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Fluoride can cause developmental neurotoxicity; however, the precise mechanism has yet to be determined. We aimed to explore the possible role and mechanism of fluoride-induced developmental neurotoxicity, specifically the significance of the lysosomal stress response. As an in vivo model, Sprague Dawley rats were exposed to sodium fluoride (NaF) from embryo to 2 months of age. We found that NaF caused autophagic flux blockage and apoptosis in the rat hippocampus. These results were validated in human neuroblastoma (SH-SY5Y) cells in vitro. In addition, in SH-SY5Y cells, NaF hindered autophagosome-lysosome fusion, decreased lysosomal degradation, and elevated lysosomal pH, which is the most prominent hallmark of a lysosomal stress response. Interestingly, rapamycin promoted autophagosome-lysosome fusion, effectively restoring autophagic flux and reducing apoptosis. Notably, bafilomycin A1, a lysosomal lumen alkalizer, unsurprisingly exacerbated the NaF-induced increase in lysosomal pH and decreased lysosomal degradability, as well as enhanced apoptosis of SH-SY5Y cells. In conclusion, our results suggest that NaF exposure initiates excessive lysosomal stress response, resulting in elevated lysosomal pH, decreased lysosomal degradation, and blocked autophagic flux, which leads to neuronal apoptosis. Thus, the lysosomal stress response may be a promising target for the prevention and treatment of fluoride-induced developmental neurotoxicity.

Manganese (Mn) intake has been found to be linked with risk of type 2 diabetes. However, the role of Mn in the development of gestational diabetes mellitus (GDM) remains to be investigated. This prospective study included pregnant women from the Tongji Maternal and Child Health Cohort. A total of 2327 participants with plasma specimens before 20 weeks were included. Among the pregnant women, 9.7% (225/2327) were diagnosed with GDM. After adjustment, pregnant women with the third and highest quartile of plasma Mn levels had 1.31-fold (RR, 2.31 [1.48, 3.61]) and 2.35-fold (RR, 3.35 [2.17, 5.17]) increased risk of GDM compared with those with the lowest quartile. A 1 standard deviation increment of ln-transformed plasma Mn levels (0.53 μg/L) was related to elevated risks of GDM with RRs of 1.28 [1.17, 1.40]. The positive associations between Mn and GDM remained consistent in all the subgroups. The weighted quantile sum index was significantly related to GDM (RR, 1.60 [1.37, 1.86]). The contribution of Mn (58.69%) to the metal mixture index was the highest related to GDM. Higher plasma Mn levels were found to be linked with elevated fasting and 2 h post-load blood glucose. This study revealed relationships of higher plasma Mn levels in early pregnancy and increased risk of GDM, suggesting that though essential, excess Mn in the body might be a potential important risk factor for GDM.

This study was intended to delineate the profile of double-negative T cells (DNTs) in NOD.Cg-Prkdcscid Il2rgtm1wj /SzJ mice and cytokines released from DNTs in vivo and in vitro. Total 4 × 107 cells of RC1012 injection per mice were intravenously infused. IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10 were measured in vivo and in vitro. A quantitative polymerase chain reaction (PCR) was employed to determine the gene copies of Notch2-NLA per DNT cell from collected organs. Cytokines were significantly increased in vitro (4 h) and in vivo (3 h). DNT cells were distributed into the lung, liver, heart, and kidney earlier, and redistributed to lymphocyte homing spleen and bone marrow, which seemed to frame a two-compartment pharmacokinetics (PK) model but more data are needed to confirm this, and the clearance of DNT cells fell into first-order kinetics.

The cerebral cortex is closely associated with learning and memory, and fluoride is capable of inducing cortical toxicity, but its mechanism is unclear. This study aimed to investigate the role of endoplasmic reticulum stress and autophagy in fluoride-induced cortical toxicity. Rats exposed to sodium fluoride (NaF) were used as an in vivo model. The results showed that NaF exposure impaired the learning and memory capacities and increased urinary fluoride levels in rats. In addition, NaF exposure induced excessive endoplasmic reticulum stress and associated apoptosis, as evidenced by elevated IRE1α, GRP78, cleaved caspase-12, and cleaved caspase-3, as well as defective autophagy, as evidenced by increased expression of Beclin1, LC3-II, and p62 in cortical areas. Importantly, the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated endoplasmic reticulum stress as well as defective autophagy, thus confirming the critical role of endoplasmic reticulum stress and autophagy in fluoride-induced cortical toxicity. Taken together, these results suggest that excessive endoplasmic reticulum stress and its mediated defective autophagy lead to fluoride-induced cortical toxicity. This provides new insights into the mechanisms of fluoride-induced neurotoxicity and a new theoretical basis for the prevention and treatment of fluoride-induced neurotoxicity.

Background Breastfeeding has many established health benefits to both babies and mothers. There is limited evidence on the association between delayed lactogenesis and breastfeeding practices. Objective We assessed the association between delayed lactogenesis and breastfeeding practices in women initiating breastfeeding. Design We used data from a prospective cohort study in Wuhan, China, which enrolled pregnant women at 8-16 weeks of gestation and followed up to postpartum. Women were included who had a singleton live birth, initiated breastfeeding, and provided information on infant feeding. Maternal lactogenesis status was assessed by face-to-face interview at day 4 postpartum. Breastfeeding practices (full breastfeeding and/or any breastfeeding) were queried by telephone interview at 3, 6, and 12 mo postpartum. Poisson regression and Cox regression were used to identify the association between delayed lactogenesis and breastfeeding practices. Results Delayed lactogenesis was reported by 17.9% of the 2877 participants. After adjusting for potential confounders, when compared with timely lactogenesis, delayed lactogenesis was significantly associated with higher risk of inability to sustain full breastfeeding at 3 mo postpartum (RR: 1.24, 95% CI: 1.10, 1.39) and 6 mo postpartum (RR: 1.14, 95% CI: 1.04, 1.24). Delayed lactogenesis was also significantly associated with early termination of any breastfeeding (HR: 1.15, 95% CI: 1.01, 1.30) in the adjusted model. In a combined analysis, women with higher gestational weight gain (GWG, ≥16 kg for underweight and normal weight, 15 kg for overweight/obesity) and who subsequently experienced delayed lactogenesis had the highest risk of ending any breastfeeding earlier (adjusted HR: 1.32, 95% CI: 1.11, 1.55) compared with those who gained less GWG and experienced timely lactogenesis. Conclusions This study shows that delayed lactogenesis was associated with low rate of full breastfeeding and shorter duration of any breastfeeding. Greater efforts to promote breastfeeding should be targeted towards women with delayed lactogenesis.

Background: Few studies have investigated the association of maternal longitudinal hemoglobin (Hb) with small for gestational age during pregnancy. The current study examined the associations of maternal Hb concentrations and Hb changes throughout the middle and late stages of pregnancy with small for gestational age (SGA) in a large prospective cohort study. Methods: This was a prospective cohort study, which enrolled pregnant women at 8–16 weeks of gestation and followed up regularly. Maternal Hb concentrations were measured at the middle (14–27 weeks) and late (28–42 weeks) stages of pregnancy, and the Hb change from the middle to late stage of pregnancy was assessed. The Log-Poisson regression model was used to identify the association of maternal Hb with SGA, including the implications of Hb during specific pregnancy periods and Hb change across the middle to late stages of pregnancy. Of the total 3233 singleton live births, 208 (6.4%) were SGA. After adjusting for potential confounders, compared with Hb 110–119 g/L, Hb ≥ 130 g/L at late pregnancy was significantly associated with a higher risk of SGA (adjusted RR: 2.16; 95% CI: 1.49, 3.13). When Hb changes from the middle to late stages of pregnancy were classified by tertiles, the greatest change in the Hb group (

Background: Compliance with dietary guidelines among pregnant women can positively influence not only their own health but also the health of their babies. Measuring the compliance requires professional skills in nutrition and dietary counseling. In China, few simple and effective techniques assess dietary quality among pregnant women, especially in rural areas. We aimed to establish a new simple and effective assessment technique, the “Chinese Dietary Guidelines Compliance Index for Pregnant Women (CDGCI-PW)” and assess the association between maternal dietary compliance and risks of pregnancy complications. Methods: The CDGCI-PW consists of 13 main components which were based on the 2016 edition of the Chinese dietary guidelines for pregnant women. Each component was assigned a different score range, and the overall score ranged from 0 to 100 points. The Tongji Maternal and Child Health Cohort study (from September 2013 to May 2016) was a prospective cohort study designed to examine maternal dietary and lifestyle effects on the health of pregnant women and their offspring. The maternal diet during the second trimester was compared with the corresponding recommended intake of the Chinese balanced dietary pagoda for pregnant women to verify their compliance with dietary guidelines. The association between maternal dietary quality and risks of pregnancy complications was estimated by regression analysis. Receiver operating characteristic (ROC) curves were constructed to identify the optimal cut-off values of CDGCI-PW for gestational hypertension and gestational diabetes mellitus (GDM). Results: Among the 2708 pregnant women, 1489 were eventually followed up. The mean CDGCI-PW score was 74.1 (standard deviation (SD) 7.5) in the second trimester. The majority of foods showed the following trend: the higher the CDGCI-PW score, the higher the proportion of pregnant women who reported food intake within the recommended range. Moreover, a higher maternal CDGCI-PW score was significantly associated with lower risks of gestational hypertension [odds ratio (OR) (95% confidence interval [(CI): 0.30 (0.20, 0.37)] and GDM [OR (95% CI): 0.38 (0.31, 0.48)]. The optimal CDGCI-PW cut-off value for gestational hypertension was ≥68.5 (sensitivity 82%, specificity: 61%, area under the ROC curve, AUC = 0.743), and the optimal CDGCI-PW cut-off score for GDM was ≥75.5 (sensitivity 43%, specificity: 81%, area under the ROC curve, AUC = 0.714). Conclusions: The CDGCI-PW is a simple and useful technique that assesses maternal diet quality during pregnancy, while adherence to the CDGCI-PW is associated with a lower risk of gestational hypertension and GDM.

Introduction Allogeneic Double Negative T (DNT, CD3+CD4-CD8-) cells have shown great potential as a novel off-the-shelf immunotherapy drug candidate in clinic trials for r/r/AML patients. This is our first report to demonstrate that CD19-CAR-DNT cells with high percentage of Tscm+Tcm phenotypes have been successfully developed with strong immunotherapeutic effects on Raji-luciferase tumor cells from non-Hodgkin’s lymphoma both in vitro and in vivo. Methods DNT cells were expanded ex vivo from healthy donors and then were transduced with CD19-CAR lentivirus in the presence of IL-2. The CD19-CAR-DNT cell expansions were performed under GMP condition and then harvested and cryo-preserved by CryStor®CS5 in liquid nitrogen for future use. Summary The ex vivo expanded CD19-CAR-DNT cells has more than 50% of Tscm and Tcm phenotypes. The viability and CAR+ percentage of CD19-CAR-DNT cells were 84.40% and 34.98% respectively. The killing of CD19-CAR-DNT cells on Raji-luciferase cells was 77.92% (n=6) at the effector to target ratio of 4:1. Elevated IFN-γ release from CD19-CAR-DNT cells after overnight co-culture with Raji cells was observed. The antitumor efficacy was evaluated in the xenografted NHL mice model. After the first infusion of the cells, the tumor growth inhibitory rates (TGI %) of CD19-CAR-DNT cells at 1×106, 5×106 and 1×107 per mouse on day14 were 80.54%, 98.31% and 99.05% respectively, the killing effects were in a dose-dependent manner. After the second infusion of the CD19-CAR-DNT cells at day 14, median survival times (MST) of the treated three groups mice were elongated till Day60, that is twice longer than that of the xenografted vehicle group. In the subsequent PKPD study, infusion CD19-CAR-DNT cells into Raji-luciferase cell xenografted mice were primarily distributed in lungs, peripheral blood, spleen, and bone marrow within 72h, homing back to liver and spleen on Day36. All animal body weights in both fresh and frozen reconstituted CD19-CAR-DNT cells treated mice were increased with no observed toxicities. Conclusions ex vivo expansion of CD19-CAR-DNT cells were successfully developed to explore its potential as a novel off-the-shelf universal CART drug for malignant B cells leukemia. The cell subsets consist of more than 50% of Tscm and Tcm cells whereas most immunological check point inhibitors were not elevated after priming by target tumor cells except a slight increase of PD-1 molecule. Fresh or frozen CD19-CAR-DNT cells can kill Raji cells in vitro and in vivo studies in a dose-dependent manner although the frozen one showed a delayed killing in vivo. The tumor cells were almost depleted and the MST was significantly increased with NOAEL at 1x107 cells/mouse. The amounts of CD19-CAR-DNT cells are re-distributed from early lungs, peripheral blood to live, spleen later. Citation Format: Liming Yang, Dan Wang, Shangzhi Xu, Liuyang Wang, Jianjun Tong, Honglin Zhu, Man Xu, Xiancai Li, Letu Ji, Chuntao Zheng, Zhiqiang Xiang, Qinghua Sun, Hengcai Wang. Preclinical study of allogeneic CD19-CAR-DNT cells as an off-the-shelf immunotherapy drug for NHL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5510.

Background The association between iron supplementation and gestational diabetes mellitus (GDM) is still inconclusive, and this association has not been extensively studied in relation to plasma ferritin in the early second trimester. Objectives We aimed to prospectively examine the independent and combined associations of plasma ferritin concentrations and iron supplement use with GDM. Methods We studied 2117 women from the Tongji Maternal and Child Health Cohort in Wuhan, China. Plasma ferritin around 16 weeks' gestation was measured by ELISA kits and information on iron supplement use was collected by questionnaires. GDM was diagnosed by a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks' gestation. A log-Poisson regression model was used to estimate the RR of GDM associated with plasma ferritin and iron supplementation. Results The median and IQR of plasma ferritin was 52.1 (29.6-89.9) ng/mL, and 863 (40.8%) participants reported use of iron supplements during the second trimester. A total of 219 (10.3%) participants developed GDM. Adjusted RRs (95% CIs) for GDM across increasing quartiles of plasma ferritin were 1.00 (reference), 2.14 (1.37, 3.34), 2.03 (1.30, 3.19), and 2.72 (1.76, 4.21), respectively. After adjustment, supplemental iron ≥60 mg/d during the second trimester was associated with an increased risk of GDM compared with nonusers (RR: 1.37; 95% CI: 1.02, 1.84). Conclusions Both elevated plasma ferritin concentrations in the early second trimester and use of ≥60 mg/d of supplemental iron during pregnancy are independently associated with increased risk of GDM. Further clinical trials with precision nutrition approaches considering both baseline iron status and supplement use are needed to evaluate the benefits and risks of iron supplementation during pregnancy.

Current results regarding the effect of folic acid (FA) supplement use on gestational hypertension (GH) and preeclampsia are limited and inconsistent. We aimed to investigate whether FA supplement use was associated with GH and preeclampsia. Participants from the Tongji Maternal and Child Health Cohort with information on periconceptional FA supplement use and diagnosis of GH/preeclampsia were included (n=4853). Robust Poisson regression was used to assess the association of FA supplement use and GH and preeclampsia. Among the 4853 participants in this study, 1161 (23.9%) and 161 (3.3%) women were diagnosed with GH and preeclampsia, respectively. The risk ratio of developing GH was higher in women who used ≥800 µg/d FA supplement from prepregnancy through midpregnancy than nonusers (risk ratio, 1.33 [1.08–1.65]). After adjusting for social-demographic, reproductive, lifestyle factors, family history of hypertension, other supplement use, and gestational weight gain, the adverse association remained significant (risk ratio, 1.32 [1.06–1.64]). Restricting the analysis among women with normal weight, without family history of hypertension, and without gestational diabetes mellitus, the positive FA-GH association still existed. We did not find any significant association between FA supplement use and preeclampsia regardless of adjustment. High-dose (≥800 µg/d) FA supplement use from prepregnancy through midpregnancy was associated with increased risk of GH. Attention should be given to avoid the potential risk of GH due to inappropriate FA supplement use in women who are planning or capable of pregnancy.

Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw). Mice exposed to NaF showed typical poisoning changes of morphology, increased aspartate aminotransferase and alanine aminotransferase activities in the liver. NaF treatment also increased MDA accumulation, decreased GSH-Px, SOD and T-AOC levels in liver, indicative of oxidative stress. Intriguingly, all these detrimental effects were alleviated by GSPE. Further study revealed that NaF induced disorders of iron metabolism, as manifested by elevated iron level with increased hepcidin but decreased ferroportin expression, which contributed to hepatic oxidative stress. Importantly, the iron dysregulation induced by NaF could be normalized by GSPE. Collectively, these data provide a novel insight into mechanisms underlying fluorosis and highlight the potential of GSPE as a naturally occurring prophylactic treatment for fluoride-induced hepatotoxicity associated with iron overload.

In this paper, an extended car-following model which depends not only on the difference of the optimal velocity and the current velocity but also on self-stabilizing control is presented and analyzed in detail. The self-stabilizing control is constructed into the new model by utilizing the historical traffic data (the historical velocity and the historical optimal velocity of the considered vehicle). We derive the stability condition of the extended model against a small perturbation around the homogeneous flow. Theoretical results reveal that the self-stabilizing control in historical optimal velocity difference can further stabilize traffic system on the basis of the self-stabilizing control in historical velocity difference. It is also derived that the time gap between the current traffic data and the historical ones has an important impact on the stability criterion. We clarify the advantages of the self-stabilizing control over the cooperatively driving control and the flexibility in the choice of suppressing in traffic jams. Moreover, from the nonlinear analysis to the proposed model, the historical traffic data dependence of the propagating kink solutions for jam waves is achieved by deriving the modified KdV equation near critical point by using the reductive perturbation method. Finally, theoretical results are confirmed by direct simulations.

Background: A growing number of epidemiologic studies have estimated associations between type 2 diabetes mellitus and exposure to metals. However, studies on the associations of internal assessments of metal exposure and gestational diabetes mellitus (GDM) are limited in scope and have inconsistent outcomes. Objectives: This investigation aimed to explore the associations between urinary nickel (Ni), arsenic (As), cadmium (Cd), antimony (Sb), cobalt (Co), or vanadium (V) in early pregnancy and the subsequent risk of GDM in Chinese pregnant women. Methods: The study population included 2090 women with singleton pregnancy from the Tongji Maternal and Child Health Cohort (TMCHC). Urine samples were collected before 20 gestational weeks, and an oral glucose tolerance test (OGTT) was conducted at 24–28 gestational weeks to diagnose GDM. The concentrations of urinary metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) and were corrected for urinary creatinine. The associations between the risk of GDM and urinary metals were assessed using Poisson regression with a robust error variance with generalized estimating equations (GEE) models and Bayesian kernel machine regression (BKMR). Results: A total of 241 participants (11.53%) were diagnosed with GDM. Five metals (Ni, As, Sb, Co, and V) were found significantly and positively associated with GDM based on single-metal models. In multiple-metal models, for each unit increase of ln-transformed urinary Ni or Sb, the risk of GDM increased 18% [relative risk (RR):1.18, 95%confidence interval (CI): 1.00, 1.38 or RR: 1.18, 95%CI: 1.00, 1.39, respectively]. The BKMR analysis revealed a statistically significant and positive joint effect of the six metals on the risk of GDM, when the urinary levels of the six metals were all above the 55th percentile, compared to the median levels. The effect of metal Ni was significant when the concentrations of the other metals were all fixed at their 25th percentile, and metal Sb displayed a significant and positive effect when all the other metals were fixed at 25th, 50th, and 75th percentiles. Conclusions: To the best of our knowledge, this study is the first to demonstrate that increased concentrations of urinary Ni in early pregnancy are associated with an elevated risk of GDM, either evaluated individually or as a metal mixture. All six metals mixed exposure was positively associated with the risk of GDM, while Sb and Ni were demonstrated more important effects than the other four metals in the mixture. Keywords: GDM, Urinary metals, Single-metal models, Multiple-metal models, BKMR models

To examine optimal gestational weight gain(GWG) for Chinese pregnant women.A total of 6998 women with singleton and term pregnancy recruited to the Tongji Maternal and Child Health Cohort during January 2013 to May 2016 in Wuhan, Hubei were included. Information on sociodemographic, medical and family history of disease was obtained by questionnaire, body weight and height were measured at the first antenatal care during 8-16 weeks of gestation. Prenatal weight of mothers were measured, and gestational week, mode of delivery, pregnancy complications, gender of newborn, birth weight and length were collected from medical records after delivery. Restricted cubic spline was used to model nonlinear relationships between GWG and the occurrence of small for gestational age(SGA), large for gestational age(LGA), low birth weight(LBW), macrosomia, cesarean, gestational hypertension(GH)and gestational diabetes mellitus(GDM), respectively. The GWG of the lowest risks for adverse pregnant outcomes was regarded as optimal GWG recommended by Tongji(TJ) for pregnant women. The P25-P75 of GWG was defined as the optimal GWG recommended by percentile method. Logistic regression was used to analyze the effect of excessive or insufficient GWG on adverse pregnancy outcomes, while the recommendations of TJ and percentile method were used as references, respectively.(1) The GWG with lower risk of adverse pregnant outcomes based on pre-gravid body mass index(BMI) are 12. 0-17. 0 kg for underweight, 9. 0-14. 0 kg for normal weight and 7. 0-11. 0 kg for overweight, respectively, which are defined as TJ recommendations. The recommended GWG by percentile method are 14. 0-19. 0 kg for underweight, 13. 0-19. 0 kg for normal weight, 10. 8-18. 0 kg for overweight and 9. 0-15. 8 kg for obesity, respectively. (2) Compared to women gain within the TJ recommendations, OR of LGA is 2. 94(95%CI 2. 31-3. 73), macrosomia is 3. 13(95%CI 2. 38-4. 13), cesarean is 1. 53(95%CI 1. 38-1. 71) and GH is 2. 18(95%CI 1. 50-3. 17) for those with excessive GWG, OR of SGA is 1. 82(95%CI 1. 32-2. 53) for those who gain less. The corresponding ORs according to percentile method are 2. 11(95%CI 1. 76-2. 54) for LGA, 2. 16(95%CI 1. 76-2. 65) for macrosomia, 1. 53(95%CI 1. 36-1. 72) for cesarean, 1. 39(95%CI 1. 02-1. 90) for GH and 1. 60(95%CI 1. 29-1. 99) for SGA, respectively.The optimal GWG of Chinese pregnant women recommended by the study are 12. 0-17. 0 kg for pre-gravid underweight women, 9. 0-14. 0 kg for normal weight women and 7. 0-11. 0 kg for overweight, respectively.

Investigators in previous studies have drawn inconsistent conclusions regarding the relationship between relatively low exposure to fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5)) and risk of gestational diabetes mellitus (GDM), while the association between high PM2.5 exposure and GDM risk has not been well studied. We investigated the association of high PM2.5 exposure during pregnancy with blood glucose levels and GDM risk in Chinese women. The present study was conducted from August 2013 to May 2016 among 3,967 pregnant women in the Tongji Maternal and Child Health Cohort in Wuhan, China. PM2.5 exposure during pregnancy for each participant was estimated by means of land-use regression models. An interquartile-range increase in PM2.5 exposure (33.84 μg/m3 for trimester 1 and 33.23 μg/m3 for trimester 2) was associated with 36% (95% confidence interval (CI): 1.15, 1.61) and 23% (95% CI: 1.01, 1.50) increased odds of GDM during trimester 1 and trimester 2, respectively. An interquartile-range increment of PM2.5 exposure during trimester 1 increased 1-hour and 2-hour blood glucose levels by 1.40% (95% CI: 0.42, 2.37) and 1.82% (95% CI: 0.98, 2.66), respectively. The same increment of PM2.5 exposure during trimester 2 increased fasting glucose level by 0.85% (95% CI: 0.41, 1.29). Our findings suggest that high PM2.5 exposure during pregnancy increases blood glucose levels and GDM risk in Chinese women.

We investigate the traffic states transition and jamming induced by a slow car in two-lane traffic of cars by using a generalized optimal velocity model, which is based on the optimal velocity model. We obtain the relationship between current and density under the circumstance when a slow car was introduced into the original high speed moving highway where cars change lanes frequently. It is found that the entire density space is divided to four distinct area, symbolizing different traffic states. The spatiotemporal diagram of each state is presented. Through the diagram, the evolution and development of traffic flow, jamming as well, is demonstrated.

Different from the existing lattice model that considers the impact of a single ramp on the traffic flow in a closed single-lane traffic flow this paper considers a traffic flow model with dual ramps, including one on-ramp and one off-ramp, and further studies the influence of the position relationship between consecutive ramps. Based on previous studies which show that historical speed and historical headway information have a positive effect on traffic in a closed single-lane environment, the historical flow information is introduced to study the ability of historical flow information to correct road instability caused by ramp crossings. Through linear analysis theory, we obtain the neutral stability curve and the stability critical condition of the model. Then we verify the results of the previous theoretical analysis through numerical simulations.

Aims Iron supplementation has been recommended for healthy pregnancy, but concerns have been raised regarding the potential adverse effects. We sought to examine the impact of periconceptional iron supplement use on subsequent gestational diabetes mellitus (GDM) risk. Methods Participants (N = 5101) with information on periconceptional micronutrient supplementation and diagnosis of GDM were involved. Information on iron supplementation and general characteristics were collected at enrollment and follow-up visits. GDM was diagnosed by oral glucose tolerance tests (OGTT) conducted at 24–28 weeks of gestation. Robust Poisson regression model was used to estimate the relative risks (RRs) and 95% confidence intervals (CI) for the effect of iron supplement use on GDM. Results 10.5% of the participants were diagnosed with GDM and the incidence was significantly higher in users with iron >30 mg/d for more than 3 months (Iron >30-L) than in nonusers. Adjusted RRs (95% CI) were 1.53 (1.21, 1.93) in Iron >30-L group, 1.14 (0.80, 1.61) in users with iron >30 mg/d for 30-S) and 1.15 (0.86, 1.54) in users with iron ≤30 mg/d for any duration (Iron ≤30) respectively, compared to nonusers. This link in Iron >30-L group was even stronger (adjusted RR: 1.70, 95% CI: 1.25, 2.31) when restricting the analysis among primiparous and iron-replete participants without family history of diabetes. There were no significant differences in birth outcomes among groups. Conclusions Periconceptional iron supplementation >30 mg/d for long-term was associated with increased GDM risk. The need and safety of prophylactic iron supplement in iron-replete pregnant women should be reconsidered.

This paper attempts to study the use of multiple historical speed information of the target vehicle as an auxiliary control strategy for vehicle power output, which is different from other single-data self-stability control modes. We separately study the different weight distributions of historical data with using data completely recorded and part of the using data randomly lost. Then we compare the different coefficient distributions, and find that considering the reversed Poisson distribution of data in driving with complete data recorded is more beneficial to the stability of traffic flow than other distributions, but the traffic flow stability is most easily affected after the data is lost during driving operation. Furthermore, we try to fill the lost data with the remaining recorded data in the case of long-term defects in the use of data, trying to make up for the lack of reversed Poisson weight distribution.

Cooperative adaptive cruise control (CACC) system possesses more remarkable ability to suppress disturbance and enhance the traffic capacity than adaptive cruise control (ACC). However, CACC asks for strict requirement on wireless communication and precise equipment, which remains a big difficulty to implement. This paper extends a new ACC model by introducing the self-stabilizing control with historical data, aimed at achieving the close performance of CACC and make it practicable. Substituting real-time information with pre-stored data substantially reduces the technical demand and offers high reliability to withstand the network delay. Linear stability analysis for this model points out enhancing the value of the gain or time delay of self-stabilizing control benefits to stabilize the traffic. The theories are corroborated via the simulation and further numerical simulations explicate the impact on fuel consumption and emissions and traffic capacity.

This paper discusses and implements the application of Mask R-CNN in railway passenger flow statistics. Mask R-CNN is a target detector based on candidate region, combining deep learning, neural network and image recognition technology, and has a wide range of application value in the field of intelligent monitoring.The paper focuses on the algorithm named Mask-Flow that Mask R-CNN uses the same color for tracking on the same target, and counts the number of pedestrians. And the passenger flow statistics are compared with Retina-Net in the railway scene of the dense crowd, which proves the accuracy of the method in the paper.

Periconceptional folic acid (FA) supplementation is widely recommended for substantial benefits on preventing neural tube defects (1), but concerns regarding the potential side effects on both mothers and their infants have been raised recently (2,3). Higher plasma folate was found to be associated with higher risk of gestational diabetes mellitus (GDM) (4). A Chinese cohort had reported association between FA supplement use in early pregnancy and increased GDM risk (5). However, no details on FA doses and durations had been addressed. To further understand the safe dose and duration of FA supplement use regarding GDM risk, for the first time, we evaluated the impact of FA supplement use on GDM with consideration of both doses and durations. Participants came from the Tongji Maternal and Child Health Cohort (TMCHC), a cohort investigating the role of maternal nutritional, environmental, and lifestyle influences on the outcomes of pregnant women and their offspring. Information on social-demographic status, reproductive factors, lifestyle factors, illnesses, and medical records was collected via questionnaire-based interviews at enrollment (

Background: Antimony (Sb) has been associated with type 2 diabetes in previous studies. However, the role of Sb in the incidence of Gestational diabetes mellitus (GDM) remains unclear. Objectives: We investigated the association between Sb exposure during early pregnancy and the risk of GDM. Methods: We performed a prospective study of 2093 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC). Sb concentrations were measured in urine samples during early pregnancy by ICP-MS. The association between urinary Sb concentration and GDM incidence was assessed using robust Poisson regression model after adjustment for confounders. Results: The 95th percentile value of creatinine-corrected Sb (CC-Sb) concentration in the urine of all pregnant women was 1.33 μg/g. The CC-Sb concentrations were significantly higher in women with GDM than those without GDM (median value: 0.49 μg/g vs. 0.38 μg/g, p = 0.001). After adjustment for potential confounders, for each one natural logarithmic unit increase in Sb concentration, there was 29% [adjusted relative risk (RR) = 1.29; 95% confidence interval (CI): 1.06, 1.57] increase in the risk of GDM. Women in the highest tertile for CC-Sb had a 1.92-fold (95% CI: 1.42, 2.60) higher risk of GDM compared with women in the lowest tertile (p-value for trend

Arsenic is known to cause oxidative damage. Nuclear factor E2-relate factor-2 (Nrf2) can resist this toxicity. Scholars demonstrated that Nrf2 pathway was activated by arsenic. In contrast, other articles established arsenic-induced inhibition of Nrf2 pathway. To resolve the contradiction and elucidate the mechanism of Nrf2 induced by arsenic, 39 publications involving mouse models were identified through exhaustive database retrieval and were analyzed. The pooled results suggested that arsenic obviously elevated transcription and translation levels of Nrf2 and its downstream genes, NAD(P)H dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and GST-glutathione-S-transferase1/2 (GSTO1/2). Arsenic increased the level of reactive oxygen species (ROS), but reduced the level of glutathione (GSH). Subgroup analysis between arsenic and control groups showed that the levels of Nrf2 and its downstream genes are greater in high dose than that in the low dose, higher in short-term exposure than long term, female subjects tolerated better than males, higher in mice than the rats, and greater in other organs than the liver. However, the contents of genes of Nrf2 pathway between the arsenic and control groups were lower in rats than in mice and were less for long-term exposure than the short term (P

In this paper, we propose a heterogeneous car following model in terms of an extension to the original optimal velocity model characterizing two classes of different self-stabilizing control vehicles. Linear stability analysis method is utilized to the extended model, for purpose to explore how the varying percentages of the vehicles with short-duration self-stabilizing control influence the stability of the heterogeneous traffic flow. We obtain the neutral stability lines for different percentages of two classes of vehicles, with finding that the traffic flow trends to stable with the decrease of the percentage for short-duration self-stabilizing control vehicles. Moreover, we explore a special case that the same numbers of two different classes of vehicles with self-stabilizing control. We theoretically derive the stability condition of the special case, and conclude the effect of the average value and the standard deviation of two time gaps, on the heterogeneous traffic stability. At last, direct simulations are conducted to verify the conclusion of theoretical analysis.

To investigate whether grape seed proanthocyanidin extract (GSPE) antagonizes fluoride-induced oxidative injury by regulating iron metabolism, human embryo hepatic cells (L-02) were incubated with sodium fluoride (NaF, 80 mg/L) and/or GSPE (100 μmol/L) for 24 h. Results showed the glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC) level of the NaF group were significantly lower than that of the control group (P

The drivers in actual traffic differ in the aggressiveness in driving behaviors, which will finally be reflected in the interaction between vehicles and fluctuations in flows. In this paper, we try to study the effect of driving aggressiveness on the traffic stability by proposing an extended microscopic car-following model, in which the optimal velocity is reconstructed to divide the drivers in traffic system into two groups according to driving aggressiveness of each individual. The stability condition of the proposed model is derived to explore its ability against a small perturbation by use of the linear stability theory. We obtain the neutral stability lines for different percentages of drivers with a higher driving aggressiveness, finding that the traffic flow trends to stable with the increase in the percentage for higher driving aggressiveness drivers when the average headway is less than a critical value or greater than another critical value, but when the average headway falls into the intermediate range between the two critical values, the traffic flow becomes more and more unstable with increase in the percentage of drivers with a higher driving aggressiveness. Finally, numerical simulations are conducted to verify these theoretical results and examine how the percentage of vehicles driven by higher driving aggressiveness drivers affects the traffic flux of the vehicle system.

Arsenic is a toxic metal, which ultimately leads to cell apoptosis. ERK is considered a key transcriptional regulator of arsenic-induced apoptosis. Due to a few controversial issues about arsenic-mediated extracellular signal-regulated MAP kinases (ERK) signaling, a meta-analysis was performed. Subgroup analyses demonstrated that high doses (≥2 µmol/l) of arsenic increased the expression of Ras, ERK, ERK1, ERK2, phosphorylated (p)-ERK, p-ERK1, and p-ERK2, while low doses (24 h) to arsenic led to inhibition of expression of ERK1, p-ERK1, and p-ERK2, whereas short-term exposure (≤24 h) triggered the expression of ERK1, ERK2, p-ERK, p-ERK1, and p-ERK2. Furthermore, normal cells exposed to arsenic exhibited higher production levels of Ras and p-ERK. Conversely, exposure of cancer cells to arsenic showed a lower level of production of Ras and p-ERK as well as higher level of p-ERK1 and p-ERK2 as compared to control group. Short-term exposure of normal cells to high doses of arsenic may promote ERK signaling pathway. In contrast, long-term exposure of cancer cells to low doses of arsenic may inhibit ERK signaling pathway. This study may be helpful in providing a theoretical basis for the diverging result of arsenic adverse effects on one hand and therapeutic mechanisms on the other concerning arsenic-induced apoptosis.

This paper presents an extended intelligent driver traffic flow model, in which the power of the considered vehicle is strengthened in proportion to that of the immediately preceding vehicle. We analyze the stability against a small perturbation by use of the linear stability method for the proposed traffic flow model on a single lane under open boundary condition, with the finding that the traffic flow stability can be improved by increasing the proportion of the direct power cooperation of the preceding vehicle. The participation of forward power cooperation can help to stabilize the traffic flow and suppress the traffic jams. In addition, the simulations under open boundary single lane are conducted to validate the correctness on theoretical deduction, which shows that numerical results in large-wave and short-wave stability are in good agreement with those of theoretical analysis.

Existing improved versions of the optimal velocity model have been proved to be capable to enhance the traffic flow stability against a small perturbation with the cooperative control of other vehicles. In this paper, we propose an extended optimal velocity model with consideration of velocity difference between the current velocity and the historical velocity of the considered vehicle. We conduct the linear stability analysis to the extended model with concluding that the traffic flow can be stabilized by taking into account the velocity difference between the current velocity and the historical velocity of the considered vehicle. Namely, the traffic stability can be improved only by each vehicle’s self-stabilizing control, without the cooperative driving control from others. It is also found that the time gap between the current velocity and the historical velocity has an important impact on the stability criterion. To describe the phase transition, the mKdV equation near the critical point is derived by using the reductive perturbation method. The theoretical results are verified using numerical simulation. Finally, it is clarified that the self-stabilizing control in velocity is essentially equivalent to the parameter adjusting of the sensitivity.