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Mitophagy is a selective cellular process critical for the removal of damaged mitochondria. It is essential in regulating mitochondrial number, ensuring mitochondrial functionality, and maintaining cellular equilibrium, ultimately influencing cell destiny. Numerous pathologies, such as neurodegenerative diseases, cardiovascular disorders, cancers, and various other conditions, are associated with mitochondrial dysfunctions. Thus, a detailed exploration of the regulatory mechanisms of mitophagy is pivotal for enhancing our understanding and for the discovery of novel preventive and therapeutic options for these diseases. Nanomaterials have become integral in biomedicine and various other sectors, offering advanced solutions for medical uses including biological imaging, drug delivery, and disease diagnostics and therapy. Mitophagy is vital in managing the cellular effects elicited by nanomaterials. This review provides a comprehensive analysis of the molecular mechanisms underpinning mitophagy, underscoring its significant influence on the biological responses of cells to nanomaterials. Nanoparticles can initiate mitophagy via various pathways, among which the PINK1‐Parkin pathway is critical for cellular defense against nanomaterial‐induced damage by promoting mitophagy. The role of mitophagy in biological effects was induced by nanomaterials, which are associated with alterations in Ca2+ levels, the production of reactive oxygen species, endoplasmic reticulum stress, and lysosomal damage. Mitophagy, a form of selective autophagy that maintains mitochondrial homeostasis and protects cells, is closely associated with the pathogenesis of numerous diseases. Given the widespread use and increasing exposure of nanomaterials to the human body, it is crucial to comprehend their biological effects. Therefore, we conducted a comprehensive review of the regulatory mechanisms of mitophagy and its impact on cellular responses to nanomaterials, in order to provide intervention strategies for diagnosing and treating mitochondria‐related disorders. [ABSTRACT FROM AUTHOR]

A mechanism exploration is an important part of toxicological studies. However, traditional cell and animal models can no longer meet the current needs for in-depth studies of toxicological mechanisms. The three-dimensional (3D) organoid derived from human embryonic stem cells (hESC) or induced pluripotent stem cells (hiPSC) is an ideal experimental model for the study of toxicological effects and mechanisms, which further recapitulates the human tissue microenvironment and provides a reliable method for studying complex cell–cell interactions. This article provides a comprehensive overview of the state of the 3D organoid technology in toxicological studies, including a bibliometric analysis of the existing literature and an exploration of the latest advances in toxicological mechanisms. The use of 3D organoids in toxicology research is growing rapidly, with applications in disease modeling, organ-on-chips, and drug toxicity screening being emphasized, but academic communications among countries/regions, institutions, and research scholars need to be further strengthened. Attempts to study the toxicological mechanisms of exogenous chemicals such as heavy metals, nanoparticles, drugs and organic pollutants are also increasing. It can be expected that 3D organoids can be better applied to the safety evaluation of exogenous chemicals by establishing a standardized methodology. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are widely used in many commercial and medical products. Serious concerns are paid on their adverse potentials to the environment and human health. In this study, toxic effects and oxidative stress induced by AgNPs with different sizes and coatings (20 nm AgNPs, 20 nm polyvinylpyrrolidone (PVP) -AgNPs and 50 nm AgNPs) in Caenorhabditis elegans (C. elegans) were investigated. The toxic effects including the shortened lifespan and decreased frequency of head thrashes and body bends of C. elegans were induced in a dose-dependent manner by AgNPs. The reactive oxygen species (ROS) production and the oxidative stress-related indicators including malondialdehyde (MDA) and glutathione (GSH) in nematodes were changed after exposure to three kinds of AgNPs. These effects were the most obvious in a 20 nm PVP-AgNPs exposure group. AgNPs could also induce the expression of genes related to oxidative stress in nematodes. In addition, the up-regulation of mtl-1 and mtl-2 in nematodes might reduce the oxidative damage caused by AgNPs, by using transgenic strains CF2222 and CL2120 nematodes. Metallothionein (MT), an antioxidant, could relieve the oxidative damage caused by AgNPs. These results suggested that 20 nm PVP-AgNPs with a smaller particle size and better dispersion have stronger toxic effects and the oxidative damage to nematodes. Mtl-1 and mtl-2 might be involved in alleviating the oxidative damage caused by AgNPs. Our findings provide clues for the safety evaluation and mechanism information of metal nanoparticles. Graphical Abstract [ABSTRACT FROM AUTHOR]

Recombinant human metallothionein III (rh‐MT‐III) is a genetically engineered product produced by Escherichia coli fermentation technology. Its molecules contain abundant reducing sulfhydryl groups, which possess the ability to bind heavy metal ions. The present study was to evaluate the binding effects of rh‐MT‐III against copper and cadmium in vitro and to investigate the antioxidant activity of rh‐MT‐III using Caenorhabditis elegans in vivo. For in vitro experiments, the binding rates of copper and cadmium were 91.4% and 97.3% for rh‐MT‐III at a dosage of 200 μg/mL at 10 h, respectively. For in vivo assays, the oxidative stress induced by copper (CuSO4, 10 μg/mL) and cadmium (CdCl2, 10 μg/mL) was significantly reduced after 72 h of exposure to different doses of rh‐MT‐III (5–500 μg/mL), indicated by restoring locomotion behavior and growth, and reducing malondialdehyde and reactive oxygen species levels in C. elegans. Moreover, rh‐MT‐III decreased the deposition of lipofuscin and fat content, which could delay the progression of aging. In addition, rh‐MT‐III (500 μg/mL) promoted the up‐regulation of Mtl‐1 and Mtl‐2 gene expression in C. elegans, which could enhance the resistance to oxidative stress by increasing the enzymatic activity of antioxidant defense system and scavenging free radicals. The results indicated that supplemental rh‐MT‐III could effectively protect C. elegans from heavy metal stress, providing an experimental basis for the future application and development of rh‐MT‐III. Rh‐MT‐III is a genetically engineered product fermented by Escherichia coli. This study evaluated the binding effects of rh‐MT‐III against copper and cadmium and the antioxidant activity of rh‐MT‐III in Caenorhabditis elegans. The data showed that rh‐MT‐III had high affinity for copper and cadmium and enhanced the stress resistance of nematodes by increasing the enzymatic activity of antioxidant defense system and scavenging free radicals. The results indicated that rh‐MT‐III could be used as an antioxidant to protect organisms from oxidative damage. [ABSTRACT FROM AUTHOR]

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. In this study, C. elegans was used as a model to evaluate the neurotoxicity of longer‐term exposure of 20nm AgNPs with/without PVP coating at low concentrations. The decreased survival rate and damaged neurobehavior, as well as impaired neurons and neurotransmitters in C. elegans, were observed. The PVP‐AgNPs caused a higher fatality rate and neurotoxicity. The results indicated that AgNPs caused neurotoxicity on nematodes at the doses over 0.1 mg·L−1, which provided clues for the safe application of AgNPs. [ABSTRACT FROM AUTHOR]

With the development of nanotechnology, metal‐containing nanoparticles are used widely in the diagnosis, monitoring and treatment of central nervous system (CNS) diseases. The neurotoxicity of these nanoparticles has drawn attention. Glial cells (particularly microglial cells and astrocytes) have important functions in the CNS. Neural disorders are related to functional/histologic damage to glial cells. Dysfunctions of microglial cells or astrocytes injure the brain, and cause the neurodegeneration seen in Alzheimer's disease and Parkinson's disease. We have summarized the route of access of metal‐containing nanoparticles to the CNS, as well as their neurotoxicity and potential molecular mechanisms involved in glial cells. Metal‐containing nanoparticles cross or bypass the blood‐brain barrier, access the CNS and cause neurotoxicity. The potential mechanisms are related to inflammation, oxidative stress, DNA and/or mitochondrial damage and cell death, all of which are mediated by microglial cell activation, inflammatory factor release, generation of reactive oxygen species, apoptosis and/or autophagy in glial cells. Moreover, these processes increase the burden of the CNS and even accelerate the occurrence or development of neurodegenerative diseases. Some important signaling pathways involved in the mechanism of neurotoxicity in glial cells caused by nanoparticles are also discussed. We summarized the route of metal‐containing NPs to the CNS, their neurotoxicity and molecular mechanisms in glial cells. After entry, these NPs can induce BBB damage or dysfunction of cognition, learning and memory. The potential mechanisms involved in neuroinflammation are oxidative stress, DNA and/or mitochondrial damage and cell death. These mechanisms are mediated by activation of microglial cells, release of inflammatory factors, ROS generation, and apoptosis or autophagy in glial cells. [ABSTRACT FROM AUTHOR]

This study evaluated the biodistribution and organ oxidative effects of silver nanoparticles (AgNPs) coated with/without polyvinylpyrrolidone (PVP) (AgNP‐20 and AgNP‐PVP) in mice; these were administered by gavage at a dose of 10‐250 mg/kg body weight per day for 28 days. The results showed that both the AgNPs could induce subacute toxicity and oxidative damage to mice and were mainly accumulated in the liver and spleen and excreted by feces. AgNPs could be absorbed into blood and might cross the blood‐brain barrier, and be distributed extensively in mice. The malondialdehyde content in the liver, lungs and kidneys increased in both AgNP groups, while the content of glutathione decreased, and the activity of superoxide dismutase increased at first and then decreased along with the increased doses. Inflammatory pathological changes in the lung and liver at high dose of both AgNPs were consistent with increases in glutamate pyruvic transaminase, glutamate oxaloacetic transaminase and the total protein in serum detection. The Ag content was detected in organs, with the highest content in the liver, followed by spleen, while the Ag content in feces was about 500 times higher than that in urine. AgNP‐PVP could induce higher oxidative stress and subacute toxicity than AgNP‐20 at the same dose, which might be related to the higher concentrations and more Ag+ ions released in mice after AgNP‐PVP exposure. The data from this research provided information on toxicity and biodistribution of AgNPs following gavage administration in mice, and might shed light for future application of AgNPs in daily life. The biodistribution and organ oxidative effects of nanosilver with/without coating were evaluated by general behavior, body weight, organ coefficient, serum biochemistry, histopathology and Ag content detection following oral administration in mice for 28 days. It was found that the two Ag nanoparticles (NPs) could cause subacute toxicity and organ oxidative damage to mice, and were distributed extensively in the body of mice. The toxicity caused by 20 nm silver nanoparticles coated with polyvinylpyrrolidone (AgNPs‐PVP) was greater than that caused by silver nanoparticles without coating at 20 nm (AgNPs‐20). [ABSTRACT FROM AUTHOR]

We designed a dual-color fluorescent nanoprobe for simultaneous detection and imaging of adenosine triphosphate and glutathione in living cells based on porous carbon nanospheres and a DNA hybrid hydrogel. Due to the non-template synthesis process and good biocompatibility, the nanohydrogel displayed a short preparation time and anti-nonspecific adsorption. [ABSTRACT FROM AUTHOR]

The present study shows that a dual-signal nanoprobe consisting of DNAzyme-functionalized porous carbon nanospheres (PCNs) responds to microRNA-21 and zinc ion (Zn2+). The fluorescent probe undergoes an increase in the fluorescence intensity of fluorescein isothiocyanate (FITC) (with excitation/emission wavelengths at 488/517 nm) and the fluorescence intensity of cyanine-5 (Cy5) (with excitation/emission wavelengths at 633/670 nm) in the presence of microRNA-21 and Zn2+. The recognition between microRNA-21 and its complementary strand in the PCNs induces the separation of Zn2+-specific DNAzyme from PCNs, thus resulting in the increase of green fluorescence, and the exogenous Zn2+ triggers the rupture of cleavage strand of DNAzyme and recovery of red fluorescence. This nanoprobe allows us to acquire in vitro the determination of microRNA-21 in the range of 2–300 nM with a detection limit of 0.57 nM and the determination of Zn2+ in the range 2–100 nM with a detection limit of 0.43 nM, and in situ simultaneous imaging in MCF-7 breast cancer cells. Therefore, this strategy permits to obtain the expression levels of different biomarkers in living cells, providing a useful tool for diagnosis of cancers and understanding their biological process. [ABSTRACT FROM AUTHOR]

The DNA tetrahedron has developed a broad spectrum of applications in biosensor construction thanks to its excellent mechanical rigidity and structural stability. However, how to construct a highly sensitive biosensor using a DNA tetrahedron is still a challenge. In this work, an ultrasensitive electrochemical biosensor based on a DNA tetrahedral nanostructure was developed with the help of synergy from proximity-dependent hybridization. To decrease the steric hindrance of DNA tetrahedra to proximity-dependent hybridization, the detection signal was set on the inclined side chain structure of a DNA tetrahedral sensing system. Additionally, when the target hybridized with the DNA probe, the ferrocene (Fc) labeled on the end of the DNA probe was driven close to the surface of the biosensor, providing a sensitive faradaic current. The experimental results exhibited a good linear relationship from 1 fM to 10 pM with a linear correlation coefficient of 0.9977, and a high sensitivity with a detection limit of 0.2 fM. Our DNA biosensor also showed good stability according to electrode characterization and target detection at different time scales and the anti-jamming capabilities in a complicated biological extraction environment were excellent. The electrochemical sensing system established here has greatly improved the detection sensitivity of a DNA biosensor based on a DNA tetrahedron, which will further promote its practical applications. [ABSTRACT FROM AUTHOR]

Herein, we have designed a ratiometric fluorescent nanoprobe for adenosine triphosphate sensing and imaging in living cells, based on silica nanoparticles and a DNA-functionalized hybrid hydrogel. This ratiometric detecting method could validly avoid false-positive signals. Due to its controllable size, favorable biocompatibility and biostability, the nanohydrogel exhibited high cellular permeability and fast response in living cells. [ABSTRACT FROM AUTHOR]

A novel nonenzymatic sensor based on gold nanoparticle-nitrogen-doped graphene was synthesized by electrochemical sequential deposition on the surface of a glassy carbon electrode. Nitrogen-doped graphene was synthesized by a hydrothermal method using graphene oxide and carbamide as the raw materials mixed in specific proportions. The gold nanoparticles were used in the electrochemical sensor to provide unique electronic and electrochemical properties. Under the optimized conditions, hydrogen peroxide was determined by differential pulse voltammetry with a linear relationship for concentrations from 1.0 × 10−7 to 1.0 × 10−5 mol L−1. The detection limit was 4.9 × 10−8 mol · L−1 (according to the 3σ rule) and the recoveries were 95.0-98.0%. This sensor is simple, reproducible, and demonstrates that nitrogen-doped graphene oxide has potential applications for electrochemical sensors. [ABSTRACT FROM AUTHOR]

A one-step, rapid, and visual method was developed for the detection of RNA viruses and a few copies of the Zika RNA virus were directly detected within 25 min by naked-eye observation. This method will prove to be promising for point-of-care testing in out-of-lab and inconvenient settings. [ABSTRACT FROM AUTHOR]

A polythiophene–graphene oxide compound membrane and Prussian blue were deposited sequentially on the surface of a glassy carbon electrode by cyclic voltammetry. Due to its excellent electrocatalysis and its analogy with peroxidase enzymes, Prussian blue has been widely used in amperometric biosensors. The polythiophene–graphene oxide compound membrane exhibited good electroconductibility and a large specific surface area. The fabricated Prussian blue/polythiophene/graphene oxide/glassy carbon electrode was characterized by transmission electron microscopy, scanning electron microscopy, and cyclic voltammetry. Under the optimal experimental conditions, the detection of hydrogen peroxide was studied by its amperometric current–time curve. Due to the presence of polythiophene–graphene oxide compound membrane and Prussian blue, the hydrogen peroxide sensor shows a linear calibration range of 1.0 × 10−6–1.0 × 10−4 mol L−1, detection limits of 3.2 × 10−7 mol L−1at a signal-to-noise ratio of 3, and recoveries from 95.0 to 105.0%. The results show that the modified glassy carbon electrode has potential practical application for the determination of hydrogen peroxide based on its sensitivity and long-term stability. [ABSTRACT FROM PUBLISHER]

A facile and sensitive fluorescent strategy for the determination of dopamine is reported using 2, 3-diaminophenazine. Dopamine caused autooxidation in the presence of oxygen with catalysis by Mn2+and formed 2, 3-dihydro-1H-indole-5,6-dione. 2, 3-Diaminophenazine provided relatively strong fluorescence. 2, 3-Diaminophenazine in aqueous solution caused fluorescence quenching when the aminochrome condensed with 2, 3-diaminophenazine to allow the determination of dopamine. Under the optimized conditions, the linear dynamic range for dopamine was from 2.0 × 10−6 mol · L−1to 6.1 × 10−5 mol · L−1with a detection limit of 1.76 × 10−6 mol · L−1. [ABSTRACT FROM PUBLISHER]

In this report, a strategy based on an aptameric molecule switch to realize homogeneous and isothermal signal exponential amplification and protein detection has been described. This method was simple and sensitive, allowing detection of as low as 2.6 × 10−12 M thrombin. [ABSTRACT FROM AUTHOR]

Graphite oxide was prepared by oxidizing graphite powder, reduced to graphene using hydrazine hydrate, and the grapheme was mixed with chitosan to form a composite that was used to modify a glassy carbon electrode for the determination of copper(II). The electrochemical behavior of the modified electrode was studied by cyclic and square wave voltammetries. The morphology and structure of the composite were characterized by infrared spectroscopy, transmission electron microscopy, and scanning electron microscopy. In addition, the proportion of composite material, pH, and adsorption time was optimized. Under the optimized experimental conditions, the sensor showed a linear dynamic range from 1.0 × 10−9to 1.5 × 10−8 mol · L−1for copper(II) with a limit of detection of 4.3 × 10−10 mol · L−1at a signal-to-noise ratio of three. The sensor displayed excellent electrochemical response and high sensitivity. [ABSTRACT FROM AUTHOR]

Cation-exchange-based chemiluminescence amplification (CXCLAmp) was developed in this study. After amplification by rolling circle amplification (RCA), the proposed RCA–CXCLAmp strategy was used to detect miRNA sensitively. [ABSTRACT FROM AUTHOR]

We report on an electrochemical immunoassay for simultaneous detection of the tumor markers carcinoembryonic antigen (CEA) and α-fetoprotein (AFP). Gold nanoparticles (AuNPs) were synthesized inside the internal pore walls of mesoporous silica (MPS). Then, Methylene blue (MB) and 6-ferrocenylhexanethiol (FeC), which act as electrochemical substrates, were incorporated into the channels via the formation of Au-S bonds. Finally, monoclonal antibodies against CEA (anti-CEA) and AFP (anti-AFP) were immobilized in the channels of MB-AuNPs-MPS and FeC-AuNPs-MPS, respectively. Suspensions of anti-CEA/MB-AuNPs-MPS and of anti-AFP/FeC-AuNPs-MPS were deposited on two different sites of the ITO electrode. When incubated with samples containing the two analytes, the formation of electrically nonconductive immunoconjugates blocks electron transfer. Simultaneous detection of CEA and AFP was accomplished by monitoring the current change before and after an immunoreaction has occurred. The AuNPs confined inside the channels are promoting the electron transport and thus improve detection limits. The immunoelectrode responds to CEA in the 0.5-50 ng mL concentration range, and to AFP in concentrations between 0.5 and 100 ng mL. The detection limits (at an S/N of 3) are 0.1 ng mL in both cases. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A novel fluorescence assay, based on the signal amplification through cycling reactions of aptameric recognition and nucleic acid exo-cleaving, was established for the sensitive detection of cocaine. In this assay, a new single fluorophore-labeled DNA-hairpin probe was used. This smart probe was established based on the significant nucleobase quenching between the nucleobases and the fluorophore. In the presence of cocaine and its aptamer, the structure of the smart probe changed to recover the fluorescence. In order to enhance the sensitivity of this assay, exonuclease III was introduced to enable the inputted cocaine to react with multiple probes in a recycling manner. Under the optimal conditions, a linear range for cocaine from 4.0 × 10−9 to 8.0 × 10−8 M with a detection limit of 1.76 × 10−9 M (3σ, n = 11) was obtained. [ABSTRACT FROM PUBLISHER]

The electrooxidation of 3,3′, 5,5′-tetramethylbenzidine (TMB) is dependent on the pH value of Britton-Robinson (B-R) buffer solution. In this work, the electrooxidation behavior of TMB was investigated with a SnO2:F film optically transparent thin-layer spectroelectrochemical cell. TMB underwent one two-electron electrooxidation process in the pH range from 2.0 to < 4.0, and two successive one-electron electrooxidation processes in the pH range from 4.0 to < 7.0 in the B-R buffer solution. At pH 6.5, the electrooxidative product of TMB generated a subsequent chemical reaction to yield an azo compound. Several spectroelectrochemical techniques, such as thin-layer cyclic voltammetry, thin-layer cyclic voltabsorptometry, thin-layer potential-controlled electrolysis absorptometry, thin-layer single-potential-step chronoabsorptometry, thin-layer double-potential-step chronoabsorptometry, thin-layer single-potential-step open-circuit relaxation chronoabsorptometry, were applied to this investigation. The formal potential E0′ and the electron transfer number corresponding to the electrooxidation of TMB in B-R buffer solution, and the reaction rate constant of the subsequent chemical reaction were determined. [ABSTRACT FROM AUTHOR]