A new strategy based on a cascade amplification strategy biosensor for on-site eDNA detection and outbreak warning of crown-of-thorns starfish.

Population outbreaks of the crown-of-thorns starfish (COTS) seriously threaten the sustainability of coral reef ecosystems. However, traditional ecological monitoring techniques cannot provide early warning before the outbreaks, thus preventing timely intervention. Therefore, there is an urgent need for a more accurate and faster technology to predict the outbreaks of COTS. In this work, we developed an electrochemical biosensor based on a programmed catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) cyclic amplification strategy for sensitive and selective detection of COTS environmental DNA (eDNA) in water bodies. This biosensor exhibited excellent electrochemical characteristics, including a low limit of detection (LOD = 18.4 fM), low limit of quantification (LOQ = 41.1 fM), and wide linear range (50 fM - 10 nM). The biosensing technology successfully allowed the detection of COTS eDNA in the aquarium environment, and the results also demonstrated a significant correlation between eDNA concentration and COTS number (r = 0.990; P < 0.001). The reliability and accuracy of the biosensor results have been further validated through comparison with digital droplet PCR (ddPCR). Moreover, the applicability and accuracy of the biosensor were reconfirmed in field tests at the COTS outbreak site in the South China Sea, which has shown potential application in dynamically monitoring the larvae before the COTS outbreak. Therefore, this efficient electrochemical biosensing technology offers a new solution for on-site monitoring and early warning of the COTS outbreak.

The combination of paeonol, diosmetin-7-O-ß-D-glucopyranoside, and 5-hydroxymethylfurfural from Trichosanthis pericarpium alleviates arachidonic acid-induced thrombosis in a zebrafish model.

Trichosanthis fruit (TF) is a classic medicinal material obtained from Shandong, China. The peel of this fruit (Trichosanthis pericarpium, TP) is known to exert anti-thrombotic effects. However, the anti-thrombotic active components and mechanisms of TP have yet to be fully elucidated. Combined with zebrafish models and high-performance liquid chromatography (HPLC), this study evaluated the endogenous anti-thrombotic effects with the combination of three compounds from TP. First, we used HPLC to investigate the components in the water extract of TP. Next, we used the zebrafish model to investigate the anti-thrombotic activity of the three compound combinations by evaluating a range of indicators. Finally, the expression of related genes was detected by real-time quantitative polymerase chain reaction (qPCR). HPLC detected a total of eight components in TP water extract, with high levels of paeonol (Pae), diosmetin-7-O-ß-D-glucopyranoside (diosmetin-7-O-glucoside), and 5-hydroxymethylfurfural (5-HMF). The most significant anti-thrombotic activity was detected when the Pae: diosmetin-7-O-glucoside:5-HMF ratio was 4:3:3. qPCR analysis revealed that the abnormal expression levels of f2, fga, fgb, vwf, ptgs1, and tbxas1 induced by arachidonic acid (AA) were improved. The combination of Pae, diosmetin-7-O-glucoside, and 5-HMF may alleviate AA-induced thrombosis by inhibiting the inflammatory reaction, coagulation cascade reaction, and arachidonic acid metabolism pathways.

Manganese activates autophagy and microglia M2 polarization against endoplasmic reticulum stress-induced neuroinflammation: Involvement of GSK-3ß signaling.

BACKGROUND: Endoplasmic reticulum (ER) stress-induced nerve cell damage has been known to be a hallmark feature of Mn-induced parkinsonism pathogenesis. However, several compensatory machineries, such as unfolded protein response (UPR), autophagy, and immune response, play an essential role in this damage, and the underlying molecular mechanisms are poorly understood. METHODS: Neurobehavioral impairment was assessed using catwalk gait analysis and open field test. RNA-seq analyzed the differentially expressed genes (DEGs). TUNEL staining and immunohistochemical analysis evaluated the nerve cells apoptosis and microglial cell activation. Flow cytometry assay measured microglia M1/M2 polarization. Western blotting measured protein expression. Immunofluorescence staining was used to observe the target molecules' subcellular localization. RESULTS: The study revealed that Mn caused a reduction in motor capacity, nerve cell apoptosis, and microglia activation with an imbalance in M1/M2 polarization, coupled with NF-κB signaling and PERK signaling activation. 4-PBA pretreatment could counteract these effects, while 3-MA administration exacerbated them. Additionally, autophagy could be activated by Mn. This activation could be further upregulated by 4-PBA pretreatment, whereas it was suppressed under 3-MA administration. Mn also decreased inactive GSK-3ß, increased STAT3 signaling activation, and increased colocalization of GSK-3ß and STAT3. These effects were strengthened by 4-PBA pretreatment, while 3-MA administration reversed them. DISCUSSION: This study suggests that autophagy and M2 microglia polarization might be protective in Mn-induced ER stress damage, possibly through GSK-3ß-ULK1 autophagy signaling and STAT3 signaling activation.

Agromyces chromiiresistens sp. nov., Novosphingobium album sp. nov., Sphingobium arseniciresistens sp. nov., Sphingomonas pollutisoli sp. nov., and Salinibacterium metalliresistens sp. nov.: five new members of Microbacteriaceae and Sphingomonadaceae from polluted soil.

There are many unidentified microbes in polluted soil needing to be explored and nominated to benefit the study of microbial ecology. In this study, a taxonomic research was carried out on five bacterial strains which were isolated and cultivated from polycyclic aromatic hydrocarbons, and heavy metals polluted soil of an abandoned coking plant. Phylogenetical analysis showed that they belonged to the phyla Proteobacteria and Actinobacteria, and their 16S rRNA gene sequence identities were lower than 98.5% to any known and validly nominated bacterial species, suggesting that they were potentially representing new species. Using polyphasic taxonomic approaches, the five strains were classified as new species of the families Microbacteriaceae and Sphingomonadaceae. Genome sizes of the five strains ranged from 3.07 to 6.60 Mb, with overall DNA G+C contents of 63.57-71.22 mol%. The five strains had average nucleotide identity of 72.38-87.38% and digital DNA-DNA hybridization of 14.0-34.2% comparing with their closely related type strains, which were all below the thresholds for species delineation, supporting these five strains as novel species. Based on the phylogenetic, phylogenomic, and phenotypic characterizations, the five novel species are proposed as Agromyces chromiiresistens (type strain H3Y2-19aT = CGMCC 1.61332T), Salinibacterium metalliresistens (type strain H3M29-4T = CGMCC 1.61335T), Novosphingobium album (type strain H3SJ31-1T = CGMCC 1.61329T), Sphingomonas pollutisoli (type strain H39-1-10T = CGMCC 1.61325T), and Sphingobium arseniciresistens (type strain H39-3-25T = CGMCC 1.61326T). Comparative genome analysis revealed that the species of the family Sphingomonadaceae represented by H39-1-10T, H39-3-25T, and H3SJ31-1T possessed more functional protein-coding genes for the degradation of aromatic pollutants than the species of the family Microbacteriaceae represented by H3Y2-19aT and H3M29-4T. Furthermore, their capacities of resisting heavy metals and metabolizing aromatic compounds were investigated. The results indicated that strains H3Y2-19aT and H39-3-25T were robustly resistant to chromate (VI) and/or arsenite (III). Strains H39-1-10T and H39-3-25T grew on aromatic compounds, including naphthalene, as carbon sources even in the presence of chromate (VI) and arsenite (III). These features reflected their adaptation to the polluted soil environment.

The diversity, community dynamics, and interactions of the microbiome in the world's deepest blue hole: insights into extreme environmental response patterns and tolerance of marine microorganisms.

IMPORTANCE: This study comprehensively examined the community dynamics, functional profiles, and interactions of the microbiome in the world's deepest blue hole. The findings revealed a positive correlation between the α-diversities of Symbiodiniaceae and archaea, indicating the potential reliance of Symbiodiniaceae on archaea in an extreme environment resulting from a partial niche overlap. The negative association between the α-diversity and ß-diversity of the bacterial community suggested that the change rule of the bacterial community was consistent with the Anna Karenina effects. The core microbiome comprised nine microbial taxa, highlighting their remarkable tolerance and adaptability to sharp environmental gradient variations. Bacteria and archaea played significant roles in carbon, nitrogen, and sulfur cycles, while fungi contributed to carbon metabolism. This study advanced our understanding of the community dynamics, response patterns, and resilience of microorganisms populating the world's deepest blue hole, thereby facilitating further ecological and evolutional exploration of microbiomes in diverse extreme environments.

Qilong capsule alleviates ponatinib-induced ischemic stroke in a zebrafish model by regulating coagulation, inflammation and apoptosis.

ETHOPHARMACOLOGICAL RELEVANCE: Qilong capsule (QLC) is a compound traditional Chinese medicine commonly used to treat ischemic stroke (IS). QLC is made of eight kinds of medicinal materials. It has two kinds of monarch medicine and six kinds of minister medicine. However, the pharmacodynamic mechanism of QLC is still unknown. AIM OF THE STUDY: The aim of this paper was to evaluate the pharmacology mechanism of QLC against ischemic stroke through coagulation, inflammation and apoptosis. MATERIALS AND METHODS: We used an existing zebrafish model to explore the protective mechanism of QLC on IS. We treated normally-developing zebrafish larvae with QLC and ponatinib 2 days post fertilization (dpf), and used the area of cerebral vascular thrombosis, red blood cell staining intensity, and brain cell apoptosis to quantitate QLC efficacy against IS. Evaluation of brain inflammation in zebrafish by observing macrophage aggregation and migration. In addition, we also explored the effect of QLC on zebrafish angiogenesis. Quantitative polymerase chain reaction (qPCR) was used to detect changes in the expression of genes involved in coagulation, inflammation, vascular endothelium, and apoptosis. RESULTS: We found that QLC reduced the area affected by ponatinib-induced cerebral vascular embolism, erythrocyte staining intensity, and the number of apoptotic brain cells. For inflammation, QLC can improve the aggregation and migration of macrophages. QLC can significantly promote the formation of blood vessels in zebrafish. qPCR showed that QLC inhibited the expression of genes related to coagulation, inflammation, and apoptosis. CONCLUSION: Qilong capsule had a significant protective efficacy in ponatinib-induced IS.

SIRT1/FOXO3-mediated autophagy signaling involved in manganese-induced neuroinflammation in microglia.

Manganese (Mn), as one of the environmental risk factors for Parkinson's disease (PD), has been widely studied. Though autophagy dysfunction and neuroinflammation mainly are responsible for the causative issue of Mn neurotoxicity, the molecular mechanism of parkinsonism caused by Mn has not been explored clearly. The results of in vivo and in vitro experiments showed that overexposure to Mn caused neuroinflammation impairment and autophagy dysfunction, accompanied by the increase of IL-1ß, IL-6, and TNF-α mRNA expression, and nerve cell apoptosis, microglia cell activation, NF-κB activation, poor neurobehavior performance. This is due to Mn-induced the downregulation of SIRT1. Upregulation of SIRT1 in vivo and in vitro could alleviate Mn-induced autophagy dysfunction and neuroinflammation, yet these beneficial effects were abolished following 3-MA administration. Furthermore, we found that Mn interfered with the acetylation of FOXO3 by SIRT1 in BV2 cells, leading to a decrease in the nuclear translocation of FOXO3, and its binding of LC3B promoter and transcription activity. This could be antagonized by the upregulation of SIRT1. Finally, it is proved that SIRT1/FOXO3-LC3B autophagy signaling involves in Mn-induced neuroinflammation impairment.

Qilong Capsule Alleviated MPTP-Induced Neuronal Defects by Inhibiting Apoptosis, Regulating Autophagy in Zebrafish Embryo Model.

Qilong capsule (QLC) originates from the famous "Buyang Huanwu decoction" prescription. It is representative of drugs used in China during recovery from stroke, but its neuroprotective mechanism of action remains obscure. HPLC was used to evaluate the similarity of 10 batches of QLC samples. Then we used a zebrafish model to study the neuroprotective effect of QLC. At 24 hpf, embryos were treated with QLC and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and zebrafish were observed the neuronal length and the number of apoptotic cells in the brain at 72 hpf. At 120 hpf, we conduct zebrafish behavioural tests. We then also used qPCR to detect the expression of genes related to autophagy and apoptosis. The results showed that QLC significantly reduced the damage of dopaminergic neurons, the number of apoptotic cells in the brain, and alleviated motor disturbances induced by MPTP. We found that the mechanism of QLC activity involved decreased neuron cell death by inhibiting mitochondrial apoptosis and autophagy, promoting autophagy, degradation of alpha-synuclein, and neuron cell growth, and rescuing the function of neurons damaged by MPTP. The results indicated that QLC protected against MPTP-induced neuron injury and provided pharmacological evidence for clinical use of QLC.

Melatonin alleviates BDE-209-induced cognitive impairment and hippocampal neuroinflammation by modulating microglia polarization via SIRT1-mediated HMGB1/TLR4/NF-κB pathway.

Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with developmental neurotoxicity, the mechanism of which remains obscure. The present study aimed to evaluate cognitive deficits and microglia-originated neuroinflammation in the hippocampus of offspring rats exposed to BDE-209 (30 and 100 mg/kg) during perinatal period. Compared to the control, BDE-209-treated rats showed significant longer escape latency and less platform crossings in tests of Morris water maze. Besides obvious hippocampal neuron damage, increased microglial activation and pro-inflammatory markers (CD86, TNFα, and IL-1ß), meanwhile, decreased anti-inflammatory molecules (CD206, IL-10, and Arg1) were induced by BDE-209. Furthermore, we investigated the neuroprotection of melatonin against BDE-209 and whether through sirtuin 1 (SIRT1). Consistent with restored SIRT1 activity, enhanced deacetylation of HMGB1 and inhibited cytoplasmic translocation of HMGB1, reduced expression of proteins involved in TLR4-NF-κB pathway and nuclear transfer of phosphorylated-NF-κB p65, and ultimately suppressed microglial activation and improved spatial memory were observed in 10 mg/kg melatonin-pretreated rats, compared with BDE-209-exposed alone. These results demonstrated that melatonin ameliorated BDE-209-caused cognitive impairment partially through shifting microglia polarization towards anti-inflammatory phenotype in a SIRT1-dependent manner, suggesting a potential mechanism for prevention.

Soil microbiomes divergently respond to heavy metals and polycyclic aromatic hydrocarbons in contaminated industrial sites.

Contaminated sites from electronic waste (e-waste) dismantling and coking plants feature high concentrations of heavy metals (HMs) and/or polycyclic aromatic hydrocarbons (PAHs) in soil. Mixed contamination (HMs + PAHs) hinders land reclamation and affects the microbial diversity and function of soil microbiomes. In this study, we analyzed HM and PAH contamination from an e-waste dismantling plant and a coking plant and evaluated the influences of HM and PAH contamination on soil microbiomes. It was noticed that HMs and PAHs were found in all sites, although the major contaminants of the e-waste dismantling plant site were HMs (such as Cu at 5,947.58 ± 433.44 mg kg-1, Zn at 4,961.38 ± 436.51 mg kg-1, and Mn at 2,379.07 ± 227.46 mg kg-1), and the major contaminants of the coking plant site were PAHs (such as fluorene at 11,740.06 ± 620.1 mg kg-1, acenaphthylene at 211.69 ± 7.04 mg kg-1, and pyrene at 183.14 ± 18.89 mg kg-1). The microbiomes (diversity and abundance) of all sites were determined via high-throughput sequencing of 16S rRNA genes, and redundancy analysis was conducted to investigate the relations between soil microbiomes and contaminants. The results showed that the microbiomes of the contaminated sites divergently responded to HMs and PAHs. The abundances of the bacterial genera Sulfuritalea, Pseudomonas, and Sphingobium were positively related to PAHs, while the abundances of the bacterial genera Bryobacter, Nitrospira, and Steroidobacter were positively related to HMs. This study promotes an understanding of how soil microbiomes respond to single and mixed contamination with HMs and PAHs.

Structural insights into the substrate specificity of 5-chloro-2-hydroxymuconate tautomerase CnbG.

The catechol meta-cleavage pathway is widely involved in the degradation of aromatic compounds, including those halogenated aromatic hydrocarbons and their derivatives. CnbG is a kind of 4-oxalocrotonate tautomerase (4-OT) located in the catechol meta-cleavage pathway, catalyzes the ketonization of cis,cis-5-chloro-2-hydroxymuconate and cis,cis-2-hydroxymuconate to yield 5-chloro-2-oxo-3-hexene-1,6-dioate and 2-oxo-3-hexene-1,6-dioate, and contributes to the degradation of 4-chloronitrobenzene and chlorobenzene in Comamonas testosteroni CNB-1. Yet, the reason why CnbG and those 4-OTs could recognize various substrates is not well explained. Here, we determined the crystal structure of CnbG at resolution of 2.0 Å and identified that the potential substrate pocket involved in four conserved residues, residues Pro1, Arg11, Arg39 and Trp50, but not five conserved residues as those reported in other 4-OTs. We also found the four conserved residues assemble different sequence patterns in different 4-OTs, indicating their potential roles in catalysis and substrate binding. Via molecular docking, we found the 5-chloro group was clamped by two residues and extended to the solvent, indicating a substrate binding mode that could bear the substitution of different groups in the 5-position. Our work extends the knowledge of the substrate specificity of enzymes in the catechol meta-cleavage pathway.

Causes of death in primary plasma cell leukemia differ from multiple myeloma: A STROBE-compliant descriptive study based on SEER database.

The primary plasma cell leukemia (pPCL) is a rare but aggressive variant of multiple myeloma (MM). Few studies have focused on the differences in the causes of death between pPCL and MM. This study aimed to compare and evaluate the causes of death of patients with pPCL and MM. The data were collected from the Surveillance Epidemiology, and End Results (SEER) database. The demographic characteristics, survival, and causes of death in pPCL and MM patients were evaluated and compared. The competing risk regression model was performed to predict the cause of death. Between 1975 and 2009, the overall mortality rate was 96.13% and 88.71% for pPCL and MM, and the median survival was 9 and 26 months, respectively. In pPCL, leukemia caused 45.05% of the deaths, followed by myeloma (38.83%). In MM, myeloma was the leading cause of death, accounting for 74.89% of the deaths. Older age at diagnosis was a risk factor for dying of leukemia in pPCL patients (HR = 1.49, 95% CI: 1.16-1.91), while older age at death was associated with reduced risk (HR = 0.67, 95% CI: 0.52-0.86). Although the survival of pPCL patients increased with time periods of diagnosis since 1975 to 2009, the risk of dying of leukemia increased with the periods. For MM, most of the demographic characteristics were found to have independently predicting influence on the cause of death. Patients with pPCL and MM had distinct causes of death. Leukemia was the leading and the most serious cause of death in pPCL patients. The demographic factors could not predict the causes of death in pPCL. More large-scale and multi-center studies are needed to evaluate the effect of novel agents in pPCL patients, especially for patients who have progressed to leukemia.

Resveratrol Attenuated Manganese-Induced Learning and Memory Impairments in Mice Through PGC-1Alpha-Mediated Autophagy and Microglial M1/M2 Polarization.

Overexposure to manganese (Mn) can induce cognitive deficits, but the underlying mechanisms are unclear. Microglial dysfunction and autophagic dysfunction have been implicated in Mn neurotoxicity. The neuroprotective effects of resveratrol (RSV) have been studied extensively, but the potential protective effects of RSV against Mn-induced cognitive dysfunction have not been evaluated. We investigated the effects of RSV on Mn-induced changes in PGC-1α, microglial M1/M2 polarization, and autophagy in vivo and in vitro. Kunming mice were treated with saline, MnCl2, RSV, or MnCl2 + RSV. The results showed that RSV improved cognitive dysfunction, suppressed release of inflammatory cytokines, promoted M2 microglial polarization, and increased autophagy in the hippocampi of Mn-treated mice. Furthermore, we also showed that Mn treatment significantly decreased the expression of PGC-1α, ULK1, BDNF, and activated NF-κB signaling. These effects were reversed by RSV pretreatment. In addition, RSV inhibited STAT6 acetylation, but did not affect ULK1 acetylation. Knockdown of PGC-1α using LV-PGC-1α shRNA reversed RSV-induced increases in the expression levels of PGC-1α, ULK1, LC3-II, and mitigated the RSV-induced decrease in the expression level of p62, in Mn-treated BV2 cells. Resveratrol-induced M2 polarization and autophagic flux were abolished by LV-PGC-1α shRNA pretreatment. These results showed that RSV exerted neuroprotective effects against Mn-induced learning and memory impairment partially through PGC-1α-mediated microglial M1/M2 polarization and autophagy.

Protective effects of salvianolic acid A on clozapine-induced cardiotoxicity in zebrafish.

The clinical use of clozapine (CLZ), an atypical antipsychotic drug, was affected by side effects, such as cardiotoxicity. We selected normally developing zebrafish embryos to explore the antagonism of salvianolic acid A (SAA) against clozapine-induced cardiotoxicity. Embryos were treated with CLZ and SAA, and zebrafish phenotypes were observed at 24 h, 48 h, 72 h, and 96 h after treatment. The observed phenotypes included heart shape, heart rate, and venous sinus-arterial bulb (SV-BA) interval. Real-time quantitative PCR was used to detect changes in the expression of genes involved in heart inflammation, oxidative stress, and apoptosis. The results showed that SAA relieved pericardial edema, increased heart rate, and reduced the SV-BA interval. The PCR results also showed that when the zebrafish embryos were incubated with SAA and CLZ for 96 h, the expression of il-1b and nfkb2 were significantly downregulated, the expression of sod1 and cat were significantly upregulated, and the expressions of mcl1a and mcl1b were significantly downregulated. In summary, SAA can antagonize clozapine-induced cardiotoxicity.

Cost-effectiveness of comprehensive preventive measures for coal workers' pneumoconiosis in China.

BACKGROUND: Coal workers' pneumoconiosis (CWP) remains one of the most severe occupational diseases in China. Despite the implementation of CWP comprehensive preventive measures, the unreasonable allocation of investment by coal enterprises limits the effect of preventing CWP, especially when the health resources are inadequate. This study aims to evaluate the cost-effectiveness of comprehensive measures for CWP from the perspective of coal enterprises. METHODS: Comprehensive measures and two primary interventions (engineering controls and individual protective equipment) were selected. A time-dependent Markov model was developed to evaluate cost and quality-adjusted life-years (QALYs). The input data were collected from the survey and literature. A hypothetical null situation, in which the currently implemented interventions were eliminated, was used as a comparator based on the generalised cost-effectiveness analysis (GCEA) recommended by the World Health Organization (WHO). The primary outcomes of the model were reported in terms of incremental cost-effectiveness ratios (ICERs). Uncertainty was verified using one-way and probabilistic sensitivity analyses. RESULTS: The QALYs of the comprehensive measures, engineering controls, and individual protective equipment were 17.60, 17.50, and 16.85 years, respectively. Compared with null, the ICERs of the interventions were 65,044.73, 30,865.15, and 86,952.41 RMB/QALY, respectively. Individual protective equipment was dominated by an ICER of -11,416.02 RMB/QALY compared to engineering controls. Sensitivity analysis suggested the robustness of the results. CONCLUSIONS: The comprehensive preventive measures for CWP that are currently implemented in Chinese state-owned mines are cost-effective. In comprehensive measures, engineering controls are more cost-effective than individual protective equipment. Investment in engineering controls should be increased to improve the cost-effectiveness of preventing CWP.

Effects of manganese on microglia M1/M2 polarization and SIRT1-mediated transcription of STAT3-dependent genes in mouse.

Overexposure to manganese (Mn) can lead to neurological diseases, characterized by behavioral and motor impairments. Microglia-mediated neuroinflammation is involved in the pathogenesis and progression of neurodegenerative diseases. Microglial M1 and M2 phenotypes play pro-inflammatory and anti-inflammatory roles, respectively, in response to microenvironmental disturbances. Silent information regulator (SIRT1) has been demonstrated to play an important role in the neuroinflammatory response by deacetylating various transcription factors, such as proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 3 (STAT3). In addition, PGC-1α and STAT3 have been implicated in microglial polarization and inflammatory response. In this study, Mn exposure (50, 100, 200 µmol/kg) induced neuroinflammatory injury and interfered with microglial M1/M2 polarization in mice, as indicated by the upregulated expression of M1 polarization marker mRNA (IL-1ß, IL-6, TNF-α, and iNOS), whereas changes in M2 polarization markers (IL-4, TGF-ß, and Arg1) varied, with some increasing and some decreasing, in response to increasing Mn doses, which was consistent with the flow cytometry results used to detect the percentages of each microglial type. We found that Mn could downregulate SIRT1 expression and activate NF-κB signaling. Following mice in the 200 µmol/kg Mn treatment, STAT3 and PGC-1α levels in the nuclear fraction both significantly decreased, and the interaction between the proteins decreased, affecting the transcription of STAT3-mediated genes. These findings provide new insights regarding the role played by Mn neurotoxicity in the suppression of neuroinflammation through the regulation of microglial polarization.

Moderating Effect of Family Support on the Mediated Relation Between Negative Life Events and Antisocial Behavior Tendencies via Self-Esteem Among Chinese Adolescents.

Adolescents are particularly prone to antisocial behavior. The promoting effect of negative life events on antisocial behavior has been well-documented. However, the internal influence mechanisms between negative life events and antisocial behavior tendencies in adolescents are still unknown. The aim of this study was to explore the mediation effect of self-esteem and the moderated mediation effect of family support between negative life events and antisocial behavior tendencies in 8,958 adolescents who were selected from three Chinese provinces. Robust maximum likelihood estimator (MLR) of a structural equation model (SEM) was applied to test the mediation model and the moderated mediation model. The results revealed that negative life events had a positive effect on antisocial behavior tendencies in adolescents, with a direct effect of 0.082 (95% CI: 0.052, 0.111) and an indirect effect via self-esteem of 0.168 (95% CI: 0.146, 0.191). Negative life events had a 67.20% effect on antisocial behavior tendencies, where self-esteem showed mediation. The indirect effect was 2.049-fold greater than the direct effect. Furthermore, the effect of latent interaction of subjective family support and negative life events on self-esteem was negatively significant (ß = -0.018, p = 0.032, 95% CI: -0.035, -0.002). The indirect effect of negative life events was greater, where subjective family support was below 1 SD of the mean (conditional indirect effect = 0.227, 95% CI = 0.200, 0.255) than where it was above 1 SD of the mean (conditional indirect effect = 0.203, 95% CI = 0.177, 0.229). The moderated mediation effect index was -0.012, p = 0.033. Moderated mediation showed that the mediated path was less evident in the students who had greater subjective support from family. The results of the current study demonstrated the important role that self-esteem and subjective family support played in minimizing the adverse effect of negative life events on antisocial behavior development of adolescents. These findings have important implications for preventing antisocial behavior in adolescents by developing interventions aimed at enhancing their self-esteem and providing support-skill training to parents aimed at improving subjective family support of adolescents.

The mediating role of resilience and self-esteem between negative life events and positive social adjustment among left-behind adolescents in China: a cross-sectional study.

BACKGROUND: In China, adolescents are frequently left behind by their parents. A great deal of scientific evidence demonstrates considerable psychological and social impacts that negative life events may have on adolescents who are left behind. While a direct relationship between negative life events and psychological and social effects has been observed, indirect effects have yet to be examined. Therefore, the objective of this study was to determine the association between negative life events and positive social adjustment and how resilience and self-esteem mediate this association. METHODS: A cross-sectional study was carried out in the provinces of Shandong, Henan, and Sichuan in China. A questionnaire was distributed to 4716 left-behind adolescents in ten middle/high schools. We performed Bayesian estimations in structural equation modeling using the Markov Chain Monte Carlo algorithm to test our hypotheses. RESULTS: Negative life events were significantly related to resilience (rs = - 0.402), self-esteem (rs = - 0.292), and positive social adjustment (rs = - 0.239). Positive social adjustment was directly affected by resilience (ß = 0.639) and self-esteem (ß = 0.448). Negative life events were not only directly related to positive social adjustment (ß = - 0.187, 95% credible interval: - 0.233 ~ - 0.139), but also showed an indirect effect on positive social adjustment (ß = - 0.541, 95% credible interval: - 0.583 ~ - 0.501) through resilience (ß = - 0.370) and self-esteem (ß = - 0.171). The total effect of negative life events on positive social adjustment was - 0.728, where 74.31% was mediated by resilience and self-esteem. The indirect effect of negative life events on positive social adjustment through resilience and self-esteem was 2.893 times more than the direct effect. CONCLUSIONS: Resilience and self-esteem mediated most of the effect of negative life events on positive social adjustment. Interventions should be developed to improve the social adjustment of adolescents who are left behind, particularly the enhancement of resilience and self-esteem.

The Status of Pro-social Tendency of Left-Behind Adolescents in China: How Family Function and Self-Esteem Affect Pro-social Tendencies.

In China, adolescents are frequently left behind. To date, few studies have focused on the pro-social tendencies of left-behind adolescents and the relationship of family function, self-esteem, and pro-social tendency is yet to be examined. This study, therefore, aims to understand the status of pro-social tendency of left-behind adolescents and to explore the mediating and moderating roles of self-esteem in the relationship between family function and pro-social tendency. A large, school-based survey was conducted in three Chinese provinces. An analysis of covariance was first used to identify the differences in pro-social tendency between adolescents who were and were not left behind. We then analyzed the variance within left-behind adolescents using demographics, left-behind type, years of being left-behind, and caregiver related characteristics. A structural equation model was used to analyze the relationship of family function, self-esteem, and pro-social tendency, with bootstrapping used to explore the mediating role of self-esteem. Additionally, an ordinary least squares regression was used to examine the moderating effect of self-esteem. The results showed that the pro-social tendency of left-behind adolescents was lower than in non-left-behind adolescents (F = 15.11, p = 0.0001). Family function was positive related to pro-social tendency (r = 0.259), which had not only a direct effect on pro-social tendency (ß = 0.254), but also an indirect effect through self-esteem (ß = 0.071, bias-corrected 95% CI: 0.051:0.090; percentile 95% CI: 0.053:0.092). Additionally, 21.85% of the total effect of family function on pro-social tendency was mediated by self-esteem. Furthermore, self-esteem negatively moderated the relationship between family function and pro-social tendency (ß = -0.208, p < 0.0001), such that the effect of family function on pro-social tendency became weaker as self-esteem increased. The current study verified the negative effect of being left behind on the social development of adolescents and contributed to the understanding of the importance of self-esteem in the relationship between family function and pro-social tendency. Interventions aimed at enhancing self-esteem should be developed and implemented in left-behind adolescents to promote wellness in the entirety of psychological and social outcomes.

Lanthanum Chloride Impairs the Blood-Brain Barrier Integrity by Reduction of Junctional Proteins and Upregulation of MMP-9 in Rats.

Lanthanum could cause cognitive impairment in children and rodent animals. The normal blood-brain barrier (BBB) integrity is essential for protecting the brain from systemic toxins and maintaining the homeostasis for proper neuronal function. BBB dysfunction has been implicated as a potential mechanism of heavy metal-induced neurotoxicity. The present study was aimed to investigate effects of lanthanum on BBB integrity and endothelial junctional complexes in the cerebral cortex of young rats. Animals were exposed to lanthanum chloride (LaCl3) through drinking water under 0, 0.25, 0.5, and 1.0% concentrations from postnatal day 0 until 30 days after weaning. LaCl3-exposure increased BBB permeability, caused ultrastructure changes in cerebral capillaries, and reduced protein expression of claudin-5, occludin, and VE-cadherin. Due to the critical role of matrix metalloproteinases (MMPs) in BBB integrity, we further examined alterations in MMPs activity and expression. Enhanced gelatinase activity and upregulated MMP-9 expression were observed after LaCl3-exposure, concurrently with decreased expression of endogenous inhibitor tissue inhibitors of metalloproteinase (TIMP)-1. Taken together, this study demonstrated that postnatal lanthanum exposure caused leakage of BBB in young rats, partially attributed to upregulation of MMP-9 and reduction of junctional proteins expression.