SUMOylation modification of FTO facilitates oxidative damage response of arsenic by IGF2BP3 in an m6A-dependent manner.

N6-methyladenosine (m6A) is the most common form of internal post-transcriptional methylation observed in eukaryotic mRNAs. The abnormally increased level of m6A within the cells can be catalyzed by specific demethylase fat mass and obesity-associated protein (FTO) and stay in a dynamic and reversible state. However, whether and how FTO regulates oxidative damage via m6A modification remain largely unclear. Herein, by using both in vitro and in vivo models of oxidative damage induced by arsenic, we demonstrated for the first time that exposure to arsenic caused a significant increase in SUMOylation of FTO protein, and FTO SUMOylation at lysine (K)- 216 site promoted the down-regulation of FTO expression in arsenic target organ lung, and therefore, remarkably elevating the oxidative damage via an m6A-dependent pathway by its specific m6A reader insulin-like growth factor-2 mRNA-binding protein-3 (IGF2BP3). Consequently, these findings not only reveal a novel mechanism underlying FTO-mediated oxidative damage from the perspective of m6A, but also imply that regulation of FTO SUMOylation may serve as potential approach for treatment of oxidative damage.

Study on the mechanism of 20-hydroxyeicosatetraenoic acid in retinal ischemia-reperfusion injury.

PURPOSE: To explore the effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on retinal ischemia-reperfusion injury (RIRI) and the protective effect of N-hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine (HET0016) on RIRI. METHODS: Male Sprague-Dawley rats were randomly divided into the normal control group, experimental model group (RIRI group), experimental solvent group (RIRI + solvent group), and experimental treatment group (RIRI + HET0016 group). RESULTS: The levels of 20-HETE, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in the retina of rats at 24 h after reperfusion were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the retinal morphological and thickness changes at 24 h, 48 h, and 7 days after reperfusion. The number and localized expression of matrix metalloproteinase-9-positive cells in the retina of the rats at 24 h after reperfusion and the activation and localized expression of retinal microglia at 48 h after reperfusion were measured using an immunohistochemical method. The nuclear metastasis of nuclear factor kappa-B (NF-κB, p65) cells at 24 h after reperfusion was observed using an immunofluorescence method. CONCLUSION: Overall, 20-HETE might activate microglia to aggravate RIRI by the NF-κB pathway, but HET0016 has significant protective effects for the retina.

Associations between seminal plasma triclosan and low sperm quality: A case-control study.

OBJECTIVE: Triclosan (TCS), a novel endocrine disrupter, has induced widespread human exposure due to its widespread use in personal care products. Environmental TCS exposure was suggested to be associated with human semen quality. However, little is known about seminal plasma TCS concentration and the risk of low sperm quality. This case-control study is established to examine the relationship between seminal plasma TCS and the risk of low sperm quality. STUDY DESIGN: One hundred men with low sperm quality as cases and one hundred normal men as controls were recruited a fertility clinic in Shijiazhuang, China, during 2018-2019. Seminal plasma TCS concentration was determined using an ultrahigh-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). Sperm concentration, sperm count, sperm motility and sperm progressive motility were evaluated according to World Health Organization (WHO) guidelines to assess the sperm quality. We used the Mann-Whitney rank-sum test and Kruskal-Wallis test to assess the differences of seminal plasma TCS concentration between the cases and the controls. In addition, logistic regression analysis was used to estimate the associations between seminal plasma TCS concentrations and low sperm quality risk adjusting for age, body mass index (BMI), abstinence time, smoking, and drinking RESULTS AND CONCLUSIONS: The level of seminal plasma TCS was observed slightly but not significantly higher in the case group than the control group. We also observed significant association between seminal plasma TCS concentrations and semen parameters in both control and case groups. Moreover, the seminal plasma TCS levels at the fourth quartile were found to be more likely to exhibit low sperm quality risk with increased adjusted odds ratios of 2.36 (95% confidence interval 1.03-5.39) compared to the first quartile. Our results reveal that seminal plasma TCS concentration was positively associated with low sperm quality risk.

A natural biological adhesive from snail mucus for wound repair.

The discovery of natural adhesion phenomena and mechanisms has advanced the development of a new generation of tissue adhesives in recent decades. In this study, we develop a natural biological adhesive from snail mucus gel, which consists a network of positively charged protein and polyanionic glycosaminoglycan. The malleable bulk adhesive matrix can adhere to wet tissue through multiple interactions. The biomaterial exhibits excellent haemostatic activity, biocompatibility and biodegradability, and it is effective in accelerating the healing of full-thickness skin wounds in both normal and diabetic male rats. Further mechanistic study shows it effectively promotes the polarization of macrophages towards the anti-inflammatory phenotype, alleviates inflammation in chronic wounds, and significantly improves epithelial regeneration and angiogenesis. Its abundant heparin-like glycosaminoglycan component is the main active ingredient. These findings provide theoretical and material insights into bio-inspired tissue adhesives and bioengineered scaffold designs.

Exposure to di (2-ethylhexyl) phthalate causes locomotor increase and anxiety-like behavior via induction of oxidative stress in brain.

Di (2-ethylhexyl) phthalate (DEHP) is one of the most prevalent xenoestrogen endocrine disruptor in daily life. A growing number of studies showed that DEHP could exhibit long-term adverse health effects on the human body, particularly in the liver, kidneys, heart and reproductive systems. However, the impact of oral intake of DEHP on the nervous system is extremely limited. In the present study, the adult C57BL/6J male mice were intragastrically administered with two dosages of DEHP for 35 days. The behavioral parameters were assessed using the elevated plus maze and open-field test. The mRNA expression levels of neuropeptides and the oxidative stress-associated proteins were detected by qPCR and western blot seperately. The histopathologic alterations of the brain were observed by H&E and Nissl staining. The results demonstrated that DEHP exposure could result in neurobehavioral impairments such as locomotor increase and anxiety-like behavior. Furthermore, pathological damages were clearly observed in the cerebral cortex and hippocampus, accompanied by a decrease in neuropeptides and an increase in oxidative stress, which were all positively correlated with the dose of DEHP. Together, these findings provide valuable clues into the DEHP-induced neurotoxicity.

Antibiotics administration alleviates the high fat diet-induced obesity through altering the lipid metabolism in young mice.

Currently, there is a global trend of rapid increase in obesity, especially among adolescents. The antibiotics cocktails (ABX) therapy is commonly used as an adjunctive treatment for gut microbiota related diseases, including obesity. However, the effects of broad-spectrum antibiotics alone on young obese hosts have rarely been reported. In the present study, the 3-week-old C57BL/6J male mice fed a high-fat diet (HFD) were intragastric administration with ampicillin, vancomycin, metronidazole or neomycin for 30 days. The lipid metabolites in plasma were assessed by biochemical assay kits, and genes related to lipid metabolite in the white adipose were assessed by qPCR. To further analyze the underlying mechanisms, the expression of genes related to lipid metabolism, inflammatory reactions and oxidative stress in the liver were determined by qPCR assay. In addition, the expression of oxidative damage-associated proteins in the liver were detected by western blot. The results showed that oral antibiotics exposure could reduce body weight and fat index in HFD-fed mice, concurrent with the increase of white adipose lipolysis genes and the decrease of hepatic lipogenic genes. Furthermore, antibiotics treatment could clearly reverse the HFD-induced elevation of oxidative damage-related proteins in the liver. Together, these findings will provide valuable clues into the effects of antibiotics on obesity.

CircMAP3K4 protects human lens epithelial cells from H2O2-induced dysfunction by targeting miR-193a-3p/PLCD3 axis in age-related cataract.

Circular RNAs (circRNAs) have shown pivotal regulatory roles in multiple human ocular diseases, including age-related cataract (ARC). Here, we explored the role of circRNA mitogen-activated protein kinase kinase kinase 4 (circMAP3K4, hsa_circ_0078619) in ARC pathology and its associated mechanism. The expression of RNAs and proteins was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell viability, senescence, proliferation, and apoptosis were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, senescence-associated-ß-galactosidase (SA-ß-Gal) staining, 5-ethynyl-20-deoxyuridine (EdU) assay, and flow cytometry. The oxidative stress status of SRA01/04 cells was analyzed using the commercial kits. The interaction between microRNA-193a-3p (miR-193a-3p) and circMAP3K4 or phospholipase C delta 3 (PLCD3) was verified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay. CircMAP3K4 was significantly down-regulated in ARC patients and H2O2-induced SRA01/04 cells. H2O2 treatment restrained the viability and proliferation and promoted the senescence, apoptosis, and oxidative stress of SRA01/04 cells, and circMAP3K4 overexpression protected SRA01/04 cells from H2O2-induced dysfunction. MiR-193a-3p was a direct target of circMAP3K4, and circMAP3K4 overexpression-mediated protective effects in H2O2-induced SRA01/04 cells were largely reversed by the accumulation of miR-193a-3p. MiR-193a-3p interacted with the 3' untranslated region (3'UTR) of PLCD3, and PLCD3 knockdown largely overturned miR-193a-3p silencing-induced protective effects in H2O2-induced SRA01/04 cells. CircMAP3K4 up-regulated the expression of PLCD3 via sponging miR-193a-3p in SRA01/04 cells. In conclusion, circMAP3K4 protected SRA01/04 cells from H2O2-induced dysfunction in ARC through mediating miR-193a-3p/PLCD3 axis.

Analysis of m6A modification regulators in the substantia nigra and striatum of MPTP-induced Parkinson's disease mice.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders of aging that impairs predominately dopaminergic neurons. N6-methyladenosine (m6A) is the most prevalent form of internal RNA modification in eukaryotes and it plays an essential role in normal brain development and neurodegenerative diseases. The m6A status is dynamically modulated by diverse types of genes called "writers", "erasers" and "readers". However, whether these m6A regulators are perturbed in PD remains poorly understood. To clarify this point, we established a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The motor as well as learning and memory ability of mice were evaluated through and rotarod and Y maze spontaneous alternation tests. Morphological characteristics of tyrosine hydroxylase (TH)-positive cells were visualized using immunohistochemistry, while expressions of alpha-synuclein (α-syn) and TH were determined by using western blot. Furthermore, the expressions of the m6A regulators in the substantia nigra and striatum were evaluated by using qRT-PCR and western blot. As a result, the MPTP-induced PD mice suffered from learning and memory as well as motor defects. Additionally, there were significant TH+ neuron losses in the substantia nigra and striatum of MPTP-injected mice. In the PD mice, proteins including ALKBH5, IGF2BP2 were up-regulated in the substantia nigra, while YTHDF1 and FMR1 was down-regulated. For the striatum, FMR1 and CBLL1 were up-regulated, while IGF2BP3, METTL3 and RBM15 were down-regulated. The expression of genes at the mRNA level were partially in accordance with the protein changes. These findings indicate the m6A regulators may participate in PD pathogenesis.

Asparagus cochinchinensis alleviates disturbances of lipid metabolism and gut microbiota in high-fat diet-induced obesity mice.

Asparagus cochinchinensis is a valuable traditional Chinese medicine that has anti-inflammatory ability and effectively regulates the dysbiosis within the body. Obesity is usually characterized by chronic low-grade inflammation with aberrant gut microbiota. However, the role of Asparagus cochinchinensis against obesity remains unknown. Therefore, a high-fat diet (HFD)-induced obese mouse model with or without aqueous extract from Asparagus cochinchinensis root (ACE) treatment was established herein to determine whether ACE alleviated obesity and its involved mechanisms. Our results showed that ACE administration significantly decreased the weight gain and relieved dyslipidemia induced by HFD Treatment of ACE also improved glucose tolerance and insulin resistance in obese animal model, and remarkably decreased inflammation and lipogenesis in the liver and adipose. Moreover, administration of ACE significantly reshaped the gut microbiota of obese mice. These findings together suggest that ACE has beneficial effect against HFD-induced obesity and will provide valuable insights for the therapeutic potential of ACE against obesity and may aid in strategy-making for weight loss.

Polystyrene nanoparticles enhance the adverse effects of di-(2-ethylhexyl) phthalate on male reproductive system in mice.

Coexposure of nanoplastics (NPs) with other pollutants adsorbed from the surroundings has received extensive attention. Currently, the combined effects of NPs and plasticizers remain unclear. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer that has raised much concern owing to its ubiquitous pollution and endocrine-disrupting potential. This study aimed to investigate the toxic effects on the male reproductive system upon coexposure to NPs and DEHP. The C57BL/6J mice were orally administrated with polystyrene nanoparticles (PSNPs), DEHP or both for 35 days to evaluate their effects on sperm quality, histology of testes and epididymides, testicular transcriptomic characteristics as well as expression of some important genes in the epididymides. The low-dose PSNPs used here did not induce significant changes in sperm quality, while DEHP alone or cotreatment with DEHP and PSNPs caused notable impairment, mainly manifesting as decreased sperm quality and aberrant structure of the testis and epididymis. Moreover, enhanced toxic effects were found in the cotreatment group when compared with the individual DEHP treatment group, as manifested by more obvious alterations in the sperm parameters as well as histological changes in the testis and epididymis. Testicular transcriptomic analysis revealed differential regulation of genes involved in immune response, cytoplasmic pattern recognition receptor signaling pathways, protein ubiquitination, oxidative stress, necrotic cell death, ATP synthesis and the cellular respiratory chain. RT-qPCR verified that the expression patterns of Cenpb, Crisp1 and Mars were changed in testes, and genes relevant to epididymal function including Aqp9 and Octn2 were downregulated in epididymides, particularly in the cotreatment group. Collectively, our results emphasize that DEHP at an environmentally relevant dose can induce male reproductive toxicity, and PSNPs may aggravate the toxic effects.

The role of PP2A /NLRP3 signaling pathway in ambient particulate matter 2.5 induced lung injury.

Ambient particulate matter 2.5 (PM2.5) exposure has been linked to pulmonary fibrosis. However, the key signaling pathways remained unclear. In the present study, we applied a mouse model with myeloid-specific deletion of Ppp2r1a gene (encoding protein phosphatase 2 A (PP2A) A subunit) to identify the key signaling pathways involved in PM2.5-induced pulmonary fibrosis. PP2A Aα-/- homozygote mice and matched wild-type (WT) littermates were exposed to filtered air (FA), unfiltered air (UA), and concentrated PM2.5 (CA) in a real-ambient PM exposure system for 8 weeks and 16 weeks, respectively. The mice exposed to PM2.5 displayed a progressive inflammation and pulmonary fibrosis. Moreover, the expressions of NLRP3, pro-caspase-1, caspase-1, ASC and IL-1ß were increased in mice lung following PM2.5 exposure, indicating PM2.5 exposure caused pulmonary inflammation by the NLRP3 pathways activation. Furthermore, the effects of PM exposure on pulmonary inflammation, pulmonary fibrosis, oxidative stress, and pulmonary function damage were significantly enhanced in PP2A-/- mice compared to WT mice, indicating the role of PP2A in the regulation of pulmonary injury induced by PM exposure. In vitro study confirmed that PP2A was involved in the PM2.5-induced inflammation response and NLRP3 inflammasome activation. Importantly, we identified PP2A regulated the activation of NLRP3 pathways by direct dephosphorylating IRE1α in response to PM2.5 exposure. Taken together, our results demonstrated that PP2A-IRE1α-NLRP3 signaling pathway played a crucial role in regulating the inflammation response, triggering the lung fibrogenesis upon PM2.5 exposure. Our findings provide new insights into regulatory role of PP2A in human diseases upon the PM exposure.

Polystyrene nanoparticles aggravate the adverse effects of di-(2-ethylhexyl) phthalate on different segments of intestine in mice.

Emerging evidence indicates that nanoplastics (NPs) can transport organic pollutants such as di-(2-ethylhexyl) phthalate (DEHP) into organisms and induce adverse health effects. Nevertheless, the toxic effects of NPs combined with DEHP on mammalian intestine are still unclear. In this study, the C57BL6J mice were exposed to polystyrene nanoparticles (PSNPs), DEHP or them both for 30 days to determine their effects on different segments of intestine and the gut microbiota. As a result, DEHP alone or co-exposure to DEHP and PSNPs induced histological damages in all intestinal parts, mainly manifested as the decreased villus lengths, increased crypt depths in the duodenum, jejunum and ileum and decreased villus counts accompanied with decreased epithelial area in the colon. Moreover, decreased mucus coverage, down-regulated Muc2 expression levels as well as the broken tight junctions were observed in intestinal epithelium of mice, particularly obvious in the co-treatment groups. In general, as manifested by greater alterations in most of the parameters mentioned above, simultaneously exposed to PSNPs and DEHP seemed to induce enhanced toxic effects on intestine of mouse when compared with DEHP alone. Furthermore, the altered community composition of gut microbiota might at least partially contribute to these abnormalities. Overall, our results highlight the aggravated toxicity on different segments of intestine in mammalians due to co-exposure of PSNPs and DEHP, and these findings will provide valuable insights into the health risk of NPs and plastic additives.

Repression of autophagy leads to acrosome biogenesis disruption caused by a sub-chronic oral administration of polystyrene nanoparticles.

As a new widespread contaminant, nanoplastics (NPs) pose a potential risk to human health. Nevertheless, the adverse effects of NPs on the male reproductive system are poorly understood. In this study, we aimed to determine the effects of polystyrene nanoplastics (PS-NPs) (50 nm) on sperm quality, with a focus on the acrosome defects. After 35 days of intragastric administration, sperm quality was decreased and testicular structures were impaired in mice exposed to PS-NPs in both the medium (1.0 mg/kg) and high dose (10 mg/kg) groups. No significant changes were observed in the low dose (0.2 mg/kg) group. Meanwhile, acrosome parameters including acrosome integrity and acrosome reaction were decreased after the administration of PS-NPs. These findings were consistent with the disruption of acrosome biogenesis, as identified by the changed testicular ultrastructure. Additionally, the findings were further validated using seven marker genes (Gba2, Pick1, Gopc, Hrb, Zpbp1, Spaca1 and Dpy19l2) essential for acrosome formation, which showed that two of these genes (Gopc and Dpy19l2) were significantly down-regulated. Moreover, repressed autophagy was observed in the testes of PS-NPs-exposed mice based on autophagy-related protein expression. This phenomenon was further verified in GC-2spd cells treated with PS-NPs (50 µg/mL, 100 µg/mL, 200 µg/mL for 24 h). The potential role of autophagy in such acrosome defects was explored by using the autophagy inhibitor 3-methyladenine (3-MA), autophagy activator rapamycin or beclin-1 siRNA. The results showed that Golgi-associated vesicle disorganization was exacerbated with the 3-MA and beclin-1 siRNA pretreatments, but decreased with the rapamycin pretreatment, and the expression of GOPC and DPY19L2 was also altered. These results indicated that autophagy might be involved in the PS-NPs-induced acrosome lesions based on the regulation of two key acrosome-formation proteins, GOPC and DPY19L2. Altogether, our results will provide new insights into the PS-NPs-induced male reproductive impairment.

Applying Visual-Motor Training Combined with an Eye Relaxation System Based on Far-Infrared Nanomaterials in Pseudomyopia.

To explore the effect of far-infrared nanomaterial eye relaxation system combined with visual-motor training in pseudomyopia, 120 patients with pseudomyopia were included in the experiment and randomly divided into nanomaterial and control groups. The control group received visual-motor training, and the nanomaterial group was treated with an eye relaxation system. This study found that nanozirconia and nanotitanium dioxide used in eye relaxation systems could maintain good stability in acidic and alkaline conditions. Additionally, nanozirconia could produce a warm effect, and nanotitanium dioxide had a clear sterilization effect. Moreover, the two abovementioned nanoparticles could be closely combined with fiberoptic materials. After treatment, the eye adjustment function, visual acuity, and diopter of the two groups were significantly improved, especially in the nanomaterial group. Additionally, using the nanomaterial eye relaxation system could better control intraocular pressure, reduce lens thickness, and improve the symptoms of eye fatigue. Furthermore, anxiety and depression were better reduced in the nanomaterial group, and their quality of life was greatly improved. Therefore, the far-infrared nanomaterial eye relaxation system combined with visual-motor training can be used as a new and effective scheme for pseudomyopia.

Results of a 30-day safety assessment in young mice orally exposed to polystyrene nanoparticles.

Polystyrene nanoparticles (PSNPs) are a newly emerging pollutant in the natural environment. However, due to the lack of sufficient toxicological studies in mammals, the potential effects of PSNPs on human health remain largely undefined. Therefore, in this study, young mice aged four weeks old were subjected to oral administration of 0, 0.2, 1, or 10 mg/kg PSNPs for 30 days. Our results demonstrated for the first time that oral exposure to PSNPs affected the expressions of mucus secretion-related genes and altered the community composition of intestinal microbiota, although this treatment did not cause behavioral impairments in young mice. No significant alterations in inflammatory or oxidative stress-related indicators were observed in the liver, lung, intestine, cortex or serum of PSNPs-treated animals. Moreover, exposure to PSNPs did not cause pathological changes in the liver, lung, or cortex tissues. Notably, although oral administration of PSNPs did not produce obvious toxic effects in the major organs of young mice, the possible toxicity of PSNPs remains unresolved and it may depend on the dose, exposure route and species. The potential hazardous effects of PSNPs still need to be systematically assessed, especially for children who are susceptible to exposure to nanoparticles.

Neonicotinoid insecticide metabolites in seminal plasma: Associations with semen quality.

Animal studies have revealed that exposure to neonicotinoid insecticides (NNIs) could compromise male reproductive function; however, related data on the occurrence of NNIs and their specific metabolites in human seminal plasma are scarce. To explore the potential effects of NNI exposure on male semen quality, we determined the concentrations of NNIs and some of their metabolites (collectively defined as mNNIs) in seminal plasma samples collected from men (n = 191) who visited a fertility clinic in Shijiazhuang, North China from 2018 to 2019. Associations between the mNNI concentrations and semen quality parameters were assessed using linear regression models, adjusting for important covariates. In the seminal plasma samples, desmethyl-acetamiprid (DM-ACE, detection frequency: 98.4%), imidacloprid-olefin (IMI-olefin, detection frequency: 86.5%), and desmethyl-clothianidin (DM-CLO, detection frequency: 70.8%) were frequently detected at median concentrations of 0.052, 0.003, and 0.007 ng/mL, respectively; meanwhile other compounds were detected at less than the method detection limits. In the single-mNNI models, the IMI-olefin concentration was associated with decreased progressive motility [IMI-olefin concentration: percent change (%Δ) = -17.0; 95% confidence interval (CI) = -30.3, -0.92; the highest tertile compared with the lowest tertile: %Δ = -21.1; 95% CI = -37.5, -0.23]. Similar results were found in the multiple-mNNIs models. No other inverse associations were found between the other mNNI concentrations and semen quality parameters. This is the first study to identify the occurrence of mNNIs in the seminal plasma and the potential associations of their concentrations with human semen quality parameters. These findings imply an inverse association between the IMI-olefin concentration and semen quality.

Fipronil and its metabolites in human seminal plasma from Shijiazhuang, north China.

Fipronil (FP) is an emerging insecticide which could induce reproductive toxicity in male rats at very low dosage, but the occurrence of FP and its transformation products (FPs) in human seminal plasma and their impacts on human semen quality have not been documented. In this study, FPs including FP, fipronil desulfinyl (FP-DES), fipronil sulfone (FP-SFO), fipronil amide (FP-AM), and fipronil sulfide (FP-SFI), were measured in seminal plasma samples (n = 200), which were collected from Shijiazhuang, north China. The cumulative concentration of FPs (ΣFPs), in the seminal plasma samples ranged from 0.003 to 0.180 ng/mL (median: 0.043 ng/mL). FP-SFO was the major target analyte (median: 0.040 ng/mL), accounting for approximately 42.3-100.0% of the ΣFPs. Significantly higher exposure levels of FPs were found in the overweight or obese group (≥25 kg/m2) vs. the normal BMI group (18.5-25 kg/m2) (ΣFPs: 0.047 vs. 0.033 ng/mL), never smoking group vs. current smoking group (ΣFPs: 0.057 vs. 0.037 ng/mL), and low sexual frequency group (<1 time/week) vs. high sexual frequency group (≥3 times/week) (ΣFPs: 0.048 vs. 0.030 ng/mL). No significant association between FPs and impaired semen quality parameter was found in this study. This is the first time to report FPs' occurrence in human seminal plasma and variations in their concentrations among people with different demographic and behavioral characteristics. Further studies on adverse effects of exposure to FPs on reproductive function are needed.

Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring.

BACKGROUND: Pregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs on the neurodevelopmental process should be seriously concerned in health risk assessment, especially for the pregnant women who are susceptible to the neurodevelopmental toxicity of nano-sized particles. However, the available evidence of neurodevelopmental toxicity of TiO2NPs remains very limited. METHODS: In the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO2NPs from gestational day (GD) 8 to 21, the maternal behaviors and neurodevelopment-related indicators in offspring were all assessed at different time points after delivery. The gut microbial community in both dams and their offspring were detected by using 16S ribosomal RNA (rRNA) gene sequencing. The gut-brain axis related indicators were also determined in the offspring. RESULTS: The results clearly demonstrated that exposure to TiO2NPs did not affect the maternal behaviors of pregnant mice, or cause the deficits on the developmental milestones and perturbations in the early postnatal development of offspring. Intriguingly, our data revealed that pregnancy exposure of TiO2NPs did not affect locomotor function, learning and memory ability and anxiety-like behavior in offspring at postnatal day (PD) 21, but resulted in obvious impairments on these neurobehaviors at PD49. Similar phenomena were obtained in the composition of gut microbial community, intestinal and brain pathological damage in offspring in adulthood. Moreover, the intestinal dysbiosis induced by TiO2NPs might be highly associated with the delayed appearance of neurobehavioral impairments in offspring, possibly occurring through disruption of gut-brain axis. CONCLUSIONS: This is the first report elucidated that pregnancy exposure to TiO2NPs caused delayed appearance of neurobehavioral impairments in offspring when they reached adulthood, although these perturbations did not happen at early life after delivery. These findings will provide valuable insights about neurodevelopmental toxicity of TiO2NPs, and call for comprehensive health risk assessment of TiO2NPs on the susceptible population, such as pregnant women.

Sperm mtDNA copy number, telomere length, and seminal spermatogenic cells in relation to ambient air pollution: Results of a cross-sectional study in Jing-Jin-Ji region of China.

Evidences on the association of air pollutants and semen quality were limited and mechanism-based biomarkers were sparse. We enrolled 423 men at a fertility clinic in Shijiazhuang, China to evaluate associations between air pollutants and semen quality parameters including the conventional ones, sperm mitochondrial DNA copy number (mtDNAcn), sperm telomere length (STL) and seminal spermatogenic cells. PM2.5, PM10, CO, SO2, NO2 and O3 exposure during lag0-90, lag0-9, lag10-14 and lag70-90 days were evaluated with ordinary Kringing model. The exposure-response correlations were analyzed with multiple linear regression models. CO, PM2.5 and PM10 were adversely associated with conventional semen parameters including sperm count, motility and morphology. Besides, CO was positively associated with seminal primary spermatocyte (lag70-90, 0.49; 0.14, 0.85) and mtDNAcn (lag0-90, 0.37; 0.12, 0.62, lag10-14, 0.31; 0.12, 0.49), negatively associated with STL (lag0-9, -0.30; -0.57, -0.03). PM2.5 was positively associated with mtDNAcn (0.50; 0.24, 0.75 and 0.38; 0.02, 0.75 for lag0-90 and lag70-90) while negatively associated with STL (lag70-90, -0.49; -0.96, -0.01). PM10 and NO2 were positively associated with mtDNAcn. Our findings indicate CO and PM might impair semen quality testicularly and post-testicularly while seminal spermatogenic cell, STL and mtDNAcn change indicate necessity for more attention on these mechanisms.

Activation of forkhead box O3a by mono(2-ethylhexyl)phthalate and its role in protection against mono(2-ethylhexyl)phthalate-induced oxidative stress and apoptosis in human cardiomyocytes.

Mono(2-ethylhexyl)phthalate (MEHP), the active metabolite of di(2-ethylhexyl)phthalate (DEHP), is known to exert cardiotoxicity. The aim of the present study was to investigate the role of forkhead box O3a (FOXO3a) in MEHP-induced human AC16 cardiomyocyte injuries. MEHP reduced cell viability and mitochondrial membrane potential (ΔΨm), whereas it increased lactate dehydrogenase (LDH) leakage, production of reactive oxygen species (ROS), and apoptosis in cardiomyocytes. The expression of FOXO3a and its target genes, mitochondrial superoxide dismutase (Mn-SOD) and apoptosis repressor with caspase recruitment domain (ARC), increased after MEHP exposure, but the expression of p-FOXO3a protein was decreased. Overexpression of FOXO3a decreased the production of ROS and the apoptosis rate induced by MEHP, and the expression of Mn-SOD and ARC was further increased after MEHP exposure. In contrast, knockdown of FOXO3a resulted in increased ROS production and apoptosis and suppressed the expression of Mn-SOD and ARC in the presence of MEHP. However, overexpression or knockdown of FOXO3a did not affect MEHP-induced loss of ΔΨm. In conclusion, the loss of ΔΨm and apoptosis are involved in MEHP-induced cardiomyocyte toxicity. Activation of FOXO3a defends against MEHP-induced oxidative stress and apoptosis by upregulating the expression of Mn-SOD and ARC in AC16 cardiomyocytes.