Modulations of resting-static functional connectivity on insular by electroacupuncture in subjective tinnitus.

Objective: To explore the modulations of electroacupuncture in subjective tinnitus (ST) by comparing the difference of functional connectivity (FC) in ST patients and healthy volunteers between the insular (INS) and the whole brain region. Methods: A total of 34 ST patients were selected into electroacupuncture group (EG) and 34 age- and sex-matched normal subjects were recruited into control group (CG). The EG received acupuncture at SI19 (Tinggong), GB11 (Touqiaoyin), TE17 (Yifeng), GV20 (Baihui), GV15 (Yamen), GV14 (Dazhui), SJ13 (Zhongzhu), among which the points of SI19 and GB11 were connected to the electroacupuncture instrument with the density wave of 2/50 Hz, and 3 treatments per week for 10 sessions in total. The severity of tinnitus was evaluated by Tinnitus Handicap Inventory (THI), the hearing status was recorded using pure tone audiometry, and resting-state functional magnetic resonance imaging (rs-fMRI) was performed on the brain before and after treatment, the CG received no intervention yet only rs-fMRI data were collected. Results: With the electroacupuncture treatment, the total THI score, average air conduction threshold of patients of EG were significantly lower than before (p < 0.01), and the total effective rate was 88.24%. Compared with CG, FC of ST patients between INS and left superior temporal gyrus and right hippocampal significantly decreased before treatment, while FC of ST patients between INS and right superior frontal gyrus, left middle frontal gyrus and right anterior cuneus significantly decreased after treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of ST patients between the INS and right middle frontal gyrus, left superior frontal gyrus and right paracentral lobule showed a significant decrease after treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). In addition, THI score in EG was negatively correlated with the reduction of FC value in INS-left superior frontal gyrus before treatment (r = -0.41, p = 0.017). Therefore, this study suggests that abnormal FC of INS may be one of the significant central mechanisms of ST patients and can be modulated by electroacupuncture. Discussion: Electroacupuncture treatment can effectively reduce or eliminate tinnitus symptoms in ST patients and improve the hearing by decreasing FC between the INS and the frontal and temporal brain regions.

Nucleation of Pitting and Evolution of Stripping on Lithium-Metal Anodes.

The stripping reaction of lithium (Li) will greatly impact the cyclability and safety of Li-metal batteries. However, Li pits' nucleation and growth, the origin of uneven stripping, are still poorly understood. In this study, we analyze the nucleation mechanism of Li pits and their morphology evolution with a large population and electrode area (>0.45 cm2). We elucidate the dependence of the pit size and density on the current density and overpotential, which are aligned with classical nucleation theory. With a confocal laser scanning microscope, we reveal the preferential stripping on certain crystal grains and a new stripping mode between pure pitting and stripping without pitting. Descriptors like circularity and the aspect ratio (R) of the pit radius to depth are used to quantify the evolution of Li pits in three dimensions. As the pits grow, growth predominates along the through-planedirection, surpassing the expanding rate in the in-plane direction. After analyzing more than 1000 pits at each condition, we validate that the overpotential is inversely related to the pit radius and exponentially related to the rate of nucleation. With this established nucleation-overpotential relationship, we can better understand and predict the evolution of the surface area and roughness of Li electrodes under different stripping conditions. The knowledge and methodology developed in this work will significantly benefit Li-metal batteries' charging/discharging profile design and the assessment of large-scale Li-metal foils.

Skin Conductance-Based Acupoint and Non-Acupoint Recognition Using Machine Learning.

Acupoints (APs) prove to have positive effects on disease diagnosis and treatment, while intelligent techniques for the automatic detection of APs are not yet mature, making them more dependent on manual positioning. In this paper, we realize the skin conductance-based APs and non-APs recognition with machine learning, which could assist in APs detection and localization in clinical practice. Firstly, we collect skin conductance of traditional Five-Shu Point and their corresponding non-APs with wearable sensors, establishing a dataset containing over 36000 samples of 12 different AP types. Then, electrical features are extracted from the time domain, frequency domain, and nonlinear perspective respectively, following which typical machine learning algorithms (SVM, RF, KNN, NB, and XGBoost) are demonstrated to recognize APs and non-APs. The results demonstrate XGBoost with the best precision of 66.38%. Moreover, we also quantify the impacts of the differences among AP types and individuals, and propose a pairwise feature generation method to weaken the impacts on recognition precision. By using generated pairwise features, the recognition precision could be improved by 7.17%. The research systematically realizes the automatic recognition of APs and non-APs, and is conducive to pushing forward the intelligent development of APs and Traditional Chinese Medicine theories.

Investigation of the Presence of Fibrillin in Sea Cucumber (Apostichopus japonicus) Body Wall by Utilizing Targeted Proteomics and Visualization Strategies.

Fibrillin is an important structural protein in connective tissues. The presence of fibrillin in sea cucumber Apostichopus japonicus is still poorly understood, which limits our understanding of the role of fibrillin in the A. japonicus microstructure. The aim of this study was to clarify the presence of fibrillin in the sea cucumber A. japonicus body wall. Herein, the presence of fibrillin in sea cucumber A. japonicus was investigated by utilizing targeted proteomics and visualization strategies. The contents of three different isoforms of fibrillin with high abundance in A. japonicus were determined to be 0.96, 2.54, and 0.15 µg/g (wet base), respectively. The amino acid sequence of fibrillin (GeneBank number: PIK56741.1) that started at position 631 and ended at position 921 was selected for cloning and expressing antigen. An anti-A. japonicus fibrillin antibody with a titer greater than 1:64 000 was successfully obtained. It was observed that the distribution of fibrillin in the A. japonicus body wall was scattered and dispersed in the form of fibril bundles at the microscale. It further observed that fibrillin was present near collagen fibrils and some entangled outside the collagen fibrils at the nanoscale. Moreover, the stoichiometry of the most dominant collagen and fibrillin molecules in A. japonicus was determined to be approximately 250:1. These results contribute to an understanding of the role of fibrillin in the sea cucumber microstructure.

Changes in the chemical properties and metabolite profiling of fish sauce prepared from underutilized large yellow croaker roes during fermentation at different temperatures.

Fish sauce is a popular aquatic condiment with unique flavor. In this study, the changes in the chemical properties and metabolite profiling of fish sauce from large yellow croaker roes during fermentation at different temperatures were revealed. The results found that the contents of total acid, amino acid nitrogen, total soluble nitrogen and soluble salt-free solids of fish sauce fermented at 40 °C were higher than those in other temperatures groups (25 °C and 32 °C), while the contents of total volatile basic nitrogen were lower than other temperatures. Therefore, 40 °C was the ideal fermentation temperature for fish sauce. The metabolomics analysis showed that organic acids, amino acids, nucleotide, and lipid compounds were found to participate in the biosynthesis pathway. Compared to 25 °C and 32 °C, fermented at 40 °C could increase the abundance of metabolic substances in the fish sauce, such as sugar alcohols, L-Citrulline, L-Aspartic acid, L-Cysteine, Glutathione, and L-Arginine. These results provide a theoretical basis for the production of high-quality fish sauce and the high-value utilization of fish roes.

The persistence and antitumor efficacy of CAR-T cells are modulated by tonic signaling within the CDR.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable clinical efficacy, but challenges related to relapse and CAR-T cell exhaustion persist. One contributing factor to this exhaustion is CAR tonic signaling, where CAR-T cells self-activate without antigen stimulation, leading to reduced persistence and impaired antitumor activity. To address this issue, we conducted a preclinical study evaluating tonic signaling using nanobody-derived CAR-T cells. Our investigation revealed that specific characteristics of the complementary determining regions (CDRs), including low solubility, polarity, positive charge, energy, and area of ionic and positive CDR patches of amino acids, were associated with low antigen-independent tonic signaling. Significantly, we observed that stronger tonic signaling directly impacted CAR-T cell proliferation in vitro, consequently leading to CAR-T cell exhaustion and diminished persistence and effectiveness in vivo. Our findings provide compelling preclinical evidence and lay the foundation for the clinical assessment of CAR-T cells with distinct tonic signaling patterns. Understanding the role of CDRs in modulating tonic signaling holds promise for advancing the development of more efficient and durable CAR-T cell therapies, thereby enhancing the treatment of cancer and addressing the challenges of relapse in CAR-T cell therapy.

Insight into the effect of large yellow croaker roe phospholipids on the physical properties of surimi gel and their interaction mechanism with myofibrillar protein.

BACKGROUND: The present study aimed to investigate the effects of large yellow croaker roe phospholipids (LYCRPLs) on the physical properties of surimi gels and to clarify their interaction mechanism with myofibrillar proteins (MPs) in terms of chemical forces and the spatial conformation. RESULTS: LYCRPLs could improve the gel strength, textural properties, rheological properties and water-holding capacity of surimi gels. Moreover, the interaction mechanism between LYCRPLs with MPs was revealed through intermolecular forces, Fourier transform infrared spectroscopy and ultraviolet visible absorption spectroscopy. The findings demonstrated that LYCRPLs enhanced the surface hydrophobicity and particle size of MPs, facilitating expansion and cross-linking of MPs. CONCLUSION: These results provide a theoretical basis for improving the characteristics of surimi gels and thus facilitate the application of LYCRPLs in the aquatic food industry. © 2023 Society of Chemical Industry.

The national, regional, and global impact of glaucoma as reported in the 2019 Global Burden of Disease Study.

Introduction: We investigated the disability-adjusted life years (DALYs) of glaucoma. Methods: The estimated annual percentage change (EAPC) was measured to assess trends in the age-standardized DALY rate from 1990 to 2019. Results: The global age-standardized DALY rate of glaucoma decreased with an EAPC of -1.00. The age-standardized DALY rate decreased least in high-SDI regions. Eastern sub-Saharan Africa had highest age-standardized DALY rate in 2019. At the national level, Mali had the highest age-standardized DALY rate in 2019. Conclusions: Although the global burden of glaucoma has decreased, the burden remain high in regions with low SDI values and in sub-Saharan Africa.

Scale Effect of Land Cover Classification from Multi-Resolution Satellite Remote Sensing Data.

Land cover data are important basic data for earth system science and other fields. Multi-source remote sensing images have become the main data source for land cover classification. There are still many uncertainties in the scale effect of image spatial resolution on land cover classification. Since it is difficult to obtain multiple spatial resolution remote sensing images of the same area at the same time, the main current method to study the scale effect of land cover classification is to use the same image resampled to different resolutions, however errors in the resampling process lead to uncertainty in the accuracy of land cover classification. To study the land cover classification scale effect of different spatial resolutions of multi-source remote sensing data, we selected 1 m and 4 m of GF-2, 6 m of SPOT-6, 10 m of Sentinel-2, and 30 m of Landsat-8 multi-sensor data, and explored the scale effect of image spatial resolution on land cover classification from two aspects of mixed image element decomposition and spatial heterogeneity. For the study area, we compared the classification obtained from GF-2, SPOT-6, Sentinel-2, and Landsat-8 images at different spatial resolutions based on GBDT and RF. The results show that (1) GF-2 and SPOT-6 had the best classification results, and the optimal scale based on this classification accuracy was 4-6 m; (2) the optimal scale based on linear decomposition depended on the study area; (3) the optimal scale of land cover was related to spatial heterogeneity, i.e., the more fragmented and complex was the space, the smaller the scale needed; and (4) the resampled images were not sensitive to scale and increased the uncertainty of the classification. These findings have implications for land cover classification and optimal scale selection, scale effects, and landscape ecology uncertainty studies.

Sulfated fucan could serve as a species marker of sea cucumber with endo-1,3-fucanase as the essential tool.

In the past few decades, sulfated fucan from sea cucumber had attracted considerable interest owing to its abundant physiological activities. Nevertheless, its potential for species discrimination had not been investigated. Herein, particular attention was given to sea cucumber Apostichopus japonicus, Acaudina molpadioides, Holothuria hilla, Holothuria tubulosa, Isostichopus badionotus and Thelenota ananas to examine the feasibility of sulfated fucan as a species marker of sea cucumber. The enzymatic fingerprint suggested that sulfated fucan exhibited significant interspecific discrepancy and intraspecific stability, which revealed that sulfated fucan could serve as the species marker of sea cucumber, by utilizing the overexpressed endo-1,3-fucanase Fun168A and the ultra-performance liquid chromatography-high resolution mass spectrum. Moreover, oligosaccharide profile of sulfated fucan was determined. The oligosaccharide profile combined with hierarchical clustering analysis and principal components analysis further confirmed that sulfated fucan could serve as a marker with a satisfying performance. Besides, load factor analysis showed that the minor structure of sulfated fucan also contributed to the sea cucumber discrimination, besides the major structure. The overexpressed fucanase played an indispensable role in the discrimination, due to its specificity and high activity. The study would lead to a new strategy for species discrimination of sea cucumber based on sulfated fucan.

Enhancement in the physicochemical properties, antioxidant activity, volatile compounds, and non-volatile compounds of watermelon juices through Lactobacillus plantarum JHT78 fermentation.

In this study, the influences of Lactobacillus plantarum JHT78 fermentation on the physiological properties, antioxidant activities, and volatile/non-volatile metabolites of watermelon juices were comprehensively investigated. The results indicated that total polyphenols flavonoids and anthocyanin in the watermelon juices remarkably increased through L. plantarum JHT78 fermentation. L. plantarum JHT78 fermentation enhanced the antioxidant activities, lipase inhibition, and α-glucosidase activities of watermelon juices. A total of 62 volatile compounds were detected using HS-SPME-GC-MS, mainly including 11 acids, 8 aldehydes, 7 ketones, and 7 alcohols. The abundance of 19 volatile compounds especially for acids remarkably increased for the fermentated watermelon juice. Furthermore, non-volatile compounds detected by UHPLC-QTOF-MS revealed that L. plantarum JHT78 significantly altered the non-volatile compounds of watermelon juices, especially increased indole-3-lactic acid. The results confirmed that L. plantarum JHT78 enhanced the functionality of watermelon juices thus providing a theoretical basis for the development of LAB on plant-based beverages.

Gasdermin E regulates the stability and activation of EGFR in human non-small cell lung cancer cells.

BACKGROUND: Lung cancer is the most lethal malignancy, with non-small cell lung cancer (NSCLC) being the most common type (~ 85%). Abnormal activation of epidermal growth factor receptor (EGFR) promotes the development of NSCLC. Chemoresistance to tyrosine kinase inhibitors, which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. Therefore, more thorough understanding of EGFR expression and dynamics are needed. METHODS: Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of gasdermin E (GSDME) regulating EGFR stability by Western blot analysis, immunoprecipitation and immunofluorescence. GSDME and EGFR siRNAs or overexpression plasmids were used to characterize the functional role of GSDME and EGFR in vitro. EdU incorporation, CCK-8 and colony formation assays were used to determine the proliferation ability of non-small cell lung cancer cells. RESULTS: GSDME depletion reduced the proliferation of non-small cell lung cancer cells in vitro. Importantly, both GSDME-full length (GSDME-FL) and GSDME-N fragment physically interacted with EGFR. GSDME interacted with cytoplasmic fragment of EGFR. GSDME knockdown inhibited EGFR dimerization and phosphorylation at tyrosine 1173 (EGFRY1173), which activated ERK1/2. GSDME knockdown also promoted phosphorylation of EGFR at tyrosine 1045 (EGFRY1045) and its degradation. CONCLUSION: These results indicate that GSDME-FL increases the stability of EGFR, while the GSDME N-terminal fragment induces EGFR degradation. The GSDME-EGFR interaction plays an important role in non-small cell lung cancer development, reveal a previously unrecognized link between GSDME and EGFR stability and offer new insight into cancer pathogenesis. Video abstract.

The effect of sinomenine on ERK1/2, JNK and p38 phosphorylation in LPS-stimulated endothelial cells.

This study was to investigate the effect of sinomenine by LPS-induced MAPK phosphorylation in endothelial cells. Endothelial cells were challenged with different doses LPS and/or treated with sinomenine at three concentrations (1, 5, or 10 µg/mL) in pathological model, drug safety, treatment and prevention experiments. The cells were incubated at 37 °C in a cell incubator total for 24 h. The lysate cells were collected and analyzed the phosphorylation of ERK1/2, JNK and p38 by MAPK phosphoprotein assay whole cell lysate kit. As expected, LPS could significantly elevated phosphorylation of ERK1/2, JNK and p38, but sinomenine not. The results revealed that sinomenine significantly reduced the phosphorylation of ERK1/2 and p38 in treatment experiment, and inhibited phosphorylation of ERK1/2, JNK and p38 in prevention experiment. Our findings demonstrated that sinomenine protects endothelial cells from LPS-induced inflammation, which might be associated with depressing MAPK signaling pathway.

PB@PDA nanocomposites as nanolabels and signal reporters for separate-type cathodic photoelectrochemical immunosensors in the detection of carcinoembryonic antigens.

Photoelectrochemical (PEC) immunoassays exhibiting high sensitivity and decent operability have considerable potential in areas such as cancer diagnostics. In particular, cathodic PEC configurations can prevent interference from reductive substances, which can occur in biological samples; however, challenges remain in terms of sensitivity and operability. In this study, separate-type PEC immunoassays were developed for carcinoembryonic antigen (CEA) by combining microplate-based immune recognition and off-on cathodic PEC detection. Polydopamine (PDA)-coated Prussian blue (PB) nanoparticles (PB@PDA NPs) were used as signal tags to label the detection antibody. The PB NPs and PDA captured on the microplates both disassembled under strongly alkaline conditions to generate redox-active electron acceptors. The disassembled products were quantitatively transferred to PEC detection cells and synergistically enhanced the PEC current with microstructured BiOI, which operated as a cathodic semiconductor electrode. As proof of principle, carcinoembryonic antigen (CEA) was applied to elucidate the potential application of PEC immunoassay in clinical diagnosis, and the obtained linear range of the sensor was 0.001-100 ng mL-1 with the detection limit of 54.9 fg mL-1 (S/N = 3). The proposed separate-type off-on PEC strategy showed high sensitivity and decent operability for CEA detection, indicating its potential for the identification of other tumor markers.

Efficacy of non-surgical periodontal treatment on patients with coronary artery disease: a meta-analysis of randomized controlled trials

Background: Coronary artery disease (CAD) is defined as one of the most common cardiovascular diseases (CVDs). Periodontitis is one of the risk factors for CAD. Material and methods: PubMed, Embase and Cochrane Library databases were carefully and thoroughly retrieved until October 2021. On the basis of the inclusion and exclusion criteria, eligible articles were selected strictly to identify randomized controlled trials (RCTs). Using Cochran's Q statistic, Review Manager 5.4 and Stata 16, data were extracted, and a comprehensive analysis was carried out. Results: Six RCTs of 619 patients were included in this study, including 360 in the intervention group (IG) and 259 in the control group (CG). Meta-analysis showed significant difference for C-reactive protein (CRP) (1.20mg/L, 95% CI: 1.13 to 1.27, p < 0.00001) after non-surgical periodontal therapy (NSPT), but showed no significant difference for interleukin-6 (IL-6) (1.19mg/L, 95% CI: -1.03 to 3.40, p=0.29), flow-mediated dilation (FMD) (-1.64%, 95% CI: -4.95 to 1.67, p=0.33), triacylglycerol (TG) (-0.02mg/dL, 95% CI: -0.31 to 0.27, p=0.90), total cholesterol (TC) (0.04mg/dL, 95% CI: -0.25 to 0.33, p=0.90), low-density lipoprotein cholesterol (LDL-C) (0.00mg/dL, 95% CI: -0.29 to 0.29, p=0.99) and high-density lipoprotein cholesterol (HDL-C) (0.11mg/dL, 95% CI: -0.18 to 0.40, p=0.46). Conclusions: The impact of NSPT on the reduction of CRP in patients of CAD with periodontitis is significant. NSPT can be considered as an important preventive strategy for major cardiovascular events in CAD. (AU)

Spatial Autocorrelation Analysis of Land Use and Ecosystem Service Value in the Huangshui River Basin at the Grid Scale.

The Huangshui River Basin is one of the most densely populated areas on the Qinghai-Tibet Plateau and is characterized by a high level of human activity. The contradiction between ecological protection and socioeconomic development has become increasingly prominent; determining how to achieve the balanced and coordinated development of the Huangshui River Basin is an important task. Thus, this study used the Google Earth Engine (GEE) cloud-computing platform and Sentinel-1/2 data, supplemented with an ALOS digital elevation model (ALOS DEM) and field survey data, and combined a remote sensing classification method, grid method, and ecosystem service value (ESV) evaluation method to study the spatial correlation and interaction between land use (LU) and ESV in the Huangshui River Basin. The following results were obtained: (1) on the GEE platform, Sentinel-1/2 active and passive remote sensing data, combined with the gradient tree-boosting algorithm, can efficiently produce highly accurate LU data with a spatial resolution of 10 m in the Huangshui River Basin; the overall accuracy (OA) reached 88%. (2) The total ESV in the Huangshui River Basin in 2020 was CNY 33.18 billion (USD 4867.2 million), of which woodland and grassland were the main contributors to ESV. In the Huangshui River Basin, the LU type, LU degree, and ESV have significant positive spatial correlations, with urban and agricultural areas showing an H-H agglomeration in terms of LU degree, with woodlands, grasslands, reservoirs, and wetlands showing an H-H agglomeration in terms of ESV. (3) There is a significant negative spatial correlation between the LU degree and ESV in the Huangshui River Basin, indicating that the enhancement of the LU degree in the basin could have a negative spatial spillover effect on the ESV of surrounding areas. Thus, green development should be the future direction of progress in the Huangshui River Basin, i.e., while maintaining and expanding the land for ecological protection and restoration, and the LU structure should be actively adjusted to ensure ecological security and coordinated and sustainable socioeconomic development in the Basin.

The inhibitory effect of paeoniflorin on reactive oxygen species alleviates the activation of NF-κB and MAPK signalling pathways in macrophages.

Paeoniflorin (PF) has been proven to possess a protective effect in some inflammatory diseases, but the underlying mechanism remains unclear. Macrophages play central roles in inflammatory responses and LPS-stimulated RAW264.7 macrophage is an ideal model for studying the anti-inflammatory effects and mechanisms of drugs. Thus, it was used to explore the anti-inflammatory mechanism of PF in this study. The results showed that PF markedly attenuated the activation of NF-κB, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen activated protein kinase (p38) signalling pathways induced by LPS exposure. In addition, PF pretreatment dose-dependently suppressed the production of cytokines and the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Concomitantly, PF pretreatment dramatically inhibited the accumulation of intracellular reactive oxygen species (ROS) without affecting the phagocytosis of macrophages. Furthermore, it has proved the scavenging effect of PF on ROS was involved in the anti-inflammatory process. This study provides a novel aspect to the understanding of the anti-inflammatory mechanism of PF.

Decabromodiphenyl ethane affects embryonic development by interfering with nuclear F-actin in zygotes and leads to cognitive and social disorders in offspring mice.

Decabromodiphenyl ethane (DBDPE) is a novel retardant. DBDPE is used in various flammable consumer products such as electronics, building materials, textiles, and children's toys. The presence of DBDPE in humans makes it extremely urgent to assess the health effects of DBDPE exposure. Here, we used female mice as an animal model to investigate the effects of DBDPE on embryonic development and offspring health. The results showed that 50 µg/kg bw/day of DBDPE exposure did not affect spindle rotation in oocytes after fertilization, but led to a decrease of pronuclei (PN) in zygotes. Further investigation found that DBDPE interferes with the self-assembly of F-actin in PN, resulting in PN reduction, DNA damage, and reduced expression of zygotic genome activating genes, and finally leading to abnormal embryonic development. More importantly, we found that maternal DBDPE exposure did not affect the growth and development of the first generation of offspring (F1) mice, but resulted in behavioral defects in F1 mice. Female F1 mice from DBDPE-exposed mothers exhibited increased motor activity and deficits in social behavior. Both female and male F1 mice from DBDPE-exposed mothers exhibited cognitive memory impairment. These results suggest that DBDPE has developmental toxicity on embryos and has a cross-generational interference effect. It is suggested that people should pay attention to the reproductive toxicity of DBDPE. In addition, it also provides a reference for studying the origin of neurological diseases and indicates that adult diseases caused by environmental pollutants may have begun in the embryonic stage.

Exogenous melatonin protects preimplantation embryo development from decabromodiphenyl ethane-induced circadian rhythm disorder and endogenous melatonin reduction.

Decabromodiphenyl ethane (DBDPE) is a novel flame retardant that is widely used in plastics, electronic products, building materials and textiles. Our previous studies have revealed the oocyte toxicity of DBDPE, but the effect of DBDPE on preimplantation embryo development has not been reported. Here, we investigated whether and how DBDPE exposure affects preimplantation embryo development. Adult female mice were orally exposed to DBDPE (0, 5, 50, 500 µg/kg bw/day) for 14 days. First, we found that after DBDPE exposure, mice showed obvious circadian rhythm disorder. Moreover, the development of preimplantation embryos was inhibited in DBDPE-exposed mice after pregnancy. Then, we further explored and revealed that DBDPE exposure reduced the endogenous melatonin (MLT) level during pregnancy, thereby inhibiting the development of preimplantation embryos. Furthermore, we discovered that exogenous MLT supplementation (15 mg/kg bw/day) rescued the inhibition of preimplantation embryo development induced by DBDPE, and a mechanistic study demonstrated that exogenous MLT inhibited the overexpression of ROS and DNA methylation at the 5-position of cytosine (5-mC) in DBDPE-exposed preimplantation embryos. Simultaneously, MLT ameliorated the DBDPE-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential (MMP), ATP, and Trp1 expression. Additionally, MLT restored DBDPE-induced changes in zona pellucida (ZP) hardness and trophectoderm (TE) cortical tension. Finally, the protective effect of MLT on embryos ameliorated the adverse reproductive outcomes (dead fetus, fetus with abnormal liver, fetal weight loss) induced by DBDPE. Collectively, DBDPE induced preimplantation embryo damage leading to adverse reproductive outcomes, and MLT has emerged as a potential tool to rescue adverse reproductive outcomes induced by DBDPE.

Protective effect of surfactin on copper sulfate-induced inflammation, oxidative stress, and hepatic injury in zebrafish.

Surfactin, an antibacterial peptide, produced by various Bacillus subtilis strains, have broad-spectrum antibacterial and immune-enhancing functions. In this study, we investigated the anti-inflammatory, antioxidant, and hepatoprotective effect of surfactin on zebrafish (Danio rerio) larvae following their exposure to copper sulfate (CuSO4 ). The mature AB wild-type and a transgenic line of zebrafish larvae that expressed enhanced GFP (EGFP) named Tg (Lyz:EGFP) were exposed to 0, 20, 40, and 60 µg/mL surfactin after incubation with 3.2 µg/mL CuSO4 for 2 h from 72 h postfertilization (hpf). Different endpoints, such as migration of GFP-labeled neutrophils, analysis of inflammatory cytokines and transaminases, markers of oxidation, expression of certain genes, and histological changes of liver, were studied to evaluate the function of surfactin. The protein expression levels of NF-κBp65, TNF-α, cyclooxygenase-2 (COX-2), and iNOS were determined in murine macrophage RAW 264.7 cells by western blotting. Our results show that surfactin reduced migration of neutrophils and relieved hepatic injury. In addition, surfactin reduced the index levels of inflammatory factors, oxidative stress response, and improved hepatic function. Surfactin also significantly inhibited the expression of IL-1ß, IL-8, TNF-α, nitric oxide, NF-κBp65, COX-2, and iNOS, and increased the expression of IL-10. Thus, our results demonstrate that surfactin has anti-inflammatory, antioxidant, and hepatoprotective activities. Surfactin has potential as a novel inflammation and immune adjustment.