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Hirschsprung's disease ( HSCR) is a rare congenital disease caused by impaired proliferation and migration of neural crest cells. We investigated changes in expression of micro RNAs (mi RNAs) and the genes they regulate in tissues of patients with HSCR. Quantitative real-time PCR and immunoblot analyses were used to measure levels of mi RNA, mRNAs, and proteins in colon tissues from 69 patients with HSCR and 49 individuals without HSCR (controls). Direct interactions between mi RNAs and specific mRNAs were indentified in vitro, while the function role of miR-218-1 was investigated by using miR-218 transgenic mice. An increased level of miR-218-1 correlated with increased levels of SLIT2 and decreased levels of RET and PLAG1 mRNA and protein. The reductions in RET and PLAG1 by miR-218-1 reduced proliferation and migration of SH-SY5Y cells. Overexpression of the secreted form of SLIT2 inhibited cell migration via binding to its receptor ROBO1. Bowel tissues from miR-218-1 transgenic mice had nerve fibre hyperplasia and reduced numbers of gangliocytes, compared with wild-type mice. Altered miR-218-1 regulation of SLIT2, RET and PLAG1 might be involved in the pathogenesis of HSCR. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene ( hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene ( CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes ( esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo. Environ. Toxicol. Chem. 2013;32:353-360. © 2012 SETAC [ABSTRACT FROM AUTHOR]

Cobalt oxides have been intensely explored as anodes of lithium-ion batteries to resolve the intrinsic disadvantages of low electrical conductivity and volume change. However, as a precursor of preparing cobalt oxides, Co(OH)2 has rarely been investigated as the anode material of lithium-ion batteries, perhaps because of the complexity of hydroxides. Hybridized Co(OH)2 nanomaterial structures were synthesized by the water bath method and exhibited high electrochemical performance. The initial discharge and charge capacities were 1703.2 and 1262.9 mAh/g at 200 mA/g, respectively. The reversible capacity was 1050 mAh/g after 150 cycles. The reversible capability was 1015 mAh/g at 800 mA/g and increased to 1630 mAh/g when driven back to 100 mA/g. The electrochemical reaction kinetics study shows that the lithium-ion diffusion-controlled contribution is dominant in the energy storage mechanism. The superior electrochemical performance could result from the water bath method and the hybridization of nanosheets and nanoparticles structures. These hybridized Co(OH)2 nanomaterial structures with high electrochemical performance are promising anodes for lithium-ion batteries. [ABSTRACT FROM AUTHOR]

• We studied the effect of low-dose DEHP exposure on metabolic syndrome in offspring. • Prenatal low-dose DEHP exposure results in male offspring metabolic syndrome and gut microbiome dysbiosis. • Low-dose DEHP exposure reprograms hepatic thiamine transporters disrupting glucose metabolism. • Thiamine ameliorates DEHP-induced adipogenesis and insulin resistance. Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and is widely used in industrial plastics. However, the long-term health implications of prenatal exposure to DEHP remains unclear. We set out to determine whether prenatal DEHP exposure can induce metabolic syndrome in offspring and investigate the underlying mechanisms. A mouse model of prenatal DEHP exposure (0.2, 2, and 20 mg/kg/day) was established to evaluate the long-term metabolic disturbance in offspring. The mice were profiled for the hepatic metabolome, transcriptome and gut microbiota to determine the underlying mechanisms. Thiamine supplementation (50 mg/kg/day) was administered to offspring to investigate the role of thiamine in ameliorating metabolic syndrome. Prenatal exposure to low-dose DEHP (0.2 mg/kg/day) resulted in metabolic syndrome, including abnormal adipogenesis, energy expenditure and glucose metabolism, along with dysbiosis of the gut microbiome, in male offspring. Notably, hepatic thiamine metabolism was disrupted in these offspring due to the dysregulation of thiamine transport enzymes, which caused abnormal glucose metabolism. Prenatal low-dose DEHP exposure caused life-long metabolic consequences in a sex-dependent manner, and these consequences were be attenuated by thiamine supplementation in offspring. Our findings suggest low-dose DEHP exposure during early life stages is a potential risk factor for later obesity and metabolic syndrome. [ABSTRACT FROM AUTHOR]

A numerical investigation is conducted to study the propulsive performance of the semi-active flapping foil of the wave glider, where the heaving smotion is fully prescribed, and the pitching motion is determined by the hydrodynamic force and torsion spring. A mesh for two-dimensional NACA0012 foil with the Reynolds number Re = 42000 is produced, and a dynamic mesh and sliding interface are used in the computation. The influences of reduced frequency, spring stiffness, and critical pitching amplitude on the hydrodynamic characteristics of semi-active flapping foil are systematically investigated. We find that there is a critical reduced frequency: When the reduced frequency is lower than the critical value, the propulsive performance of flapping foil can be improved exponentially, and when the reduced frequency is higher than the critical value, the semi-active flapping foil cannot provide an effective thrust. For a greater reduced frequency, there is an optimal spring stiffness value, which corresponds to the maximum value of the output power coefficient. For a lower reduced frequency, the mean value of the output power coefficient monotonically decreases as the spring stiffness increases. We also notice that the propulsive efficiency of flapping foil monotonically decreases as the spring stiffness increases. Finally, we find that the appropriate critical pitching amplitude can improve the propulsive performance of semi-active flapping foil, especially for greater heaving amplitudes. [ABSTRACT FROM AUTHOR]

An investigation is conducted on the propulsion performance of semi-active flapping foils in tandem configuration of the wave glider, considering different vortex effects and tandem distances. The Finite Volume Method is utilized with commercial CFD software Fluent to solve the URANS equations around the flapping foil. A mesh comprising a 2D NACA0012 foil with Reynolds number Re = 42,000 is used in all simulations. The study investigates the propulsion performance of tandem flapping foil systems, focusing on the differing impacts of wave interaction on the front and rear foils. It explores how varying tandem distances and reduced frequencies influence thrust enhancement and degradation. The research reveals that while the front foil consistently benefits from thrust enhancement, the rear foil's performance is more complex, being subject to thrust enhancement or reduction due to wake vortex interactions. Detailed analyses of instantaneous thrust coefficients, pitching trajectories, and pressure contours provide insights into the hydrodynamic performance of these systems. The findings emphasize the importance of synchronization in motion between the foils for optimal propulsion and highlight the rear foil's susceptibility to changes in the wake flow, affecting its thrust generation capability. Thus, the optimal tandem distance can fully capitalize on the thrust enhancement effect of the wake interaction to improve the performance of the tandem flapping foil propulsion system. • Semi-Active Tandem Flapping Foils : The research centers on the propulsion performance of semi-active tandem flapping foils in tandem configurations for wave gliders. • Front and Rear Foil Dynamics : Explores how thrust enhancement and degradation are influenced by tandem distances and reduced frequencies, noting distinct effects on front and rear foils. • Wake Vortex Interactions : Highlights the complex performance of the rear foil due to wake vortex interactions and the importance of motion synchronization. • Optimal Tandem Distance : Concludes that optimal tandem distance significantly improves propulsion performance by maximizing the thrust enhancement effect of wake interactions. [ABSTRACT FROM AUTHOR]

Bisphenol S (BPS), a substitute for bisphenol A, is widely used in the manufacture of food packaging materials, raising concern over its toxicity. However, evidence is still lacking on whether gut microbiota involved in BPS induced intestinal inflammation in mammals, as well as its underlying mechanism. Using mouse BPS exposure model, we found intestinal inflammation characterized by shortened colon length, crypt distortion, macrophage accumulation and increased apoptosis. As for gut microbiota, 16s rRNA gene amplicon sequencing showed BPS exposure induced gut dysbiosis, including increased pro-inflammatory microbes such as Ileibacterium , and decreased anti-inflammatory genera such as Lactobacillus , Blautia and Romboutsia. Besides, LC-MS/MS-based untargeted metabolomic analysis indicated BPS impaired both bacteria and host metabolism. Additionally, transcriptome analysis of the intestine revealed abnormal gene expression in intestinal mucosal barrier and inflammation. More importantly, treating mice with antibiotics significantly attenuated BPS-induced gut inflammation via the regulation of both bacterial and host metabolites, indicating the role of gut microbiota. Collectively, BPS exposure induces intestinal inflammation via altering gut microbiota in mouse. This study provides the possibility of madecassic acid, an anti-inflammatory metabolite, to prevent BPS-induced intestinal inflammation and also new insights in understanding host-microbiota interaction in BPS toxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • FPNUS was tested for microalgae-based in-situ nutrient removal. • N transfer rate across FPNUS varied with membrane pore size and type of N. • NH 4 +-N and NO 3 –-N removal in aquaculture wastewater reached 1.32 and 1.89 mg L-1d-1. • Modelled FPNUS to pond area ratio of 13% could balance typical N loading. Large area requirements and huge energy consumption restrict the applications of microalgae in wastewater treatment. In this study, in-situ nutrient removal was tested using a floating permeable nutrients uptake system with pore sizes of 1, 5, 10, and 40 µm, and Chlorella sorokiniana and Scenedesmus acuminatus. Results showed that N transfer rate across FPNUS varied with membrane pore size and N-type. Average transfer rate of NH 4 +-N, NO 3 –-N, and NO 2 –-N across 1 µm membrane was 2.6, 14.6, and 2.3 mg m-2h−1, respectively, sufficient to support microalgal growth. The NH 4 +-N and NO 3 –-N removal rate in shrimp wastewater reached 1.32 and 1.88 mg L-1d-1, comparable to some BNR processes used in RAS. According to the developed area ratio prediction model, FPNUS to pond area ratio of 21% is sufficient to balance N loading of 0.05 mg L-1d-1. These results indicate extraordinary potential of in-situ nutrient removal from wastewaters using FPNUS. [ABSTRACT FROM AUTHOR]

Prothioconazole (PTC) is a new broad-spectrum triazole antibacterial agent that is being widely used in agriculture. PTC has been linked to a number of reproductive outcomes including embryo implantation disorder; however, the exact mechanism underlying this relationship has yet to be determined. Proper trophoblast proliferation and migration is a prerequisite for successful embryo implantation. To elucidate the underlying molecular perturbations, we detect the effect of PTC on extravillous trophoblast cells proliferation and migration, and investigate its potential mechanisms. Exposure to different concentrations of PTC (0–500 μM) significantly inhibited the cell viability and migration ability (5 μM PTC exposure), and also caused the cell cycle arrest at the lowest dose (1 μM PTC exposure). Transcriptome analysis revealed that PTC exposure disturbed multiple biological processes including cell cycle and apoptosis, consistent with cell phenotype. Specifically, eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1, 4E-BP1) was identified as up-regulated in PTC exposure group and knockdown of EIF4EBP1, and attenuated the G1 phase arrest induced by PTC exposure. In summary, our data demonstrated that 4E-BP1 participated in PTC-induced cell cycle arrest in extravillous trophoblast cells by regulating cyclin D1. These findings shed light on the potential adverse effect of PTC exposure on the embryo implantation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Multi-omics approach uncovers the hepatotoxicity and mechanism of BPF. • BPF exposure remodels hepatic chromatin structure and transcriptome. • BPF exposure alters genes involved in ER stress and lipid metabolism pathway. Bisphenol F (BPF), a substitute for bisphenol A (BPA), is ubiquitous existed in various environmental media. Exposure to BPF may promote non-alcoholic fatty liver disease (NAFLD), while the potential mechanism is still unknown. In current study, we used in vitro and in vivo model to evaluate its hepatotoxicity and molecular mechanism. Using multi-omics approach, we found that BPF exposure led to changes in hepatic transcriptome, metabolome and chromatin accessible regions that were enriched for binding sites of transcription factors in bZIP family. These alterations were enriched with pathways integral to the endoplasmic reticulum stress and NAFLD. These findings suggested that BPF exposure might reprogram the chromatin accessibility and enhancer landscape in the liver, with downstream effects on genes associated with endoplasmic reticulum stress and lipid metabolism, which relied on bZIP family transcription factors. Overall, our study describes comprehensive molecular alterations in hepatocytes after BPF exposure and provides new insights into the understanding of the hepatoxicity of BPF. [ABSTRACT FROM AUTHOR]

[Display omitted] • BPS exposure impairs axonal and dendritic development. • Oxidative phosphorylation is a significantly enriched pathway when exposed to BPS. • Mitochondrial dysfunction underlies BPS-induced injury of axons and dendrites. • A putative Myo19/oxidative phosphorylation axis engages in mitochondrial dysfunction. Exposure to bisphenol S (BPS) is known to adversely affect neuronal development. As pivotal components of neuronal polarization, axons and dendrites are indispensable structures within neurons, crucial for the maintenance of nervous system function. Here, we investigated the impact of BPS exposure on axonal and dendritic development both in vivo and in vitro. Our results revealed that exposure to BPS during pregnancy and lactation led to a reduction in the complexity, density, and length of axons and dendrites in the prefrontal cortex (PFC) of offspring. Employing RNA sequencing technology to elucidate the underlying mechanisms of axonal and dendritic damage induced by BPS, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted a significant alteration in the oxidative phosphorylation (OXPHOS) pathway, essential for mitochondrial function. Subsequent experiments demonstrate BPS-induced impairment in mitochondrial function, including damaged morphology, decreased adenosine triphosphate (ATP) and superoxide dismutase (SOD) levels, and increased reactive oxygen species and malondialdehyde (MDA). These alterations coincided with the downregulated expression of OXPHOS pathway-related genes (ATP6V1B1, ATP5K, NDUFC1, NDUFC2, NDUFA3, COX6B1) and Myosin 19 (Myo19). Notably, Myo19 overexpression restored the BPS-induced mitochondrial dysfunction by alleviating the inhibition of OXPHOS pathway. Consequently, this amelioration was associated with a reduction in BPS-induced axonal and dendritic injury observed in cultured neurons of the PFC. [ABSTRACT FROM AUTHOR]

Abstract Research question : What is the role of mitochondrial DNA (mtDNA) in the pathogenesis of non-obstructive azoospermia (NOA)? Design : mtDNA genome sequencing followed by an independent population validation were performed in 628 NOA cases and 584 healthy controls. Antioxidant capacity of serum was evaluated in 54 randomly selected cases out of 536 and 49 out of 489 controls. Results : In the screening stage, 13 mtDNA haplogroups (hg) were ascertained, and 10 susceptible variants were observed. In the validation stage, hg M8* in individuals was found to be associated with increased risk of NOA [odds ratio (OR) 2.61, 95% confidence interval (CI) 1.47–4.61] (P =0.001). Unexpectedly, the frequency of m.8684C>T, the defining marker for hg M8a, was also higher in NOA (OR 4.14, 95% CI 1.56–11.03) (P =0.002). Subsequently, the frequency distributions were compared among the sub-hg of hg M8* (including hg M8a, C and Z) and, intriguingly, no significance was found in hg C and Z. Additionally, the level of total antioxidant capacity was significantly decreased (P< 0.05) compared with the control group. Conclusions : hg M8a background in general played an active role in the penetrance of 8684C>T in NOA, and mtDNA genetic variants (causing low antioxidant levels) might increase mtDNA damage and impair normal spermatogenesis. [ABSTRACT FROM AUTHOR]

Bisphenol AP (BPAP), a structural analog of bisphenol A (BPA), has been widely detected in environment and biota. BPAP was reported to interfere with hormone and metabolism, while limited data were available about its effects on neurobehavior, especially exposure to it during early-life time. A mouse model of early-life BPAP exposure was established to evaluate the long-term neurobehaviors in offspring. Collectively, early-life BPAP exposure caused anxiety-like behaviors and impaired learning and memory in adult offspring. Through brain bulk RNA-sequencing (RNA-seq), we found differential expressed genes were enriched in pathways related to behaviors and neurodevelopment, which were consistent with the observed phenotype. Besides, single-nucleus RNA-sequencing (snRNA-seq) showed BPAP exposure altered the transcriptome of microglia in hippocampus. Mechanistically, BPAP exposure induced inflammations in hippocampus through upregulating Iba-1 and activating the microglia. In addition, we observed that BPAP exposure could activate peripheral immunity and promote proportion of macrophages and activation of dendritic cells in the offspring. In conclusion, early-life exposure to BPAP impaired neurobehaviors in adult offspring accompanied with excessive activation of hippocampal microglia. Our findings provide new clues to the underlying mechanisms of BPAP's neurotoxic effects and therefore more cautions should be taken about BPAP. [Display omitted] • Early life BPAP exposure induced abnormal neurobehavior in the offspring. • Early life BPAP exposure activated peripheral immunity in the offspring. • Early life BPAP exposure induced inflammations in hippocampus. • Early life BPAP exposure upregulated IBA-1 and activated the microglia. [ABSTRACT FROM AUTHOR]

Cadmium has been suggested to accumulate in the body over a lifetime, posing a great threat to human health. So far, few studies have studied the association between cadmium exposure and long-term health outcomes in adults. To investigate the risk of mortality with blood cadmium level in adults (participants of NHANES, 1999–2014). We evaluated the associations between cadmium and risk of mortality. Data on mortality and cadmium exposure were collected in NHANES database including 39,865 participants. Multivariate Cox regression models were established for calculating hazard ratios (HRs) and 95%CI between cadmium exposure and all-cause and specific-cause mortality outcomes. Totally, 39,865 individuals with 19,260 males (48.3%) and 20,605 females (51.7%) were included in the study. During a total of 341,017 person-years of follow-up 5,094 deaths were documented, including 1,067 cardiovascular disease (CVD) and 890 cancers. Compared with the lowest quantile of cadmium exposure level group, the adjusted HRs in the highest quantile cadmium exposure level group were 1.73 (95%CI: 1.52–1.97) for all-cause mortality, 1.72 (95%CI: 1.28–2.30) for CVD mortality and 1.87 (95%CI: 1.49–2.36) for cancer mortality, respectively (P for trend: <0.001). Additionally, significant interactions with smoking status in the stratified analyses of all-cause mortality and cancer mortality, age in the stratified analyses of cancer mortality were found (P for interaction: 0.002, <0.001 and 0.012). In this nationwide representative sample of the population, we found that higher blood cadmium concentration was associated with increased risks of all-cause and specific-cause mortality. These data further evidence the link between mortality and cadmium concentration. It is of great importance for both policy makers and the public to minimize cadmium exposure, and to reduce long-term adverse health effects. [Display omitted] • We explored independent effects of cadmium on all-cause and specific cause mortality. • Cadmium was positively related to all-cause, CVD and cancer mortality. • Smoking modified upwards the association between Cd and all-cause, cancer mortality. • Age modified upwards the association between Cd and cancer mortality. • The U-shaped dose-response curves between cadmium and mortality were observed. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) is believed to be both the source and target of reactive oxygen species (ROS), and mtDNA genetic alterations have been reported to be associated with molecular defects in the oxidative phosphorylation (OXPHOS) system. In order to investigate the potentially susceptible mtDNA genetic variants to oligoasthenospermia, we conducted a two-stage study in 921 idiopathic infertile men with oligoasthenospermia and 766 healthy controls using comprehensive molecular analysis. In the screen stage, we used next generation sequencing (NGS) in 233 cases and 233 controls to screen oligoasthenospermia susceptible mitochondrial genetic variants. In total, seven variants (C5601T, T12338C, A12361G, G13928C, A15235G, C16179T and G16291A) were screened to be potentially associated with idiopathic oligoasthenospermia. In the validation stage, we replicated these variants in 688 cases and 533 healthy controls using SNPscan. Our results demonstrated that the genetic alteration of C16179T was associated with idiopathic male infertility (odds ratio (OR) 3.10, 95% CI 1.41–6.79) ( p = 3.10 × 10 − 3 ). To elucidate the exact role of the genetic variants in spermatogenesis, two main sperm parameters (sperm count and motility) were taken into account. We found that C16179T was associated with both low sperm count and motility, with ORs of 4.18 (95% CI 1.86–9.40) ( p = 1.90 × 10 − 4 ) and 3.17 (95% CI 1.40–7.16) ( p = 3.50 × 10 − 3 ), respectively. Additionally, A12361G was found to be associated with low sperm count, with an OR of 3.30 (95% CI 1.36–8.04) ( p = 5.50 × 10 − 3 ). These results indicated that C16179T influenced both the process of spermatogenesis and sperm motility, while A12361G may just only participate in the process of spermatogenesis. Further investigation in larger populations and functional characterizations are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggested that cytochrome P450 participated in the tumor metastasis and migration. CYP2B6 also acts as an important enzyme which metabolize partially or primarily metabolism of drugs, environmental contaminants, and mutagens. The objective of this study was to investigate the influence of CYP2B6 polymorphism on susceptibility of Hirschsprung disease. Methods: TaqMan assay was performed to determine the genotypes of CYP2B6 rs707265, rs1042389, rs2054675 in 262 cases and 290 control subjects. Logistic regression was used to assess the associations between these polymorphisms and HSCR. Results: We observed a significant association of CYP2B6 rs707265 (G>A) polymorphism and HSCR susceptibility ( p < 0.001). Besides, rs707265 A presented a significant risk of HSCR ( p < 0.001). Conclusions: Our result suggested that CYP2B6 rs707265 modified the risk of HSCR. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and has been identified as a male prenatal reproductive toxicant. A high fat diet (HFD) has also been suggested as another potential disruptor of male reproductive function. Despite this potential synergism between DEHP exposure and HFD, little is known about the concomitant effects of prenatal DEHP and a subsequent HFD exposure on male offspring reproductive injury. Here we established a mouse model of prenatal exposure to DEHP (0.2 mg/kg/day) to assess the testicular development and spermatogenesis in offspring subjected to obesogenic diet during the pubertal period. Gross phenotype, hormone profiles and the testicular metabolome were analyzed to determine the underlying mechanism. We found that prenatal exposure to low-dose DEHP resulted in decreased sperm density, decreased testosterone (T) levels, increased luteinizing hormone (LH) levels and testicular germ cell apoptosis. Furthermore, these injury phenotypes were aggravated by pubertal HFD treatment. Testicular riboflavin and biotin metabolites were enriched implying their roles in contributing HFD to exacerbate offspring spermatogenesis disorders due to prenatal low-dose DEHP exposure. Our findings suggest that pubertal HFD exacerbates reproductive dysfunction associated with prenatal exposure to low-dose DEHP in male adult offspring. [Display omitted] • Pubertal HFD exacerbates the male offspring reproductive dysfunction resulting from prenatal low-dose DEHP exposure. • Pubertal HFD exacerbates sex hormone alterations and testicular apoptosis in offspring exposed to prenatal low-dose DEHP. • Testicular metabolites are significantly associated with the phenotypes altered by prenatal DEHP exposure and pubertal HFD. • Riboflavin and biotin contribute to HFD exacerbated spermatogenesis disorders due to prenatal low-dose DEHP exposure. [ABSTRACT FROM AUTHOR]