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The effectiveness of resveratrol (RES) on intestinal barrier dysfunction and colitis has been extensively studied. However, the specific effects of its microbial metabolites on gut barrier function remain unclear. Hence, we compared the protective effects of RES and its microbial metabolites dihydroresveratrol (DHR) and 3-(4-hydroxyphenyl)-propionic acid (4HPP) against intestinal barrier injury and colitis. Only 4HPP and RES significantly reduced paracellular permeability and the secretion of proinflammatory cytokines in lipopolysaccharides (LPS)-treated intestinal Caco-2 cells, which was consistent with the upregulation in tight junction (TJ) proteins. Furthermore, RES and 4HPP ameliorated intestinal barrier dysfunction and colonic inflammation in colitis mice, while DHR did not. In particular, the expressions of intestinal TJ proteins and Muc2 were restored by RES and 4HPP. The molecular mechanism involved the adenosine monophosphate-activated protein kinase (AMPK)-mediated activation of CDX2 and the regulation of the SIRT1/NF-κB pathway. These findings provide new insights into understanding the protective effects of RES against intestinal barrier damage and colitis.

Non-small cell lung cancer (NSCLC) is currently one of the malignant tumors with the highest incidence and mortality rate in China. Circular RNA hsa_circ_0000896 (circFARSA) has been reported as being an oncogene and a potential biomarker for NSCL. However, the functional role and action mechanism of circFARSA in NSCLC progression have not been fully elucidated. The present study demonstrated that circFRASA was upregulated in NSCLC tissues and cell lines, and its expression was positively correlated with poor prognosis of patients with NSCLC. Further experiments revealed that circFARSA knockdown inhibited cell proliferation, migration, and invasion

The toxicity of organophosphate esters (OPEs) on embryonic development is well noted in animal experiments, but epidemiological studies are still lacking. This study evaluated the prenatal exposure of OPEs and its trimester-specific and gender-specific effects on fetal growth. The correlations between OPE exposure and fetal growth were investigated by linear mixed-effect models and multivariable linear regression analyses. Prenatal exposure to tributyl phosphate (TBP) was negatively associated with a

Surgery plays an irreplaceable role in the prevention, diagnosis, staging, reconstruction, and rehabilitation in the overall management of cancer. Nevertheless, it is difficult for surgeons and nurses to take into account the details of medication management, considering the impact of surgery on the patient's physical function and the complexity of anti-tumor treatment with comorbidity. The pharmaceutical care services previously provided by pharmacists in oncology focus more on the internal medicine system, not widely the surgical field. At present, the pharmaceutical working mode in oncology surgery has not well been formed around China, and the whole process medication management needs to be improved. In 2015, the GuangDong Pharmaceutical Association came up with the concept of surgical pharmacist in China and subsequently created its position. In 2021, the GuangDong Pharmaceutical Association established a new discipline termed "surgical pharmacy", which is the knowledge system of surgical pharmacists, and also tried to differentiate surgical pharmacy into diverse areas, such as oncology surgical pharmacy. This article introduced a working mode of surgical pharmacists in China that providing pharmaceutical care services in perioperative period around anti-tumor, anti- infection, anesthesia, anticoagulation, blood pressure, blood glucose, nutrition, and pain management, to improve quality of life for patients.La cirugía desempeña un papel insustituible en la prevención, diagnóstico, estadificación, reconstrucción y rehabilitación en el tratamiento global del cáncer. Sin embargo, es difícil que cirujanos y personal de enfermería tengan en cuenta todos los aspectos de la gestión de la medicación, como el impacto de la cirugía en la función física del paciente y la complejidad del tratamiento antitumoral con sus comorbilidades. Los servicios de atención farmacéutica que anteriormente prestaban los farmacéuticos en oncología se centraban más en aspectos de la medicina interna, y no ampliamente en el ámbito quirúrgico. En la actualidad, el modo de trabajo farmacéutico en la cirugía oncológica aún no está definido en China, y existe una necesidad de mejorar la gestión de la medicación de todo el proceso asistencial. En 2015, la Asociación Farmacéutica de GuangDong propuso la creación del rol de farmacéutico quirúrgico en China y posteriormente creó su puesto de trabajo. En 2021, la Asociación Farmacéutica de GuangDong Estableció una nueva disciplina denominada “farmacia quirúrgica”, que es el área de conocimiento de los farmacéuticos quirúrgicos, y también intentó diferenciar la farmacia quirúrgica en distintas subáreas, como la farmacia quirúrgica oncológica. Este artículo presenta el modo de trabajo de los farmacéuticos quirúrgicos en China, que proporciona servicios de atención farmacéutica en el periodo perioperatorio de los pacientes incorporando los distintos aspectos del tratamiento antitumoral, control de infecciones, anestesia, anticoagulación, control de la presión arterial y la glucosa en sangre, nutrición y tratamiento del dolor, con el objetivo de mejorar la calidad de vida de los pacientes.

An imbalance of human mesenchymal stem cells (hMSCs) adipogenic and osteogenic differentiation is crucial in the pathogenesis of osteoporosis, and elucidation of the underlying mechanism is urgently needed. APPL1, an adaptor protein of the adiponectin receptor, was recently shown to be closely related to bone mass. However, the role of APPL1 in the imbalance of hMSC differentiation in osteoporosis is unclear. Therefore, we aimed to explore the mechanisms by which APPL1 alters hMSCs adipogenic differentiation in osteoporosis. Here, we found that APPL1 expression was downregulated in elderly patients with osteoporosis and in mouse osteoporosis model. APPL1 negatively regulated hMSC adipogenic differentiation in vivo and in vitro. Mechanistically, by enhancing ubiquitination-mediated Myoferlin degradation, downregulated APPL1 expression increased the risk of lysosome dysfunction during hMSCs adipogenic differentiation. Lysosomal dysfunction inhibited autophagy flux by suppressing autophagosome degradation and promoted hMSC differentiation towards the adipocyte lineage. Our findings suggest that APPL1/Myoferlin downregulation promoted hMSCs adipogenic differentiation by inhibiting autophagy flux, further impairing the balance of hMSCs adipogenic and osteogenic differentiation in osteoporosis; the APPL1/ Myoferlin axis may be a promising diagnostic and therapeutic target for osteoporosis.

Maternal sleep patterns during pregnancy are drawing increased attention to examine its role in the regulation of maternal glycemia and physical growth of offspring within 24 months. Among 3329 eligible mother–child pairs included in the Shanghai Maternal–Child Pairs Cohort, sleep patterns of pregnant women were assessed by Pittsburgh Sleep Quality Index and objective measurement in early and late pregnancy. Offspring physical growth within 24 months was primarily indicated by the body mass index Z-score (BAZ), catch-up growth, and overweight/obesity. In total, 3329 and 382 pregnant women were included with subjectively assessed and objectively measured sleep pattern, respectively. The increased risk of GDM was associated with maternal night-time sleep duration ≥8.5 h in early pregnancy, or sleep quality change from poor to good during pregnancy (OR = 1.48; 95% CI, 1.06 to 2.07). In the GDM group, the effect of sleep duration in early pregnancy on overweight/obesity in offspring within 24 months showed a U-shaped curve, with a 1.73-fold and 1.43-fold increased risk of overweight/obesity of offspring in pregnant women with

Associations of air pollution with anxiety and depression were found in previous studies. However, whether air pollution exposure during pregnancy contributes to prenatal anxiety and depression or not is under-investigated. In this study, we aimed to analyze associations between fine particulate matter (PMThis study was based on the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). We used a gap-filling random forest model to estimate PMTotally 3731 pregnant women were included, with the age of 28.85 ± 3.97 years old. Anxiety and depression rates were 10.8 % and 11.5 % respectively, according to the cut-off value of SAS and CES-D. Generalized linear regression results showed that the increase of PMThe increased risk of anxiety or depression was related to PM

Background Maternal stress and nutrition during pregnancy are two of the most commonly studied factors in the context of fetal development. However, few investigators have considered the combined effects of stress and diet in pregnant women and their offspring. Aims To determine the impact of maternal stress on offspring birth weight, and the potential mediating role of maternal dietary patterns. Methods A total of 3542 pregnant women and their singleton live births were recruited from Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). Maternal stress was assessed using the Life Event Scale for Pregnant Women (LESPW) in early and late pregnancy. Food frequency questionnaire (FFQ) was performed to evaluate maternal diet in late pregnancy. Multiple linear regression was conducted to estimate the associations between maternal stress and child birth weight. Logistic regression was performed to calculate the association between maternal stress and small for gestational age (SGA)/large for gestational age (LGA). The bootstrap method was used to investigate the mediating effects of maternal dietary patterns. Results Maternal subjective events stress (β = 0.367) and total stress (β = 0.079) in early pregnancy, and positive objective life events stress (β = 0.275) in late pregnancy, were positively associated with birth weight. Maternal dietary pattern of “high-fat and sugar” mediated the associations between subjective events stress and total stress during early pregnancy and birth weight. An increased risk for LGA was observed among women exposed to relatively higher stress during early pregnancy (OR, 1.416; 95% CI, 1.035-1.937). No statistically significant associations were found between maternal stress during late pregnancy and child birth weight or SGA/LGA. Conclusions Maternal life events stress during early pregnancy significantly increases neonatal birth weight and risk for LGA, which may mediate by a “high-fat and sugar” dietary pattern. Limitations The lack of biological markers limits the explanation of the mechanism. The assessment of diet used food intake frequency to evaluate dietary characteristics, which may miss information of energy intake.

Poly- and perfluoroalkyl substances (PFASs) and organophosphorus flame retardants (OPFRs) are two types of emerging organic pollutants with potential human health hazards. Here, a rapid and sensitive method was developed for the determination of sixteen PFASs and seven OPFRs in human serum by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS).After optimizing the chromatographic and mass spectrometric conditions, respectively, 100 μL of serum sample was liquid-liquid extracted using 8 mL of methyl tert-butyl ether. The 23 targets were quantified within 8 min. All targets were quantified by the isotope-internal standard method in both negative- and positive-ion mode by UPLC/MS/MS.The method was validated in terms of sensitivity, linearity, precision, and accuracy. The limit of detection ranged between 0.004 and 0.650 ng/mL. Recoveries ranged from70.0% to 118.9% with a relative standard deviation lower than 20%. The developed method was successfully applied to analyze targeted analytes in human serum samples. A total of 13 of 23 analytes were detected in over 50% of samples.A sensitive and rapid method was developed to quantify sixteen PFASs and seven OPFRs in serum. Sensitivity, linearity, recovery, and precision were validated and found to be satisfactory. This method can be a valuable tool for evaluation of exposure to both PFASs and OPFRs with high separation efficiency and sensitivity.

Background Recent research suggested that oxytocin might be associated with prenatal anxiety or depression. Also, our previous study indicated that resilience could buffer the effect of stress on prenatal anxiety and depression, which is a kind of psychological adjustment ability to stress in life. The effects of oxytocin and resilience are supposed to be similar but no study was carried out to find the association between them. Current evidence on the effect of oxytocin on prenatal mental health were with small sample size and equivocal results, especially with a lack of studies in Chinese pregnant women. Aims To investigate the relationship between oxytocin and resilience, and its role in regulating prenatal anxiety and depression among Chinese women. Methods The study was based on a sub-sample of the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC) by stratified random sampling. A total of 632 participants completed blood collection for serum oxytocin measurement and questionnaires pertaining to early pregnancy stress and resilience in the second trimester, which were assessed by the Life Event Scale for Pregnancy Women (LESPW) and the revised Resilience Scale for Adults (RSA), respectively. Prenatal anxiety and depression were assessed by Self-Rating Anxiety Scale (SAS) and the Center for Epidemiological Survey, Depression Scale (CES-D), respectively, at the third trimester. Correlation analysis and stratified linear regression analyses were conducted to understand the role of oxytocin in regulating prenatal anxiety and depression. Results The concentration of serum oxytocin in the second trimester ranged from 98.14 pg⋅ml−1 to 197.28 pg⋅ml−1, and there was no significant difference between different gestational age (r = 0.024, P = 0.579). The association between stress and prenatal anxiety was stronger in high oxytocin group than that in low oxytocin group, with B value of 3.338 and 2.638, respectively, after adjusting for residence, educational level, family income and parity. The same effect was found in the association between stress and prenatal depression, with B value of 2.360 and 2.060, respectively. However, it was not significantly associated with early pregnancy stress (Z = 1.933, P = 0.630), prenatal anxiety (Z = 1.387, P = 0.165), prenatal depression (Z = −0.027, P = 0.978), nor resilience (F = 1.282, P = 0.280). Limitations The existence of recall bias and restricted residential areas of the participants may limit the extrapolation of the study. Also, unsynchronized sampling timing of the oxytocin and psychological resilience measures is another limitation. Conclusions Serum oxytocin levels in the second trimester had an effect of modification between early pregnancy stress and prenatal anxiety and depression. Pregnant women with high oxytocin in the second trimester should receive more attention and further study is needed on the mechanism of oxytocin for the mental health of pregnant women.

Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits.In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared.CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p 0.001), had less symptoms related with rhinitis/sinusitis and gastroesophageal reflux (p 0.05) than CA patients. Comorbidities including rhinitis and gastroesophageal reflux were similar, while the proportion of COPD and bronchiectasis was higher in CA patients. There were no differences in FeNO levels, sputum eosinophil and neutrophil counts, FEV1 (%pred) decreased from CVA to CPA to CA patients (p 0.001). Cough sensitivity was higher in CVA and CPA compared to CA (p 0.001), and was positively correlated with LCQ scores.CVA, CPA and CA can be distinguished by the presence of laryngeal symptoms, cough sensitivity and airflow obstruction. Asthma-associated chronic cough was not associated with airway inflammation or comorbidities in our cohort. Trial registration The Chinese Clinical Trial Registration Center, ChiCTR-POC-17011646, 13 June 2017.

Coxsackievirus A10 (CV-A10), the causative agent of hand, foot, and mouth disease (HFMD), caused a series of outbreaks in recent years and often leads to neurological impairment, but a clear understanding of the disease pathogenesis and host response remains elusive. Cellular microRNAs (miRNAs), a large family of non-coding RNA molecules, have been reported to be key regulators in viral pathogenesis and virus-host interactions. However, the role of host cellular miRNAs defensing against CV-A10 infection is still obscure. To address this issue, we systematically analyzed miRNA expression profiles in CV-A10-infected 16HBE cells by high-throughput sequencing methods in this study. It allowed us to successfully identify 312 and 278 miRNAs with differential expression at 12 h and 24 h post-CV-A10 infection, respectively. Among these, 4 miRNAs and their target genes were analyzed by RT-qPCR, which confirmed the sequencing data. Gene target prediction and enrichment analysis revealed that the predicted targets of these miRNAs were significantly enriched in numerous cellular processes, especially in regulation of basic physical process, host immune response and neurological impairment. And the integrated network was built to further indicate the regulatory roles of miRNAs in host-CV-A10 interactions. Consequently, our findings could provide a beneficial basis for further studies on the regulatory roles of miRNAs relevant to the host immune responses and neuropathogenesis caused by CV-A10 infection.

It is of great significance to develop a dietary intervention strategy to prevent inflammatory bowel disease (IBD). A millet-rich diet can ameliorate IBD, but the active ingredients and mechanisms remain to be studied. Our results showed that the oral administration of foxtail millet protein hydrolysates (FMPH) reduced the disease activity index (DAI) score and improved the colon symptoms of dextran sulfate sodium (DSS)-induced colitis mice. FMPH reduced the serum LPS level, increased intestinal ZO-1 and occludin expression, inhibited NF-κB phosphorylation, and reduced the levels of TNF-α and IL-6. Further, FMPH inhibited Th17 cell differentiation, and inhibited inflammasome activation and IL-1β expression through the NLRP3/ASC/caspase-1 pathway. The results on Caco-2 cells confirmed the role of FMPH on tight junction and inflammasomes activation. A total of 2620 peptides were identified in FMPH by UPLC-MS/MS, of which 22 peptides were predicted as potential biopeptides, and the key sequences were LPF, ANP, PY, YW, and IPP. This study supports the effect of a diet rich in millet on the improvement of IBD and provides a scientific basis for the use of millet protein as a functional food to improve intestinal inflammation.

Early pregnancy is crucial for fetal growth. Maternal thyroid hormone is critical for fetal growth and can be disturbed under exogenous exposure. However, it's uncertain whether exposure to PM

Associations between individual exposure to ozone (OWe aimed to explore the associations of gestational OA total of 7834 pregnant women were included. Individual ONearly 13.29 % of participants developed GDM. After controlling for covariates, we observed increased GDM risks per IQR increment of OIn summary, we found that gestational O

Interspecies competition affects the distribution, quantity, and community structure of insects, especially among closely-related (congeners) species. Some ecological factors differentially affect the fitness of co-existing species, thus conferring an advantage on one competitor, and then the structure of communities. The present work evaluated the effects of high temperature and natural enemies on the interspecific competition between the grain aphid Sitobion miscanthi (Takahashi) (Aphididae: Hemiptera) and bird cherry-oat aphid Rhopalosiphum padi (L.) (Hemiptera: Aphididae), two key pests of wheat in China. Results showed that the population growth of R. padi was faster at 30°C, and the intrinsic rate of natural increase (rm) value was 5 times that of S. miscanthi, indicating that R. padi was more high-temperature resistant and has advantages in interspecific competition at high temperature. Moreover, compared to S. miscanthi, the population of R. padi was less affected by their predator, larvae of the multicolored Asian lady beetle, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), and aphid parasitoids, Aphidius avenae (Haliday) or Aphidius gifuensis (Ashmead) (Hymenoptera: Aphidiidae), which made them gain an advantage in the interspecific competition. Our results enrich the knowledge of phytophagous insect interspecific completion and implicate the ecological mechanism of R. padi may become the dominant species in wheat fields in China.

Prebiotics are effective in modulating gut microbiota and may further benefit colitis remission. 2'-fucosyllactose (2'FL) and galactooligosaccharide (GOS) are the main prebiotics in human and animal milk, respectively. This study aimed to investigate the colitis-preventing effects of 2'FL and GOS, and explore the underlying mechanisms involving the gut microbiota. The chronic colitis was induced by 1.5 % dextran sulfate sodium (DSS) for 4 consecutive cycles and manifested as aggravation of colitis symptoms, gut barrier disruption, and colonic inflammation. We found that 2'FL was more effective than GOS against colitis at the same dosage (500 mg/kg bw). 2'FL and GOS have a differential response on gut microbiota, reflecting the inhibition of Romboutsia and the enrichment of Akkermansia, Bifidobacterium, Faecalibaculum, and unclassified_f_Lachnosipiaceae. In addition, the differential response on microbial metabolome was reflected in the elevation of secondary bile acids, which activated Takeda G protein-coupled receptor 5 (TGR5) and further suppressed the nuclear factor-κB (NF-κB) pathway. Furthermore, fecal bacterial transplantation confirmed the critical role of gut microbiota in the prevention of colitis by 2'FL and GOS. Overall, microbiota and microbial metabolites are essential parts of 2'FL and GOS against colitis, and their differential responses may account for different effects in alleviating colitis.

Prenatal fine particulate matter (PMWe included 267 mother-child pairs in this analysis. Prenatal PMThe PMPrenatal exposure to PM

Soil pollution is one of the major threats to the environment and jeopardizes the provision of key soil ecosystem services. Vertical barriers, including slurry trench walls and walls constructed with soil mix technology, have been employed for decades to control groundwater flow and subsurface contaminant transport. This paper comprehensively reviewed and assessed the typical materials and mechanical and permeability properties of soil–bentonite, cement–bentonite and soil mix barriers, with the values of mix design and engineering properties summarized and compared. In addition, the damage and durability of barrier materials under mechanical, chemical, and environmental stresses were discussed. A number of landmark remediation projects were documented to demonstrate the effectiveness of the use of barrier systems. Recent research about crack-resistant and self-healing barrier materials incorporating polymers and minerals at Cambridge University and performance monitoring techniques were analyzed. Future work should focus on two main areas: the use of geophysical methods for non-destructive monitoring and the optimization of resilient barrier materials.

Background UV filters are emerging contaminants with endocrine disrupting effects, but little is known about their health effects, especially for children. Objective To assess the association between multiple organic UV filters exposure and adiposity measures and by gender in peripubertal children. Methods This prospective follow-up study included 327 children aged 7–15 years old. Urinary organic UV filters including benzophenone derivatives (BP-2, BP-3), octyl dimethyl para-aminobenzoic acid (OD-PABA), ethylhexyl methoxycinnamate (EHMC) and its metabolite (4-MCA and 4′-MAP) were quantified. Six adiposity biometrics including height, weight, waist and hip circumferences, and triceps and subscapular skinfold thickness were measured with 1.5-year duration. The Bayesian kernel machine regression method was used to estimate the associations of UV filters mixture with adiposity measurements, and longitudinal analyses were then considered to further evaluate the associations between individual UV filters and trajectories of growth development using linear mixed models or generalized linear mixed models. Results Exposure to mixture of UV filters was negatively associated with most adiposity measurements, with a reduction of 1.399 kg/m2 (95% CI: −2.246 to −0.551 kg/m2) in BMI, 0.674 (95% CI: −1.045 to −0.304) in BMI z-score, 0.033 BF% (95% CI: −0.053 to −0.013), and 2.301 mm (95% CI: −3.823 to −0.78) in subscapular skinfold thickness at baseline, comparing the 75th percentile to the 25th level of UV filters mixture exposure. Consistent associations were found at follow-up. Both baseline and follow-up results suggested that EHMC was identified as the most important contributor to lower adiposity measurements, which was also confirmed by linear mixed models in longitudinal analyses. No significant effects were found in girls. Conclusion This study found that childhood organic UV filters exposure was negatively associated with adiposity measures in peripubertal boys, but not girls.

Ethylhexyl methoxycinnamate (EHMC) is one of the most frequently used UV filters in sunscreens and other cosmetic products. Its ubiquitous presence in various environmental matrices and its endocrine disrupting properties have been widely reported. However, we know little about the effect of EHMC exposure on humans, mainly due to its fast metabolism. In this study, urine and plasma of EHMC-dosed rats were analysed to identify its major metabolites. Five metabolites were found, with four firstly reported. Two metabolites were putatively identified as 4-methoxycinnamic acid (4-MCA) and 4'-methoxyacetophenone (4'-MAP). Quantitative results revealed that their excretion concentrations were much higher than the parent compound. Because of these high concentrations, for the human biomonitoring study, EHMC and these two metabolites were detected simultaneously in urine samples from Chinese children and adolescents. The results indicated wide exposure to EHMC, 4-MCA and 4'-MAP. The correlation between urinary concentration of EHMC and 4-MCA as well as 4-MCA and 4'-MAP provided important clues as to the sources and metabolic pathways among these three compounds. Several demographic factors were also assessed with the exposure level. As the first human exposure study of EHMC in a Chinese population, this report would help to establish an exposure database facilitating health risk assessment of EHMC.

Increasing evidence supports that maternal exposure to vanadium (V) is associated with adverse birth outcomes including preterm birth and low birth weight. However, the effect of V exposure on intrauterine fetal growth and the underlying biological mechanism are still unclear. The present study includes 227 mother-infant pairs from the Shanghai Maternal-Child Pairs Cohort to assess the gender-specific effect of intrauterine V exposure on fetal growth and related cytokines. Maternal blood samples were collected to measure V concentration and biomarkers of growth. We used multiple linear regression to evaluate the gender-specific effect of prenatal V exposure on birth parameter and growth-related cytokines. Mixed-effect models were applied to assess the non-linear association between gestational V exposure and intrauterine fetal growth. Covariates adjusted in the regression models as potential confounders including maternal age, pre-pregnancy body mass index, gestational weeks, parity, socio-demographic status, etc. Results showed that prenatal V exposure was negatively associated with birth weight (β = −64.73) in female newborns and body length (β = −0.10) in male. During the fetal period, maternal V exposure was associated with decreased biparietal diameter (β = −0.91), head circumference (β = −2.96), femur length (β = −0.72) and humerus length (β = −0.64) in male. Trimester-specific analyses showed that serum V concentration in the second trimester was associated with significant reductions in intrauterine growth parameters. Besides, prenatal V exposure could down-regulate the expression of growth hormone (GH) in both maternal blood (β = −0.23) and umbilical cord blood (β = −1.66) in male fetuses, and the expression of brain derived neurotrophic factor (BDNF) in cord blood in females (β = −0.52). Our results suggest that prenatal V exposure has a gender-specific effect on fetal growth and the second trimester may be a sensitive window. The disruption of grow-related cytokines may potentially be the biological mechanism of these effects.

Background Prenatal anxiety/depression has been a major public health problem globally with higher prevalence in developing countries, which leads to negative health outcomes for both mothers and children. Maternal stress varies over the course of pregnancy and the stress occurring in early pregnancy is the most critical. However, few studies have focused on the impact of resilience to stress on mental health of pregnant women. Aims To explore the effect of resilience to stress on prenatal anxiety/depression in pregnant women. Methods 2813 participants were recruited from Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC) in this study. The Life Event Scale for Pregnancy Women (LESPW) was used to assess stress at 12–16 weeks of pregnancy and at 32–36 weeks of pregnancy, respectively. Resilience was assessed by the revised Resilience Scale for Adults (RSA) at 12–16 weeks of pregnancy. The prenatal anxiety and depression were assessed at 32–26 weeks of pregnancy by Self-Rating Anxiety Scale (SAS) and the Center for Epidemiological Survey, Depression Scale (CES-D), respectively. Hierarchical linear regression analyses were conducted to explore the direct effect of stress and resilience on prenatal anxiety and depression. The indirect effects of mediation were analyzed by structural equation models, and the indirect effect of modification was examined by stratification analysis. Results There were 11.1% and 10.3% of pregnant women in Shanghai MCPC indicating anxiety and depressive mood, respectively. The stress caused by both subjective and objective events at 32–36 weeks of pregnancy is less than that at 12–16weeks of pregnancy. We found that resilience was a protective factor for maternal mental health and meanwhile it was both an effect modifier and a mediator to the association between stress and prenatal anxiety/depression, with the mediating effect ratio of 15.1% and 23.8%, respectively. Limitations The existence of recall bias, missing data, and restricted residential areas of the participants may limit the generalizability of the study. The measurements of resilience, prenatal anxiety, and depression were not designed specifically for pregnant women, so that they might have missed some important indications of mental issues related to pregnant women only. Conclusions Resilience could be a direct and indirect protective factor for prenatal anxiety and depression caused by pregnancy stress.

Background: The association between antibiotic use during pregnancy and neonatal birth outcomes has received considerable attention. Most of the previous assessment of antibiotic exposure during pregnancy relied on questionnaires and clinical prescriptions, and very few studies examined pregnancy exposure to antibiotics using human biomonitoring data. Objective: To explore the association between the cumulative exposure of antibiotics during the whole pregnancy and neonatal birth measurements using biomonitoring data of antibiotics in meconium. Methods: Three hundred and sixty nine pregnant women within the Maternal Psychological and Environmental Assessments of Kids Cohort Study were randomly selected into this study. Eighteen common antibiotics of six categories (six β‑lactams, three tetracyclines, four sulfonamides, one phenicols, one lincosamides and three fluoroquinolones) were selected as the target antibiotics in meconium. The measurement was conducted by ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry platform. Neonatal birth measurements were obtained from the medical records. Multiple linear regression models were used to examine the associations of antibiotic exposure with neonatal birth outcome (birth weight, birth length) and placental growth indicators (placental surface area, placental weight). Logistic regressions were used to evaluate associations with small for gestational age (SGA) and large for gestational age (LGA). Results: Twelve of the eighteen antibiotics were found in 62.1% of the meconium, with detection rates ranging from 0.3% to 43.9%. The three antibiotics with the highest detection rates were chlortetracycline (43.9%), penicillin (16.5%) and chloramphenicol (10.8%), respectively. The highest antibiotic concentration among detected antibiotics was penicillin (24,243.15 μg/kg). The concentration of penicillin was positively associated with the birth weight (β: 0.025; 95% CIs: 0.003–0.047). A significant positive association was also observed between the concentration of chlortetracycline and the placental surface area (β: 2.559; 95% CIs: 0.296–4.822). These associations were sex related and mainly observed in female newborns. Exposure to penicillin was also found to be associated with increased risk of LGA, which was consistent with changes in birth weight. Conclusions: Pregnancy exposure to certain antibiotics was associated with altered fetal growth and development, which may affect the normal growth trajectory of infants and children in later life. Keywords: Cumulative exposure of antibiotics, Meconium, Biomonitoring data, Birth outcomes, Placental growth indicators, LGA

Maternal emotional symptoms during pregnancy increase the risk of neurodevelopmental problems in offspring, and microbiota have been shown to be a potential mechanism underlying the link. However, the associations among maternal prenatal emotional symptoms, the meconium microbiota, and offspring neurodevelopment have yet to be fully elucidated. The aim of this prospective cohort study was to assess the relationship between maternal prenatal emotional symptoms and neurodevelopment of the child at 24 months of age, and to investigate the potential role of the neonatal meconium microbiota in the relationship.A total of 410 mother-child pairs (152 women in the Symptoms group vs. 258 women in the No-symptoms group) were recruited from the ongoing Shanghai Maternal-Child Pairs Cohort. This study included a subgroup of women who were assessed for maternal anxiety and depressive symptoms at 32-36 weeks of gestation. Neonatal meconium samples were collected after birth for 16 S sequencing. Children's neurodevelopment was measured using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and Strengths and Difficulties Questionnaire (SDQ) at 24 months postnatally (n = 287).Compared with the No-symptoms group, children in the Symptoms group had a higher degree of hyperactivity and total difficulties at 24 months of age. Increases in alpha diversity, distinct overall composition, enriched relative abundance of Proteobacteria, and different predicted microbial functions were observed in the meconium of neonates exposed to maternal prenatal emotional symptoms. The neonatal gut microbiota alpha diversity and relative abundance of genera from the Proteobacteria phylum and Lactobacillus were negatively correlated with children's degree of prosocial behavior, tendency toward hyperactivity, and poor fine motor development. In addition, mediating effects of neonatal meconium microbial richness and the relative abundance of Lactobacillus were observed between maternal emotional symptoms and children's prosocial behavior.Maternal prenatal emotional symptoms are associated with alterations in the offspring meconium microbiota and children's neurodevelopment at 24 months of age, and the microbial richness indices and Lactobacillus may play a mediating role. Future research is needed to identify and understand the biological pathways and metabolisms linking the relationships among maternal emotional symptoms, meconium microbiota, and neurodevelopment of children.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen for human infection. Hospital-acquired (HA) and community-acquired (CA) MRSA infections are serious clinical problems worldwide. In this study, we selected typical HA-MRSA strain and CA-MRSA isolates from our previous research and compared their phenotypic and pathogenic abilities both in vitro and in vivo. Results ST59-t437-SCCmecIVa (YNSA7) and ST59-t437-SCCmecVb (YNSA53) belonged to two prevalent subclones of CA-MRSA, while ST239-t030-SCCmecIII (YNSA163) was an HA-MRSA epidemic clone in Southwest China. ST59-t437 strains demonstrated faster growth ability, higher survival rate resistance to human blood, and more toxin secretion levels and cytotoxicity than ST239-t030. The virulence and regulatory genes of hld, psm-α, RNAIII, agrA, and crtN were highly expressed on CA-MRSA isolates, especially the ST59-t437-SCCmecIVa subclone. However, the ST239-t030 strain had the strongest adhesion and biofilm ability among these MRSA bacteria. Animal experiments revealed the most serious lethal effect on BALB/c mice caused by the YNSA7 strain infection. The survival rates of BALB/c mice infected with the three MRSA strains were 16.7, 50.0 and 100.0% for YNSA7, YNSA53 and YNSA163, respectively. Histopathological analyses of infected animals indicated that the lungs were the most seriously damaged organs, especially for ST59-t437 MRSA. Severe inflammatory reactions, tissue destruction, and massive exudation of inflammatory mediators and cells could be identified in ST59-t437 strain-infected animals. Conclusions In general, ST59-t437 strains showed higher pathogenic ability than the ST239-t030 isolate, while ST239-t030 MRSA revealed the features prevalent in hospital settings, specifically for adhesion and biofilm ability.

The contamination of soil by lead (Pb) is a serious and widespread problem in China, especially in mining areas. This paper summarized the available data regarding Pb-contaminated soils around various metal mines in China. Based on these data, the Pb concentration in the soil and its temporal and spatial changes were analyzed. Potential ecological hazards and adult lead models were also used to estimate ecological and health risks. The results indicated that the concentration of Pb was closely related with the type of mine. Compared with other types of mine, soil around lead-zinc (Pb-Zn) and tin (Sn) mines with high Pb contents in the metallic ores and high pollutant emission coefficient were more strongly polluted by Pb. The characteristic spatial and temporal variations of Pb pollution status in China were clarified, and the results showed that the concentration was high in the southern, southwestern, and central regions of China where many mining areas were located, and the mean value passed a turning point in 2012. Ecological risk assessments indicated that some areas around mines were at considerable to high risk, and the risk was relatively severe in Pb-Zn mining areas. According to the adult lead model, Pb-Zn mines had a greater impact on blood Pb concentration than the other types of mine.

Groundwater of alluvial fan plains is the foremost water source, especially in arid/semiarid regions. Its contaminants are big issues for water supply and public health concern. To reveal the groundwater chemistry, contaminants sources and health threats in alluvial aquifers, 81 groundwaters were collected from a typical alluvial fan plain of northern China for nitrogen, fluoride and major ions analysis. Statistical analysis and hydrochemical diagrams as well as human health risk assessment were performed. Nitrate is widely distributed and 53% of groundwaters exceed the permissible limit with the maximum concentration up to 326 mg/L. The distributions of nitrite, ammonia and fluoride contaminants are sporadic in spatial, and the concentrations of fluoride in groundwaters are slightly beyond the permissible limit of 1 mg/L. The hydrochemical facies shift from HCO3-Ca or Mixed HCO3-Na·Ca type to Mixed Cl-Mg·Ca and Cl Ca type with the increase of nitrate content. Two factors (Factor-1 and Factor-2) are extracted by factor analysis and account 63% of the total variances. The positive loading of F− and negative loading of NO3− on Factor-2 reveal geogenic and anthropogenic origins, respectively. The significant positive loadings of TDS, TH, SO42−, Cl−, Ca2+, Mg2+ on Factor-1 reveal the governing mechanisms on groundwater chemistry by intermixed sources of geogenic origins and anthropogenic inputs. Hydrogeochemical evolution in the study area is driven by both water-rock interaction and anthropogenic forces. Anthropogenic inputs/influences are the dominated forces increasing groundwater nitrate content and salinity in the piedmont zone and the residential and industrial zone of the southeastern lower parts, and would pose potential non-carcinogenic risks to various populations via oral intake pathway. Rational measures should be taken to protect groundwater quality out of the threats of anthropogenic pollution. The geogenic fluoride in groundwater would threat the health of children through oral pathway and should be also concerned. Capsule The driving forces of groundwater chemistry in alluvial fan plains were revealed using integrated approach of factor analysis and geostatistical modelling.

Coxsackievirus A16 (CV-A16) has caused worldwide epidemics of hand, foot, and mouth disease (HFMD), particularly among infants and preschool children. Circular RNAs (circRNAs) are a recently identified class of noncoding RNA molecules that participate in the occurrence and development of numerous infectious diseases. To date, the function of circRNAs has been a heavily researched topic, and their role in CV-A16 infection has not been fully elucidated. In this study, the viral effects of CV-A16 on the cellular circRNA transcriptome were investigated using next-generation sequencing technology. In this study, a total of 8726, 8611 and 6826 circRNAs were identified in the control, CV-A16-12 h and CV-A16-24 h groups, respectively. Further analysis showed that 1769 and 1192 circRNAs were differentially expressed in the CV-A16-12 h and CV-A16-24 h groups, respectively. Moreover, the common differentially expressed circRNAs were screened out and used for functional annotation analysis, which demonstrated that the parent genes of differentially expressed circRNAs might be associated with the viral infection process, especially the “Immune system process” in GO analysis and the “Inflammation mediated by chemokine and cytokine signaling pathway” in KEGG analysis. Additionally, 6 dysregulated circRNAs were selected for validation and were verified to be consistent with the sequencing results. Additionally, we further constructed a circRNA-miRNA-mRNA regulatory network that suggested the putative function of circRNAs as cellular miRNA decoys to indirectly regulate gene expression during CV-A16 infection, especially the hsa_circ_0004447/hsa-miR-942-5p/MMP2, hsa_circ_0078617/hsa-miR-6780b-5p/MMP2 and hsa_circ_0078617/hsa-miR-5196-5p/MMP2 regulatory axes. Considering all of these results, to the best of our knowledge, this study is the first to present a comprehensive overview of circRNAs induced by CV-A16, and this research demonstrated that a network of enriched circRNAs and circRNA-associated competitive endogenous RNAs (ceRNAs) is involved in the regulation of CV-A16 infection, thereby helping to elucidate the mechanisms underlying CV-A16-host interactions.

Assessments for groundwater quality and potential health risk are significant for better utilization and exploitation. In the present study, seventy groundwater samples were collected from domestic tube wells and public water-supply wells in the Nanchong area, southwestern China. The integration of statistical analysis, ion correlation, geomodelling analysis, entropy water quality index and health risks assessment were compiled in this study. Statistical analysis indicated the cations followed the concentration order as Ca2+ > Na+ > Mg2+ > K+, while anions' concentrations were HCO3- > SO42- > Cl- > NO3- > F- based on Box and Whisker plot. Piper triangle diagram proposed the hydrochemical type was characterized as Ca-HCO3. Correlations of ions and geomodelling revealed the concentrations of major ions were mainly determined by calcite dissolution and ion exchange process and NO3- concentrations were controlled by agriculture activities. Entropy water quality index computation demonstrated that 96% of groundwater samples possessed the EWQI values of 29-95, and thus were suitable for drinking purpose. The HITotal values for 66% groundwater samples exceeded the acceptable limit for non-carcinogenic risk (HI =1) for infants, followed by 41% for children, 37% for adult males, and 30% for adult females. The non-carcinogenic human health risk of different population groups followed the order of infants > children > adult males > adult females. In future, targeted measures for human health risks of NO3- will focus on the improvements for agricultural activities, including reducing the use of nitrogenous fertilizer, changing irrigation pattern, etc. Our study provides the vital knowledge for groundwater management in the Nanchong and development of the Cheng -Yu Economic Circle.

Although previous studies have reported the adverse effect of air pollution exposure during pregnancy on neurodevelopment in children, epidemiological evidence is limited, and the results are inconsistent. This study aimed to explore the association between prenatal ambient fine particulate matter (PM2.5) exposure and early childhood neurodevelopment in a large birth cohort study of 4009 maternal-child pairs. Prenatal daily PM2.5 exposure concentrations at 1 km spatial revolution were estimated using high-performance machine-learning models. Neurodevelopmental outcomes of children at ages 2, 6, 12, and 24 months were assessed using the Ages and Stages Questionnaire (ASQ). Distributed lag nonlinear models were used to identify critical windows of prenatal PM2.5 exposure. General linear mixed models with binomially distributed errors were used to estimate the effect of prenatal PM2.5 exposure on suspected developmental delay (SDD) in five developmental domains based on the longitudinal design. Prenatal PM2.5 exposure was significantly associated with decreased scores for all neurodevelopmental domains of children at ages 2, 6, and 24 months. Each 10-μg/m3 increase in PM2.5 exposure was significantly associated with increased risk of SDD for all subjects (RR: 1.52 95% CI: 1.19, 2.03), specifically, in problem-solving domain for girls (RR: 2.23, 95% CI: 1.22, 4.35). Prenatal PM2.5 exposure in weeks 18 to 34 was significantly associated with both ASQ scores and SDDs. Our study proposed that prenatal PM2.5 exposure affected early childhood neurodevelopment evaluated with the ASQ scale. PM2.5 exposure might increase the risk of SDD for boys and girls, specifically in the problem-solving domain for girls.

Although abundant evidence has suggested that early-life antibiotic exposure was associated with adipogenesis later in life, limited data were available on the effect of intrauterine antibiotic exposure on infant growth and growth speed. Additionally, few studies have investigated the role of the neonatal gut microbiota in the above association. In this study, we examined the association between intrauterine cumulative antibiotic exposure and infant growth and explored the potential role of the neonatal gut microbiota in the association. 295 mother-child pairs from the Shanghai Maternal-Child Pairs Cohort (MCPC) study were included, and meconium samples and infant growth measurements were assessed. Z-scores of length-for-age, weight-for-age (weight-for-age), and body mass index (BMI)-for-age (BMI-for-age) were calculated. Eighteen common antibiotics were measured in meconium. Multivariable linear regression models were applied to test the interrelationships between antibiotic exposure, diversity indicators, and the relative abundance of selected bacterial taxa from phylum to genus levels from least absolute shrinkage and selection operator (LASSO) and infant growth indicators. The detection rates of the 18 antibiotics, except for chlortetracycline, penicillin, and chloramphenicol, were below 10 %. Penicillin was found to be positively associated with infant growth at birth and with growth speed from 2 to 6 months. The Pielou and Simpson indexes were negatively associated with meconium penicillin. Nominally significant associations between penicillin and the relative abundances of several bacterial taxa from the phyla Proteobacteria, Bacteroidetes, and Firmicutes were found. The Pielou and Simpson indexes were also found to be negatively associated with infant growth. Among taxa selected from LASSO regression, the relative abundances of the phyla Actinobacteria and Firmicutes and order Bifidobacteriales were found to be significantly associated with weight and BMI growth speeds from 2 to 6 months. In conclusion, intrauterine antibiotic exposure can affect infant growth. The neonatal gut microbiota might play a role in the abovementioned association.

Groundwater resource is significantly important for sustainable development of the world, especially for arid endorheic watersheds. A total of 28 groundwaters were collected for hydrogeochemical analysis from the arid Chaka watershed on Tibetan plateau to illustrate the hydrochemical evolution, formation mechanisms and feasibility of groundwater in small arid endorheic watersheds where groundwater is much scarcer. The results showed groundwater has a slightly alkaline nature, and varies from soft fresh HCO3-Ca type to hard brackish/saline Cl-Na type along the groundwater flow path in the watershed with the total hardness in the range of 270–2,127 mg/L and the total dissolved solids in the range of 282–41,770 mg/L. Nitrogen and fluoride in phreatic water are found sporadically exceeding the permissible limits with the maximum value of 118 mg/L for nitrate, 1.2 mg/L for ammonia and 1.2 mg/L for fluoride. Hydrochemistry of phreatic and confined groundwater is naturally governed by water-rock interactions including minerals (halite, gypsum and anhydrite) dissolution, silicate weathering and cation-exchange reaction. The salinity of phreatic water is also dominantly controlled by the strong evaporation. Human activity is one of the important mechanisms influencing the hydrochemical signature of groundwater regardless of the depth. Groundwater has a great hydrogeochemical discrepancy spatially across the watershed and varies from excellent to extremely poor quality in phreatic aquifers. A better water quality that under the good to medium categories was observed in the confined aquifers with 80% of samples having the EWQI value less than 100 and others in the range of 100–150. Phreatic groundwater away from the river and in the downstream area has a relatively poor quality for domestic and agricultural purposes, and should be avoided to direct utilization. This research can improve the understanding of groundwater hydrogeochemical feature, genesis, and its constraints on the availability and feasibility of groundwater resources in small arid watersheds worldwide.

This study was designed to examine the impact of prenatal fine particulate matter (PM2.5) exposure on fetal growth and the underlying placental epigenetic mechanism in a cohort of Chinese women. Within the prospective Shanghai Mother-Child Pairs cohort (Shanghai MCPC), 329 women carrying singleton pregnancy with a due date in 2018 were recruited between 2017 and 2018. Maternal PM2.5 exposure levels were estimated using gestational exposure prediction model combining satellite-driven ambient concentrations and personal air sampling. Fetal growth characteristics were evaluated by prenatal ultrasound examinations and anthropometric measurements at birth. In a discovery phase, whole-genome DNA methylation analysis was performed using the Infinium 850 K array. In a validation phase, placental DNA methylation was measured using bisulfite pyrosequencing for five candidate genes that showed the most significant alterations and function relevance in our methylation array screen, including BID (BH3 interacting domain death agonist), FOXN3 (Forkhead box N3), FOXP1 (Forkhead box P1), IGF2 (Insulin-like growth factor 2) and HSD11B2 (Hydroxysteroid 11-beta dehydrogenase 2). Multivariate linear regression models were applied to examine the associations among PM2.5 exposure, fetal growth characteristics and DNA methylation on placental candidate genes. Sobel tests were used to evaluate the mediating role of DNA methylation in multivariable models. After excluding women who withdrew or failed to provide placenta, a total of 287 pregnant women with an average age of 30 entered the final analysis. Increased PM2.5 exposure was significantly associated with reduced biparietal diameter (BPD) (β: −0.136 mm, 95% CI: −0.228 to −0.043), head circumference (HC) (β: −0.462 mm, 95% CI: −0.782 to −0.142), femur length (FL) (β: −0.113 mm, 95% CI: −0.185 to −0.041) and abdominal circumference (AC) (β: −0.371 mm, 95% CI: −0.672 to −0.071) in the second trimester and birth length (β: −0.013 cm, 95% CI: −0.025 to −0.001). Prenatal PM2.5 exposure could lead to aberrant changes in DNA methylation profile of placenta genome, which were mainly enriched in reproductive development, energy metabolism and immune response. DNA methylation of IGF2 and BID showed significant associations with PM2.5 exposures during all exposure windows. In addition, BID methylation was negatively correlated with HC (β: −1.396 mm, 95% CI: −2.582 to −0.209) and BPD (β: −0.330 mm, 95% CI: −0.635 to −0.026) in the second trimester. Further mediation analysis indicated that BID methylation mediated about 30% of the effects of PM2.5 exposure on HC. These findings collectively suggested that prenatal PM2.5 exposure may cause adverse effects on fetal growth by modifying placental DNA methylation.

Vilaprisan is a novel selective progesterone receptor modulator for the long‐term treatment of uterine fibroids and endometriosis. This study investigated the pharmacokinetics, safety, and tolerability of vilaprisan in healthy Chinese postmenopausal women. Twelve participants received multiple doses of vilaprisan once daily over 14 days as a 2‐mg tablet. Plasma vilaprisan concentrations were determined using liquid chromatography–tandem mass spectrometry. The main pharmacokinetic parameters of vilaprisan were assessed with noncompartmental analysis, including maximum observed concentration (Cmax), systemic exposure (area under the plasma concentration–time curve), time to reach Cmax and terminal half‐life. Safety assessments include the documentation of adverse events, measurement of clinical/anthropometric parameters and vital signs, electrocardiogram, and physical and gynecologic examination. The participants had a mean age of 53.3 (± 4.2) years and a body mass index of 23.8 ± 2.8 kg/m2. Median time to reach Cmax was 1.5 hours after both single and multiple vilaprisan administration. Mean Cmax values obtained after multiple dosing (23.3 μg/L [standard deviation (SD) = 6.73]) were 1.92‐fold (SD = 0.554) higher compared to single dosing (12.5 μg/L [SD = 3.04]). Mean area under the plasma concentration–time curve in the dosing interval increased with an accumulation factor of 2.98 (SD = 0.767) between single (91.3 μg · h/L [SD = 20.4]) and multiple dosing (276 μg · h/L [SD = 109]). The mean terminal half‐life of vilaprisan was 44.5 hours (SD = 10.3) after multiple dosing. Mild to moderate adverse events were observed similar to previous studies. Overall, daily oral administration of the therapeutic dose of 2 mg of vilaprisan over 14 days was safe and well tolerated by all participants.

Background: UV filters, widely used in personal care and industrial products, are being found in the environment and, in humans where with limited understanding on their potential health effects, especially during puberty. Objectives: To examine the association between UV filter exposure and pubertal development in a prospective follow-up study. Methods: This study included 521 elementary and high school students from a suburban area of Shanghai. The initial study was done in October to November 2011; the follow-up study in April to May 2013. Twelve urinary organic UV filters were quantified, and the pubertal development was assessed at each study period by trained physicians using Tanner staging. We used (ordered) logistic regression model and multilevel mixed-effect (ordered) logistic regression model to assess cross-sectional and longitudinal effects between urinary concentration of five major UV filters and pubertal development of stages, onset and pace. Results: Ethylhexyl methoxycinnamate (EHMC) and its metabolite 4′-methoxyacetophenone (4′-MAP), two benzophenone derivatives (BP-2, BP-3) and Ethylhexyl dimethyl PABA (OD-PABA) were the most extensively detected UV filters in urine with geometric means (95% CI) in 2010 and 2012 as 1.77 (1.599, 1.956) and 2.28 (1.985, 2.622) ng/mL for EHMC; 4.55 (4.219, 4.907) and 5.26 (4.783, 5.775) ng/mL for 4′-MAP; 4.38 (4.011, 4.774) and 5.74 (5.023, 6.562) ng/mL for BP-2; 0.83 (0.760, 0.903) and 1.09 (0.967, 1.220) ng/mL for BP-3; 5.37 (4.949, 5.820) and 5.80 (5.193, 6.486) pg/mL for OD-PABA. Significant trend P-values (P

To prospectively analyze the effects of gestational stress around 3 months of conception and stress in the second and third trimesters of pregnancy on the dietary preferences in late pregnancy of women in Shanghai City.From April 2016 to April 2018, pregnant women who registered in 2 delivery hospitals in Shanghai were recruited as participants of Shanghai Maternal-Child Pair Cohort with informed consent. Life Events Scale for Pregnant Women was used to evaluate the gestational stress around 3 months of conception and stress during 32-36 weeks of pregnancy, respectively. Food Frequency Questionnaire and factor analysis were used to evaluate the dietary tendency in late pregnancy. Binary Logistic regression model was used to analyze the relationship between gestational stress and dietary tendency.Among the 2634 pregnant women included in this study, factor analysis revealed six dietary preferences in the third trimester of pregnancy, which wereapos;balancedapos;,apos;meat and beansapos;,apos;richer in sugar or oilapos;,apos;pickled products and gibletsapos;,apos;nutritional supplementapos; andapos;caffeineapos;, respectively. After controlling for potential confounding factors of age, education, occupation, annual family income, body mass index before pregnancy, parity, anxiety and depression in the second and third trimesters of pregnancy, higher total and subjective gestational stress around conception would make pregnant women less likely to have a "balanced" diet in late pregnancy(OR=0. 76, 95%CI 0. 61-0. 95). The higher level of gestational stress in the second and third trimesters of pregnancy was associated with a greater preference for a "balanced" diet(OR=1. 66, 95%CI 1. 22-2. 25), but it also increased the preference for a "pickled products and giblets" diet(OR=1. 32, 95%CI 0. 98-1. 78)and inhibited a preference for a "meat and beans" diet(OR=0. 72, 95%CI 0. 53-0. 96).Lower level of gestational pressure during pregnancy is beneficial to the balance of diet in late pregnancy. Compared with that in the second and third trimesters of pregnancy, gestational stress around conception is more likely to negatively affect dietary preferences in late pregnancy.

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor family, attract wide attention as promising therapeutic targets for the treatment of multiple diseases, and their target selective ligands were also intensively developed for pharmacological agents such as the approved drugs fibrates and thiazolidinediones (TZDs). Despite their potent pharmacological activities, PPARs are reported to be involved in agent- and pollutant-induced multiple organ toxicity or protective effects against toxicity. A better understanding of the protective and the detrimental role of PPARs will help to preserve efficacy of the PPAR modulators but diminish adverse effects. The present review summarizes and critiques current findings related to PPAR-mediated types of toxicity and protective effects against toxicity for a systematic understanding of PPARs in toxicology and applied pharmacology.

In China, data relating to the historic prevalence of childhood lead poisoning suggest its pervasiveness. This review analysed published epidemiological data on blood lead levels (BLLs) of 735,271 Chinese children aged 0–6 between 1987 and 2017. Among these children, the geometric mean (GM) BLL was 95.1 μg/L (geometric SD = 1.62), and 24.1% suffered lead poisoning (BLL ≥ 100 μg/L). Importantly, there was a temporal decrease in the GM BLL value, from 182.9 μg/L in 1987–1991 to 42.4 μg/L in 2012–2017. However, a rebound was seen in the most recent two years (2016 and 2017). Moreover, the GM BLL among Chinese children has not fallen as low as U.S. children. This indicates that either (1) leaded petrol or lead based-paint exposure sources have not been adequately controlled in China, or (2) other pollution sources, such as industry, traffic, and e-waste, are impacting Chinese children. Drivers behind spatio-temporal variations were explored to provide scientific evidence regarding the prevention of childhood lead poisoning. We found that BLLs among children in the central and eastern areas of China have dropped lower than those in the western area, and that the GM BLL of children living in rural areas now exceeds children in urban areas. These reversals may be associated with the industrial decentralization policy of the late 1980s, when many heavily polluting industries and manufacturers moved away from cities on the east coast. It was discovered that the BLLs of children living in areas associated with mining have remained high (GM BLL = 155.0 μg/L for 2007–2017), and that the lead poisoning rate (LPR) has become exceptionally high in areas associated with e–waste. Finally, the review offers a data comparison with other countries, an overview of potentially influencing factors and sources, as well as some suggested prevention strategies to reduce childhood lead exposure. Keywords: Blood lead levels, Childhood lead exposure, Lead poisoning, Pb, E-waste

Humans are exposed to polybrominated diphenyl ethers (PBDEs) via ingestion of food, dust inhalation, and dermal absorption. Exposure to PBDEs via the placenta and breast milk is a special and important pathway in infants. This nested case-control study aimed to investigate the levels of PBDEs in maternal serum and colostrum, and to assess the association between the occurrence of fetal growth restriction (FGR) and prenatal exposure to PBDEs. We recruited 293 mother-newborn pairs, including 98 FGR cases and 195 healthy controls in Wenzhou, China. Maternal serum and colostrum samples were collected during pregnancy and after delivery, respectively, and the levels of PBDEs were measured by gas chromatography-tandem mass spectrometry. The total levels of PBDEs in maternal serum and colostrum were found to be in equilibrium, but congener profiles of PBDEs in these matrices were different. Increased BDE-207, BDE-209, ∑BDE196-209 and ∑PBDEs levels in maternal serum and BDE-99, ∑BDE17-154 and ∑PBDEs levels in colostrum were correlated with decreased birth weight Z score. Increased concentrations of higher brominated BDEs in maternal serum (odds ratio (OR) = 1.010, 95%CI = 1.003–1.018) and low-to moderately brominated BDEs in colostrum (OR = 1.004, 95%CI = 1.000–1.009) were associated with increased risk of FGR, which showed an exposure–response relationship. In addition, infants with FGR were more exposed to PBDEs in colostrum after birth than healthy infants. Longitudinal birth cohort studies are needed to determine the prolonged effect of PBDEs exposure on the growth of FGR infants in the future.

Human exposure to lead (Pb) is a growing global public health concern. Elevated blood lead is thought to cause the mental retardation of >0.6 million children globally each year, and has recently been attributed to ~18% of all-cause mortality in the US. Due to the severe health risk, the international community, led by the United Nations Environment Programme (UNEP) and the World Health Organization (WHO), is actively supporting the global phase-out of lead-based paint by 2020. However, there are many significant hurdles on the way to achieving this goal. In light of the importance of the lead-based paint issue, and the urgency of achieving the 2020 phase-out goal, this review provides critical insights from the existing scientific literature on lead-based paint, and offers a comprehensive perspective on the overall issue. The global production and international trade of lead-based paints across Asia, Africa, Latin America, and Europe are critically discussed – revealing that lead-based paints are still widely used in many low and middle-income developing countries, and that the production and trade of lead-based paint is still wide-spread globally. In India, as well as many south-east Asian, African, Latin American and European countries, lead concentrations in paints often exceed 10,000 mg/kg. This will certainly pose a serious global threat to public health from surfaces painted with these products for many decades to come. The sources and pathways of exposure are further described to shed light on the associated health risk and socioeconomic costs. Finally, the review offers an overview of the potential intervention and abatement strategies for lead-based paints. In particular, it was found that there is a general lack of consensus on the definition of lead based paint; and, strengthening regulatory oversight, public awareness, and industry acceptance are vital in combating the global issue of lead based paint. Keywords: Lead-based paint, Lead exposure, Blood lead level, Soil contamination

Objective: Metabolomics may unravel global metabolic changes in response to environmental exposures and identify important biological pathways involved in the pathophysiology of childhood obesity. Phthalate has been considered an obesogen and contributing to overweight and obesity in children. The purpose of this study is to evaluate changes in urine metabolites in response to the environmental phthalate exposure among overweight or obese children, and to investigate the metabolic mechanisms involved in the obesogenic effect of phthalate on children at puberty. Methods: Within the national Puberty Timing and Health Effects in Chinese Children (PTHEC) study, 69 overweight/obese children and 80 normal weight children were selected into the current study according to their puberty timing and WGOC (The Working Group for obesity in China) references. Urinary concentrations of six phthalate monoesters (MMP, MEP, MnBP, MEHP, MEOHP and MEHHP) were measured using API 2000 electrospray triple quadrupole mass spectrometer (ESIMS/MS). Metabolomic profiling of spot urine was performed using gas chromatography-mass spectrometry. Differentially expressed urinary metabolites associated with phthalate monoesters exposure were examined using orthogonal partial least square-discriminant analysis and multiple linear regression models. In addition, the candidate metabolites were regressed to obesity indices with multiple linear regression models and logistic regression models in all subjects. Results: Compared with normal weight children, higher levels of MnBP were detected in urinary samples of children with overweight and obesity. After adjusting for confounders including chronological age, gender, puberty onset, daily energy intake and physical activity and socio-economic level, positive association remained between urinary MnBP concentration and childhood overweight/obesity [OR = 1.586, 95% CI:1.043,2.412]. We observed elevated MnBP concentration was significantly correlated with increased levels of monostearin, 1-monopalmitin, stearic acid, itaconic acid, glycerol 3-phosphate, 5-methoxytryptamine, kyotorphin, 1-methylhydantoin, d-alanyl-d-alanine, pyrrole-2-carboxylic acid, 3,4-Dihydroxyphenylglycol, and butyraldehyde. Meanwhile, increased MnBP concentration was also significantly correlated with decreased levels of lactate, glucose 6-phosphate, d-fructose 6-phosphate, palmitic acid, 4-acetamidobutyric acid, l-glutamic acid, n-acetyl-l-phenylalanine, iminodiacetic acid, hydroxyproline, pipecolinic acid, l-ornithine, n-acetyl-l-glutamic acid, guanosine, cytosin, and (s)-mandelic acid in the normal weight subjects. The observations indicated that MnBP exposure was related to global urine metabolic abnormalities characterized by disrupting arginine and proline metabolism and increasing oxidative stress and fatty acid reesterification. Among the metabolic markers related to MnBP exposure, 1-methylhydantoin, pyrrole-2-carboxylic acid and monostearin were found to be positively correlated with obesity indices, while hydroxyproline, l-ornithine, and lactate were negatively associated with overweight/obesity in children. Conclusions: Our results suggested that the disrupted arginine and proline metabolism associated with phthalate exposure might contribute to the development of overweight and obesity in school-age children, providing insights into the pathophysiological changes and molecular mechanisms involved in childhood obesity. Keywords: Phthalate, Childhood overweight/obesity, Metabolic profiles, Arginine and proline metabolism

Outbreaks of avian influenza virus continue to pose threats to human health. Animal models such as the mouse, ferret, and macaque are used to understand the pathogenesis of avian influenza virus infection in humans. We previously reported that the tree shrew (Tupaia belangeri, family Tupaiidae), which is regarded as a “low-level primate”, has α2,3- and α2,6-linked sialic acid receptor distributions similar to those of humans and is potentially a useful mammalian model for studying mild human influenza (H1N1) virus infection. In this study, we used the tree shrew experimental model to investigate the pathogenesis of avian influenza A (H9N2) virus infection and the effect of the E627K mutation in the PB2 gene, an adaptation to mammalian hosts. Evidence of disease, virus titers in the upper and lower respiratory tract, histopathology and induction of proinflammatory cytokines are described. We also established ex vivo culture models of tree shrew respiratory tissues to study the tropism and replication of the H9N2 virus. Our results demonstrated that the tree shrew is a viable new in vivo experimental model for avian influenza research that provides results comparable to those observed in ferrets. The disease spectrum and pathogenesis in tree shrews correlate well with what is observed in humans.

Previous studies have linked prenatal polybrominated diphenyl ether (PBDE) exposure to adverse birth outcomes. Reductions in placental size might mediate those adverse effects. We examined whether umbilical cord blood PBDEs concentrations were associated with placental size at birth. A total of 121 mother-newborn pairs residing in Wenzhou were enrolled in this study. Concentrations of 19 PBDEs in umbilical cord blood were determined by gas chromatography tandem mass spectrometry (GC-MS). Placental length, breadth and surface area was measured by medical professionals after delivery. BDE-206, 207, 208, 209 and the total of 19 PBDE congeners concentrations were negatively associated with placental length, breadth and surface area. Our results suggest that prenatal PBDEs exposure may suppress placental growth, resulting in reduced placental size.

Intrauterine modifiable maternal metabolic factors are essential to the early growth of offspring. The study sought to evaluate the associations of pre-pregnancy BMI and third-trimester fasting plasma glucose (FPG) with offspring growth outcomes within 24 months among GDM-negative pregnant women. Four hundred eighty-three mother –offspring dyads were included from the Shanghai Maternal-Child Pairs Cohort. The pregnant women were categorized into four mutually exclusive groups according to pre-pregnancy BMI as normal or overweight/obesity and third-trimester FPG as controlled or not controlled. Offspring growth in early life was indicated by the BAZ (BMI Z-score), catch-up growth, and overweight/obesity. Among those with controlled third-trimester FPG, pre-pregnancy overweight/obesity significantly increased offspring birth weight, BAZ, and risks of overweight/obesity (RR 1.83, 95% CI 1.23 to 2.73) within 24 months. Those who had uncontrolled third-trimester FPG had a reduced risk of offspring overweight/obesity within 24 months by 47%. The combination of pre-pregnancy overweight/obesity and maternal uncontrolled third-trimester FPG increased 5.24-fold risk of offspring catch-up growth within 24 months (p &lt, 0.05). Maternal pre-pregnancy overweight/obesity and uncontrolled third-trimester glycemia among GDM-negative women both have adverse effects on offspring growth within 24 months. With the combination of increasing pre-pregnancy BMI and maternal third-trimester FPG, the possibility of offspring catch-up growth increases.

Enterovirus A71 (EV-A71) is an important emerging virus posing a threat to children under five years old. Circular RNAs (circRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in the onset and development of viral diseases. However, it has not been determined which specific circRNAs are involved in the pathological mechanisms of EV-A71 infection. In this study, RNA-sequencing (RNA-seq) was conducted to characterize differentially expressed circRNAs during the process of EV-A71 infection. Overall, 8726, 10405 and 4710 circRNAs were detected in the control, EV-A71-12 h and EV-A71-24 h groups, respectively, of which 1851 and 951 circRNAs were differentially expressed in the EV-A71-12 h and EV-A71-24 h groups versus the control group. The overlapping circRNAs in the EV-A71-infected groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which further demonstrated that the host genes of these circRNAs were principally implicated in activities associated with the progression of viral infection, such as immune system process, Wnt signaling pathway, etc. Additionally, qRT-PCR detection showed that six selected circRNAs were identical to the sequencing data. To excavate the key circRNAs in EV-A71 infection, we comprehensively evaluated and integrated the relationship of circRNA/miRNA/mRNA, and eventually screened 2 key circRNA regulatory axes, namely hsa_circ_0017115/hsa-miR-150-5p/EGR1 and hsa_circ_0005060/hsa-miR-4685-5p/MMP2. In summary, our findings not only provide the first comprehensive expression and functional profile of circRNAs in response to EV-A71 infection, but also offer a novel direction to elucidate the molecular mechanism underlying viral pathogenesis and the cellular immune response in host-EV-A71 interactions.

Triptolide (TP), a primary bioactive ingredient isolated from the traditional Chinese herbal medicine Tripterygium wilfordii Hook. F. (TWHF), has attracted great interest for its therapeutic biological activities in inflammation and autoimmune disease. However, its clinical use is limited by severe testicular toxicity, and the underlying mechanism has not been elucidated. Our preliminary evidence demonstrated that TP disrupted glucose metabolism and caused testicular toxicity. During spermatogenesis, Sertoli cells (SCs) provide lactate as an energy source to germ cells by glycolysis. The transcription factors GATA-binding protein 4 (GATA4) and specificity protein 1 (Sp1) can regulate glycolysis. Based on this evidence, we speculate that TP causes abnormal glycolysis in SCs by influencing the expression of the transcription factors GATA4 and Sp1. The mechanism of TP-induced testicular toxicity was investigated in vitro and in vivo. The data indicated that TP decreased glucose consumption, lactate production, and the mRNA levels of glycolysis-related transporters and enzymes. TP also downregulated the protein expression of the transcription factors GATA4 and Sp1, as well as the glycolytic enzyme phosphofructokinase platelet (PFKP). Phosphorylated GATA4 and nuclear GATA4 protein levels were reduced in a dose- and time-dependent manner after TP incubation. Similar effects were observed in shGata4-treated TM4 cells and BALB/c mice administered 0.4 mg/kg TP for 28 days, and glycolysis was also inhibited. Gata4 knockdown downregulated Sp1 and PFKP expression. Furthermore, the Sp1 inhibitor plicamycin inhibited PFKP protein levels in TM4 cells. In conclusion, TP inhibited GATA4-mediated glycolysis by suppressing Sp1-dependent PFKP expression in SCs and caused testicular toxicity.

The aim of the study was to determine whether applying an assistance force to the pelvis and legs during treadmill training can improve walking function in children with cerebral palsy.Twenty-three children with cerebral palsy were randomly assigned to the robotic or treadmill only group. For participants who were assigned to the robotic group, a controlled force was applied to the pelvis and legs during treadmill walking. For participants who were assigned to the treadmill only group, manual assistance was provided as needed. Each participant trained 3 times/wk for 6 wks. Outcome measures included walking speed, 6-min walking distance, and clinical assessment of motor function, which were evaluated before, after training, and 8 wks after the end of training, and were compared between two groups.Significant increases in walking speed and 6-min walking distance were observed after robotic training (P = 0.03), but no significant change was observed after treadmill training only. A greater increase in 6-min walking distance was observed after robotic training than that after treadmill only training (P = 0.01).Applying a controlled force to the pelvis and legs, for facilitating weight-shift and leg swing, respectively, during treadmill training may improve walking speed and endurance in children with cerebral palsy.Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) discuss the importance of physical activity at the participation level (sports programs) for children with cerebral palsy; (2) contrast the changes in walking ability and endurance for children in GMFCS level I, II and III following sports programs; and (3) identify the impact of higher frequency of sports program attendance over time on walking ability.Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The early postnatal period is the most dynamic and vulnerable stage in the assembly of intestinal microbiota. Antibiotics are commonly prescribed to newborn preterm babies and are frequently used for a prolonged duration in China. We hypothesized that the prolonged antibiotic therapy would affect the early development of intestinal microbiota and their metabolites. To test this hypothesis, we analyzed the stool microbiota and metabolites in 36 preterm babies with or without antibiotic treatment. These babies were divided into three groups, including two groups treated with the combination of penicillin and moxalactam or piperacillin-tazobactam for 7 days, and the other group was free of antibiotics. Compared to the antibiotic-free group, both antibiotic-treated groups had distinct gut microbial communities and metabolites, including a reduction of bacterial diversity and an enrichment of harmful bacteria such as Streptococcus and Pseudomonas. In addition, there was a significant difference in the composition of gut microbiota and their metabolites between the two antibiotic-treated groups, where the piperacillin-tazobactam treatment group showed an overgrowth of Enterococcus. These findings suggest that prolonged antibiotic therapy affects the early development of gut microbiota in preterm infants, which should be considered when prescribing antibiotics for this population.