Enantioselective Toxicity and Potential Endocrine-Disruptive Effects of the Insecticides Flufiprole and Ethiprole on Danio rerio.

Phenylpyrazole insecticides are widely used as chiral pesticides. However, the enantioselective toxicity and potential endocrine-disrupting effects of these insecticides on aquatic organisms remain unclear. Herein, the enantioselective toxicity and potential endocrine-disrupting effects of flufiprole and ethiprole were investigated by using zebrafish embryos/larvae as a model. The acute toxicity of R-flufiprole and R-ethiprole toward zebrafish embryos and larvae was 1.8-3.1-fold higher than that of the S-configuration. Additionally, R-flufiprole and R-ethiprole had a greater effect on the expression of genes related to the hypothalamus-pituitary-gonad axis in zebrafish compared with the S-configuration. Nevertheless, both S-flufiprole and S-ethiprole exhibited a greater interference effect on the expression of genes related to the hypothalamus-pituitary-thyroid axis and a greater teratogenic effect on zebrafish than the R-configuration. Thus, this study demonstrates that both flufiprole and ethiprole exhibit enantioselective acute toxicity and developmental toxicity toward zebrafish. Furthermore, those pesticides potentially possess enantioselective endocrine-disrupting effects.

Microglia are necessary for probiotics supplementation to improve impaired fear extinction caused by pregnancy stress in adult offspring of rats.

The prevention and treatment of fear-related disorders in offspring affected by pregnancy stress remains challenging at clinic. Here, we examined the effects of gut microbiota of stressed pregnant rats on the fear extinction of their offsprings, and the potential mechanisms. We found that gut microbiota transplantation from rats with pregnancy stress to normal pregnant rats impaired fear extinction, induced microglial activation and synaptic phagocytosis, increased synapse loss in offsprings. Probiotics supplement during pregnancy stress partly normalized pregnancy stress-induced gut microbiota dysbiosis of pregnant rats, and promoted fear memory extinction, inhibited fear memory reappearance, and limited microglial activation and synaptic phagocytosis in offsprings. These data revealed that gut microbiota of stressed pregnant mother improved the development of fear-related disorders of offspring, which may be associated with microglial synaptic pruning.

Tefluthrin induced toxicities in zebrafish: Focusing on enantioselectivity.

Tefluthrin is one of widely used chiral pyrethroid pesticides. The potential enantioselective risk posed by tefluthrin to the aquatic ecosystem is still unclear. In this study, the toxicity differences and corresponding mechanism of tefluthrin on zebrafish were investigated at the enantiomeric level. The results indicated that two tefluthrin enantiomers showed different acute toxicity, developmental toxicity and oxidative stress to zebrafish. The acute toxicity of (1R,3R)-tefluthrin was 130-176 fold as that of (1S,3S)-tefluthrin on zebrafish embryos, larvae and adults. (1R,3R)-Tefluthrin presented approximately 10, 3 and 2 times inhibition effect on the deformity rate, hatching rate and spontaneous movements on embryos as that of (1S,3S)-tefluthrin. Meanwhile, (1R,3R)-tefluthrin caused stronger oxidative stress on zebrafish embryo than (1S,3S)-tefluthrin. The molecular docking results revealed that there were stereospecific binding affinities between tefluthrin enantimers and sodium channel protein (Nav1.6), which may lead to acute toxicity differences. Transcriptome analysis showed that the two tefluthrin enantiomers markedly disturbed differential embryonic genes expression, thereby potentially causing the chronic enantioselective toxicity. The findings of the study reveal the toxicity differences and potential mechanism of tefluthrin enantiomers on zebrafish. These results also provides a foundation for a systematic evaluation of tefluthrin at enantiomer level.

An H-GrabCut Image Segmentation Algorithm for Indoor Pedestrian Background Removal.

In the context of predicting pedestrian trajectories for indoor mobile robots, it is crucial to accurately measure the distance between indoor pedestrians and robots. This study aims to address this requirement by extracting pedestrians as regions of interest and mitigating issues related to inaccurate depth camera distance measurements and illumination conditions. To tackle these challenges, we focus on an improved version of the H-GrabCut image segmentation algorithm, which involves four steps for segmenting indoor pedestrians. Firstly, we leverage the YOLO-V5 object recognition algorithm to construct detection nodes. Next, we propose an enhanced BIL-MSRCR algorithm to enhance the edge details of pedestrians. Finally, we optimize the clustering features of the GrabCut algorithm by incorporating two-dimensional entropy, UV component distance, and LBP texture feature values. The experimental results demonstrate that our algorithm achieves a segmentation accuracy of 97.13% in both the INRIA dataset and real-world tests, outperforming alternative methods in terms of sensitivity, missegmentation rate, and intersection-over-union metrics. These experiments confirm the feasibility and practicality of our approach. The aforementioned findings will be utilized in the preliminary processing of indoor mobile robot pedestrian trajectory prediction and enable path planning based on the predicted results.

Associations of vitamin D-related single nucleotide polymorphisms with post-stroke depression among ischemic stroke population.

Objective: To investigate the relationship between single nucleotide polymorphisms (SNPs) related to vitamin D (VitD) metabolism and post-stroke depression (PSD) in patients with ischemic stroke. Methods: A total of 210 patients with ischemic stroke were enrolled at the Department of Neurology in Xiangya Hospital, Central South University, from July 2019 to August 2021. SNPs in the VitD metabolic pathway (VDR, CYP2R1, CYP24A1, and CYP27B1) were genotyped using the SNPscan™ multiplex SNP typing kit. Demographic and clinical data were collected using a standardized questionnaire. Multiple genetic models including dominant, recessive, and over-dominant models were utilized to analyze the associations between SNPs and PSD. Results: In the dominant, recessive, and over-dominant models, no significant association was observed between the selected SNPs in the CYP24A1 and CYP2R1 genes and PSD. However, univariate and multivariate logistic regression analysis revealed that the CYP27B1 rs10877012 G/G genotype was associated with a decreased risk of PSD (OR: 0.41, 95% CI: 0.18-0.92, p = 0.030 and OR: 0.42, 95% CI: 0.18-0.98, p = 0.040, respectively). Furthermore, haplotype association analysis indicated that rs11568820-rs1544410-rs2228570-rs7975232-rs731236 CCGAA haplotype in the VDR gene was associated with a reduced risk of PSD (OR: 0.14, 95% CI: 0.03-0.65, p = 0.010), whereas no significant association was observed between haplotypes in the CYP2R1 and CYP24A1 genes and PSD. Conclusion: Our findings suggest that the polymorphisms of VitD metabolic pathway genes VDR and CYP27B1 may be associated with PSD in patients with ischemic stroke.

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

Background: The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association. Methods: According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1ß, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay. Results: Fifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014). Conclusions: Our findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

Association of homocysteine and polymorphism of methylenetetrahydrofolate reductase with early-onset post stroke depression.

Background: Homocysteine (Hcy) has been indicated to be involved in pathophysiology of post stroke depression (PSD). There is a lack of research to study the relationship between Hcy metabolism genes and PSD. Our study aims to investigate the relationship among Hcy metabolism genes, Hcy, and early-onset PSD. Materials and methods: We recruited 212 patients with stroke and collected their peripheral blood sample, clinical data, and laboratory test on admission. 12 single nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) genes were genotyped by high-resolution melt analysis. PSD was diagnosed by DSM-V at 2 weeks after stroke. Binary logistic regression and haplotype analysis were used to examine the association between Hcy metabolism genes and PSD. Mediation analysis was performed to clarify whether the SNPs exerted their effect on PSD by affecting the Hcy level. Results: 81 patients were diagnosed with PSD, and the incidence rate was 38.2%. Hcy level in PSD group was significantly higher than it in non-PSD group (p = 0.019). MTHFR rs1801133 AA genotype an A allele were associated with an elevated risk of PSD after adjustment for some confounding factors (OR = 4.021, 95% CI: 1.459∼11.080, p = 0.007 for AA genotype; OR = 1.808, 95% CI: 1.172∼2.788, p = 0.007 for A allele). Furthermore, the effect of MTHFR rs1801133 AA genotype on PSD was mediated by Hcy (OR = 1.569, 95% CI: 0.013∼3.350, p < 0.05). Conclusion: MTHFR rs1801133 and Hcy were associated with PSD, and MTHFR rs1801133 may exert an effect on PSD via mediating Hcy level. This offers a new perspective for treating PSD and understanding the mechanism of PSD.

Autophagy in glaucoma pathogenesis: Therapeutic potential and future perspectives.

Glaucoma is a common blinding eye disease characterized by progressive loss of retinal ganglion cells (RGCs) and their axons, progressive loss of visual field, and optic nerve atrophy. Autophagy plays a pivotal role in the pathophysiology of glaucoma and is closely related to its pathogenesis. Targeting autophagy and blocking the apoptosis of RGCs provides emerging guidance for the treatment of glaucoma. Here, we provide a systematic review of the mechanisms and targets of interventions related to autophagy in glaucoma and discuss the outlook of emerging ideas, techniques, and multidisciplinary combinations to provide a new basis for further research and the prevention of glaucomatous visual impairment.

In vitro fermentation of flaxseed polysaccharide by fecal bacteria inhibits energy intake and adipogenesis at physiological concentration.

Obesity and its related metabolic disorders have been a global pandemic. Recently, we found an anti-obesity effect of flaxseed polysaccharide (FP) that could be achieved by regulating intestinal microbiota. The anti-obesity effect of FP is mainly attributed to the metabolites produced by the interaction with FP, which remains to be elucidated. In this research, the in vitro effects of metabolites of FP fermented by fecal bacteria on energy metabolism and adipogenesis were investigated. The effect of energy metabolism was analyzed by mRNA and protein expression of the intestinal glucose transporters, including sodium dependent glucose transporter (SGLT1) and glucose transporter 2 (GLUT2), and glucose uptake in intestinal Caco-2 cells. The lipogenic effect were evaluated by Oil red O staining of intracellular lipid droplets and the mRNA and protein expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT-enhancer-binding proteins (C/EBP) α and ß in 3T3-L1 cells. The results showed the metabolites significantly inhibited glucose intake through downregulating the mRNA and protein expression of GLUT2 and SGLT1 in Caco-2 cells. Besides, they also led to the decrease of lipid accumulation through downregulating the mRNA and protein expression of PPARγ, C/EBPα, and C/EBPß in differentiating adipocytes. The inhibitory effects on energy intake and adipogenesis were concentration dependent, and metabolites at physiological concentration showed the most significant effect. Metabolites of fecal bacteria fermenting FP inhibited energy intake and adipogenesis at physiological concentration, which might be one of the weight-loss mechanisms of FP-diet.

iTRAQ-based proteomic analysis of the hippocampus of pentylenetetrazole-kindled epileptic rats.

Epilepsy can severely affect the quality of life of patients, who are often at higher risk of mortality. However, the molecular mechanisms and pathogenesis underlying epileptogenesis are poorly understood. In this study, we performed a proteomic analysis of the hippocampus in pentylenetetrazole (PTZ)-kindled epileptic rats to explore the molecular mechanisms of epileptogenesis. We established an epileptic model in Sprague Dawley rats by injecting PTZ intraperitoneally and applied isobaric tags for relative and absolute quantification (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins (DEPs) in the hippocampus. A total of 99 proteins, comprising 93 upregulated and 6 downregulated proteins, were identified based on a fold change >1.2 (or <0.83) and a p-value < .05. A further bioinformatics analysis suggested that the candidate proteins were mainly involved in the ubiquitin ligase complex or metabolite homeostasis or acted as intrinsic components of the membrane. A Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway enrichment analysis identified a series of representative pathological pathways, including the calcium signaling pathway, neuroactive ligand-receptor interaction pathway, and the NF-kappa B pathway. The mass spectrometry results were further confirmed by assessing five representative proteins (Akt1, Syvn1, Amfr, Lamb1, and Cox17) using western blotting and immunohistochemistry. These results may help to reveal the molecular mechanisms underlying epileptogenesis and provide new directions or targets for epilepsy research.

Control of the gyrotron filament power supplies for the experimental advanced superconducting tokamak.

The electron cyclotron heating system including four gyrotrons is being developed in the Institute of Plasma Physics, Chinese Academy of Sciences. The filament is an important part of the gyrotron, which is used to heat the cathode. The gyrotron output power can be controlled by adjusting the filament power. We have developed the filament power control and measurement system using Labview. The filament characteristics were tested using this power control system. The test results show that the filament current can be fitted with the e-exponential function of the filament voltage. It can be seen that as the voltage increases, the filament resistance gradually increases. We have developed a new "burst" function to prevent the beam current from dropping too fast, which is conducive to long pulse stable operation of the gyrotrons.

The Influence of A Mo Addition on the Interfacial Morphologies and Corrosion Resistances of Novel Fe-Cr-B Alloys Immersed in Molten Aluminum.

The influence of a Mo addition on the interfacial morphologies and corrosion resistances of novel Fe-Cr-B alloys in molten aluminum at 750 °C was systematically investigated using scanning electron microscopy, X-ray diffractometer, electron probe microanalysis, and transmission electron microscopy. The results indicated that Mo could not only strengthen the matrix but also facilitate the formation of borides. Furthermore, the microstructures of Mo-rich M2B boride changed from a local eutectic net-like structure to a typical coarse dendritic structure and a blocky hypereutectic structure with increasing Mo addition. This was true of the blocky Mo-rich M2B boride, rod-like Cr-rich M2B boride and the corrosion products, which had a synergistic effect on retarding of the diffusion of molten aluminum. Notably, the corrosion resistance of the Fe-Cr-B-Mo alloy, with an 8.3 wt.% Mo addition, was 3.8 times higher than that of H13 steel.

Selective enhancement of synaptic inhibition by hypocretin (orexin) in rat vagal motor neurons: implications for autonomic regulation.

The hypocretins (orexins) are hypothalamic neuropeptides implicated in feeding, arousal, and autonomic regulation. These studies were designed to determine the actions of hypocretin peptides on synaptic transmission in the dorsal motor nucleus of the vagus nerve (DMV). Whole-cell patch-clamp recordings were made from DMV neurons in transverse slices of rat brainstem. Some of the neurons were identified as gastric-related by retrograde labeling after inoculation of the stomach wall with pseudorabies virus 152, a viral label that reports enhanced green fluorescent protein. Consistent with previous findings, hypocretins caused an inward current (6-68 pA) in most neurons at holding potentials near rest. In addition, the frequency of spontaneous IPSCs was increased in a concentration-related manner (up to 477%), with little change in EPSCs. This effect was preserved in the presence of tetrodotoxin, suggesting a presynaptic site of action. Hypocretins increased the amplitude of IPSCs evoked by electrical stimulation of the nucleus tractus solitarius (NTS) but not evoked EPSCs. Hypocretin-induced increases in the frequency of IPSCs evoked by photoactivation of caged glutamate within the NTS were also observed. Identical effects of the peptides were observed in identified gastric-related and unlabeled DMV neurons. In contrast to some previous studies, which have reported primarily excitatory actions of the hypocretins in many regions of the CNS, these data support a role for hypocretin in preferentially enhancing synaptic inhibition, including inhibitory inputs arising from neurons in the NTS. These findings indicate that the hypocretins can modulate and coordinate visceral autonomic output by acting directly on central vagal circuits.