Competitive-like binding between carbon black and CTNNB1 to ΔNp63 interpreting the abnormal respiratory epithelial repair after injury.

Airway epithelium is extraordinary vulnerable to damage owning to continuous environment exposure. Subsequent repair is therefore essential to restore the homeostasis of respiratory system. Disruptions in respiratory epithelial repair caused by nanoparticles exposure have been linked to various human diseases, yet implications in repair process remain incompletely elucidated. This study aims to elucidate the key stage in epithelial repair disturbed by carbon black (CB) nanoparticles, highlighting the pivotal role of ΔNp63 in mediating the epithelium repair. A competitive-like binding between CB and beta-catenin 1 (CTNNB1) to ΔNp63 is proposed to elaborate the underlying toxicity mechanism. Specifically, CB exhibits a remarkable inhibitory effect on cell proliferation, leading to aberrant airway epithelial repair, as validated in air-liquid culture. ΔNp63 drives efficient epithelial proliferation during CB exposure, and CTNNB1 was identified as a target of ΔNp63 by bioinformatics analysis. Further molecular dynamics simulation reveals that oxygen-containing functional groups on CB disrupt the native interaction of CTNNB1 with ΔNp63 through competitive-like binding pattern. This process modulates CTNNB1 expression, ultimately restraining proliferation during respiratory epithelial repair. Overall, the current study elucidates that the diminished interaction between CTNNB1 and ΔNp63 impedes respiratory epithelial repair in response to CB exposure, thereby enriching the public health risk assessment on CB-related respiratory diseases.

Exploring Prenatal Exposure to Halogenated Compounds and Its Relationship with Birth Outcomes Using Nontarget Analysis.

Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks.

Transcriptomic alterations in cortical astrocytes following the development of post-traumatic epilepsy.

Post-traumatic epilepsy (PTE) stands as one of the numerous debilitating consequences that follow traumatic brain injury (TBI). Despite its impact on many individuals, the current landscape offers only a limited array of reliable treatment options, and our understanding of the underlying mechanisms and susceptibility factors remains incomplete. Among the potential contributors to epileptogenesis, astrocytes, a type of glial cell, have garnered substantial attention as they are believed to promote hyperexcitability and the development of seizures in the brain following TBI. The current study evaluated the transcriptomic changes in cortical astrocytes derived from animals that developed seizures as a result of severe focal TBI. Using RNA-Seq and ingenuity pathway analysis (IPA), we unveil a distinct gene expression profile in astrocytes, including alterations in genes supporting inflammation, early response modifiers, and neuropeptide-amidating enzymes. The findings underscore the complex molecular dynamics in astrocytes during PTE development, offering insights into therapeutic targets and avenues for further exploration.

Atmospheric fine particulate matter (PM2.5) induces pulmonary fibrosis by regulating different cell fates via autophagy.

The presence of respiratory diseases demonstrates a positive correlation with atmospheric fine particulate matter (PM2.5) exposure. The respiratory system is the main target organ affected by PM2.5, and exposure to PM2.5 elevates the likelihood of developing pulmonary fibrosis (PF). In this study, lung epithelial cell (BEAS-2B) and fibroblast (NIH-3T3) were used as in vitro exposure models to explore the mechanisms of PF. PM2.5 exposure caused mitochondrial damage in BEAS-2B cells and increased a fibrotic phenotype in NIH-3T3 cells. Epithelial cells and fibroblasts have different fates after PM2.5 exposure due to their different sensitivities to trigger autophagy. Exposure to PM2.5 inhibits mitophagy in BEAS-2B cells, which hinders the removal of damaged mitochondria and triggers cell death. In this process, the nuclear retention of the mitophagy-related protein Parkin prevents it from being recruited to mitochondria, resulting in mitophagy inhibition. In contrast, fibroblasts exhibit increased levels of autophagy, which may isolate PM2.5 and cause abnormal fibroblast proliferation and migration. Fibrotic phenotypes such as collagen deposition and increased α-actin also appear in fibroblasts. Our results identify PM2.5 as a trigger of PF and delineate the molecular mechanism of autophagy in PM2.5 induced PF, which provides new insights into the pulmonary injury.

Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsy.

Traumatic brain injury (TBI) can lead to post-traumatic epilepsy (PTE). Blast TBI (bTBI) found in Veterans presents with several complications, including cognitive and behavioral disturbances and PTE; however, the underlying mechanisms that drive the long-term sequelae are not well understood. Using an unbiased proteomics approach in a mouse model of repeated bTBI (rbTBI), this study addresses this gap in the knowledge. After rbTBI, mice were monitored using continuous, uninterrupted video-EEG for up to four months. Following this period, we collected cortex and hippocampus tissues from three groups of mice: those with post-traumatic epilepsy (PTE+), those without epilepsy (PTE-), and the control group (sham). Hundreds of differentially expressed proteins were identified in the cortex and hippocampus of PTE+ and PTE- relative to sham. Focusing on protein pathways unique to PTE+, pathways related to mitochondrial function, post-translational modifications, and transport were disrupted. Computational metabolic modeling using dysregulated protein expression predicted mitochondrial proton pump dysregulation, suggesting electron transport chain dysregulation in the epileptic tissue relative to PTE-. Finally, data mining enabled the identification of several novel and previously validated TBI and epilepsy biomarkers in our data set, many of which were found to already be targeted by drugs in various phases of clinical testing. These findings highlight novel proteins and protein pathways that may drive the chronic PTE sequelae following rbTBI.

STING-Dependent Signaling in Microglia or Peripheral Immune Cells Orchestrates the Early Inflammatory Response and Influences Brain Injury Outcome.

While originally identified as an antiviral pathway, recent work has implicated that cyclic GMP-AMP-synthase-Stimulator of Interferon Genes (cGAS-STING) signaling is playing a critical role in the neuroinflammatory response to traumatic brain injury (TBI). STING activation results in a robust inflammatory response characterized by the production of inflammatory cytokines called interferons, as well as hundreds of interferon stimulated genes (ISGs). Global knock-out (KO) mice inhibiting this pathway display neuroprotection with evidence that this pathway is active days after injury; yet, the early neuroinflammatory events stimulated by STING signaling remain understudied. Furthermore, the source of STING signaling during brain injury is unknown. Using a murine controlled cortical impact (CCI) model of TBI, we investigated the peripheral immune and microglial response to injury utilizing male chimeric and conditional STING KO animals, respectively. We demonstrate that peripheral and microglial STING signaling contribute to negative outcomes in cortical lesion volume, cell death, and functional outcomes postinjury. A reduction in overall peripheral immune cell and neutrophil infiltration at the injury site is STING dependent in these models at 24 h. Transcriptomic analysis at 2 h, when STING is active, reveals that microglia drive an early, distinct transcriptional program to elicit proinflammatory genes including interleukin 1-ß (IL-1ß), which is lost in conditional knock-out mice. The upregulation of alternative innate immune pathways also occurs after injury in these animals, which supports a complex relationship between brain-resident and peripheral immune cells to coordinate the proinflammatory response and immune cell influx to damaged tissue after injury.

Immunoregulatory and neutrophil-like monocyte subsets with distinct single-cell transcriptomic signatures emerge following brain injury.

Monocytes represent key cellular elements that contribute to the neurological sequela following brain injury. The current study reveals that trauma induces the augmented release of a transcriptionally distinct CD115+/Ly6Chi monocyte population into the circulation of mice pre-exposed to clodronate depletion conditions. This phenomenon correlates with tissue protection, blood-brain barrier stability, and cerebral blood flow improvement. Uniquely, this shifted the innate immune cell profile in the cortical milieu and reduced the expression of pro-inflammatory Il6, IL1r1, MCP-1, Cxcl1, and Ccl3 cytokines. Monocytes that emerged under these conditions displayed a morphological and gene profile consistent with a subset commonly seen during emergency monopoiesis. Single-cell RNA sequencing delineated distinct clusters of monocytes and revealed a key transcriptional signature of Ly6Chi monocytes enriched for Apoe and chitinase-like protein 3 (Chil3/Ym1), commonly expressed in pro-resolving immunoregulatory monocytes, as well as granule genes Elane, Prtn3, MPO, and Ctsg unique to neutrophil-like monocytes. The predominate shift in cell clusters included subsets with low expression of transcription factors involved in monocyte conversion, Pou2f2, Na4a1, and a robust enrichment of genes in the oxidative phosphorylation pathway which favors an anti-inflammatory phenotype. Transfer of this monocyte assemblage into brain-injured recipient mice demonstrated their direct role in neuroprotection. These findings reveal a multifaceted innate immune response to brain injury and suggest targeting surrogate monocyte subsets may foster tissue protection in the brain.

Hepatotoxicity assessment investigations on PFASs targeting L-FABP using binding affinity data and machine learning-based QSAR model.

Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants that have been detected in various environmental media and human serum, but their safety assessment remains challenging. PFASs may accumulate in liver tissues and cause hepatotoxicity by binding to liver fatty acid binding protein (L-FABP). Therefore, evaluating the binding affinity of PFASs to L-FABP is crucial in assessing the potential hepatotoxic effects. In this study, two binding sites of L-FABP were evaluated, results suggested that the outer site possessed high affinity to polyfluoroalkyl sulfates and the inner site preferred perfluoroalkyl sulfonamides, overall, the inner site of L-FABP was more sensitive to PFASs. The binding affinity data of PFASs to L-FABP were used as training set to develop a machine learning model-based quantitative structure-activity relationship (QSAR) for efficient prediction of potentially hazardous PFASs. Further Bayesian Kernel Machine Regression (BKMR) model disclosed flexibility as the determinant molecular property on PFASs-induced hepatotoxicity. It can influence affinity of PFASs to target protein through affecting binding conformations directly (individual effect) as well as integrating with other molecular properties (joint effect). Our present work provided more understanding on hepatotoxicity of PFASs, which could be significative in hepatotoxicity gradation, administration guidance, and safer alternatives development of PFASs.

Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy.

BACKGROUND: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under investigation. The dentate gyrus-a structure that is highly susceptible to injury-has been implicated in the evolution of seizure development. METHODS: Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2-4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by unbiased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching, and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-Seq were performed to determine differential gene expression in animals that developed post-traumatic epilepsy (PTE+) vs. those animals that did not (PTE-), which may be associated with epileptogenesis. RESULTS: CCI injury resulted in 37% PTE incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions, which showed increased astroglial expression in the PTE+ hilus. CONCLUSIONS: These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.

The genomic characteristics affect phenotypic diversity from the perspective of genetic improvement of economic traits.

The genetic improvement of economic traits suggests that chicken is an excellent model for exploring the genetic changes and molecular mechanisms underlying phenotypic diversity and artificial selection. Here, the sequencing data including 477 samples from 25 breeds worldwide were used to reveal the genomic patterns of chicken domestication. We analyzed 7.4 Tb clean data with 14.8× per individual to identify 23,504,766 SNPs, 3,289,782 InDels, and 27,027 SVs. The diversity analysis indicates that high-intensity artificial selection would accelerate population differentiation. We also found that the human-driven traits are controlled by polygenes and major genes, such as the primary candidates SOX5 and IGF1 for body size, and NEDD4 for sperm storage capacity. Our findings provide an important reference for understanding how genomic patterns shape phenotypes in livestock.

2D MoS2 Nanosheets Induce Ferroptosis by Promoting NCOA4-Dependent Ferritinophagy and Inhibiting Ferroportin.

The exposure of MoS2 nanosheets can cause cytotoxicity, which causes health risks and affects its medical applications. However, knowledge of the underlying molecular mechanisms remains limited. This study reports that MoS2 nanosheets induces ferroptosis in vivo and in vitro, which is caused by the nanosheet themselves rather than by the dissolved ions. MoS2 nanosheets induce ferroptosis in epithelial (BEAS-2B) and macrophage (RAW264.7) cells due to nuclear receptor coactivator 4 (NCOA4)-dependent excusive ferritinophagy and the inhibition of ferroportin-1 (FPN). In this process, most of the MoS2 nanosheets enter the cells via macropinocytosis and are localized to the lysosome, contributing to an increase in the lysosomal membrane permeability. At the same time, NCOA4-dependent ferritinophagy is activated, and ferritin is degraded in the lysosome, which generates Fe2+ .Fe2+ leaks into the cytoplasm, leading to ferroptosis. Furthermore, the inhibition of FPN further aggravates the overload of Fe2+ in the cell. It has also been observed that ferroptosis is increased in lung tissue in mouse models exposed to MoS2 nanosheets. This work highlights a novel mechanism by which MoS2 nanosheets induce ferroptosis by promoting NCOA4-dependent ferritinophagy and inhibiting FPN, which could be of importance to elucidate the toxicity and identify the medical applications of 2D nanoparticles.

PyCoCa:A quantifying tool of carbon content in airway macrophage for assessment the internal dose of particles.

Given the lack of a comprehensive understanding of the complex metabolism and variable exposure environment, carbon particles in macrophages have become a potentially valuable biomarker to assess the exposure level of atmospheric particles, such as black carbon. However, the tedious and subjective quantification method limits the application of carbon particles as a valid biomarker. Aiming to obtain an accurate carbon particles quantification method, the deep learning and binarization algorithm were implemented to develop a quantitative tool for carbon content in airway macrophage (CCAM), named PyCoCa. Two types of macrophages, normal and foamy appearance, were applied for the development of PyCoCa. In comparison with the traditional methods, PyCoCa significantly improves the identification efficiency for over 100 times. Consistency assessment with the gold standard revealed that PyCoCa exhibits outstanding prediction ability with the Interclass Correlation Coefficient (ICC) values of over 0.80. And a proper fresh dye will enhance the performance of PyCoCa (ICC = 0.89). Subsequent sensitivity analysis confirmed an excellent performance regarding accuracy and robustness of PyCoCa under high/low exposure environments (sensitivity > 0.80). Furthermore, a successful application of our quantitative tool in cohort studies indicates that carbon particles induce macrophage foaming and the foaming decrease the carbon particles internalization in reverse. Our present study provides a robust and efficient tool to accurately quantify the carbon particles loading in macrophage for exposure assessment.

Effect of silica nanoparticles on cell membrane fluidity: The role of temperature and membrane composition.

The increasing production and application of silica nanoparticles (SiO2 NPs) raise public concern regarding their environmental and health risks. The fluidity of the cell membrane is essential for supporting membrane proteins and regulating membrane transport. Changes in membrane fluidity inevitably influence the physiological activities of cells and even cause biological effects. In this study, the effect of SiO2 NPs on membrane fluidity was studied at 25 °C and 37 °C, and the role of membrane components in SiO2 NP-membrane interactions was investigated using giant plasma membrane vesicles (GPMVs) isolated from RBL-2H3 cells. SiO2 NPs cause a more serious membrane fluidity decrease at 37 °C than at 25 °C, which is revealed by the shift of Laurdan fluorescence emission and further quantified via forster resonance energy transfer (FRET) experiments. In addition, after the removal of 75 % cholesterol from the membrane, SiO2 NPs caused a greater extent of membrane gelation. These results indicate that SiO2 NPs prefer to interact with membranes that are more dynamic and less densely packed. Moreover, fluorescent experiments confirmed that the existence of phosphatidyl ethanolamine (PE) and phosphoinositide (PI) can mitigate NP-induced membrane gelation. Molecular dynamics simulation further demonstrated that SiO2 NPs form hydrogen bonds with the terminal of PE or PI but with the -PO4-- group in the middle of phosphatidylcholine (PC). The bonding that occurs in the terminal gives less restriction of phospholipid movement and a weaker effect on membrane fluidity. This research provides both evidence and mechanisms of SiO2 NP-induced membrane fluidity changes, which are helpful for understanding cell membrane damage and the biological effects of NPs.

Transcriptomic and metabolomic insights into the variety of sperm storage in oviduct of egg layers.

In birds, the sperm storage tubules (SST) are dispersed in uterovaginal junction (UVJ) and highly correlated with differential capacity of sperm storage (SS) in and among species with unspecified mechanisms. Here, the SS duration of 252 egg layer breeders was evaluated in 5 rounds with 3 phenotypic traits to screen high- and low-SS individuals, respectively, followed with transcriptome of UVJ tissues and metabolome of serum (high-SS vs. low-SS) to decipher the candidate genes and biochemical markers correlated with differential SS capacity. Histological characterization suggested slightly higher density of SST in UVJ (high-SS vs. low-SS). Transcriptome analyses identified 596 differentially expressed genes (336 upregulated vs. 260 downregulated), which were mainly enriched in gene ontology terms of homeostasis, steroid and lipid metabolism and hormone activity, and 12 significant pathways (P < 0.05) represented by calcium, steroid, and lipid metabolism. Immunohistochemical staining of GNAQ, ST6GAL1, ADFP, and PCNA showed similar distribution in UVJ tissues between 2 groups. Several candidates (HSD11B2, DIO2, AQP3, GNAQ, NANS, ST6GAL1) combined with 4 (11ß-prostaglandin F2α, prostaglandin B1, 7α-hydroxytestosterone, and N-acetylneuraminic acid) of 40 differential metabolites enriched in serum metabolome were considered as regulators and biomarkers of SS duration in egg layer breeders. The integrated transcriptome and metabolome analyses of chicken breeder hens will provide novel insights for exploration and improvement of differential SS capacity in birds.

Transcriptome analysis and identification of age-associated fertility decreased genes in hen uterovaginal junction.

Avian sperm storage tubules (SSTs), which are located in the uterovaginal junction (UVJ) of the oviduct, are primary sperm storage sites after mating or artificial insemination. The mechanism underlying reduced sperm storage efficiency of SSTs which is highly correlated with decreased fertility rates in aged laying breeders remains largely unclear. Here, comparative transcriptomic analysis between the aged and young White Leghorn hens (120 vs. 30 wk) was applied to identify gene expression changes of UVJs containing SSTs. Bioinformatics analysis revealed 567 upregulated and 1998 downregulated differentially expressed genes. Gene ontology analysis was highly enriched in terms of immune system, cell adhesion, and cytoskeleton proteins. Kyoto Encyclopedia of Genes and Genomes analysis revealed 5 significant (P < 0.05) pathways including inositol phosphate and glycerophospholipid metabolism. ß-Galactosidase staining of chicken UVJ sections suggested increased cell senescence via aging. Oil Red O staining and immunohistochemistry detection of ADFP both confirmed distribution of lipid droplets in SST cells with increased intensity in aged breeders. The lipid synthesis and metabolism-related genes represented by TFAP2 and PLD1 were differentially expressed in aged laying breeders. The upregulation of IL15 and downregulation of a large number of immune-related genes in aged breeders indicate altered immune homeostasis in UVJs and SSTs. The increased accumulation of lipids, and altered immunity homeostasis, combined with other factors (TJP1, MYL9, AFDN, and RPL13, etc.) are potentially dominant effectors to decrease the sperm storage efficiency and egg fertility in aged laying breeders.

The promotion of tetrabromobisphenol A exposure on Ishikawa cells proliferation and pivotal role of ubiquitin-mediated IκB' degradation.

Tetrabromobisphenol A (TBBPA), one of the highly common industrial brominated flame retardants (BFRs), has been recently reported to influence the progression of endometrial carcinoma. However, the underlying mechanism between them has not been fully illuminated. Our findings demonstrated that treatment with low concentrations of TBBPA significantly induced the proliferation of Ishikawa cells in a concentration- and time-dependent manner. Mechanically, TBBPA stimulation led to the elevation of NF-κB expression, accompanied by the occurrence of ubiquitin-mediated IκB' degradation. Additionally, the upregulation of pro-inflammatory cytokines upon TBBPA exposure was observed in both mRNA and protein levels. Interestingly, the above toxic effects of TBBPA on Ishikawa cells were markedly attenuated by the addition of MG-132, a proteasome inhibitor, suggesting the crucial role of ubiquitin-mediated IκB' degradation in the TBBPA-stimulated proliferation of Ishikawa cells. Confirmation using in vivo model was also presented in this work. Accordingly, our data indicated that ubiquitin-mediated IκB' degradation and inflammatory response could serve as critical and sensitive biomarkers for the TBBPA-induced endometrial carcinoma, which would be helpful for the future carcinogenic risk assessments of TBBPA exposure on uterus.

Carbon content in airway macrophages and genomic instability in Chinese carbon black packers.

Carbon black (CB) particulates as virtually pure elemental carbon can deposit deep in the lungs of humans. International Agency for Research on Cancer classified CB as a Group 2B carcinogen due to inconclusive human evidence. A molecular epidemiological study was conducted in an established cohort of CB packers (CBP) to assess associations between CB exposure and genomic instability in peripheral lymphocytes using cytokinesis-block micronucleus assay (CBMN). Carbon content in airway macrophages (CCAM) was quantified as a bio-effective dosimeter for chronic CB exposure. Dose-response observed in CBPs was compared to that seen in workers exposed to diesel exhaust. The association between CB exposure status and CBMN endpoints was identified in 85 CBPs and 106 non-CBPs from a 2012 visit and replicated in 127 CBPs and 105 non-CBPs from a 2018 visit. The proportion of cytoplasm area occupied by carbon particles in airway macrophages was over fivefold higher in current CBPs compared to non-CBPs and was associated with CBMN endpoints in a dose-dependent manner. CB aerosol and diesel exhaust shared the same potency of inducing genomic instability in workers. Circulatory pro-inflammatory factors especially TNF-α was found to mediate associations between CB exposure and CBMN endpoints. In vitro functional validation supported the role of TNF-α in inducing genomic instability. An estimated range of lower limits of benchmark dose of 4.19-7.28% of CCAM was recommended for risk assessment. Chronic CB exposure increased genomic instability in human circulation and this provided novel evidence supporting its reclassification as a human carcinogen.

Bionanosensor based on N-doped graphene quantum dots coupled with CoOOH nanosheets and their application for in vivo analysis of ascorbic acid.

Herein, we employ 3D nitrogen-doped porous graphene frameworks (NPG) as raw material to prepare emissive nitrogen doped graphene quantum dots (r-NGQDs) via chemical oxidation method. The as-prepared fluorescent r-NGQDs was integrated with CoOOH nanosheets to construct a sensing platform for in vivo ascorbic acid (AA) analysis. Initially, the fluorescence emission intensity of r-NGQDs was quenched by CoOOH nanosheets based on the inner filter effect (IFE). Then the quenched intensity of r-NGQDs and CoOOH nanosheets system was enlightened by addition of AA, since AA could consume CoOOH nanosheets through redox reaction, leading to the release of r-NGQDs and fluorescence restoration. Moreover, the restored fluorescence intensity of r-NGQDs is highly dependent on the concentration of AA which endows them as a quantitative analysis of AA with a limit of detection (LOD) reach up to1.85 µM (n = 3) in aqueous solution. Finally, the as constructed bionanosensor was further employed for in vivo analysis of AA in living rat brain microdialysate with basal value up to 9.4 ± 1.4 µM (n = 3).

Crystalline phase and surface coating of Al2O3 nanoparticles and their influence on the integrity and fluidity of model cell membranes.

Aluminium oxide nanoparticles (Al2O3 NPs) potentially cause health hazards after their release into the environment. The crystalline phase of Al2O3 NPs determines their surface structure and the number of functional groups. The adsorption of natural organic matter (NOM) or biomolecules on the surface Al2O3 NPs also alters their surface properties and subsequent interactions with organisms. In this study, the roles of the Al2O3 crystalline phase and the surface coating of the nanoparticles on the membrane integrity and fluidity were investigated. Giant and small unilamellar vesicles (GUVs and SUVs) were prepared as model cell membranes to detect membrane disruption after exposure to Al2O3 NPs. Due to amorphous structure and high surface activity of γ-Al2O3 NPs, they had a stronger affinity with the membrane and caused more serious membrane rupture than that of α-Al2O3 NPs. The deposition of Al2O3 NPs on the membrane and the induced membrane disruption were monitored by a quartz crystal microbalance with dissipation (QCM-D) method. HA-coated Al2O3 NPs disrupted the SUV layer on the QCM-D sensor, while BSA-coated Al2O3 NPs only adhered to the membrane and induced unremarkable vesicle disruption. In addition, untreated γ-Al2O3 NPs induced remarkable gelation of a negatively charged membrane, but other types of Al2O3 NPs caused negligible membrane phase changes. The outcomes of this study demonstrate that the crystalline phase of the Al2O3 NPs affects the integrity and fluidity of cell membranes. The protein coatings on the NPs weaken the NP-membrane interaction, while HA coatings increase the damage of the NP-induced interaction.

Advances in methods and software for RNA cytosine methylation analysis.

Our understanding of RNA modifications has been growing rapidly over the last decade. Epitranscriptomics has recently emerged as an exciting, new field for understanding the fundamental mechanisms underlying RNA modifications and their impact on gene expression. Among the over one hundred different kinds of RNA modifications, cytosine methylation in mRNA (5-mrC) is now recognized as an important epigenetic mark that modulates mRNA transportation, translation, and stability at the post-transcriptional level. Across plant and animal species, recent studies have revealed the roles of mRNA cytosine methylation in several fundamental biological processes. In mammals, genome-wide profiling has determined thousands of mRNA transcripts carrying the 5-mrC modification in a tissue specific manner. Here, we summarize the experimental techniques that were exploited to determine 5-mrC in mRNA and the computational procedures implemented for RNA bisulfite sequencing data analysis.