Correlating chemistry and mass transport in sustainable iron production.

Steelmaking contributes 8% to the total CO2 emissions globally, primarily due to coal-based iron ore reduction. Clean hydrogen-based ironmaking has variable performance because the dominant gas-solid reduction mechanism is set by the defects and pores inside the mm- to nm-sized oxide particles that change significantly as the reaction progresses. While these governing dynamics are essential to establish continuous flow of iron and its ores through reactors, the direct link between agglomeration and chemistry is still contested due to missing measurements. In this work, we directly measure the connection between chemistry and agglomeration in the smallest iron oxides relevant to magnetite ores. Using synthesized spherical 10-nm magnetite particles reacting in H2, we resolve the formation and consumption of wüstite (Fe1-xO)-the step most commonly attributed to whiskering. Using X-ray diffraction, we resolve crystallographic anisotropy in the rate of the initial reaction. Complementary imaging demonstrated how the particles self-assemble, subsequently react, and grow into elongated "whisker" structures. Our insights into how morphologically uniform iron oxide particles react and agglomerate in H2 reduction enable future size-dependent models to effectively describe the multiscale aspects of iron ore reduction.

Network pharmacology-based approach uncovers the pharmacodynamic components and mechanism of Fructus Tribuli for improving endothelial dysfunction in hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Tribuli (FT), a traditional Chinese medicinal herbal, has been used for the clinical treatment of cardiovascular diseases for many years and affects vascular endothelial dysfunction (ED) in patients with hypertension. AIM OF THE STUDY: This study aimed to demonstrate the pharmacodynamic basis and mechanisms of FT for the treatment of ED. MATERIALS AND METHODS: The present study used ultra-high-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze and identify the chemical components of FT. The active components in blood were determined after the oral administration of FT by comparative analysis to blank plasma. Then, based on the active components in vivo, network pharmacology was performed to predict the potential targets of FT in treating ED. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed, and component-target-pathway networks were constructed. Interactions between the major active components and main targets were verified by molecular docking. Moreover, spontaneously hypertensive rats (SHRs) were divided into the normal, model, valsartan, low-dose FT, medium-dose FT, and high-dose FT experimental groups. In pharmacodynamic verification studies, treatment effects on blood pressure, serum markers (nitric oxide [NO], endothelin-1 [ET-1,], and angiotensin Ⅱ [Ang Ⅱ)]) of ED, and endothelial morphology of the thoracic aorta were evaluated and compared between groups. Finally, the PI3K/AKT/eNOS pathway was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot of the thoracic aorta of rats in each group to detect the mRNA expression of PI3K, AKT, and eNOS and the protein expression of PI3K, AKT, p-AKT, eNOS, and p-eNOS. RESULTS: A total of 51 chemical components were identified in FT, and 49 active components were identified in rat plasma. Thirteen major active components, 22 main targets, and the PI3K/AKT signaling pathway were screened by network pharmacology. The animal experiment results showed that FT reduced systolic blood pressure and ET-1 and Ang Ⅱ levels and increased NO levels in SHRs to varying degrees. The therapeutic effects were positively correlated with the oral dose of FT. Hematoxylin-eosin (HE) staining confirmed that FT could alleviate the pathological damage of the vascular endothelium. qRT-PCR and Western blot analysis confirmed that up-regulated expression of the PI3K/AKT/eNOS signaling pathway could improve ED. CONCLUSIONS: In this study, the material basis of FT was comprehensively identified, and the protective effect on ED was confirmed. FT had a treatment effect on ED through multi-component, multi-target, and multi-pathways. It also played a role by up-regulating the PI3K/AKT/eNOS signaling pathway.

Comparing high-dose dual therapy with bismuth-containing quadruple therapy for the initial eradication of Helicobacter pylori infection on Hainan Island: A randomized, multicenter clinical trial.

BACKGROUND: Traditional bismuth-containing quadruple therapy, as a first-line eradication treatment for Helicobacter pylori (H. pylori), has several disadvantages, including drug side effects, low medication adherence, and high costs. Trials of high-dose dual treatment have demonstrated its advantages, which include good safety and adherence profiles. In this study, we investigated the efficacy, safety, and compliance of a high-dose dual therapy when compared with bismuth-based quadruple treatment for the initial eradication of H. pylori infection on Hainan Island, China. METHODS: We randomized 846 H. pylori-infected patients into two groups. A bismuth-containing quadruple therapy group was administered the following: esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily, and colloidal bismuth pectin in suspension 150 mg three times/day for 2 weeks. A high-dose dual therapy group was administered the following: esomeprazole 20 mg four times/day and amoxicillin 1000 mg three times/day for 2 weeks. Patients were given a 13C urea breath test at 4 weeks at treatment end. Adverse effects and compliance were evaluated at follow-up visits. RESULTS: Eradication rates in the high-dose dual therapy group were: 90.3% (381/422, 95% confidence interval [CI]: 87.1%-92.9%) in intention-to-treat (ITT) and 93.6% (381/407, 95% CI: 90.8%-95.8%) in per-protocol (PP) analyses. Eradication rates were 87.3% in ITT (370/424, 95% CI: 83.7%-90.3%) and 91.8% in PP analyses (370/403, 95% CI: 88.7%-94.3%) for quadruple therapy, with no statistical differences (P = 0.164 in ITT and P = 0.324 in PP analyses). Adverse effects were 13.5% (55/407) in the dual group and 17.4% (70/403) in the quadruple group (P = 0.129). Compliance was 92.4% (376/407) in the dual group and 86.6% (349/403) in the quadruple group (P = 0.007). CONCLUSIONS: High-dose dual therapy had high eradication rates comparable with bismuth-based quadruple treatment, with no differences in adverse effects, however higher adherence rates were recorded.

[Comparison of alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata based on UHPLC-Q-Exactive Orbitrap MS/MS].

UHPLC-Q-Exactive Orbitrap MS/MS was used to systematically analyze and compare the alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata. After the samples were pretreated in the solid-phase extraction cartridges, 0.1% ammonium hydroxide(A)-acetonitrile(B) was used for gradient elution. The LC-MS method for characterization of alkaloids in the three herbal medicines was established in ESI positive ion mode to collect high resolution MS data of reference substances and samples. On the basis of the information of reference substance cracking behavior, retention time, accurate molecular mass, and related literature, a total of 155 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Prae-parata. Specifically, 130, 127, and 92 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata, respectively. Monoester alkaloids and amino-alcohol alkaloids were dominant in the three herbal medicines, and the alkaloids in Aconiti Kusnezoffii Radix and Aconiti Radix were similar. This paper can provide a reference for elucidating the pharmacological effects and clinical application differences of the three herbal medicines produced from plants of Aconitum.

[Effects of different drying methods on ginsenosides based on UHPLC-Q-Exactive Orbitrap MS technique].

The present study quickly identified the ginsenosides in fresh Panax ginseng and specified the effects of different drying methods(50 ℃-drying, 80 ℃-drying, and-70 ℃ freeze-drying) on ginsenosides.Three P.ginseng products by different drying methods were prepared, and the UHPLC-Q-Exactive Orbitrap high-resolution liquid mass spectrometry(MS) technique was applied to perform gradient elution using water-acetonitrile as the mobile phase, and the data collected in the negative ion mode were analyzed using X Calibur 2.2.The results showed that 57 saponins were identified from fresh P.ginseng.As revealed by the comparison with the fresh P.ginseng, in terms of the loss of ginsenosides, the dried products were ranked as the dried product at 50 ℃, freeze-dried products at-70 ℃, and the dried product at 80 ℃ in the ascending order.This study elucidated the effects of different drying methods on the types and relative content of ginsenosides, which can provide references for the processing of P.ginseng in the producing areas.

Rescue of social deficits by early-life melatonin supplementation through modulation of gut microbiota in a murine model of autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a rapidly increasing global prevalence. Early unstable and immature microbiota are often observed in ASD patients, resulting in neurobehavioral dysfunction. Since the establishment of stable gut microbiota in early life falls into the same critical time window as neurodevelopment, manipulations of the gut microbiota during early life could become a promising strategy for ASD. Melatonin is an endogenous hormone and can restore gut microbial dysbiosis under various disease conditions. Here, we explored the effects of melatonin supplementation during early life on the gut microbiota of the offspring and the subsequent impact on ASD-associated behaviors. Using the valproic acid (VPA) - induced mouse model of autism, we found that melatonin supplementation during late gestation and early postnatal development rescued the social deficits of the offspring. In addition, melatonin restored gut microbial dysbiosis in the VPA-exposed offspring, which was characterized by the significant upregulation of Akkermansia spp. Furthermore, supplementation of Akkermansia spp. alleviated the social deficits induced by VPA exposure via activating the dopaminergic neurons in the ventral tegmental area. These findings discover a novel mechanism underlying the gut microbiota regulation of social behaviors and provide the biological basis for developing gut microbiota-based therapeutics for ASD.

Characterization of the complete chloroplast genome of Clematis orientalis (Ranunculaceae).

The medicinal plant Clematis orientalis L. belongs to the family Ranunculaceae. In this study, we determined the complete chloroplast genome sequence of C. orientalis and its phylogenetic relationships with other species. The complete chloroplast genome of C. glauca is 159,518 bp in length, circular in structure, and has four regions including a large single-copy (LSC) region of 79,453 bp; a small single-copy (SSC) region of 17,997 bp; and two inverted repeat (IR) regions of 31,034 bp. The GC content of the genome is 38%, and those of LSC, SSC, and IR regions are 36.2, 31.4, and 42%, respectively. The genome encodes 129 unique genes, including 85 protein-coding genes, 36 tRNA genes, and eight rRNA genes. Phylogenomic analysis reveals that C. orientalis is most closely related to C. aethusifolia. This study contributes to better understanding of phylogenetic relationships of Ranunculaceae.

[Identification of metabolites of imperatorin in rats: based on UHPLC-Q-Exactive Orbitrap MS].

This study aims to identify and analyze the metabolites of imperatorin in rats by UHPLC-Q-Exactive Orbitrap MS. Specifically, after rats were treated(ig) with imperatorin, the plasma, urine, and feces were collected, and the samples were processed by solid phase extraction. Then, UHPLC-Q-Exactive Orbitrap MS was performed. In MS, 0.1% formic acid water(A)-acetonitrile(B) was applied as mobile phase for gradient elution and the data of MS in both positive and negative ion modes were collected. The metabolites of imperatorin in blood, urine, and feces of rats were analyzed to explore the metabolic pathways of imperatorin in rats. According to accurate molecular weight, multistage MS data, MS fragmentation rule of the standard substance, and previous reports, a total of 51 metabolites were identified, with 35, 40, and 16 from plasma, urine, and feces, separately. The main metabolic pathways were oxidization, glucuronidation, isopentenyl removal, sulphation, carboxylation, among others. The conclusion in this study is expected to serve as a reference for the further development and the further pharmacodynamics study of imperatorin.

The complete chloroplast genome of Clematis hexapetala (Ranunculaceae) and its phylogenetic analysis.

Clematis hexapetala Pall. (1776) is a traditional Chinese medicine belonging to the Ranunculaceae. In this study, the complete chloroplast genome was sequenced through Illumina platform, cp was circular DNA molecule of 159,538 bp in length with a typical quadripartite structure, consisting of four regions: two copies of inverted repeat region (IRs: 31,039 bp), a large single-copy (LSC: 79,333 bp) region, a small single-copy (SSC: 18,127 bp) region. The chloroplast genome encodes a total of 135 genes, including 91 CDS genes, 36 tRNA genes, 8 rRNA genes. Phylogenetic analysis based on complete genes shows that C. hexapetala closely related to C. taeguensis in the genus Clematis. This study improves our comprehension of the chloroplast genome and its phylogenetic relationships within Ranunculaceae.

Activation of farnesoid X receptor signaling by geniposidic acid promotes osteogenesis.

BACKGROUND: New targets and strategies are urgently needed for the identification and development of anabolic drugs for osteoporosis. Farnesoid X receptor (FXR) is a promising novel therapeutic target for bone metabolism diseases. Although used clinically, FXR agonists have obvious side effects; therefore, the development of new FXR agonists for the treatment of osteoporosis would be welcomed. Geniposidic acid (GPA) is a bioactive compound extracted from Eucommiae cortex, which is used for treating arthritis, osteoporotic fractures, and hypertension. However, the therapeutic effects of GPA against osteoporosis remain underexplored. PURPOSE: This study aims to reveal the potential osteogenic effects of FXR and to explore the effect of GPA on bone formation, osteoporosis treatment, and FXR signaling. STUDY DESIGN & METHODS: The role of FXR in promoting bone formation was evaluated in Fxr knockout (Fxr-/-) mice and cell models. GPA activation of FXR was evaluated by molecular docking and luciferase reporter gene assays. Thirty female C57BL/6J mice were randomly assigned into a sham operation group (Sham) and four ovariectomized (OVX) groups (n=6 each) and were treated with vehicle or different doses of GPA (25, 50, and 100 mg/kg/day). The therapeutic effect of GPA on osteoporosis was systematically analyzed by performing bone histomorphometry and measuring serum biochemical parameters, and the molecular mechanism was also evaluated. Furthermore, the action of GPA in Fxr-/- mice was evaluated to investigate its dependency on FXR in promoting bone formation and treating osteoporosis. RESULTS: We found that FXR was highly expressed in bone tissues and enriched in osteoblasts. Notably, deletion of FXR significantly reduced the bone formation rate and bone mass of the Fxr-/- mice compared with wild-type mice. Furthermore, using a high throughput drug screening strategy based on fluorescent reporter genes, we found that GPA functions as a natural agonist of FXR. We confirmed the activities of GPA on FXR activation and osteogenesis in both osteoblast differentiation models and OVX-induced osteoporosis models. We revealed that GPA strongly promotes bone formation by activating FXR/RUNX2 signaling. Moreover, the osteoporotic therapeutic effect of GPA was abolished in Fxr-/- mice. CONCLUSION: This study demonstrated that FXR is a promising target for treating osteoporosis and that GPA promotes bone formation in OVX-induced osteoporosis by activating FXR signaling. These findings provide novel insight into the mechanism by which GPA promotes bone formation and more evidence for its application in the treatment of osteoporosis.

[UHPLC-Q-Exactive Orbitrap MS/MS-based rapid identification of chemical components in substance benchmark of Kaixin San].

Ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS/MS) was used for rapid identification of the chemical components in Kaixin San substance benchmark. The gradient elution was performed through a Waters ACQUITY~(TM) BEH C_(18) column(2.1 mm×150 mm, 1.7 µm) with water-acetonitrile as mobile phase, a column temperature of 30 ℃, a flow rate of 0.3 mL·min~(-1), and a sample size of 1 µL. The scanning was performed in the negative ion mode. The complex component groups in Kaixin San substance benchmark were quickly and accurately identified and clearly assigned based on the comparison of the retention time and MS data with those of the reference substance as well as the relative molecular weight of the same or similar components in the mass spectrum database and literature. A total of 77 compounds were identified, including 26 saponins, 13 triterpenoid acids, 20 oligosaccharide esters, 5 xanthones, and 13 other compounds. The qualitative method established in this study can systematically, accurately, and quickly identify the chemical components in Kaixin San substance benchmark, which can provide a basis for the further analysis of its active components in vivo and the establishment of its quality control system.

Biomass production of carbohydrate-rich filamentous microalgae coupled with treatment and nutrients recovery from acrylonitrile butadiene styrene based wastewater: Synergistic enhancement with low carbon dioxide supply strategy.

This study attempted to remove acrylonitrile and acetophenone from simulated acrylonitrile butadiene styrene (ABS) based wastewater while recovering nitrogen and phosphorus using the carbohydrate-rich filamentous microalgae Tribonema sp.. Results showed that typical acetophenone and acrylonitrile presented significant inhibitory effect on Tribonema sp. growth and co-metabolism of CO2 improved the tolerance of Tribonema sp. to toxic pollutants. The microalgae biomass increased by 34.47% (3.16 g/L) and 58.17% (3.97 g/L) via supplementing 2% CO2 in the 100 mg/L acrylonitrile and acetophenone groups, respectively. The filamentous microalga was rich in carbohydrates and its productivity was further enhanced by 32.52% and 70.34%, respectively, in 100 mg/L acrylonitrile and acetophenone groups with 2% CO2 supplement. The synergistic CO2 supply strategy effectively enhanced the biomass production of filamentous microalgae, and moreover, improved the treatment efficiency of ABS based wastewater simulated by acetophenone or acrylonitrile addition, while at same time enhanced the recovery of nitrogen and phosphorus nutrients.

Effects of dietary citrus extract on growth performance, carcass characteristics and meat quality of pigs.

This study investigated the effects of citrus extract on growth, carcass and meat quality of Duroc × Landrace × Large White pigs. One hundred and eight pigs (54 barrows, 54 females) were assigned to one of three dietary treatments for 138 days. The dietary treatments were (1) basic diet; (2) basic diet supplemented with 75 mg/kg chlortetracycline; and (3) basic diet supplemented with citrus extract (0.25 ml/kg during 56-112 days of age and 0.20 ml/kg during 113-194 days of age). No significant differences among treatments were found for growth performance, carcass characteristics, meat quality and free amino acids (p > 0.05). Feeding citrus extract tended to increase intramuscular fat (p = 0.052). Citrus extract and chlortetracycline increased C15:0 concentration (p = 0.016) and superoxide dismutase activity (p = 0.004). The pigs that received chlortetracycline exhibited the lowest (p = 0.033) muscle malondialdehyde concentration. Overall, citrus extract ameliorated some meat quality indicators without adverse effects on pig growth or carcass performance.

Efficacy of Acupuncture for Herpes Zoster: A Systematic Review and Meta-Analysis.

INTRODUCTION: This study aimed to assess the efficacy of acupuncture in patients with herpes zoster (HZ) based on current randomized clinical trials (RCTs). METHODS: Five databases were screened for RCTs published until August 2019. Studies that assessed the efficacy of acupuncture when used as an independent intervention for HZ were included. The outcomes of interest were pain intensity, as assessed using the visual analog scale (VAS), incrustation time, decrustation time, and incidence of post-herpetic neuralgia (PHN). RESULTS: In total, 21 RCTs were included in this research. Compared with antiviral therapy, acupuncture was associated with a reduction in VAS score by 16.13, incrustation time by 1.86 days, decrustation time by 2.19 days, and incidence of PHN by 83%. According to a meta-regression analysis, the main sources of heterogeneity were sample size and duration of treatment. There was no publication bias except on decrustation time. A sensitivity analysis showed that the outcomes were relatively stable and reliable. CONCLUSION: Acupuncture may be effective for patients with HZ. Nevertheless, this finding should be validated by conducting high-quality trials with a larger sample size.

Evaluation on curative effects of combined acupuncture plus physical therapy for treating idiopathic facial paralysis: A protocol for a systematic review and meta-analysis.

BACKGROUND: The present study primarily aims to evaluate how effective acupuncture combined with physical therapy for the treatment of idiopathic facial paralysis. METHODS: The PubMed database was searched (1946 to September 2020), the EMBASE data were also searched (January 1946 to September 2020), moreover, the Cochrane Central Register of Controlled Trials was searched (all years), and finally, the China National Knowledge Infrastructure (CNKI) was also included in the searching of electronic databases. The searching of publications did not include any language constraints. The titles and abstracts were scrutinized by a pair of authors to identify relevant studies. The efficacy of the association in the combination of acupuncture and physical therapy as a method of treatment for idiopathic facial paralysis was evaluated according to the pooled risk ratio (RR), mean differences (MD), or standardized mean difference (SMD) with the corresponding 95% confidence intervals (95% CI). A pair of authors conducted an autonomous risk assessment of the bias that would be introduced when the Cochrane Risk of Bias Tool is used. A pair of authors autonomously extracted data with the aid of a customized data extraction form. The RevMan 5.3 statistical analysis software was utilized for conducting the statistical analysis. RESULTS: The final results will be presented in a scientific journal that will be peer-reviewed. CONCLUSION: It is expected that the proposed systematic review and meta-analysis of acupuncture combined with physical therapy for treating idiopathic facial paralysis will provide reliable evidence for clinical application. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/RPCSE (https://osf.io/rpcse/).

Diethylhexyl phthalate induces teratogenic effects through oxidative stress response in a chick embryo model.

Diethylhexyl phthalate (DEHP) is known as a persistent environmental pollutant. However, the possible effects of DEHP on human neural tube defects (NTDs) remain elusive. We set out to investigate the exposure of DEHP in human and explore the association of DEHP and NTDs. The level of DEHP in maternal urine was measured and analyzed by GC-MS. To further validate the results in human NTDs, chick embryos were used as animal models. Viability, reactive oxygen species (ROS) level, oxidative stress indicators and apoptosis were detected in DEHP-treated chick embryos. Our research revealed that the detection ratio of positive DEHP and its metabolites in maternal urine were observed dramatically higher in NTDs population than that in normal controls (P < 0.01, P < 0.05, respectively). Moreover, DEHP treatment (10-6 M) led to developmental toxicity in chick embryos via accelerating oxidative stress response and cell apoptosis, and changing the level of oxidative stress-related indicators. Moreover, high dose choline (100 µg/µl) could partially restrain the toxicity effects induced by DEHP. Our data collectively imply that the incidence of NTDs may closely associate with DEHP exposure, which disturbs the development of neural tubes by enhancing oxidative stress.

Oxidative stress response associates with the teratogenic effects of benzyl butyl phthalate (BBP).

Benzyl butyl phthalate (BBP) is a persistent environmental pollutant. BBP exposure and the possible effects on human neural tube defects (NTDs) remain elusive. In this study, we found that the detection ratio of positive BBP and its metabolites in maternal urine was obviously higher in NTDs' population than that in normal controls by GC-MS (P < 0.01, P < 0.05, respectively). Animal experiments showed that BBP treatment induced developmental toxicity in chick embryo by enhancing the levels of oxidative stress and cell apoptosis (P < 0.01). More interestingly, the supplement of high-dose choline (CHO, 10 5  µg/mL) could partially restore the teratogenic effects of BBP by inhibiting the occurrence of oxidative stress. Our data collectively suggest that BBP exposure may disturb neural tube development by strengthening oxidative stress. CHO can partially restore the toxicity effects of BBP. This study may provide new insight for NTD prevention.

Choroid Plexus Enlargement and Allostatic Load in Schizophrenia.

Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = -0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia.

Choline, not folate, can attenuate the teratogenic effects ofdibutyl phthalate (DBP) during early chick embryo development.

Dibutyl phthalate (DBP), a persistent environmental pollutant, can induce neural tube abnormal development in animals. The possible effects of DBP exposure on human neural tube defects (NTDs) remain elusive. In this study, the distribution of DBP in the body fluid of human NTDs was detected by GC-MS. Then, chick embryos were used to investigate the effects of DBP on early embryonic development. Oxidative stress indicators in chick embryos and the body fluid of human NTDs were detected by ELISA. The cell apoptosis and total reactive oxygen species (ROS) level in chick embryos were detected by whole-mount TUNEL and oxidized DCFDA, respectively. The study found that the detection ratio of positive DBP and its metabolites in maternal urine was higher in the NTD population than that in normal controls. 8-hydroxy-2 deoxyguanosine (8-OHDG) and malondialdehyde (MDA) were evidently upregulated and superoxide dismutase (SOD) was observably downregulated in amniotic fluid and urine. Animal experiments indicated that DBP treatment induced developmental toxicity in chick embryos by enhancing the levels of oxidative stress and cell apoptosis. MDA was increased and SOD was decreased in DBP-treated embryos. Interestingly, the supplement of high-dose choline (100 µg/µL), not folic acid, could partially restore the teratogenic effects of DBP. Our data collectively suggest that the incidence of NTDs is closely associated with DBP exposure. This study may provide new insight for NTD prevention.