Dinotefuran exposure alters biochemical, metabolomic, gut microbiome, and growth responses in decapoda pacific white shrimp Penaeus vannamei.

Dinotefuran, a neonicotinoid insecticide, may impact nontarget organisms such as Decapoda P. vannamei shrimp with nervous systems similar to insects. Exposing shrimp to low dinotefuran concentrations (6, 60, and 600 µg/L) for 21 days affected growth, hepatosomatic index, and survival. Biomarkers erythromycin-N-demethylase, alanine aminotransferase, and catalase increased in all exposed groups, while glutathione S-transferase is the opposite; aminopyrin-N-demethylase, malondialdehyde, and aspartate aminotransferase increased at 60 and 600 µg/L. Concentration-dependent effects on gut microbiota altered the abundance of bacterial groups, increased potentially pathogenic and oxidative stress-resistant phenotypes, and decreased biofilm formation. Gram-positive/negative microbiota changed significantly. Metabolite differences between the exposed and control groups were identified using mass spectrometry and KEGG pathway enrichment. N-acetylcystathionine showed potential as a reliable dinotefuran metabolic marker. Weighted correlation network analysis (WGCNA) results indicated high connectivity of cruecdysone in the metabolite network and significant enrichment at 600 µg/L dinotefuran. The WGCNA results revealed a highly significant negative correlation between two key metabolites, caldine and indican, and the gut microbiota within co-expression modules. Overall, the risk of dinotefuran exposure to non-target organisms in aquatic environments still requires further attention.

Seascapes Shaped the Local Adaptation and Population Structure of South China Coast Yellowfin Seabream (Acanthopagrus latus).

Understanding the genetic composition and regional adaptation of marine species under environmental heterogeneity and fishing pressure is crucial for responsible management. In order to understand the genetic diversity and adaptability of yellowfin seabream (Acanthopagrus latus) along southern China coast, this study was conducted a seascape genome analysis on yellowfin seabream from the ecologically diverse coast, spanning over 1600 km. A total of 92 yellowfin seabream individuals from 15 sites were performed whole-genome resequencing, and 4,383,564 high-quality single nucleotide polymorphisms (SNPs) were called. By conducting a genotype-environment association analysis, 29,951 adaptive and 4,328,299 neutral SNPs were identified. The yellowfin seabream exhibited two distinct population structures, despite high gene flow between sites. The seascape genome analysis revealed that genetic structure was influenced by a variety of factors including salinity gradients, habitat distance, and ocean currents. The frequency of allelic variation at the candidate loci changed with the salinity gradient. Annotation of these loci revealed that most of the genes are associated with osmoregulation, such as kcnab2a, kcnk5a, and slc47a1. These genes are significantly enriched in pathways associated with ion transport including G protein-coupled receptor activity, transmembrane signaling receptor activity, and transporter activity. Overall, our findings provide insights into how seascape heterogeneity affects adaptive evolution, while providing important information for regional management in yellowfin seabream populations.

kcnj13 regulates pigment cell shapes in zebrafish and has diverged by cis-regulatory evolution between Danio species.

Teleost fish of the genus Danio are excellent models to study the genetic and cellular bases of pigment pattern variation in vertebrates. The two sister species Danio rerio and Danio aesculapii show divergent patterns of horizontal stripes and vertical bars that are partly caused by the divergence of the potassium channel gene kcnj13. Here, we show that kcnj13 is required only in melanophores for interactions with xanthophores and iridophores, which cause location-specific pigment cell shapes and thereby influence colour pattern and contrast in D. rerio. Cis-regulatory rather than protein coding changes underlie kcnj13 divergence between the two Danio species. Our results suggest that homotypic and heterotypic interactions between the pigment cells and their shapes diverged between species by quantitative changes in kcnj13 expression during pigment pattern diversification.

Experimental Investigation of Reynolds Number and Spring Stiffness Effects on Vortex-Induced Vibration Driven Wind Energy Harvesting Triboelectric Nanogenerator.

Vortex-induced vibration (VIV) is a process that wind energy converts to the mechanical energy of the bluff body. Enhancing VIV to harvest wind energy is a promising method to power wireless sensor nodes in the Internet of Things. In this work, a VIV-driven square cylinder triboelectric nanogenerator (SC-TENG) is proposed to harvest broadband wind energy. The vibration characteristic and output performance are studied experimentally to investigate the effect of the natural frequency by using five different springs in a wide range of stiffnesses (27 N/m

Combined toxic effects of thiamethoxam on intestinal flora, transcriptome and physiology of Pacific white shrimp Litopenaeus vannamei.

The environmental accumulation of thiamethoxam has increasingly become a risk for the health of aquatic animals, especially crustacean species in the same phylum as the target pests. The lack of knowledge on the toxicity of thiamethoxam to crustaceans motivates our research to study the acute and chronic toxicity of decapod crustaceans Litopenaeus vannamei, exposed to thiamethoxam. A 28-day chronic toxicity test followed a 96 h acute toxicity test. Thiamethoxam induced oxidative stress and decreased growth performance in shrimp. In addition, thiamethoxam has led to a substantial imbalance of the micro-ecosystem in the intestine. The composition of the intestinal flora changed significantly, and the balance of the interaction network in genera was broken. The competitive interaction of many bacteria becomes an unstable cooperative interaction. Transcriptomic analysis showed that the numbers of up- and down-regulated differentially expressed genes (DEGs) increased in a dose-dependent manner. These DEGs were significantly enriched in pathways related to detoxification, and the expression of most detoxification genes was upregulated. DEGs related to detoxification were positively correlated with Shimia and negatively correlated with Pseudoalteromonas. This study provides evidence for the first time on the toxic effects of thiamethoxam on the growth, biochemistry, intestinal flora, and transcriptome in crustaceans.

Circular RNA circ-PLCD1 functions as a tumor suppressor in non-small cell lung cancer by inactivation of PI3K/AKT signaling pathway.

Circular RNAs (circRNAs) are emerging as crucial regulators in tumorigenesis and aggressive progression. However, their biological roles in non-small cell lung cancer (NSCLC) remain largely unknown. Here, by performing circRNA high throughput sequencing in 4 paired NSCLC and normal tissues, we found a NSCLC-associated circRNA, circ-PLCD1, which was evidently downregulated in NSCLC tissues and cell lines. Circ-PLCD1 was transcriptionally activated by tumor-inhibiting protein p53, and exogenous expression of circ-PLCD1 inhibited NSCLC cell proliferation, invasion and induced apoptosis. Mechanistically, circ-PLCD1 acted as a competitive endogenous RNA (ceRNA) to sponge miR-375 and miR-1179 and elevate PTEN, a well-known inhibitor of oncogenic PI3K/AKT signaling, thereby repressing NSCLC tumorigenesis. Importantly, we also identified this ceRNA regulatory axis of circ-PLCD1/miR-375/miR-1179/PTEN in vivo by establishing a xenograft tumor model. Clinically, NSCLC patients with low circ-PLCD1 expression had larger tumor size, later clinical stage and shorter survival time than those with high circ-PLCD1 expression. Altogether, our findings reveal the important tumor suppressive role of circ-PLCD1 in NSCLC, reactivation of this circRNA may be considered as a novel therapeutic avenue for patient with NSCLC.

Impact of imidacloprid exposure on the biochemical responses, transcriptome, gut microbiota and growth performance of the Pacific white shrimp Litopenaeus vannamei.

The widespread use of neonicotinoid insecticides, such as imidacloprid, in agriculture is one of the key factors for the drop in the survival of invertebrates, including decapod crustaceans. However, there is currently a lack of comprehensive studies on the chronic toxicity mechanisms in decapod crustaceans. Here, the concentration-dependent effects of imidacloprid on the physiology and biochemistry, gut microbiota and transcriptome of L. vannamei , and the interaction between imidacloprid, gut microbiota and genes were studied. Imidacloprid caused oxidative stress, leading to reduced growth and to immunity and tissue damage in L. vannamei . Imidacloprid increased the gut pathogenic microbiota abundance and broke the steady state of the gut microbiota interaction network, resulting in microbiota function disorders. Chronic imidacloprid exposure induced overall transcriptome changes in L. vannamei . Specifically, imidacloprid caused a large number of differentially expressed genes (DEGs) to be significantly downregulated. The inhibition of autophagy-related pathways revealed the toxic process of imidacloprid to L. vannamei . The changes in phase I and II detoxification gene expression clarified the formation of a detoxification mechanism in L. vannamei . The disturbance of circadian rhythm (CLOCK) caused by imidacloprid is one of the reasons for the increase in gut pathogenic microbiota abundance.

Knockdown of XIST Attenuates Cerebral Ischemia/Reperfusion Injury Through Regulation of miR-362/ROCK2 Axis.

Long non-coding RNAs (lncRNAs) are considered as critical regulators in the pathogenesis of cerebral ischemia. In this present study, we aimed to investigate the impact and underlying mechanism of lncRNA X-inactive specific transcript (XIST) in cerebral ischemia/reperfusion (I/R) injury. An oxygen-glucose deprivation/reperfusion (OGD/R) model in PC12 cells was applied to mimic cerebral I/R injury in vitro and middle cerebral artery occlusion/reperfusion (MCAO/R) model was performed in mice to mimic cerebral I/R injury in vivo. Real-time PCR, fluorescence in situ hybridization (FISH) assay, and western blotting assay were carried out to detect the expression levels of XIST, miR-362, and Rho-related coiled-coil containing protein kinase 2 (ROCK2). The functional experiments were measured by CCK-8 assay, immumofluorescence assay, ELISA assay, TUNEL, and TTC staining. Results displayed that XIST was elevated in PC12 cells with OGD/R, as well as in the ischemic penumbra of mice with MCAO/R. In vitro, knockdown of XIST facilitated cell survival, inhibited apoptosis, and alleviated inflammation injury in OGDR PC12 cells. In vivo, inhibition of XIST remarkably reduced the neurological impairments, promoted neuron proliferation, and suppressed apoptosis in MCAO mice. Mechanistically, XIST acted as a competing endogenous RNA of miR-362 to regulate the downstream gene ROCK2. In conclusion, depletion of XIST attenuated I/R-induced neurological impairment and inflammatory response via the miR-362/ROCK2 axis. These findings offer a potential novel strategy for ischemic stroke therapy.

Long noncoding RNA HAGLROS regulates apoptosis and autophagy in Parkinson's disease via regulating miR-100/ATG10 axis and PI3K/Akt/mTOR pathway activation.

Parkinson's disease (PD) is a common age-related neurodegenerative disease resulted from the progressive degeneration of dopaminergic neurons in the pars compacta region of substantia nigra. The goal of this study was to investigate the effects and mechanisms of long noncoding RNA (lncRNA) HAGLROS on the apoptosis and autophagy in PD. The MPTP-induced PD mouse model and MPP+-intoxicated SH-SY5Y cell model were established, and the expression levels of HAGLROS and miR-100 were determined. Subsequently, the effects of suppression of HAGLROS on apoptosis and autophagy in MPTP-induced PD mouse model and in MPP+-intoxicated SH-SY5Y cells were investigated. In addition, the association between HAGLROS and miR-100 as well as HAGLROS and activation of phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in MPP+-intoxicated SH-SY5Y cells was explored. HAGLROS was increasingly expressed in MPTP-induced PD mouse model and MPP+-intoxicated SH-SY5Y cells and suppression of HAGLRO decreased apoptosis and autophagy in both in vivo and in vitro PD models. Further in vitro studies showed that HAGLRO negatively regulated miR-100 expression, and HAGLROS regulated apoptosis and autophagy of MPP+-intoxicated SH-SY5Y cells through sponging miR-100. Moreover, ATG10 was identified as a target of miR-100. Besides, suppression of HAGLROS alleviated MPP+-intoxicated SH-SY5Y cell injury by activating PI3K/AKT/mTOR pathway. Our findings reveal that upregulation of HAGLROS may contribute to the development of PD via inhibiting apoptosis and autophagy, which may be achieved by regulating miR-100/ATG10 axis and PI3K/AKT/mTOR pathway activation.

Fluoxetine-mediated inhibition of endoplasmic reticulum stress is involved in the neuroprotective effects of Parkinson's disease.

BACKGROUND: Accumulating evidence suggests that Fluoxetine (FLX), an anti-depressant drug, has broad neurobiological functions and neuroprotective effects in central nervous system injury, but its roles in Parkinson's disease (PD) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates rotenone-induced neurodegeneration in PD. METHODS: Male Sprague-Dawley rats were randomly allocated to control, rotenone-treated, rotenone + FLX-treated and FLX-treated groups. Behavioral tests including open field behavioral test and catalepsy measurement were taken to evaluate neurological behavioral measurements. Apoptosis was detected by TUNEL assay. Endoplasmic reticulum (ER)-related gene expressions were detected by qRT-PCR and western blot. Immunohistochemistry was performed to assess dopaminergic neuronal degeneration. RESULTS: We demonstrated that pretreatment with FLX (10.0 mg/kg, i.p.) significantly ameliorated the catalepsy symptom and increased locomotor activity. In addition, FLX markedly reversed the loss of dopaminergic neurons and suppressed the X­box­binding protein 1 (XBP1)/caspase-3-activated ER stress. Furthermore, FLX inhibited rotenone-mediated neurodegeneration through caspase-3-mediated neuronal apoptosis. CONCLUSION: Taken together, our findings indicate that FLX has beneficial neuroprotective effects in PD and FLX might be a potential therapeutic agent for the treatment of PD. In light of its favorable properties, FLX should be evaluated in the treatment of PD as well as related neurologic disorders.

The Neurovascular Protective Effect of S14G-Humanin in a Murine MCAO Model and Brain Endothelial Cells.

Endothelial dysfunction is fundamental to ischemic stroke and brain injury. The humanin analogue S14G-humanin (HNG) has been shown to be a cytoprotective derivative. In this study, we investigated the neuroprotective effects of HNG in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, HNG ameliorates cerebral infarction and suppresses the production of TNF-α, IL-1ß, IL-6 and MCP-1 cytokines. HNG inhibits the expression of vascular adhesion molecules such as VCAM-1 and ICAM-1 in the cortex tissue. In mouse brain endothelial cells bEnd.3, HNG protects cell survival under oxygen deprivation (OGD) conditions. HNG suppresses ROS production as well as that of the same panel of cytokines and vascular adhesion molecules induced by OGD. HNG also reduces the numbers of THP-1 cells attached to bEnd.3 by OGD. Mechanistically, we show that HNG exerts its effect via inhibition of the NF- κB pathway factor IKKα, activation of IκBα and accumulation of p65 in the nucleus. Our data conclude that S14G-humanin serves as a neuroprotective factor, especially in brain vascular disorders. © 2018 IUBMB Life, 70(7):691-699, 2018.

Pitavastatin treatment induces neuroprotection through the BDNF-TrkB signalling pathway in cultured cerebral neurons after oxygen-glucose deprivation.

OBJECTIVES: Along with their lipid-lowering effect, statins have been reported to have neuroprotective function in both in vivo and in vitro models of neurodegenerative diseases. We conducted this study in order to uncover the he neuroprotective effect of the lipophilic statin pitavastatin (PTV) and investigate the underlying molecular mechanisms using primary cultured cerebral neurons exposed to oxygen-glucose deprivation (OGD). METHODS: The primary cultured cerebral neurons were randomly assigned into four groups: the control group, the pitavastatin treatment group, the OGD group and the OGD + pitavastatin treatment group. The pitavastatin's concentration were set as follows: 1µM, 15µM, 30µM. After 3 hours OGD treatment, we use MTT method to assessment cell viability, immunofluorescence to observe neuron morphology and western blot method analysis the BDNF, TrkB. RESULTS: PTV at concentrations of 1 µM and 15 µM elevated the survival rate of cortical neurons exposed to OGD, whereas 30 µM PTV did not show such an effect. Moreover, PTV promoted neuronal dendrite growth at concentrations of 1 µM and 15 µM. Increased expression levels of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) were observed in both of the following two scenarios: when neurons were treated with PTV for 48 hours and when PTV was added after the OGD procedure. CONCLUSION: Pitavastatin treatment induces neuroprotection in cultured cerebral neurons after oxygen-glucose deprivation this neuroprotection induced by PTV involves the BDNF-TrkB signalling pathway.

Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.

The long noncoding RNA Malat1 has been reported to be an oncogene that promotes tumor progress and correlates with prognosis in glioma. Growing evidence shows that autophagy plays a very important role in tumorigenesis and tumor cell survival, but whether Malat1 regulates autophagy in glioma is still unclear. In this study, we found that Malat1 expression and autophagy activity were significantly increased in glioma tissues compared with adjacent normal tissues. Additionally, Malat1 level was positively correlated with the expression of LC3-II (autophagy marker) mRNA in vivo. In vitro assays revealed that Malat1 significantly promoted autophagy activation and cell proliferation in glioma cells. More importantly, inhibition of autophagy by 3-MA relieved Malat1-induced cell proliferation. These data demonstrated that Malat1 activates autophagy and increases cell proliferation in glioma. We further investigated the molecular mechanisms whereby Malat1 functioned on glioma cell autophagy and proliferation. We found that Malat1 served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malat1 abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D. Overall, our study elucidated a novel Malat1-miR-101-STMN1/RAB5A/ATG4D regulatory network that Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma cells.

Non-tumor-Associated Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis in Chinese Girls With Positive Anti-thyroid Antibodies.

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a new category of autoimmune encephalitis associated with anti-NMDA receptor antibodies. The disease was first described in 2007, and it predominantly affects young women with or without ovarian teratomas. Most patients typically present with seizures, a decreased consciousness level, dyskinesia, autonomic dysfunction, and psychiatric symptoms. The presence of anti-thyroid antibodies in non-tumor-associated anti-NMDA receptor encephalitis was first described in 2010. Additionally, anti-thyroid antibodies were found in teratoma-associated anti-NMDA receptor encephalitis. We report the cases of 3 Chinese girls with non-tumor-associated anti-NMDA receptor encephalitis with positive anti-thyroid antibodies. We followed up the details of their titers and suggest that anti-thyroid antibodies were an indicator of autoimmune predisposition in the development of non-tumor-associated anti-NMDA receptor encephalitis.

Local thrombolysis for patients of severe cerebral venous sinus thrombosis during puerperium.

OBJECTIVE: To explore and evaluate the efficacy of intrasinus thrombolysis (IST) in patients with cerebral venous sinus thrombosis (CVST) during postpartum period. METHODS: 11 patients during postpartum period with CVST who received IST during July 2007-November 2011 were included. Urokinase was infused into the sinuses via a microcatheter. Magnetic resonance venography (MRV) was performed to assess the recanalization of venous sinuses. RESULTS: Before discharge, the intracranial pressure in 11 patients was under 200 mmH(2)O. MRV confirmed that venous sinus of 9 patients were smooth. The cortex venous and deep venous recovered to normal. Venous sinus of 2 patients recanalized partly, and cortex venous and deep venous had compensation. 9 patients had good outcome and 2 patients had only mild deficits. CONCLUSION: Intrasinus thrombolysis is safe and effective in patients with severe cerebral venous sinus thrombosis during postpartum period.