Improved ambient air quality is associated with decreased prevalence of childhood asthma and infancy shortly after weaning is a sensitive exposure window.

BACKGROUND: The urban ambient air quality has been largely improved in the past decade. It is unknown whether childhood asthma prevalence is still increasing in ever top-ranking city of Shanghai, whether the improved air quality is beneficial for children's asthma and what time window of exposure plays critical roles. METHODS: Using a repeat cross-sectional design, we analyzed the association between early life exposure to particles and wheezing/asthma in each individual and combined surveys in 2011 and 2019, respectively, in 11,825 preschool children in Shanghai. RESULTS: A significantly lower prevalence of doctor-diagnosed asthma (DDA) (6.6% vs. 10.5%, p < 0.001) and wheezing (10.5% vs. 23.2%, p < 0.001) was observed in 2019 compared to 2011. Exposure to fine particulate matter (PM2.5 ), coarse particles (PM2.5-10 ) and inhalable particles (PM10 ) was decreased in 2019 by 6.3%, 35.4%, and 44.7% in uterus and 24.3%, 20.2%, and 31.8% in infancy, respectively. Multilevel log-binomial regression analysis showed exposure in infancy had independent association with wheezing/DDA adjusting for exposure in uterus. For each interquartile range (IQR) increase of infancy PM2.5 , PM2.5-10 and PM10 exposure, the odds ratios were 1.39 (95% confidence interval (CI): 1.24-1.56), 1.51 (95% CI:1.15-1.98) and 1.53 (95% CI:1.27-1.85) for DDA, respectively. The distributed lag non-linear model showed the sensitive exposure window (SEW) was 5.5-11 months after birth. Stratified analysis showed the SEWs were at or shortly after weaning, but only in those with <6 months of exclusive breastfeeding. CONCLUSIONS: Improved ambient PM benefits in decreasing childhood asthma prevalence. We firstly reported the finding of SEW to PM at or closely after weaning on childhood asthma.

Impact of environmental characteristics on children's gut microbiota - A pilot study in assessing the role of indoor microbiome and metabolites.

BACKGROUND: A diverse and balanced human gut microbiota is crucial for maintaining normal human physiological functions. However, the impact of indoor microbiome and metabolites on gut microbiota is not well understood. METHODS: A self-administered questionnaire was used to collect information on more than 40 personal and environmental characteristics and dietary habits from 56 children in Shanghai, China. Shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS) were used to characterize the indoor microbiome and metabolomic/chemical exposure in children's living rooms. PacBio full-length 16 S rRNA sequencing was used to characterize children's gut microbiota. Associations between environmental characteristics and gut microbiota diversity/composition were assessed using PERMANOVA and regression. RESULTS: In total, 6247 and 318 indoor and gut microbial species and 1442 indoor metabolites were characterized. Age of children (R2 = 0.033, p = 0.008), age start kindergarten (R2 = 0.029, p = 0.03), living adjacent to heavy traffic (R2 = 0.031, p = 0.01) and drinking soft drinks (R2 = 0.028, p = 0.04) significantly impacted overall gut microbial composition, consistent with previous studies. Having pets/plants and frequent vegetable intake were positively associated with gut microbiota diversity and the Gut Microbiome Health Index (GMHI), while frequent juice and fries intake decreased gut microbiota diversity (p < 0.05). The abundance of indoor Clostridia and Bacilli was positively associated with gut microbial diversity and GMHI (p < 0.01). Total indoor indole derivatives and 6 indole metabolites (L-tryptophan, indole, 3-methylindole, indole-3-acetate, 5-hydroxy-L-tryptophan and indolelactic acid, p < 0.05) were positively associated with the abundance of total protective gut bacteria, suggesting a potential role in promoting gut health. Neural network analysis revealed that these indole derivatives were derived from indoor microorganisms. CONCLUSIONS: The study is the first to report associations between indoor microbiome/metabolites and gut microbiota, highlighting the potential role of indoor microbiome in shaping human gut microbiota.

Maternal exposure to ambient PM2.5 perturbs the metabolic homeostasis of maternal serum and placenta in mice.

Epidemiological and animal studies have shown that maternal fine particulate matters (PM2.5) exposure correlates with various adverse pregnancy outcomes such as low birth weight (LBW) of offspring. However, the underlying biological mechanisms have not been fully understood. In this study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and metabolomics was performed to analyze the metabolic features in maternal serum and placenta by liquid chromatography-mass spectrometry (LC-MS). The partial least squares discriminate analysis (PLS-DA) displayed evident clustering of FA- and CAP-exposed samples for both maternal serum and placenta. In addition, pathway analysis identified that vitamin digestion and absorption was perturbed in maternal serum, while metabolic pathways including arachidonic acid metabolism, serotonergic synapse, 2-oxocarboxylic acid metabolism and cAMP signaling pathway were perturbed in placenta. Further analysis indicated that CAP exposure influenced the nutrient transportation capacity of placenta, by not only changing the ratios of some critical metabolites in placenta to maternal serum but also significantly altering the expressions of nutrition transporters in placenta. These findings reaffirm the importance of protecting women from PM2.5 exposure, and also advance our understanding of the toxic actions of ambient PM2.5.

Assessing the Impact of Programmed Intermittent Pulse Injection on Pelvic Floor Function Following Childbirth.

Objective: This study aimed to assess the impact of different administration timings of Programmed Intermittent Pulse Injection (PIEB) on pelvic floor function and postpartum rehabilitation in patients who underwent analgesic delivery and received postpartum rehabilitation nursing. Methods: An observational comparative study was conducted between January 2021 and October 2021. We enrolled 85 patients who received PIEB analgesia during delivery and postpartum rehabilitation nursing at our hospital. Among them, 39 women received PIEB (10 mL pulse dose) 60 minutes after analgesia, comprising group A. Additionally, 46 women received PIEB (15 mL pulse dose) 90 minutes after analgesia, forming group B. We assessed pain levels using the Visual Analogue Scale (VAS), recorded epidural drug dosage, counted the number of Patient-Controlled Epidural Analgesia (PCEA) compressions, noted cases of unilateral block, oxytocin (OT) usage, conversion to cesarean section, and adverse events (AEs). Furthermore, we evaluated pelvic floor muscle (PFM) recovery and assessed their quality of life using the World Health Organization Quality of Life assessment (WHOQOL-100). Results: Group A exhibited a lower VAS score at 1 hour after analgesia compared to group B (P < .05), with no significant differences at other time points (P > .05). Group A had lower epidural drug dosages and fewer PCEA compressions than group B (P < .05). There were no significant differences in unilateral block incidence and OT use (P > .05). PFM recovery levels were similar in both groups (P > .05), but the WHOQOL-100 score after nursing was higher in group A compared to group B (P < .05). Conclusions: Administering PIEB with a 60-minute interval after analgesia can enhance the effectiveness and safety of the intervention.

Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investigated. RESULTS: In the study, IL-6 receptor (IL-6R)-deficient (IL-6R-/-) and wildtype littermate (IL-6R+/+) mice were exposed to concentrated ambient PM2.5 (CAP) or filtered air (FA), and their pulmonary and metabolic responses to these exposures were analyzed. Our results demonstrated that IL-6R deficiency markedly alleviated PM2.5 exposure-induced increases in lung inflammatory markers including the inflammation score of histological analysis, the number of macrophages in bronchoalveolar lavage fluid (BALF), and mRNA expressions of TNFα, IL-1ß and IL-6 and abnormalities in lung function test. However, IL-6R deficiency did not reduce the hepatic insulin resistance nor systemic glucose intolerance and insulin resistance induced by PM2.5 exposure. CONCLUSION: Our findings support the crucial role of IL-6 signalling in the development of pulmonary inflammation and dysfunction due to PM2.5 exposure but question the putative central role of pulmonary inflammation for the extra-pulmonary dysfunctions following PM2.5 exposure, providing a deep mechanistic insight into the pathogenesis caused by PM2.5 exposure.

Concentrated ambient fine particles exposure affects ovarian follicle development in mice.

BACKGROUND: Ambient fine particles (PM2.5) are known to cause various reproductive and developmental diseases. However, the potential mechanisms of PM2.5 exposure induced female reproductive damage remain unclear. METHODS: Four weeks old female C57BL/6 J mice were exposed to filtered air (FA, n = 10) or concentrated ambient PM2.5 (CAP, n = 10) using a versatile aerosol concentration enrichment system. After 9 weeks of the exposure, mice were sacrificed under sevoflurane anesthesia and tissue samples were collected. Immunohistochemical analysis, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and RNA-sequencing were performed to analyze the effects of PM2.5 exposure on follicle development and elucidate its potential mechanisms. RESULTS: Chronic PM2.5 exposure resulted in follicular dysplasia. Compared to the FA-exposed group, follicular atresia in the CAP-exposed mice were significantly increased. Further studies confirmed that CAP induced apoptosis in granulosa cells, accompanied by a distortion of hormone homeostasis. In addition, RNA-sequencing data demonstrated that CAP exposure induced the alteration of ovarian gene expressions and was associated with inflammatory response. CONCLUSIONS: Chronic exposure to CAP can induce follicular atresia, which was associated with hormone modulation and inflammation.

Maternal exposure to ambient PM2.5 causes fetal growth restriction via the inhibition of spiral artery remodeling in mice.

BACKGROUND: Maternal exposure to ambient fine particulate matters (PM2.5) is associated with low birth weight (LBW) in offspring, but the underlying biological mechanisms are not yet fully understood. As the bridge that connects mother and fetus, the placenta plays a crucial role in fetal development by providing the fetus with nutrients and oxygen. However, whether PM2.5 exposure would impact the placental development and the related mechanisms are unclear. RESULTS: In the present study, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and the fetal development and placental structure were investigated. Our results showed that maternal exposure to CAP induced fetal growth restriction (FGR) and LBW. The placenta from CAP-exposed mice exhibited abnormal development including significant decrease of surface area, smaller junctional zone and impaired spiral artery remodeling. Meanwhile, CAP exposure altered trophoblast lineage differentiation and disrupted the balance between angiogenic and angiostatic factors in placenta. In addition, the inflammatory cytokines levels in lung, placenta and serum were significantly increased after ambient PM2.5 exposure. CONCLUSION: Our findings indicate that maternal exposure to PM2.5 disrupts normal structure and spiral artery remodeling of placenta and further induces FGR and LBW. This effect may be caused by the placental inflammation response subsequent to the pulmonary and systemic inflammation induced by ambient PM2.5 exposure.

Lead suppresses interferon γ to induce splenomegaly via modification on splenic endothelial cells and lymphoid tissue organizer cells in mice.

Splenomegaly is a symptom characterized by the presence of an enlarged spleen. The impact of environmental factors on splenomegaly is largely unknown. In this study, C57BL/6 mice were treated with 125 ppm or 1250 ppm lead (Pb) via drinking water for 8 wk, and the process of splenomegaly was evaluated. Treatment with 1250 ppm Pb, but not 125 ppm Pb, caused splenomegaly, which was associated with increased capacity for erythrocyte clearance. Intriguingly, Pb-caused splenomegaly was independent of lymphoid tissue inducer (LTi) cells, which produce lymphotoxins α and ß (LTα/ß) to activate endothelial cells and LT organizer (LTo) cells and drive the development of spleen physiologically. A direct action of Pb on endothelial cells and LTo cells did not impact their proliferation. On the other hand, during steady state, a tonic level of interferon (IFN)γ acted on endothelial cells and LTo cells to suppress splenomegaly, as IFNγ receptor (IFNγR)-deficient mice had enlarged spleens relative to wild-type mice; during Pb exposure, splenic IFNγ production was suppressed, thus leading to a loss of the inhibitory effect of IFNγ on splenomegaly. Mechanically, Pb acted on splenic CD4+ T cells to suppress IFNγ production, which impaired the Janus kinase (Jak)1/ signal transducer and activator of transcription (STAT)1 signaling in endothelial cells and LTo cells; the weakened Jak1/STAT1 signaling resulted in the enhanced nuclear factor-κB (NF-κB) signaling in endothelial cells and LTo cells, which drove their proliferation and caused splenomegaly. The present study reveals a previously unrecognized mechanism for the immunotoxicity of Pb, which may extend our current understanding for Pb toxicology.

Caffeine-Induced Sleep Restriction Alters the Gut Microbiome and Fecal Metabolic Profiles in Mice.

Insufficient sleep is becoming increasingly common and contributes to many health issues. To combat sleepiness, caffeine is consumed daily worldwide. Thus, caffeine consumption and sleep restriction often occur in succession. The gut microbiome can be rapidly affected by either one's sleep status or caffeine intake, whereas the synergistic effects of a persistent caffeine-induced sleep restriction remain unclear. In this study, we investigated the impact of a chronic caffeine-induced sleep restriction on the gut microbiome and its metabolic profiles in mice. Our results revealed that the proportion of Firmicutes and Bacteroidetes was not altered, while the abundance of Proteobacteria and Actinobacteria was significantly decreased. In addition, the content of the lipids was abundant and significantly increased. A pathway analysis of the differential metabolites suggested that numerous metabolic pathways were affected, and the glycerophospholipid metabolism was most significantly altered. Combined analysis revealed that the metabolism was significantly affected by variations in the abundance and function of the intestinal microorganisms and was closely relevant to Proteobacteria and Actinobacteria. In conclusion, a long-term caffeine-induced sleep restriction affected the diversity and composition of the intestinal microbiota in mice, and substantially altered the metabolic profiles of the gut microbiome. This may represent a novel mechanism by which an unhealthy lifestyle such as mistimed coffee breaks lead to or exacerbates disease.

Wnt/ß-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging.

Cadmium (Cd) is a toxic heavy metal and worldwide environmental pollutant which seriously threatens human health and ecosystems. It is easy to be adsorbed and deposited in organisms, exerting adverse effects on various organs including the brain. In a very recent study, making full use of a zebrafish model in both high-throughput behavioral tracking and live neuroimaging, we explored the potential developmental neurotoxicity of Cd2+ at environmentally relevant levels and identified multiple connections between Cd2+ exposure and neurodevelopmental disorders as well as microglia-mediated neuroinflammation, whereas the underlying neurotoxic mechanisms remained unclear. The canonical Wnt/ß-catenin signaling pathway plays crucial roles in many biological processes including neurodevelopment, cell survival, and cell cycle regulation, as well as microglial activation, thereby potentially presenting one of the key targets of Cd2+ neurotoxicity. Therefore, in this follow-up study, we investigated the implication of the Wnt/ß-catenin signaling pathway in Cd2+-induced developmental disorders and neuroinflammation and revealed that environmental Cd2+ exposure significantly affected the expression of key factors in the zebrafish Wnt/ß-catenin signaling pathway. In addition, pharmacological intervention of this pathway via TWS119, which can increase the protein level of ß-catenin and act as a classical activator of the Wnt signaling pathway, could significantly repress the Cd2+-induced cell cycle arrest and apoptosis, thereby attenuating the inhibitory effects of Cd2+ on the early development, behavior, and activity, as well as neurodevelopment of zebrafish larvae to a certain degree. Furthermore, activation and proliferation of microglia, as well as the altered expression profiles of genes associated with neuroimmune homeostasis triggered by Cd2+ exposure could also be significantly alleviated by the activation of the Wnt/ß-catenin signaling pathway. Thus, this study provided novel insights into the cellular and molecular mechanisms of Cd2+ toxicity on the vertebrate central nervous system (CNS), which might be helpful in developing pharmacotherapies to mitigate the neurological disorders resulting from exposure to Cd2+ and many other environmental heavy metals.

Differential Roles of Water-Insoluble and Water-Soluble Fractions of Diesel Exhaust Particles in the Development of Adverse Health Effects Due to Chronic Instillation of Diesel Exhaust Particles.

Ambient fine particulate matter (PM2.5) has a marked temporospatial variation in chemical composition, but how the composition of PM2.5 influences its toxicity remains elusive. To explore the roles of individual PM2.5 components in the pathogenesis following PM2.5 exposure, we prepared water-soluble (WS-DEP) and water-insoluble (WIS-DEP) fractions of diesel exhaust particles (DEP) and performed 15-week intratracheal instillation on C57Bl/6J mice using these fractions. Their effects on pulmonary and systemic inflammation, hepatic steatosis and insulin resistance, systemic glucose homeostasis, and gut microbiota were then assessed. Compared to control, instillation of DEP or WIS-DEP, but not WS-DEP, significantly increased pulmonary inflammatory scores and expression of inflammatory markers, bronchoalveolar lavage fluid cell number, and circulating pro-inflammatory cytokines. Consistently, DEP- or WIS-DEP-instilled but not WS-DEP-instilled mice versus control had significant hepatic steatosis and insulin resistance and systemic glucose intolerance. In contrast, instillation of WS-DEP versus instillation of WIS-DEP had effects on the gut microbiota more comparable to that of instillations of DEP. The pulmonary and systemic inflammation, hepatic steatosis and insulin resistance, and systemic glucose intolerance following chronic DEP instillation are all attributable to the WIS-DEP, suggesting that PM2.5 may have a solubility-dependent basal toxicity.

Paternal Exposure to PM2.5 Programs Offspring's Energy Homeostasis.

Considerable studies show that maternal exposure to ambient fine particulate matter (PM2.5) programs offspring's susceptibility to obesity. However, few studies have investigated the effect of paternal PM2.5 exposure on offspring's energy homeostasis. This study thus tested whether paternal PM2.5 exposure programs offspring's energy homeostasis. Male C57Bl/6J mice were exposed to filtered air or concentrated ambient PM2.5 (CAP) for 12 weeks and then mated with normal female C57Bl/6J mice. The offspring were assessed for growth trajectories, food intakes, and body compositions, and the sperm miRNAs of those sires were profiled by microarray. Zygotic injection was used to test whether the miRNA identified by the microarray mediates the impact of paternal PM2.5 exposure on offspring's energy homeostasis. Paternal CAP exposure resulted in significant hypophagia and weight loss in male, but not female, offspring. The weight loss of male offspring was accompanied by decreases in the liver and kidney masses and paradoxically an increase in the adipose mass. Without further exposure to CAP, this programming was three-generationally transmitted along the paternal line. The sperm miRNA profiling revealed that mmu-mir6909-5p was the sole differentially expressed sperm miRNA due to PM2.5 exposure, and zygotic injection of mmu-mir6909-5p mimicked all the effects of paternal PM2.5 exposure on offspring's energy homeostasis. Paternal PM2.5 exposure programs offspring's energy homeostasis through increasing paternal sperm mmu-mir6909-5p.

Exposure to different fractions of diesel exhaust PM2.5 induces different levels of pulmonary inflammation and acute phase response.

AIM: Ambient fine particulate matter (PM2.5) consists of various components, and their respective contributions to the toxicity of PM2.5 remains to be determined. To provide specific recommendations for preventing adverse effects due to PM2.5 pollution, we determined whether the induction of pulmonary inflammation, the putative pathogenesis for the morbidity and mortality due to PM2.5 exposure, was fractioned through solubility-dependent fractioning. METHODS: In the present study, the water and heptane solubilities-dependent serial fractioning of diesel exhaust particulate matter (DEP), a prominent source of urban PM2.5 pollution, was performed. The pro-inflammatory actions of these resultant fractions were then determined using both an intratracheal instillation mouse model and cultured BEAS-2B cells, a human bronchial epithelial cell line. RESULTS: Instillation of the water-insoluble, but not -soluble fraction elicited significant pulmonary inflammatory and acute phase responses, comparable to those induced by instillation of DEP. The water-insoluble fraction was further fractioned using heptane, a polar organic solvent, and instillation of heptane-insoluble, but not -soluble fraction elicited significant pulmonary inflammation and acute phase responses. Furthermore, we showed that DEP and water-insoluble DEP, but not water-soluble DEP, activated pro-inflammatory signaling in cultured BEAS-2B cells, ruling out the possibility that the solubility impacts the in vivo distribution and thus the pulmonary inflammatory response.

Hypothalamic-pituitary-adrenal axis mediates ambient PM2.5 exposure-induced pulmonary inflammation.

Ambient fine particulate matter (PM2.5) exposure correlates with adverse cardiometabolic effects. The underlying mechanisms have not yet been fully understood. Hypothalamic-pituitary-adrenal (HPA) axis, as the central stress response system, regulates cardiometabolic homeostasis and is implicated in the progression of various adverse health effects caused by inhalational airborne pollutant exposure. In this study, we investigated whether ambient PM2.5 exposure activates HPA axis and its effect mediating PM2.5-induced pulmonary inflammation. C57Bl/6 J mice were intratracheally instilled with different concentrations of diesel exhaust PM2.5 (DEP), and plasma was harvested at different times. Assessments of plasma stress hormones revealed that DEP instillation dose- and time-dependently increased mouse circulating corticosterone and adrenocorticotropic hormone (ACTH) levels, strongly supporting that DEP instillation activates HPA axis. To determine which components of DEP activate HPA axis, C57Bl/6J mice were intratracheally instilled with water-soluble and -insoluble fractions of DEP. Plasma analyses showed that water-insoluble but not -soluble fraction of DEP increased circulating corticosterone and ACTH levels. Consistently, concentrated ambient PM2.5 (CAP) exposure significantly increased mouse urine and hair corticosterone levels, corroborating the activation of HPA axis by ambient PM2.5. Furthermore, deletion of stress hormones by total bilateral adrenalectomy alleviated PM2.5-induced pulmonary inflammation, providing insights into the contribution of central neurohormonal mechanisms in modulating adverse health effects caused by exposure to PM2.5.

Chronic exposure to diesel exhaust particulate matter impairs meiotic progression during spermatogenesis in a mouse model.

Exposure to ambient PM2.5 may correlate with the decline of semen quality, and the underlying biological mechanism has not been fully understood. In the present study, mice were intratracheally instilled with diesel exhaust PM2.5 (DEP), and its effects on the spermatogenic process as well as the alterations of testicular gene expression profile were assessed. Our results showed that chronic exposure to DEP impaired the fertility of male mice without influencing their libido. Compared with Vehicle-exposed group, the sperm count and motility from DEP-exposed mice were significantly decreased. In addition, immunohistological staining of γH2AX and DMC1, biomarkers for meiotic double strand breaks (DSBs), demonstrated that chronic exposure to DEP comprised the repair of meiotic DSBs, thus disrupting the spermatogenesis. Deep RNA sequencing test showed altered expressions of testicular genes including the GnRH signaling pathway. In summary, our research demonstrated that chronic exposure to DEP may disrupt spermatogenesis through targeting the meiotic recombination, providing a new perspective for the research on the male reproductive system damage caused by air pollution.

Effects of filtered fresh air ventilation on classroom indoor air and biomarkers in saliva and nasal samples: A randomized crossover intervention study in preschool children.

To evaluate the short-term effects of filtered fresh air ventilation system on classroom indoor air and biomarkers in saliva and nasal samples in preschool children, a randomized crossover study was conducted in a kindergarten in Shanghai, China in 2016. Two classrooms at the same grade (n = 43) were selected and fresh air ventilation systems (FAVS) with high efficiency particulate air filter (HEPA) were installed. In the first week, FAVS-HEPA was run in one classroom for 2 continuous school days and the other classroom was remained as usual with no use of FAVS-HEPA. After one week of wash-out, the ventilation modes exchanged between two classrooms and another 2 days of intervention were repeated. Real-time indoor and outdoor air pollution and climate factors (PM2.5, Temp and relative humidity (R.H.)) were measured. Saliva and nasal internal mucosa samples were collected immediately at the end of each intervention scenario. Linear mixed-effect regression model was applied to evaluate the effects of intervention on children's health indicators controlling for age, gender, height, BMI and temperature. The results showed, with FAVS-HEPA, the classroom indoor fine particulate matter (PM2.5)(29.1 ±â€¯17.9 µg/m3) was on average significantly lower than that without FAVS-HEPA (85.7 ±â€¯43.2 µg/m3). By regression analysis, each 10 µg/m3 decrease of indoor PM2.5 during the 8 school hours in the first intervention day was associated with an average of 1.76% (95% confidence interval (CI) 0.43-3.08%) increase in saliva lysozyme. This percentage increased to 2.41% (95%CI 0.52-4.26%) if related to the PM2.5 level in 16 school hours over 2 days of intervention. A total of 19 nasal bacterial taxa were lower in subjects exposed to FAVS-HEPA, compared to that with no use of FAVS-HEPA, despite the general bacteria diversity levels in nasal samples were not statistically different. Among others, Providencia species showed significant effects in mediating the associations between higher PM2.5 and lower lysozyme. In conclusion, using FAVS-HEPA was effective in decreasing the classroom indoor PM2.5. Saliva lysozyme, as a non-specific immune biomarker, was significantly inversely associated with indoor PM2.5. Certain nasal bacteria might play key roles in mediating PM2.5 exposure and children's lysozyme levels.

Developmental programming of obesity by maternal exposure to concentrated ambient PM2.5 is maternally transmitted into the third generation in a mouse model.

BACKGROUND: Obesity is an uncontrolled global epidemic and one of the leading global public health challenges. Maternal exposure to ambient fine particulate matter (PM2.5) may adversely program offspring's adiposity, suggesting a specialized role of PM2.5 pollution in the global obesity epidemic. However, the vulnerable window for this adverse programming and how it is cross-generationally transmitted have not been determined. Therefore, in the present study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during different periods, and the development and adulthood adiposity of their four-generational offspring were assessed. RESULTS: Our data show that the pre-conceptional but not gestational exposure to CAP was sufficient to cause male but not female offspring's low birth weight, accelerated postnatal weight gain, and increased adulthood adiposity. These adverse developmental traits were transmitted into the F2 offspring born by the female but not male F1 offspring of CAP-exposed dams. In contrast, no adverse development was noted in the F3 offspring. CONCLUSIONS: The present study identified a pre-conceptional window for the adverse programming of adiposity by maternal exposure to PM2.5, and showed that it was maternally transmitted into the third generation. These data not only call special attention to the protection of women from exposure to PM2.5, but also may facilitate the development of intervention to prevent this adverse programming.

Prenatal exposure to diesel exhaust PM2.5 causes offspring ß cell dysfunction in adulthood.

Environmental stressors that encounter in early-life and cause abnormal fetal and/or neonatal development may increase susceptibility to non-communicable diseases such as diabetes. Maternal exposure to ambient fine particulate matter (PM2.5) is associated with various fetal abnormalities, suggesting that it may program offspring's susceptibility to diabetes. In the present study, we therefore examined whether maternal exposure to diesel exhaust PM2.5 (DEP), one of the major sources of ambient PM2.5 in urban areas, programs adult offspring's glucose metabolism. Female C57Bl/6J mice were intratracheally instilled with DEP or vehicle throughout a 7-wk preconceptional period, gestation, and lactation, and the glucose homeostasis of their adult male offspring was assessed. Intraperitoneal glucose tolerance test (IPGTT) revealed that the maternal exposure to DEP significantly impaired adult male offspring's glucose tolerance. Unexpectedly, it did not influence their insulin sensitivity, whereas it significantly decreased their glucose-induced insulin secretion (GIIS). This deficit in insulin secretion was corroborated by their significant decrease in arginine-induced insulin secretion. Histological analysis demonstrated that the deficit in insulin secretion was accompanied by the decrease in pancreatic islet and ß cell sizes. To differentiate the effects of maternal exposure to DEP before birth and during lactation, some offspring were cross-fostered once born. We did not observe any significant effect of cross-fostering on the glucose homeostasis of adult male offspring and the function and morphology of their ß cells. Prenatal exposure to DEP programs the morphology and function of ß cells and thus homeostatic regulation of glucose metabolism in adult male offspring.

Enhanced Rotator-Cuff Repair Using Platelet-Rich Plasma Adsorbed on Branched Poly(ester urea)s.

Platelet-rich plasma (PRP) is a clinically relevant source of growth factors used commonly by surgeons. The clinical efficacy of PRP use as reported in the literature is widely variable which is likely attributed to poorly defined retention time of PRP at the repair site. To overcome this limitation, branched poly(ester urea) (PEU) nanofibers were used to adsorb and retain PRP at the implant site in an acute rotator-cuff tear model in rats. The adsorption of PRP to the branched-PEU 8% material was characterized using quartz crystal microbalance (QCM) and immuno-protein assay. After adsorption of PRP to the nanofiber sheet, the platelets actively released proteins. The adhesion of platelets to the nanofiber material was confirmed by immunofluorescence using a p-selectin antibody. In vivo testing using a rat rotator-cuff repair model compared five groups; no repair (control), suture repair only, repair with disc implant (Disc), repair with PRP-soaked disc (Disc PRP), and a PRP injection (PRP). Mechanical testing at 84 d for the four surgical repair groups resulted in a higher stiffness (11.8 ± 3.8 N/mm, 13.5 ± 3.8 N/mm, 16.8 ± 5.8 N/mm, 12.2 ± 2.6 N/mm, respectively) for the Disc PRP group. Histological staining using trichrome, hematoxylin, and eosin Y (H&E), and safranin O confirmed more collagen organization in the Disc PRP group at 21 and 84 d. Limited inflammation and recovery toward preoperative mechanical properties indicate PEU nanofiber discs as translationally relevant.

Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model.

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) correlates with abnormal glucose homeostasis, but the underlying biological mechanism has not been fully understood. The gut microbiota is an emerging crucial player in the homeostatic regulation of glucose metabolism. Few studies have investigated its role in the PM2.5 exposure-induced abnormalities in glucose homeostasis. METHODS: C57Bl/6J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) for 12 months using a versatile aerosol concentration enrichment system (VACES) that was modified for long-term whole-body exposures. Their glucose homeostasis and gut microbiota were examined and analysed by correlation and mediation analysis. RESULTS: Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) showed that CAP exposure markedly impaired their glucose and insulin tolerance. Faecal microbiota analysis demonstrated that the impairment in glucose homeostasis was coincided with decreased faecal bacterial ACE and Chao-1 estimators (the indexes of community richness), while there was no significant change in all faecal fungal alpha diversity estimators. The Pearson's correlation analyses showed that the bacterial richness estimators were correlated with glucose and insulin tolerance, and the mediation analyses displayed a significant mediation of CAP exposure-induced glucose intolerance by the alteration in the bacterial Chao-1 estimator. LEfSe analyses revealed 24 bacterial and 21 fungal taxa differential between CAP- and FA-exposed animals. Of these, 14 and 20 bacterial taxa were correlated with IPGTT AUC and ITT AUC, respectively, and 5 fungal taxa were correlated with abnormalities in glucose metabolism. CONCLUSIONS: Chronic exposure to PM2.5 causes gut dysbiosis and may subsequently contribute to the development of abnormalities in glucose metabolism.