Neurotoxicity of dibutyl phthalate in zebrafish larvae: Decreased energy acquisition by neurons.

This work was designed to investigate the neurotoxic effects of the typical plasticizer dibutyl phthalate (DBP) using zebrafish larvae as a model. The results of exhibited that zebrafish larvae exposed to DBP at concentrations of 5 µg/L and 10 µg/L exhibited brain malformations (24 h) and behavioral abnormalities (72 h). After 72 h of exposure to DBP, microglia in the brain were over-activated, reactive oxygen species (ROS) formation was increased, and apoptosis was observed. Meanwhile, it was found that neurons exhibited impaired mitochondrial structure, absent mitochondrial membrane potential and up-regulated autophagy. Further comprehensive biochemical analyses and RNA-Seq, validated by RT-qPCR, glutamate metabolism and PPAR signaling pathway were significantly enriched in the DBP stress group, this may be the main reason for the disruption of glycolysis/gluconeogenesis processes and the reduction of energy substrates for the astrocyte-neuron lactate shuttle (ANLS). In addition, the DBP-exposed group showed aberrant activation of endoplasmic reticulum (ER) stress signaling pathway, which may be related to ROS as well as neuronal apoptosis and autophagy. In conclusion, DBP-induced neurotoxicity may be the combined result of insufficient neuronal energy acquisition, damage to mitochondrial structure, apoptosis and autophagy. These results provide a theoretical basis for understanding the neurotoxic effects of DBP.

A review of cumulative toxic effects of environmental endocrine disruptors on the zebrafish immune system: Characterization methods, toxic effects and mechanisms.

Environmental endocrine disrupting chemicals (EDCs), are a type of exogenous organic pollutants, are ubiquitous in natural aquatic environments. Currently, in addition to neurological, endocrine, developmental and reproductive toxicity, ecotoxicology studies on immunotoxicity are receiving increasing attention. In this review, the composition of immune system of zebrafish, the common indicators of immunotoxicity, the immunotoxicity of EDCs and their molecular mechanism were summarized. We reviewed the immunotoxicity of EDCs on zebrafish mainly in terms of immune organs, immunocytes, immune molecules and immune functions, meanwhile, the possible molecular mechanisms driving these effects were elucidated in terms of endocrine disruption, dysregulation of signaling pathways, and oxidative damage. Hopefully, this review will provide a reference for further investigation of the immunotoxicity of EDCs.

Integrated Positioning System of Kiwifruit Orchard Mobile Robot Based on UWB/LiDAR/ODOM.

To address the issue of low positioning accuracy of mobile robots in trellis kiwifruit orchards with weak signal environments, this study investigated an outdoor integrated positioning method based on ultra-wideband (UWB), light detection and ranging (LiDAR), and odometry (ODOM). Firstly, a dynamic error correction strategy using the Kalman filter (KF) was proposed to enhance the dynamic positioning accuracy of UWB. Secondly, the particle filter algorithm (PF) was employed to fuse UWB/ODOM/LiDAR measurements, resulting in an extended Kalman filter (EKF) measurement value. Meanwhile, the odometry value served as the predicted value in the EKF. Finally, the predicted and measured values were fused through the EKF to estimate the robot's pose. Simulation results demonstrated that the UWB/ODOM/LiDAR integrated positioning method achieved a mean lateral error of 0.076 m and a root mean square error (RMSE) of 0.098 m. Field tests revealed that compared to standalone UWB positioning, UWB-based KF positioning, and LiDAR/ODOM integrated positioning methods, the proposed approach improved the positioning accuracy by 64.8%, 13.8%, and 38.3%, respectively. Therefore, the proposed integrated positioning method exhibits promising positioning performance in trellis kiwifruit orchards with potential applicability to other orchard environments.

Phthalates (PAEs) and reproductive toxicity: Hypothalamic-pituitary-gonadal (HPG) axis aspects.

Phthalates (PAEs) are widely used for their excellent ability to improve plastic products. As an essential endocrine axis that regulates the reproductive system, whether dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis is involved in reproductive toxicity mediated by environmental endocrine disruptors PAEs has become a hot topic of widespread concern. This study systematically reviewed the adverse effects of multiple PAEs on the HPG axis in different models and objectively discussed the possible underlying mechanisms. The abnormal release of gonadotropin-releasing hormone and gonadotropin, dysfunction of sex hormone receptors and steroid hormone synthesis, and general damage, including cell proliferation, oxidative stress, apoptosis, and autophagy have been confirmed to be involved in this process. Although it is widely established that PAEs induce HPG axis dysfunction, the specific mechanisms involved remain unclear. From a systematic review of relevant publications, it appears that the abnormal expression of peroxisome proliferator-activated, aryl hydrocarbon, and insulin receptors mediated by PAEs is key upstream event that induces these adverse outcomes; however, this inference needs to be further verified. Overall, this study aimed to provide reliable potential biomarkers for future environmental risk assessment and epidemiological investigation of PAEs.

[Molecular mechanism of ligustilide attenuating OGD/R injury in PC12 cells by inhibiting ferroptosis].

The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.

One stream, two channels? A parallel-process latent class growth model of homicide rates and suicide rates in 183 countries, between 2000 and 2019.

Background: Suicide and homicide have long been viewed in Western culture as moral, ethical and legal equivalents. This view has underpinned many theoretical and empirical explorations into their relationship over the centuries. However, there has been little evaluation of longitudinal heterogeneity. Methods: Suicide and homicide rates in 183 countries between 2000 and 2019 were collected from the World Health Organization Global Health Observatory Repository. Corresponding structural variables (i.e., GDP per capita, unemployment rate, percentage of urban population, percentage of elderly population, and Gini index) were acquired from The World Bank and Standardized World Income Inequality Database. Parallel-process latent class growth modelling was applied to identify different classes within the joint suicide and homicide rate trajectories. Multinomial logistic regression examined relationships between the structural covariates and trajectory classes. Results: Four trajectory classes were identified, two with inverse relationships between suicide and homicide, and two with parallel relationships: 1) countries with increasing suicide rates and decreasing homicide rates ("suicide up, homicide down": UD, n = 41) or 2) countries with decreasing suicide rates and increasing homicide rates ("suicide down, homicide up": DU, n = 17); and 3) countries where suicide and homicide rates both trended up (UU, n = 19), or 4) both trended down (DD, n = 106). A higher average annual growth rate (AAGR) of GDP per capita was related to an increased possibility of being in DD than in DU. Countries with higher AAGR in unemployment rates were more likely to be in UD and UU than in DD, while those with higher AAGR in urbanization were less likely to be in UD than in DD. Conclusion: The over-time relationship between suicide and homicide is heterogenous and complex. It is influenced differently by GDP per capita, urbanization and unemployment in different countries, and it is not well described by a single theory.

[Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury].

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 µg·mL~(-1)) group, and TFR(30 µg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.

Helping intentions toward suicidal people among young adults: Patterns, transitions, and influencing factors.

BACKGROUND: Public involvement is an essential element of effective suicide prevention. However, few studies have investigated laypeople's intentions and behaviors in supporting suicidal people, especially within Chinese contexts. This study was conducted among young adults in Hong Kong to identify categories of helping intentions toward suicidal people, and to understand whether, and why, youth transitioned over time between helping intention categories. METHODS: A total of 807 Hong Kong young adults (18-35 years) participated in this two-wave study across 2018 (W1) and 2019 (W2). Latent class analyses were conducted to identify categories of helping intentions toward suicidal people. A latent transition analysis was applied to explore the stability of the categories over time, and the factors that influenced stability. RESULTS: Three categories were identified in both waves: 1) dedicated helpers (W1: 28.38 %, W2: 28.50 %), 2) willing helpers (W1: 30.24 %, W2: 33.83 %), and 3) inconsistent helpers (W1: 41.39 %, W2: 37.67 %). 73.48 % of the young adults stayed in the same category across two years. Gender, and attitudes toward suicide victims were related to category membership and transitions between categories. LIMITATIONS: Measurement of helping intentions may not be thorough. Further studies are required to examine whether the findings can be generalized to the other population. CONCLUSIONS: Effective community engagement is essential for suicide prevention. Young adults in Hong Kong exhibited different helping intentions toward suicidal people, that were moderately stable over a two-year period. Understanding how and why young adults behave differently toward suicidal people is important when planning effective suicide prevention programs.

Metagenomic study of carbon metabolism in black soil microbial communities under lead-lanthanum stress.

Pollution of soil environments with heavy metals (HMs) and rare earth elements (REEs) cannot be ignored. We aimed to determine the effects of lead combined with lanthanum (Pb-La) on microbial community structure, carbon metabolism, and differences in carbon source utilization in black soils using EcoPlates™ and a macrogenomic approach. We found that Pb and La contents and the microbial community structure together influence and shape the response of soil carbon metabolism to Pb-La. Compared with controls, microorganisms under pollution stress preferentially use phenolic and carboxylic acids as growth carbon sources. Under Pb-La stress, the relative abundance of Proteobacteria significantly increased, thereby selectively displacing heavy metal-sensitive phyla, such as Chloroflexi, Acidobacteria, and Thaumarchaeota. Altered functional potential of the microbial carbon cycle manifested as differences in carbon metabolism, methane metabolism, and carbon fixation pathways. Furthermore, an appropriate concentration of La can reduce the environmental toxicity of Pb, whereas a high concentration of La has synergistic toxicity with Pb. These findings have important implications for understanding the impact of HM-REE contamination in microbial communities and the functions associated with carbon metabolism in black soils.

An adaptive differential evolution algorithm with elite gaussian mutation and bare-bones strategy.

Both differential evolution algorithm (DE) and Bare-bones algorithm (BB) are simple and efficient, but their performance in dealing with complex multimodal problems still has room for improvement. DE algorithm has great advantages in global search and BB algorithm has great advantages in local search. Therefore, how to combine these two algorithms' advantages remains open for further research. An adaptive differential evolution algorithm based on elite Gaussian mutation strategy and bare-bones operations (EGBDE) is proposed in this paper. Some elite individuals are selected and then the mean and the variance of the bare-bones operation are adjusted with the information from the selected elite individuals. This new mutation strategy enhances the global search ability and search accuracy of differential evolution with parameters free. It also helps algorithm get a better search direction and effectively balance the exploration and exploitation. An adaptive adjustment factor is adopted to dynamically balance between differential mutation strategy and the elite Gaussian mutation. Twenty test functions are chosen to verify the performance of EGBDE algorithm. The results show that EGBDE has excellent performance when comparing with other competitors.

Effects of common environmental endocrine-disrupting chemicals on zebrafish behavior.

Environmental endocrine-disrupting chemicals (EDCs), a type of exogenous organic pollutants, are ubiquitous in natural aquatic environments. Therefor, this review focused on the use of the zebrafish as a model to explore the effect of different EDCs on behavior, as well as the molecular mechanisms that drive these effects. Furthermore, our study summarizes the current knowledge on the neuromodulatory effects of different EDCs in zebrafish. This study also reviews the current state of zebrafish behavior research, in addition to the potential mechanisms of single and mixed pollutant-driven behavioral dysregulation at the molecular level, as well as the applications of zebrafish behavior experiments for neuroscience research. This review broadens our understanding of the influence of EDCs on zebrafish behavior and provides guidance for future research.

Hazards of phthalates (PAEs) exposure: A review of aquatic animal toxicology studies.

Phthalates (PAEs) are of wide concern because they are commonly used in various plastic products as plasticizers, and can found their way into the environment. However, their interaction with the environment and their toxicity in aquatic animals is still a matter of intense debate. In this review on PAEs in aquatic environments (lakes, rivers and seas), it is found that there is a large variety and abundance of PAEs in developing countries, and the total concentration of PAEs even exceeds 200 µg / L. The interaction between metabolic processes involved in the toxicity induced by various PAEs is summarized for the first time in the article. Exposure of PAEs can lead to activation of the detoxification system CYP450 and endocrine system receptors of aquatic animals, which in turn causes oxidative stress, metabolic disorders, endocrine disorders, and immunosuppression. Meanwhile, each system can activate / inhibit each other, causing genotoxicity and cell apoptosis, resulting in the growth and development of organisms being blocked. The mixed PAEs shows no cumulative toxicity changes to aquatic animals. For the combined pollution of other chemicals and PAEs, PAE can act as an agonist or antagonist, leading to combined toxicity in different directions. Phthalate monoesters (MPEs), the metabolites of PAEs, are also toxic to aquatic animals, however, the toxicity is weaker than the corresponding parent compounds. This review summarizes and analyzes the current ecotoxicological effects of PAEs on aquatic animals, and provides guidance for future research.

Monobutyl phthalate can induce autophagy and metabolic disorders by activating the ire1a-xbp1 pathway in zebrafish liver.

Monobutyl phthalate (MBP) can exist in biological organisms for a long time because of its excellent fat solubility, and it has been found to have certain toxic effects. In this study, the acute effects of MBP on endoplasmic reticulum (ER) stress and metabolism in the zebrafish liver were studied. After continuous exposure to MBP (5 and 10 mg / L) for 96 h, ER damage and the appearance of apoptotic bodies and autophagosomes were found in liver. This is because MBP stimulated the ire-xbp1 pathway of ER stress, thus leading to apoptosis and autophagy. Also, through analysis of metabolic enzymes and genes, it was found that the activated ire-xbp1 pathway could promote lipid synthesis and cause the accumulation of lipid droplets. The gene pparγ related to lipid storage affected the level of insulin, which can also further affect the glucose metabolism process, that is, glycolysis and aerobic respiration were inhibited. And the pentose phosphate pathway (PPP) was activated as a compensation mechanism to alleviate glycogen accumulation. The abnormal supply of energy and the death of excessive cells will eventually severely damage the zebrafish liver. This study will enrich the knowledge about the toxic effects of MBP.

Intrinsic ferromagnetic semiconductors in rhombohedral RMnO3 (R = Sc, Y, and Lu) with high critical temperature and large ferroelectric polarization.

Ferromagnetic (FM) semiconductors have been recognized as the cornerstone for next-generation highly functional spintronic devices. However, the development in practical applications of FM semiconductors is limited by their low Curie temperatures (T C). Here, on the basis of model analysis, we find that the FM super-exchange couplings in the d 5 - d 3 system can be significantly strengthened by reducing the virtual exchange gap (G ex) between occupied and empty e g orbitals. By first-principle calculations, we predict robust ferromagnetism in three rhombohedral RMnO3 (R = Sc, Y, and Lu) compounds with the T C that is as high as ∼1510 K (YMnO3). The oxygen breathing motions open a band gap and create an unusual Mn2+/Mn4+ charge ordering of the Mn-d electrons, which play an important role in altering the G ex. Interestingly, the rhombohedral RMnO3 compounds are also ferroelectric (FE) with a large spontaneous polarization approaching that of LiNbO3. These results not only deepen the understandings of magnetic couplings in d 5 - d 3 system, but also provide a way to design room-temperature FM-FE multiferroics.

[Clinical value of cardiopulmonary exercise testing derived oxygen uptake efficiency parameters in patients with end-stage chronic heart failure].

OBJECTIVE: To assess the cardiopulmonary exercise testing (CPET) derived performance of oxygen uptake and ventilation efficiency parameters, including oxygen uptake efficiency plateau (OUEP) , oxygen uptake efficiency slope (OUES), V·E/V·CO2 slope and lowest V·E/V·CO2, in patients with end-stage chronic heart failure (CHF) and evaluate their clinical value on monitoring cardiac function and hemodynamic status. METHODS: A total of 26 end-stage CHF patients considered for heart transplantation were enrolled in this study. CPET, echocardiography and invasive hemodynamic examinations with Swan-Ganz flowing balloon catheter were performed. Correlation analysis was made between oxygen uptake and ventilation efficiency parameters from CPET and echocardiographic and hemodynamic parameters. RESULTS: OUEP and OUES showed good correlation with peak oxygen consumption (peak V·O2) (r = 0.535, P < 0.01;r = 0.840, P < 0.001). In end-stage CHF patients, the slope of OUEP with respect to peak V·O2 is about 32, but the slope of OUES with respect to peak V·O2 is only about 2. The difference was 16 times. The change of OUEP was more sensitive and significant than those of OUES and peak V·O2 (P < 0.05). OUEP, peak V·O2 (%pred), V·E/V·CO2 slope and lowest V·E/V·CO2 were all correlated well with non-invasive hemodynamic parameters peak cardiac output (r = 0.535, P < 0.01; r = 0.652, P < 0.001; r = -0.640, P < 0.001; r = -0.606, P = 0.001 respectively) and peak cardiac index (r = 0.556, P < 0.01;r = 0.772, P < 0.001; r = -0.641, P < 0.001; r = -0.620, P < 0.001 respectively) derived from CPET, but not correlated with invasive hemodynamic parameters cardiac output and cardiac index at rest (P > 0.05). Both peak V·O2 (%pred) and V·E/V·CO2 slope were significantly correlated with invasive hemodynamic parameters systolic pulmonary arterial pressure (r = -0.424, P < 0.05; r = 0.509, P < 0.01) and mean pulmonary arterial pressure (r = -0.479, P < 0.05; r = 0.405, P < 0.05). Peak V·O2 (%pred) was also significantly correlated with pulmonary capillary wedge pressure (r = -0.415, P < 0.05), and V·E/V·CO2 slope was significantly correlated with pulmonary vascular resistance (r = 0.429, P < 0.05). CONCLUSIONS: The oxygen uptake and ventilation efficiency parameters derived from CPET, including peak V·O2, OUEP, lowest V·E/V·CO2 and V·E/V·CO2 slope etc, are objectively monitoring and evaluating cardiac function and hemodynamic status. And they are useful for optimizing clinical management of patients with end-stage CHF.

Prevalence of hypertension and associated factors among older rural adults: results from Liaoning Province, China.

OBJECTIVE: The objective of the study was to estimate the prevalence of hypertension and associated factors among older rural adults in Liaoning Province, China. SUBJECTS AND METHODS: The study was conducted in 2004-2006, using a multistage, stratified clustering sampling scheme to select a representative sample. A total of 10,065 adults aged 60 years or older were examined. A survey of blood pressure and associated factors was carried out. All data analyses were conducted using SPSS 11.5 statistical software package. RESULTS: Overall, the prevalence rates of hypertension are 57, 64.4 and 64.9% for the age groups 60-69, 70-79 and >or=80 years, respectively. The prevalence of hypertension was positively correlated with age, female gender, Mongolian ethnicity, overweight and obesity, smoking and drinking, whereas income level was a protective factor for hypertension. The rates of awareness, treatment and control among older rural adults were very low (overall 35.2, 28.7 and 1.0%, respectively). CONCLUSION: Hypertension was highly prevalent among older rural adults in Liaoning Province, and it was associated with many factors. The percentages of hypertensives who were aware, treated, and controlled were very low. These data underscore the urgent need to strengthen the public health education and blood pressure monitoring system to better manage hypertension among older adults in rural China.