary to control the toxicity of NPs. Finally, the safety evaluation of nanotoxicity was addressed.

Quantum dots (QDs) could be used in the field of biology and medicine as excellent nano-scale fluorescent probes due to their unique optical properties, but the adverse effects of QDs are always the obstruction for its usage in living organisms. In this study, we observed that CdTe QDs exposure decreased the cell viability while increased the apoptosis rates in the L929 cells. Apart from QD-induced oxidative stress indicated by excessive ROS generation, three signal transductions, including Akt, p38 and JNK, played important roles on the regulation of cell apoptosis by CdTe QDs exposure as well. In order to reduce the toxicity of CdTe QDs, we explored the protective effects of three treatments, i.e. resveratrol, H2S and thermotherapy at 43°C, against the cell apoptosis elicited by CdTe QDs. The results showed that resveratrol, H2S and thermotherapy at 43°C were capable of attenuating cell apoptosis and intercellular ROS production through inhibiting signal pathways of Akt, p38 and JNK, respectively. As there is only limited number of exogenous treatments reported to diminish the toxicity of QDs, our findings will provide a novel insight for researchers who try to reduce or even eliminate the adverse health effects of QDs.

Silver selenide quantum dots (Ag

The excellent optical property and relatively low toxicity of CdTe/ZnS core/shell quantum dots (QDs) make them an advanced fluorescent probe in the application of biomedicines, particularly in neuroscience. Thus, it is important to evaluate the biosafety of CdTe/ZnS QDs on the central nervous system (CNS). Our previous studies have suggested that the high possibility of CdTe/ZnS QDs being transported into the brain across the blood-brain barrier resulted in microglial activation and a shift of glycometabolism, but their underlying mechanism remains unclear. In this study, when mice were injected intravenously with CdTe/ZnS QDs through tail veins, the microglial activation, polarized into both M1 phenotype and M2 phenotype, and the neuronal impairment were observed in the hippocampus. Meanwhile, the increased pro- and anti-inflammatory cytokines released from BV2 microglial cells treated with CdTe/ZnS QDs also indicated that QD exposure was capable of inducing microglial activation in vitro. We further demonstrated that the glycolytic shift from oxidative phosphorylation switching into aerobic glycolysis was required in the microglial activation into M1 phenotype induced by CdTe/ZnS QD treatment, which was mediated through the mTOR signaling pathway. The findings, taken together, provide a mechanistic insight regarding the CdTe/ZnS QDs inducing microglial activation and the role of the glycolytic shift in it.

In this study, a metabolomic analysis was used to reveal the neurotoxicity of the CdTe/ZnS QDs via microglia polarization. A gas chromatography-mass spectrometer (GC-MS) was applied to uncover the metabonomic changes in microglia (BV-2 cell line) after exposure to 1.25 μM CdTe/ZnS QDs. 11 annotated metabolic pathways (KEGG database) were significantly changed in all exposed groups (3 h, 6 h, 12 h), 3 of them were related to glucose metabolism. The results of the Seahorse XFe96 Analyzer indicated that the CdTe/ZnS QDs increased the glycolysis level of microglia by 86% and inhibited the aerobic respiration level by 54% in a non-hypoxic environment. In vivo study, 3 h after the injection of CdTe/ZnS QDs (2.5 mM) through the tail vein in mice, the concentration of the CdTe/ZnS QDs in hippocampus reached the peak (1.25 μM). The polarization level of microglia (Iba-1 immunofluorescence) increased 2.7 times. In vitro study, the levels of the extracellular TNF-α, IL-1β and NO of BV-2 cells were all increased significantly after a 6 h or 12 h exposure. According to the results of the Cell Counting Kit-8, after a 6 h or 12 h exposure to the CdTe/ZnS QDs, the exposed microglia could significantly decrease the number of neurons (HT-22 cell line). This study proved that CdTe/ZnS QDs could polarize microglia in the brain and cause secondary inflammatory damage to neurons. There are potential risks in the application of the CdTe/ZnS QDs in brain tissue imaging.