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Microelectrode arrays (MEAs) have been widely used in studies on the electrophysiological features of neuronal networks. In classic MEA experiments, spike or burst rates and spike waveforms are the primary characteristics used to evaluate the neuronal network excitability. Here, we introduced a new method to assess the excitability using the voltage threshold of electrical stimulation. We tested the stability of the voltage threshold during the experiment and demonstrated the reliability of our method by examining the effect of Ni 2+ on neocortical neuronal networks of acute brain slices from rats. Moreover, we compared our new method with the spontaneous activity analysis, which is one of the most commonly used methods in protocols for large-scale drug screening with MEA; our new method performed better in the experiments investigating the neocortical neuronal network excitability after the application of Ni 2+ . Based on the results from our study, our new method has great potential for use in large-scale screening of drugs.

The aim of this study was to explore the mechanisms in silver nanoparticle (AgNP)-induced cytotoxicity from gene to metabolite levels through an integrative analysis of transcriptomics and metabolomics results. First, transcriptome sequencing technology revealed 1365, 1241, and 2790 genes differentially expressed within human dermal fibroblasts (HDFs) after 4, 8, and 24 h of exposure to silver nanoparticles, which were involved in 250, 248, and 280 biological pathways. Then, by comparing with the metabolomics results, 7 metabolic pathways (purine metabolism pathway, glycerophospholipid metabolism pathway, etc.), with 9 key upstream genes ( ADCY 4, SPHK 1, etc.) and 8 downstream metabolites (xanthine, choline, etc.) jointly involved were found relate to AgNP-induced cytotoxicity. Finally, the results of the validation experiments revealed that AgNPs exerted the toxic effects through these pathways, inducing oxidative stress, affecting energy metabolism, arresting the cell cycle, disrupting the cytoskeleton, inhibiting cell proliferation, and triggering apoptosis.

The aim of this study was to investigate the toxic effects and mechanism of silver nanoparticles (SNPs) on the cytological and electrophysiological properties of rat adrenal pheochromocytoma (PC12) cells. Different concentrations of SNPs (20 nm) were prepared, and the effects of different application durations on the cell viability and electrical excitability of PC12 quasi-neuronal networks were investigated. The effects of 200 μM SNPs on the neurite length, cell membrane potential (CMP) difference, intracellular Ca 2+ content, mitochondrial membrane potential (MMP) difference, adenosine triphosphate (ATP) content, and reactive oxygen species (ROS) content of networks were then investigated. The results showed that 200 μM SNPs produced grade 1 cytotoxicity at 48 h of interaction, and the other concentrations of SNPs were noncytotoxic. Noncytotoxic 5 μM SNPs significantly increased electrical excitability, and noncytotoxic 100 μM SNPs led to an initial increase followed by a significant decrease in electrical excitability. Cytotoxic SNPs (200 μM) significantly decreased electrical excitability. SNPs (200 μM) led to decreases in neurite length, MMP difference and ATP content and increases in CMP difference and intracellular Ca 2+ and ROS levels. The results revealed that not only cell viability but also electrophysiological properties should be considered when evaluating nanoparticle-induced neurotoxicity. The SNP-induced cytotoxicity mainly originated from its effects on ATP content, cytoskeletal structure and ROS content. The decrease in electrical excitability was mainly due to the decrease in ATP content. ATP content may thus be an important indicator of both cell viability and electrical excitability in PC12 quasi-neuronal networks.

It is still challenging to achieve a complex grasp or fine finger control by using surface functional electrical stimulation (FES), which usually requires a precise electrode configuration under laboratory or clinical settings. The goals of this study are as follows: 1) to study the possibility of selectively activating individual fingers; 2) to investigate whether the current activation threshold and selective range of individual fingers are affected by two factors: changes in the electrode position and forearm rotation (pronation, neutral and supination); and 3) to explore a theoretical model for guidance of the electrode placement used for selective activation of individual fingers. A coordinate system with more than 400 grid points was established over the forearm skin surface. A searching procedure was used to traverse all grid points to identify the stimulation points for finger extension/flexion by applying monophasic stimulation pulses. Some of the stimulation points for finger extension and flexion were selected and tested in their respective two different forearm postures according to the number and the type of the activated fingers and the strength of finger action response to the electrical stimulation at the stimulation point. The activation thresholds and current ranges of the selectively activated finger at each stimulation point were determined by visual analysis. The stimulation points were divided into three groups (\"Low\", \"Medium\" and \"High\") according to the thresholds of the 1st activated fingers. The angles produced by the selectively activated finger within selective current ranges were measured and analyzed. Selective stimulation of extension/flexion is possible for most fingers. Small changes in electrode position and forearm rotation have no significant effect on the threshold amplitude and the current range for the selective activation of most fingers (p > 0.05). The current range is the largest (more than 2 mA) for selective activation of the thumb, followed by those for the index, ring, middle and little fingers. The stimulation points in the \"Low\" group for all five fingers lead to noticeable finger angles at low current intensity, especially for the index, middle, and ring fingers. The slopes of the finger angle variation in the \"Low\" group for digits 2~4 are inversely proportional to the current intensity, whereas the slopes of the finger angle variation in other groups and in all groups for the thumb and little finger are proportional to the current intensity. It is possible to selectively activate the extension/flexion of most fingers by stimulating the forearm muscles. The physiological characteristics of each finger should be considered when placing the negative electrode for selective stimulation of individual fingers. The electrode placement used for the selective activation of individual fingers should not be confined to the location with the lowest activation threshold.

The cytotoxic effects of Ni2+ released from nickel-based alloy implants on tissues have been a longstanding research focus in biocompatibility studies. However, investigations into the neurotoxicity of Ni2+ remain relatively limited. Building on our previous findings that Ni2+ can rapidly affect the excitability of neuronal networks, this study further investigated the neurotoxic effects of prolonged Ni2+ exposure. First, the cytotoxicity effects of Ni2+ on rat neocortical neurons in vitro were evaluated by MTT cell viability assay, and changes in the length of the axon initial segment of neurons caused by Ni2+ exposure were quantified. Next, transcriptome sequencing was employed to identify differentially expressed genes (DEGs) induced by Ni2+ treatment, and four DEGs—Hk2, Ldha, Cd9, and Nfasc—were selected for qRT-PCR validation. The ATP content of neurons was measured to assess cellular energy metabolism under Ni2+ influence. Finally, by comparing these experimental results with our previous findings, this study explored the neurotoxicity mechanisms of Ni2+ and analyzed the correlation between its neurotoxicity and cytotoxicity. This study revealed that the neurotoxicity mechanisms of Ni2+ are associated with the concentration of Ni2+ and the duration of its action. When at low concentrations or with short exposure times, Ni2+ suppresses the excitability of the neuronal networks by rapidly blocking Ca2+ channels, whereas at high concentrations or with prolonged exposure, it further inhibits the network’s excitability by activating the HIF-1α pathway and inducing obvious cytotoxicity.

The purpose of this article was to explore the effects of gold nanoparticles (GNPs) and silver nanoparticles (SNPs) with different cytotoxicities on human dermal fibroblasts (HDFs) at the metabolic level. First, ∼20 nm of GNPs and SNPs were prepared, and their effects on the proliferation of HDFs were evaluated. Then, a metabolomics technique was used to analyse the effects of GNPs and SNPs on the expression profiles of metabolites in HDFs after 4, 8 and 24 h of treatment. Furthermore, the key metabolites and key metabolic pathways involved in the interaction of GNPs and SNPs with HDFs were identified through expression pattern analysis and metabolic pathway analysis of differentially expressed metabolites and were finally verified by experiments. The results of the cytotoxicity experiments showed that there was no cytotoxicity after the treatment of GNPs for 72 h, while the cytotoxicity of the SNPs reached grade 1 after 72 h. By using metabolomics analysis, 29, 30 and 27 metabolites were shown to be differentially expressed in HDFs after GNP treatment, while SNPs induced the differential expression of 13, 33 and 22 metabolites after 4, 8 and 24 h of treatment, respectively. Six and four candidate key metabolites in the GNP and SNP groups were identified by expression pattern analysis and metabolic pathway analysis, respectively. The key metabolic pathways in the GNP and SNP groups were identified as the glutathione metabolic pathway (the key metabolite of which was glutathione) and the citrate cycle pathway (the key metabolite of which was malic acid). Based on the experiments used to verify the key metabolites and key metabolic pathways, it was found that the increase in glutathione after GNP treatment might trigger an oxidative stress protection mechanism and thus avoid cytotoxicity. After exposure to SNPs, the citric acid content was increased, mainly through the citrate cycle pathway, thereby inhibiting the synthesis of malic acid to affect the formation of ATP and finally leading to cytotoxicity.

Steroid hormones play essential roles in the reproductive biology of vertebrates. Estrogen exercises its effect through estrogen receptors and is not only a female reproductive hormone but acts virtually in all vertebrates, including fish, and is involved in the physiological and pathological states in all males and females. Estrogen has been implicated in mandible conservation and circulatory and central nervous systems as well as the reproductive system. This review intended to understand the structure, function, binding affinities, and activations of estrogens and estrogen receptors and to discuss the understanding of the role of sex steroid hormone estrogen receptors in mammals and fish.

Considering the importance of hydrogen peroxide (H2O2) rapid detection, a SnS2/MWCNTs composite was prepared by loading tin disulfide (SnS2) nanoparticles on a three-dimensional conductive network composed of multi-walled carbon nanotubes (MWCNTs). The obtained SnS2/MWCNTs composite was used as the modified material to prepare a chemically modified electrode (CME), which was used for the rapid detection of H2O2. The morphology and structure of the obtained samples were characterized and analyzed by scanning electron microscopy, X-ray diffraction, and energy-dispersive spectroscopy. The electrochemical performance of the modified electrode was researched by cyclic voltammetry, amperometric i–t curves, and AC impedance techniques. The results show that SnS2 nanoparticles with a size of about 33 nm are evenly dispersed on the surface of MWCNTs. The obtained SnS2/MWCNTs-CME has a strong current response to H2O2: it has a good linear relationship during the range of 0.248 ~ 16.423 mmol L−1, and its linear regression equation is Ipa (mA) = (−0.94 ± 0.05) × 10−2 + (− 0.43 ± 0.06) × 10−2c (mmol L−1) (R2 = 0.997) with a sensitivity of 87.84 μA mmol−1 L cm−2. The corresponding detection limit is 1.04 μmol L−1 (S/N = 3). At the same time, the SnS2/MWCNTs-CME has good selectivity, reproducibility, and stability.

Hierarchical network-like graphitic carbon nitride/SnIn₄S₈ (g-C₃N₄/SnIn₄S₈) composites were prepared through a facile low-temperature co-precipitation method. The g-C₃N₄/SnIn₄S₈ composite showed enhanced visible-light absorption. The band gap energies of g-C₃N₄, pure SnIn₄S₈, and 15 % g-C₃N₄/SnIn₄S₈ are 2.58, 1.8, and 1.68 eV, respectively. The photocurrent and photocatalytic activity of the g-C₃N₄/SnIn₄S₈ composites firstly increased and then decreased with increasing g-C₃N₄ content, and it was found that the optimal 15 % g-C₃N₄/SnIn₄S₈ exhibited the highest photocurrent intensity and best photocatalytic performance with complete degradation of MO within 80 min under visible-light irradiation, which is much higher than that of pure SnIn₄S₈. The effect of main reactive species on the MO degradation follows the order of h⁺ > •O₂ ⁻ > •OH, and the possible degradation mechanism was proposed. Moreover, 15 % g-C₃N₄/SnIn₄S₈ exhibits excellent reusability and stability without an obvious decrease of photocatalytic activity after four consecutive photocatalytic degradation–regeneration cycles.

Developing a cost-effective electrocatalyst with high activity and excellent stability is very significant to nonenzymatic glucose detection. Herein, we have constructed 3D NiCo/NiCoOx nanocluster electrode modified by amorphous FeOOH nanosheets owing to the similar electrocatalytic activity of FeOOH to natural peroxidases. The NiCo nanoclusters can provide an excellent conductivity and high active surface areas, while the amorphous two-dimensional ultrathin structure of FeOOH stimulates more open metal sites for glucose oxidation. Besides, the strong synergetic effects among ternary Fe, Ni and Co are beneficial to the transport of charge. Though comprehensive electrochemical measurements, it is found that the as-prepared electrode possesses the prominent activity toward glucose oxidation with high sensitivity of 7138 µA mM−1 cm−2, a wide linear range of 1 µM and 8 mM, a low detection limit of 0.82 µM, good selectivity and excellent stability, all of which is mainly derived from the more active sites, rapid mass transport and superior electron transfer. This research provides a model system for developing more available electrocatalysts for glucose detection.