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The etiology and pathogenesis of Hirschsprung's disease (HSCR) remain largely unknown. We examined colon tissues from three independent populations with a combined analysis of metabolomics, transcriptomics and proteomics to understand HSCR pathogenesis, according to which mouse model was used to examine prostaglandin E2 (PGE2) induced clinical presentation of HSCR. SH-SY5Y and SK-N-BE(2) cell lines were studied for PGE2 inhibited cell migration through EP2. Our integrated multiple 'omics'-analysis suggests that the levels of PGE2, the expression of the gene encoding PGE2 receptor (EP2), and PGE2 synthesis enzyme genes (PTGS1 and PTGES) increased in HSCR colon tissues, together with a decreased synthesis of PGE2-related byproducts. In vivo , the pregnant mice treated with PGE2 gave birth to offspring with the decrease of ganglion cells in their colon and gut function. In in vitro study, when EP2 was blocked, the PGE2-inhibited cell migration was recovered. Our study identified a novel pathway highlighting the link between expression of PTGS1 and PTGES , levels of PGE2, expression of PTGER2 , and neural crest cell migration in HSCR, providing a novel strategy for future diagnosis and prevention of HSCR. Image 1 • We studied HSCR pathogenesis with metabolomics, transcriptomics and proteomics. • Multiple "omics"-analysis highlighted PGE2 and its related genes. • PGE2 induced clinical presentation of HSCR in vivo. • PGE2-inhibited cell migration was recovered by EP2 blockage in vitro. • The pathway of PTGS1/PTGES/PGE2/EP2 was involved in HSCR. [ABSTRACT FROM AUTHOR]

Metabolic coupling between oocytes and the surrounding somatic cells allows for normal two-way communication, and their interactions is necessary for generating developmentally competent eggs. However, the metabolic framework that support oocyte maturation in surrounding cumulus cells is still lacking. Herin, we established a temporal metabolome profile of porcine cumulus cells at three key stages during oocyte maturation, illustrating the picture of global metabolic network in cumulus cells. Importantly, we discovered the novel metabolic signature in cumulus cells during meiotic maturation, in specific, significant consumption of fatty acids, elevated activity of hexosamine biosynthetic pathway (HBP), and enhanced polyamine biosynthesis. Meanwhile, we observed the different utilization of tryptophan, active biosynthesis of progesterone, and progressive decrease in purine and pyrimidine metabolism as the oocytes progress through meiosis. Collectively, our metabolomic data serves an entree to elaborate on the dynamic changes in these metabolic pathways, which not only reveals the metabolic networks controlling oocyte development, but also lays a foundation for the discovery of biomarkers in the improvement in porcine oocyte culture system. [Display omitted] • Analyzed the temporal metabolome profiles of porcine cumulus cells. • Uncovered the metabolic networks regulating oocyte development. • Discovered the active biosynthesis of progesterone and polyamines in cumulus cells during maturation. • Several of the metabolites found in our study may be helpful for the prediction of biomarkers of higher oocyte quality. [ABSTRACT FROM AUTHOR]

Although various pesticides were used globally, the pesticides profiles in human blood serum remain largely unknown. We determined pesticide exposure profiles using solid-phase extraction and gas chromatography tandem with triple quadrupole mass spectrometry in 200 human blood serum samples from the adult population in Jiangsu Province, China. A systematic and comprehensive literature review was carried out to identify the articles investigating pesticide exposure and compare exposure data. Of the 88 pesticides, 76 were found in the blood serum of the population in Jiangsu Province. To the best of our knowledge, 58 pesticides were reported in human blood serum for the first time, and among these pesticides, parathion-methyl, pyrimethanil, fluacrypyrim, simazine, cloquintocet-mexyl and barban were debatable in more than half of the samples. By statistical comparison of the blood serum levels of pesticides between this study and other countries, we found the levels of several organochlorine pesticides were significantly higher in the female population of Jiangsu Province. Health risks related to the pesticide profiling were then revealed, which identified higher carcinogenic toxicity and teratogenic toxicity risk in the female adults of Jiangsu Province caused by organochlorine pesticide exposure. This study not only provides a high-throughput pesticide screening method for future studies of the exposome, but also presents the first human data on exposure to a number of pesticides. It may provide a knowledge database for the risk assessment and management of the pesticides. [ABSTRACT FROM AUTHOR]

Infertility affects about 17% couples, and males contribute to half of the cases. Compared with independent effects of genetic and environmental factors, interactions between them help in the understanding of the susceptibility to male infertility. Thus, we genotyped 25 polymorphisms, measured 16 urinary chemical concentrations and explored interactions between gene-gene and gene-environment in 1039 Han Chinese using metabolomic analysis. We first observed that GSTT1 might interact with GSTM1 ( P inter = 6.33 × 10 − 8 ). Furthermore, an interaction between GSTM1 and 4- n -octylphenol (4- n -OP) was identified ( P inter = 7.00 × 10 − 3 ), as well as a 2-order interaction among GSTT1 , GSTM1 and 4- n -OP ( P inter = 0.04). Subjects with GSTT1 -present and GSTM1 -null genotypes were susceptible to male infertility when exposed to 4- n -OP (OR = 14.05, 95% CI = 4.78–60.20, P = 2.34 × 10 − 5 ). Most metabolites identified were involved in the tricarboxylic acid cycle. In conclusion, it is a novel study of the interaction on male infertility from the aspect of metabolomics. [ABSTRACT FROM AUTHOR]

Heat stress (HS) is a potential harmful factor for male reproduction. However, the effect of HS on Sertoli cells is largely unknown. In this study, the metabolic changes in Sertoli cell line were analyzed after HS treatment. Metabolomic analysis revealed that carnitine, 2-hydroxy palmitic acid, nicotinic acid, niacinamide, adenosine monophosphate, glutamine and creatine were the key changed metabolites. We found the expression levels of BTB factors (Connexin43, ZO-1, Vimentin, Claudin1, Claudin5) were disrupted in TM-4 cells after HS treatment, which were recovered by the addition of carnitine. RT-PCR indicated that the mRNA levels of inflammatory cytokines (IL-1α, IL-1β, IL-6) were increased after HS treatment, and their related miRNAs ( miR-132 , miR-431 , miR-543 ) levels were decreased. Our metabolomic data provided a novel understanding of metabolic changes in male reproductive cells after HS treatment and revealed that HS-induced changes of BTB factors and inflammatory status might be caused by the decreased carnitine after HS treatment. [ABSTRACT FROM AUTHOR]

During pregnancy, human exposure to endogenous estrogens and xenoestrogens (such as lignans) may comprehensively impact the gestational maintenance and fetal growth. We measured the concentrations of 5 lignans and the profile of 13 estrogen metabolites (EMs) in the urine samples of 328 pregnant women and examined their associations with birth outcomes. We found significantly positive associations between gestational age and urinary matairesinol (MAT), enterodiol (END) and enterolactone (ENL), as well as 16-hydroxylation pathway EMs. There were consistently positive relationships between END and the 16-hydroxylation pathway EMs. The positive relationships of MAT, END and ENL exposures with the length of gestation were mainly in the low exposure strata of the levels of these EMs. This study reveals that MAT, END and ENL as well as 16-hydroxylation pathway EMs are associated with birth outcomes, and that there are interactive relationships between lignans and 16-hydroxylation pathway EMs with birth outcomes. [ABSTRACT FROM AUTHOR]

• The relationship between the groundwater depth and grassland ecology was analysed; • Groundwater depth affected the composition and diversity of vegetation species; • A reasonable groundwater depth can buffer the impact of climate change on the vegetation to maintain grassland ecological stability; • The control of grassland degradation should include the potential exploitation of groundwater. Grassland degradation in the semiarid area of China is often attributed to overgrazing and expansion of irrigated agriculture without the consideration of groundwater. However, falling groundwater levels in the region have caused many problems for grassland ecology. In this paper,the typical sandy grassland- the Tongliao part of Horqin grassland was selected as the study area to study the spatial distribution of normalized difference vegetation index (NDVI) and the relationship between the NDVI and groundwater depth (GD) of each grassland pixel was studied. The temporal variation of the NDVI and its correlations with precipitation were investigated. The relationship between GD and vegetation species diversity in grassland was analyzed based on the vegetation survey. The results of the relation between GD and NDVI and vegetation species showed that GD can buffer the impact of increase in drought events on the vegetation because GD affected the composition and diversity of vegetation species. As the GD increases, the mean NDVI showed a trend of increasing first and then decreasing, and basically remained unchanged when the GD was greater than 3.5 m. The species diversity of grassland decreased with increasing GD and was not related to GD when GD was greater than 3.5 ∼ 4 m. Falling groundwater levels will cause great changes in the structure of grassland; specifically, azonal vegetation will gradually die and 3.5 m may be the critical GD needed to maintain the incomplete extinction of grassland azonal vegetation in the aeolian sandy soil. Correlation analysis proved that the correlation between NDVI and precipitation was significantly enhanced when GD increased sharply from 3 m to 6 m after 1999. This research indicates that the control of grassland degradation should pay attention to controlling the groundwater exploitation to recover a reasonable groundwater level, which was found to be necessary in the support of diverse and climate resilient of vegetation. [ABSTRACT FROM AUTHOR]

Highlights: [•] We focused on parental phenol exposure and spontaneous abortion. [•] Urinary parental concentrations of phenols were detected. [•] Paternal PCP exposure increased the risk of spontaneous abortion. [•] Maternal AP exposure increased the risk of spontaneous abortion. [Copyright &y& Elsevier]

Abstract: Phytoestrogens (PEs) are naturally occurring chemical constituents of certain plants. The internal PE exposures, mainly from diet, vary among different populations and in different regions due to various eating habits. To investigate the potential relationship between urinary PE levels and idiopathic male infertility and semen quality in Chinese adult males, 608 idiopathic infertile men and 469 fertile controls were recruited by eligibility screening procedures. Individual exposure to PEs was measured using UPLC–MS/MS as spot urinary concentrations of 6 PEs (daidzein, DAI; equol, EQU; genistein, GEN; naringenin, NAR; coumestrol, COU; and secoisolariciresinol, SEC), which were adjusted with urinary creatinine (CR). Semen quality was assessed by sperm concentration, number per ejaculum and motility. We found that exposures to DAI, GEN and SEC were significantly associated with idiopathic male infertility (P-value for trend=0.036; 0.002; and 0.0001, respectively), while these exposures had stronger association with infertile subjects with at least one abnormal semen parameter than those with all normal semen parameters. Exposures to DAI, GEN and SEC were also related to idiopathic male infertility with abnormal sperm concentration, number per ejaculum and motility (P-value for trend<0.05), while these exposures had stronger association with the infertile men with abnormal sperm number per ejaculum. These findings provide the evidence that PE exposures are related to male reproductive function and raise a public health concern because that exposure to PEs is ubiquitous in China. [Copyright &y& Elsevier]

Ni-rich LiNi x Co y Mn 1−x-y O 2 (NCM) cathode materials have received extensive attention on account of their high specific capacities and great application prospects in electric vehicles. While increasing Ni content in NCM can greatly increase initial discharge capacities, more highly reactive Ni4+ species in the delithiated state may facilitate irreversible phase transformation and undesirable interfacial reactions, leading to severe capacity degradation. Here we demonstrate an organic surface modification approach to modulate the surface coordinative structure of NCM cathode for enhanced cycling stability. We discover that the highly reactive Ni4+ cations can be anchored by strong electron-donating organic groups, especially under bidentate coordination, which mitigates excessive electrolyte decomposition and Ni dissolution into the electrolyte, inhibits the layered-to-rock salt phase transformation and suppresses the initiation and propagation of microcracks within the NCM cathodes. In consequence, the nickel-rich cathode coated with poly (acetoacetoxyethyl methacrylate) (PAAEM) with multiple ester groups exhibits a remarkable improvement in cycling stability, showing 91.3% retention of the initial capacity after 200 cycles. The present findings demonstrate that regulating surface coordinative structure is an efficient and practical strategy to modify the interfacial reactions for enhanced cyclability in Ni-rich layered oxide cathodes. Anchoring interfacial nickel cations using functionalized polymeric nanolayers shows great potential to stabilize Ni-rich LiNi x Co y Mn 1−x-y O 2 (NCM) cathodes. Compared with monodentate ligand (R−C N − Ni) provided by poly (2-cyanoethyl acrylate), poly (acetoacetoxyethyl methacrylate) with multiple carbonyls groups enables bidentate coordination (R−C O−Ni−O C−R), and is more favorable to suppress the electrolyte decomposition, the layered-to-rocksalt (NiO) transformation and subsequent Ni dissolution and the microcracks formation and propagation within the NCM particles. [Display omitted] • An organic surface modification approach was well demonstrated to modulate the surface coordinative structure of NCM cathode. • The highly reactive Ni4+ cations can be anchored by strong electron-donating organic groups, especially under bidentate coordination. • Tailoring the surface coordinative structure provides a robust strategy to address the issues of capacity/voltage decay of NCM cathode. [ABSTRACT FROM AUTHOR]

In semi-arid northwestern China, the groundwater level continues to decline with the development of the irrigated agriculture, resulting in grassland ecosystem degradation. Threshold water tables play an important role in sustaining both grassland ecology and irrigated agriculture. This paper proposes a new method to calculate the threshold water tables based on the quantification of the transport rate of wetting front, by which the optimal layout of well groups in an irrigation district will be discussed; furthermore, this paper will discuss the advantages of using the threshold water tables as the management target to regulate groundwater pumping and ensure an appropriate water table for the ecological system in the irrigation district. The proposed method is applied to an irrigation district in the West Liaohe River Plain, which is a typical area with mixed agricultural and rural lands in northwestern China. The threshold water table in the case study irrigation district is estimated as 10 m; the interference radii of the pumping wells are 340 m, 270 m and 150 m in three different sub-districts, where the well depth is greater than 100 m, 60–80 m and less than 60 m, and the interference radius values are 225–310 m, 165–225 m and 150 m, respectively. • This paper proposes a new method to calculate the threshold water tables. • Optimizing the layout of pumping wells plays a vital role in ensuring threshold water tables. • Based on the food and ecological security, this article gives the reasonable distances for pumping wells. [ABSTRACT FROM AUTHOR]

Di-n-butyl phthalate (DBP) is ubiquitously in the environment and has been detected in almost all of human bodies. Few data could be found about the effects of DBP on cardiovascular system, though its reproductive toxicities have been studied extensively. This study aimed to explore the effects of DBP on lipid metabolism, a key step during the formation of atherosclerosis, since DBP was recently reported to be associated with atherosclerosis. THP-1 macrophages were employed and exposed to various levels of DBP (10−8, 10−7, 10−6, 10−5 and 10−4 mol/L) or DMSO as control. Lipid accumulation was determined by detection of cellular total cholesterol, free cholesterol, cholesterol ester and content of lipid drops. Expressions of mRNA/miRNAs and proteins were measured by qRT-PCR and western blotting, respectively. Bioinformatic analysis and dual luciferase reporter assay were used to analyze the combination between miR200c-5p and ATP-binding cassette transporter A1 (ABCA1). Cholesterol efflux assay was executed to study the inhibitory effects of DBP on cholesterol efflux capability. Results revealed that DBP at 10−7 mol/L prompted THP-1 macrophages lipid accumulation by inhibiting cholesterol efflux via suppressing ABCA1 expression. In addition, a non-linear inverted U-shaped relationship between DBP and lipid accumulation could be observed. Moreover, miR200c-5p could directly targets to ABCA1 3′UTR and modulate ABCA1 expression. Besides, downregulation of ABCA1 expression and reduction of lipid efflux induced by DBP were due to the miR200c-5p upregulation. Collectively, these data suggested that DBP at levels relative to human exposure could increase lipid accumulation in THP-1 macrophages by decreasing cholesterol efflux through miR200c-5p-ABCA1, then potentiate the formation of atherosclerosis. Image 1 • This study is aimed to research the effects of low levels of DBP on lipid metabolism. • DBP at 10-7 mol/L increased THP-1 macrophages lipid accumulation. • DBP suppressed lipid efflux by downregulating the expression of ABCA1. • miR200c-5p targeted the 3′ UTR of ABCA1 in THP-1 macrophages. • DBP promoted lipid accumulation via the miR200c-5p-ABCA1 pathway. [ABSTRACT FROM AUTHOR]

Well-balanced and orderly metabolism is a crucial prerequisite for promoting oogenesis. Involvement of single metabolites in oocyte development has been widely reported; however, the comprehensive metabolic framework controlling oocyte maturation is still lacking. In the present study, we employed an integrated temporal metabolomic and transcriptomic method to analyze metabolism in goat oocytes at GV, GVBD, and MII stages (GV, fully-grown immature oocyte; GVBD, stage of meiotic resumption; MII, mature oocyte) during in vitro maturation, revealing the global picture of the metabolic patterns during maturation. In particular, several significantly altered metabolic pathways during goat oocyte meiosis have been identified, including active serine metabolism, increased utilization of tryptophan, and marked accumulation of purine nucleotide. In summary, the current study provides transcriptomic and metabolomic datasets for goat oocyte development that can be applied in cross-species comparative studies. • Provide the temporal metabolome and transcriptome data resources of goat oocytes. • Multiple omics revealed the characteristics of metabolic patterns during goat oocytes maturation. • Discovered diverse patterns of amino acid metabolism. • Discovered a progressive increase in nucleotide metabolism. [ABSTRACT FROM AUTHOR]

[Display omitted] • Terrestrial C 3 plants in the ATTZ were the main supporter of aquatic consumers all year round. • Seasonal and interannual WLF driven by Three Gorges Project and HC restricted autochthonous production. • Higher TPs and longer food chains were shown during the dry than the wet season. • Resource diversity and habitat complexity reduced the strength of trophic interactions. • HC and natural WLFs are crucial in maintaining ecosystem stability of large floodplain lakes. Variation in hydrological connectivity (HC) between rivers and lakes gives rise to periodic large water level fluctuation (WLF) in river-connected lakes (RCL). However, how WLF shapes the material cycling and concomitant trophodynamics of RCL remain unclear. Here we evaluated the resource availability, relative contributions of autochthonous and allochthonous carbon sources (by Bayesian mixing models) and trophic structure (using δ13C and δ15N) of Lake Poyang, the largest freshwater lake in China, during different hydrological periods. Terrestrial C 3 plants in the aquatic/terrestrial transition zones (ATTZ) were the main supporter of aquatic consumers all year round. Compared with historical data, the contributions of autochthonous production to aquatic food webs were low. This is primarily ascribed to the influences of hydrological regimes in that the operation of Three Gorges Dam and HC changed the rhythm of WLF in Lake Poyang, restricting the production of aquatic vegetation and epiphytic algae. Most common fish species indicated higher trophic positions (TPs) during the dry than wet season, but only eleven of thirty-six common species showed a statistically significant increase (p < 0.05). Our study reveals a relatively consistent trophic diversity of consumer communities (fish and aquatic invertebrates) during dry and wet seasons, but each trophic guild showed specific trophic response to WLF, as they flexibly adjusted feeding strategies and the degree of trophic niche differentiation. Although WLF triggered fluctuations in the resource availability and species composition of lake food webs, and the TPs and trophic niches of aquatic consumers during different hydrological periods, the resource diversity and habitat complexity driven by HC and WLF reduced the strength of trophic interactions, and thus resulted in overall stability of food web trophodynamics and trophic structure of Lake Poyang. Our findings highlighted the importance of HC and natural WLFs in maintaining the ecosystem stability of large floodplain lakes, and that seasonal WLF patterns should be maintained in future floodplain lake management to conserve biodiversity and the resilience of ecological functions. [ABSTRACT FROM AUTHOR]

Hirschsprung's disease (HSCR) is neonatal intestinal abnormality which derived from the faliure of enteric neural crest cells migration to hindgut during embryogenesis from 5 to 12 weeks. Currenly, the knowledge of environmental factors contributing to HSCR is still scarce. Benzophenone-3 (BP-3) is one of the most widely used UV filters, and has weak estrogen and strong anti-androgenic effects. In order to examine the effect of maternal BP-3 exposure on development of offspring and explore the potential mechanism, we conducted case and control study and in vitro study. In this work, BP-3 concertrations in maternal urine was detected by ultra-high performance liquid chromatography. Besides, we investigated the cytotoxicity and receptor tyrosine kinase (RET) expression in cells exposed to BP-3. The results showed that maternal BP-3 exposure was associated with offspring's HSCR in the population as well as inhibited migration of 293T and SH-SY5Y cells. What's more, we discovered dose–response relationship between RET expression and BP-3 exposure dose, and miR-218 and some other genes involved in SLIT2/ROBO1-miR-218-RET/PLAG1 pathway were also related to BP-3 exposure. Therefore, we deduced that BP-3 influenced cell migration via SLIT2/ROBO1-miR-218-RET/PLAG1 pathway. Our study firstly revealed the relationship between maternal BP-3 exposure and HSCR as well as its potential mechanism. [ABSTRACT FROM AUTHOR]

Abstract Early-life exposure to heavy metals and/or trace metal imbalances can have negative developmental effects. Here we sought to characterize exposure profiles for 20 heavy metals and trace elements in umbilical cord blood plasma and identify demographic predictors of exposure. Twenty metals were measured in cord plasma from 357 Chinese infants using ICP-MS. Relationships between demographic variables and metals were analyzed using generalized linear models and logistic regression. Ten metals (antimony [Sb], cobalt [Co], cesium [Cs], copper [Cu], lead [Pb], molybdenum [Mo], rubidium [Rb], selenium [Se], strontium [Sr], titanium [Ti], zinc [Zn]) were detected in all samples. Season of birth was the strongest predictor of metals in cord blood across analyses. Infants born in the spring had 0.1–0.2 μg L-1 higher logAs and logCo in their cord blood (β [95%CI] = 0.22 [0.01,0.42], p = 0.04; 0.11 [0.01,0.22], p = 0.04), while infants born in the summer had higher Sb, logB, logHg, and logZn (β [95%CI] = 0.74 [0.24,1.24], p = 0.004; 0.11 [0.00,0.21], p = 0.04; 0.29 [0.08,0.49], p = 0.007; 0.18 [0.06,0.31], p = 0.005), compared to those born in fall/winter. Prenatal heavy metal exposure and/or trace metal deficiencies are global concerns because of increasing awareness of downstream developmental effects. Highlights • Exposure to heavy metals or trace metal deficiencies/excesses can impact health. • We measured 20 toxic and essential metals in the cord blood of Chinese infants. • 10 metals (Sb,Co,Cs,Cu,Pb,Mo,Rb,Se,Sr,Ti,Zn) were detected in all blood samples. • Birth season and parent occupation were associated with infant cord blood metals. [ABSTRACT FROM AUTHOR]

Glycolysis, through anaerobic respiration, can supply energy for human sperm motility. MicroRNAs (miRNAs) could participate in the glycolytic pathway through regulating target genes. To investigate the potential role of glycolysis-related miRNAs in asthenozoospermia, TaqMan Low Density Array (TLDA) was used to screen potentially functional miRNAs, and seven glycolysis-related miRNAs were isolated to be related to asthenozoospermia. After qRT-PCR validation, only one seminal plasma miRNA, let-7b-5p, was found significantly decreased in severe asthenozoospermia cases compared with healthy controls. To further understand whether let-7b-5p is involved in asthenozoospermia by regulating the glycolytic pathway, we carried out gain-and-loss function study of let-7b-5p in GC-2 cells and detected the glycolytic activities. Our results showed that knocking down let-7b-5p could inhibit glycolytic activities. Besides, we also found overexpressed Aurkb (a target gene of let-7b-5p) could recapitulate the effects of knocking down let-7b-5p. Our findings indicated that low expression of let-7b-5p could repress glycolysis in asthenozoospermia by targeting AURKB . [ABSTRACT FROM AUTHOR]

Background: Occupational studies suggest that exposure to organophosphate insecticides (OPs) can lead to vision or hearing loss. Yet the effects of early-life exposure on visual and auditory function are unknown. Here we examined associations between prenatal OP exposure and grating visual acuity (VA) and auditory brainstem response (ABR) during infancy.Methods: 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Grating visual acuity (VA) (n = 179-200) and auditory brainstem response (ABR) (n = 139-183) were assessed at 6 weeks, 9 months, and 18 months. Outcomes included VA score, ABR wave V latency and central conduction time, and head circumference (HC). Associations between sensory outcomes during infancy and cord OPs were examined using linear mixed models.Results: Prenatal chlorpyrifos exposure was associated with lower 9-month grating VA scores; scores were 0.64 (95% CI: -1.22, -0.06) points lower for exposed versus unexposed infants (p = 0.03). The OPs examined were not associated with infant ABR latencies, but chlorpyrifos and phorate were both significantly inversely associated with HC at 9 months; HCs were 0.41 (95% CI: 0.75, 0.6) cm and 0.44 (95% CI: 0.88, 0.1) cm smaller for chlorpyrifos (p = 0.02) and phorate (p = 0.04), respectively.Conclusions: We found deficits in grating VA and HC in 9-month-old infants with prenatal exposure to chlorpyrifos. The clinical significance of these small but statistically significant deficits is unclear. However, the disruption of visual or auditory pathway maturation in infancy could potentially negatively affect downstream cognitive development. [ABSTRACT FROM AUTHOR]

Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP) are the most common endocrine disrupting chemicals. Many studies indicated the effects of MBP on male steroidogenesis, however, little attention have been paid on the effects of low levels of MBP on female steroidogenesis. This study was aimed to assess steroidogenesis stimulated by low-dose MBP on primary cultured ovarian granulosa cells (mGCs). Ovarian granulosa cells were isolated from ICR female mice. Hormone levels in medium were detected by ELISA, mRNA and protein expressions of vimentin, NF-κB p65 and phosphorylation of NF-κB p65 (p-p65) were assayed by qRT-PCR, western blot and immunohistochemistry, respectively. Besides, confocal immunofluorescence and electrophoretic mobility shift assay (EMSA) were used for detecting vimentin expression and activity of NF-κB p65 binding to the promoter of vimentin, respectively. Progesterone levels, mRNA and protein levels of vimentin and p-p65 in cells were increased significantly in mGCs treated by MBP at 10 − 10 M. Additionally, MBP-induced steroidogenesis was blocked when vimentin protein was knocked down or activity of NF-κB was inhibited. EMSA assay showed that binding activity of NF-κB to the promoter regions of vimentin was boosted after MBP exposure. Accordingly, the results suggested that MBP could up-regulated steroidogenesis through NF-κB-vimentin signal in mGCs. [ABSTRACT FROM AUTHOR]

Background Organophosphate insecticides (OPs) are used worldwide, yet despite nearly ubiquitous exposure in the general population, few have been studied outside the laboratory. Fetal brains undergo rapid growth and development, leaving them susceptible to long-term effects of neurotoxic OPs. The objective here was to investigate the extent to which prenatal exposure to OPs affects infant motor development. Methods 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Motor function was assessed at 6-weeks and 9-months using Peabody Developmental Motor Scales 2nd edition (PDMS-2) (n = 199). Outcomes included subtest scores: reflexes, stationary, locomotion, grasping, visual-motor integration (V-M), composite scores: gross (GM), fine (FM), total motor (TM), and standardized motor quotients: gross (GMQ), fine (FMQ), total motor (TMQ). Results Naled, methamidophos, trichlorfon, chlorpyrifos, and phorate were detected in ≥ 10% of samples. Prenatal naled and chlorpyrifos were associated with decreased 9-month motor function. Scores were 0.55, 0.85, and 0.90 points lower per 1 ng/mL increase in log-naled, for V-M (p = 0.04), FM (p = 0.04), and FMQ (p = 0.08), respectively. For chlorpyrifos, scores were 0.50, 1.98, 0.80, 1.91, 3.49, 2.71, 6.29, 2.56, 2.04, and 2.59 points lower for exposed versus unexposed infants, for reflexes (p = 0.04), locomotion (p = 0.02), grasping (p = 0.05), V-M (p < 0.001), GM (p = 0.007), FM (p = 0.002), TM (p < 0.001), GMQ (p = 0.01), FMQ (p = 0.07), and TMQ (p = 0.008), respectively. Girls appeared to be more sensitive to the negative effects of OPs on 9-month motor function than boys. Conclusions We found deficits in 9-month motor function in infants with prenatal exposure to naled and chlorpyrifos. Naled is being aerially sprayed to combat mosquitoes carrying Zika virus, yet this is the first non-occupational human study of its health effects. Delays in early-motor skill acquisition may be detrimental for downstream development and cognition. [ABSTRACT FROM AUTHOR]

Both bisphenol A (BPA) and obesity affect male reproductive system. However, whether there is an interaction between them remains poorly understood. The aim of the present study was to evaluate the interaction between BPA exposure and obesity on semen quality and elucidate the mechanism in humans and animals. We firstly analyzed the interaction on semen volume, sperm count per ejaculate, sperm concentration and sperm motility in 357 men, and found that urinary BPA concentration was significantly correlated with sperm count per ejaculate in obese men (β = − 34.62; 95% CI: − 60.75, − 8.48; P = 0.01). Then we validated the interaction using lean and obese mice with administration of BPA. Significant interactions between BPA exposure and obesity on sperm count and sperm concentration was observed in mice. Finally, we conducted metabolomics analyses to identify metabolites related to the interaction. Metabolites related to the interaction, including capric acid, dodecanoic acid, l -palmitoylcarnitine, niacinamide, etc., are known to play critical roles in fatty acid oxidation and tricarboxylic acid cycle indicating increased oxidative stress associated with male reproductive dysfunction. Thus, our study finds an interaction between BPA exposure and obesity on sperm count and reveals potential metabolic mechanisms. It emphasizes the importance to study interactions between endocrine disrupting chemicals and obesity, and opens avenues for the possible use of animal models in identifying the interactions. [ABSTRACT FROM AUTHOR]

Desertification and salinization are both threats to the ecosystem services in inland river oases of arid regions. Previous studies focus on either desertification or salinization, and there is a lack of joint studies on the two issues. The essential cause of desertification in a transition zone is usually concentrated irrigation water use, which leads to shrink of the subsurface flow field of groundwater, decline of the groundwater level, and loss of groundwater supply to the vegetation. The salinization problem in an oasis area is mainly caused by the local excess groundwater in the oasis, referring to secondary salinization, which leads to salt migration with the groundwater level rise to form salt crystallization at the land surface. Thus, the processes of desertification and secondary salinization are connected, and the solutions to the two problems can be complementary, i.e., by transporting the excess groundwater in the local secondary salinization area to the transition zone area where water is scarce. This paper, taking Luocheng Irrigation District in the Heihe River Basin of northwestern China as an example, estimates 1.76–4.70 million m3 of excess groundwater that can be extracted in the salinized area. Using this amount of water through engineering regulation, it is estimated that the transition zone nearby the irrigation district, which is under desertification threat, can be restored with an area of 23–212 km2. An engineering system is designed for coordinated groundwater regulation and the implementation with an experimental farm in the irrigation district is demonstrated. • Providing a new method to mitigate salinization and desertification in arid areas through groundwater regulation. • Estimating the amount of drainage from salinized oasis area in an irrigation district and the transition zone area to be recovered from desert. • Designing an engineering system for coordinated groundwater regulation. [ABSTRACT FROM AUTHOR]

Objective: To identify the differential urinary metabolic pattern of oligozoospermic infertile men and to determine the potential biomarkers indicative of infertility. Design: Observational study. Setting: University hospital. Patient(s): Totals of 158 fertile volunteers and 135 oligozoospermic infertile men. Intervention(s): None. Main Outcome Measure(s): Urinary metabolic profiles were acquired with the use of liquid chromatography/mass spectrometry. Potential oligozoospermic biomarkers were screened from orthogonal projections to latent structures discriminant analysis and further evaluated by receiver operating characteristic analysis. The Spearman correlations between the individual sets of biomarkers and between biomarkers and sperm parameters were investigated. The disrupted biologic pathways which the biomarkers were involved in also were analyzed. Result(s): Oligozoospermic infertile men could be differentiated from fertile control subjects based on altered urinary metabolic profiles. A total of ten potential biomarkers were screened and tentatively identified. Among those, decreased acylcarnitines, aspartic acid, and leucylproline and increased adenine and methylxanthine were strongly associated with oligozoospermic risk. Many biomarkers were associated with sperm concentration and amplitude of lateral head displacement. The combined pattern of acetylcarnitine, carnitine C3:1, and aspartic acid provided moderate diagnostic power. Conclusion(s): Urinary metabolomics identified unique metabolic pattern of oligozoospermic infertility. The potential biomarkers suggested that oligozoospermia may be tightly associated with energy consumption and antioxidant defenses in spermatogenesis. [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]

Highlights: [•] BPA disturbed the expression of pluripotency markers in mESC and mEB. [•] BPA enhanced differentiation toward endoderm and mesoderm in mEB. [•] BPA inhibited differentiation to ectodermal lineages in mEB. [•] The expression of miR-134 was decreased in both BPA-treated mESC and mEB. [Copyright &y& Elsevier]

Abstract: β-Microseminoprotein (MSMB) is one of the most abundant proteins in human seminal plasma. It has been identified that MSMB increased significantly in oligoasthenoteratozoospermic patients compared with fertile controls. We hypothesized that the functional polymorphism (rs10993994) of MSMB gene could be a risk factor for spermatogenic failure. For this study, 338 patients with idiopathic oligozoospermia or azoospermia and 382 fertile controls were recruited from an infertility clinic. Semen analysis was performed by computer-assisted semen analysis system. The functional polymorphism of MSMB gene was genotyped using TaqMan method. Sixty three seminal plasma samples were used to test the expression of MSMB by enzyme-linked immunosorbent assay (ELISA). The TT genotype and T allele were associated with an increased risk of idiopathic infertility with azoospermia (TT genotype: OR, 1.75; 95% CI, 1.03–2.95; T allele: OR, 1.34; 95% CI, 1.03–1.75). However, no differences were found in risk for the TT genotype or T allele among men with oligozoospermia. In addition, idiopathic infertile males have significantly higher MSMB expression levels than fertile controls. We present the first epidemiologic evidence supporting the involvement of common genetic polymorphism in MSMB gene in spermatogenic failure. These results suggest that men carrying the variant have an increased risk of spermatogenic failure associated with male infertility. Further studies are needed to confirm the roles of the polymorphism in idiopathic azoospermia and investigate the biological mechanism of elevated MSMB expression in infertile males. [Copyright &y& Elsevier]

Recent urban development in Shanghai, the largest city in China, and its impact on the water environment are examined in this study. The area of built-up surface was obtained from the classification of the Landsat 7 ETM+ images of the year 2000 for Shanghai. The proportion of built-up surface and population density were extracted from buffer zones with radii ranging from 100 to 2000 m, and used in regression analysis against various water quality parameters at 44 water quality monitoring stations across metropolitan Shanghai. Results suggest that in most cases, the pattern of urban land use as represented by the built-up surface was a stronger predictor than population density in explaining spatial patterns of water quality parameters in Shanghai. The best models of most water quality parameters were found for buffer zones of 2000 m radius rather than for smaller buffers, indicating the regional nature of the factors that influence water quality in the study area. Evidence suggests that strong associations between land use, population density, and water quality result from the contribution of untreated domestic wastewater and non-point pollution sources to waterways in Shanghai. Such relationships should remain strong in the near future until measures to increase the capacity of wastewater treatment and control of non-point pollution sources are fully implemented. [Copyright &y& Elsevier]

• The urinary detection rate of radioactive cesium in Chinese pregnant women is 100%. • Mercury, cadmium and cesium may influence maternal and neonatal thyroid function. • First trimester is a critical window for maternal metal exposure to thyroid function. China, a developing country, has a particularly serious problem with metal pollution. We evaluated the association of metal exposure during pregnancy with maternal and neonatal thyroid function, and identified the critical window for maternal metal exposure effects on maternal and neonatal thyroid functions. The maternal urinary concentrations of mercury (Hg), cadmium (Cd), arsenic (As) and cesium (Cs) were determined in pregnant women during their first (n = 389) or third (n = 257) trimesters in a prospective cohort from 2014 to 2015 in Nanjing, China, using an inductively coupled plasma mass spectrometry (ICP-MS) instrument. Maternal serum-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured by electrochemiluminescent microparticle immunoassays in the second and third trimesters. Neonatal TSH levels were detected 72 h after birth. Hg (>0.162 µg/L), Cd (>0.084 µg/L), As (>0.348 µg/L) and Cs (>0.093 µg/L) were detectable in 76.9%, 90.1%, 100% and 100% of maternal urine samples from women in the first trimester of pregnancy. In the multiple adjusted linear regression models, maternal exposures to Hg and Cd in the first trimester were positively associated with maternal TSH levels in the second trimester (P < 0.01, P = 0.02). Moreover, maternal exposures to Cd and Cs in the first trimester were positively associated with neonatal TSH levels (P = 0.04, P = 0.02). In the Bayesian kernel machine regression (BKMR) model, the results were stable and consistent with the linear regression model. Maternal exposure to Hg, Cd and Cs in the first trimester was related to TSH levels in mothers and newborns. Efforts to identify maternal and neonatal thyroid disruptors should carefully consider the effects of exposure to these metals. [ABSTRACT FROM AUTHOR]

• TiO 2 NPs impaired the invasion ability of human trophoblastic cells. • MiR-96-5p and EZR may choose as candidates to rescue TiO 2 NPs–induced trophoblastic cell invasion dysfunction. • Human placenta development might be affected after maternal exposure of TiO 2 NPs. Titanium dioxide nanoparticles (TiO 2 NPs) are used extensively in our daily lives, and their toxic effects on the placenta have been reported. Animal studies indicated that placental development is impaired after maternal exposure of TiO 2 NPs, but the underlying mechanisms remain largely unknown. In the present study, we used a human trophoblast-derived cell, HTR8-SVneo, to determine how TiO 2 NPs affected placental functions, and found out potential reversal targets. TEM was employed for TiO 2 NPs morphology observation and uptake assessment. RT-PCR was used to detect the expression of both mRNA and miRNA, and western blotting was used for protein examination. Cell invasion ability was evaluated by Transwell assay, and cytoskeletons were observed by immunofluorescence combined with confocal microscope examination. We found that TiO 2 NPs disrupted cytoskeletons and impaired cell invasion ability. Further investigations showed that TiO 2 NPs increased the expression of a microRNA (miR-96-5p), which targeted and down-regulated the translation of EZR mRNA, a gene that encodes ezrin protein, and affected the cell cytoskeletons and ultimately cell invasion ability. When the expression of miR-96-5p was down-regulated, the expression level of ezrin protein was also reversed, and cell invasion ability was partially restored. Collectively, we determined how miR-96-5p mediates TiO 2 NP-induced placental dysfunction, and provided a potential rescue target for future therapy. [ABSTRACT FROM AUTHOR]