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Patrinia scabiosaefolia Fisch (PS), a perennial herb belonging to the genus Pinus in the family Pinnacle Sauce, has been previously known for its analgesic, anti-inflammatory, antibacterial, and antitumor properties. However, the specific mechanism behind its antileukemic effect remains unknown. This study focused on the cytotoxicity and potential modes of action of the dichloromethane extract from PS (DEPS) in acute myeloid leukemia (AML) cells. Our results demonstrated that DEPS reduced cell viability, arrested the cell cycle in the G2/M phase, disrupted the mitochondrial membrane potential, increased reactive oxygen species (ROS) production, and upregulated the expression of Bax/Bcl-2 and Cleaved caspase-3. However, the impact of DEPS on cell viability and the expression of apoptosis-associated proteins was reversed upon pretreatment with the caspase-3 inhibitor (Z-DEVD-FMK) in HL-60 cells, which demonstrated that DEPS could induce apoptosis through the mitochondria-associated apoptotic pathway. Interestingly, DEPS also influenced autophagy by upregulating the expression of LC3II/I, P62, and Beclin-1 proteins, and the autophagy inhibition chloroquine(CQ) could attenuate the apoptotic effects of DEPS in HL-60 cells. Furthermore, SMART 2.0 analysis predicted that the main components present in DEPS were likely terpenoids. In conclusion, DEPS possibly exerts antileukemic effects by downregulating the PI3K/AKT and ERK pathways, thereby promoting intracellular ROS production, activating the mitochondrial apoptotic pathway, and affecting autophagy, providing valuable insights for the potential future application of PS in the treatment of AML.
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Leucemia Mieloide Aguda , Patrinia , Humanos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Patrinia/metabolismo , Cloreto de Metileno/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fosfatidilinositol 3-Quinases , Apoptose , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , AutofagiaRESUMO
Urinary cadmium (U-Cd) values are indicators for determining chronic cadmium toxicity, and previous studies have calculated U-Cd indicators using renal injury biomarkers. However, most of these studies have been conducted in adult populations, and there is a lack of research on U-Cd thresholds in preschool children. We aimed to apply benchmark dose (BMD) analysis to estimate the U-Cd threshold level associated with renal impairment in preschool children in the cadmium-polluted area. 518 preschool children aged 3-5 years were selected by systematic sampling (275 boys, 243 girls). Urinary cadmium and three biomarkers of early renal injury (urinary N-acetyl-ß-D-glucosaminidase, UNAG; urinary ß2-microglobulin, Uß2-MG; urinary retinol-binding protein, URBP) were determined. Bayesian model averaging estimated the BMD and lower confidence interval limit (BMDL) of U-Cd. The medians U-Cd levels in both boys and girls exceeded the recommended national standard threshold (5 µg/g cr) and U-Cd levels were higher in girls than in boys. Urinary N-acetyl-ß-D-glucosaminidase (UNAG) was the most sensitive biomarker of renal effects in preschool children. The overall BMDL5 (BMDL at a benchmark response value of 5) was 2.76 µg/g cr. In the gender analysis, the BMDL5 values were 1.92 µg/g cr for boys and 4.12 µg/g cr for girls. This study shows that the U-Cd threshold (BMDL5) is lower than the national standard (5 µg/g cr) and boys' BMDL5 was lower than the limit set by the European Parliament and Council in 2019 (2 µg/g cr), which provides a reference point for making U-Cd thresholds for preschool children.
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Teorema de Bayes , Biomarcadores , Cádmio , Humanos , Pré-Escolar , Masculino , Feminino , Cádmio/urina , Biomarcadores/urina , Poluentes Ambientais/urina , Acetilglucosaminidase/urina , Benchmarking , Exposição Ambiental , Microglobulina beta-2/urina , Proteínas de Ligação ao Retinol/urina , Monitoramento Ambiental/métodosRESUMO
The new hohlraum experimental platform and the quasi-3D simulation model are developed to enable the study of the indirect drive experiment using the six-cylinder-port hohlraum for the first time. It is also the first implosion experiment for the six laser-entrance-hole hohlraum to effectively use all the laser beams of the laser facility that is primarily designed for the cylindrical hohlraum. The experiments performed at the 100 kJ Laser Facility produce a peak hohlraum radiation temperature of â¼222 eV for â¼80 kJ and 2 ns square laser pulse. The inferred x-ray conversion efficiency ηâ¼87% is similar to the cylindrical hohlraum and higher than the octahedral spherical hohlraum at the same laser facility, while the low laser backscatter is similar to the outer cone of the cylindrical hohlraum. The hohlraum radiation temperature and M-band (>1.6 keV) flux can be well reproduced by the quasi-3D simulation. The variations of the yield-over-clean and the hot spot shape can also be semiquantitatively explained by the calculated major radiation asymmetry of the quasi-3D simulation. Our work demonstrates the capability for the study of the indirect drive with the six-cylinder-port hohlraum at the cylindrically configured laser facility, which is essential for numerically assessing the laser energy required by the ignition-scale six-cylinder-port hohlraum.
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The motion law of complex fluids under extreme conditions is an important aspect of high energy density physics research. It has been demonstrated that using multi-channel curved crystals and a framing camera to observe the laser-produced target pellets doped with tracer elements is an appropriate method for investigating this law. This paper presents a feasible design scheme for a multi-channel toroidal imager, with the ray trace model used to verify the rationality of the evaluation method and the aberration of single toroidal crystal imaging. We demonstrate that the field of view (FOV) consistency of the four-channel Ge(400) toroidal crystal imager is less than 50 µm, while the best spatial resolution is â¼4 µm and the FOV of each channel is >2.2 mm.
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In inertial confinement approaches to fusion, the asymmetry of target implosion is a major obstacle to achieving high gain in the laboratory. A recently proposed octahedral spherical hohlraum makes it possible to naturally create spherical target irradiation without supplementary symmetry control. Before any decision is made to pursue an ignition-scale laser system based on the octahedral hohlraum, one needs to test the concept with the existing facilities. Here, we report a proof-of-concept experiment for the novel octahedral hohlraum geometry on the cylindrically configured SGIII laser facility without a symmetry control. All polar and equatorial self-emission images of the compressed target show a near round shape of convergence ratio 15 under both square and shaped laser pulses. The observed implosion performances agree well with the ideal spherical implosion simulation. It also shows limitations with using the existing facilities and adds further weight to the need to move to a spherical port geometry for future ignition laser facilities.
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BACKGROUND: The effects of COVID-19 lockdown measures on maternal and fetal health remain unclear. We examined the associations of COVID-19 lockdown with gestational length and preterm birth (PTB) in a Chinese population. METHODS: We obtained medical records of 595,396 singleton live infants born between 2015 and 2020 in 5 cities in Guangdong Province, South China. The exposed group (N = 101,900) included women who experienced the COVID-19 Level I lockdown (1/23-2/24/2020) during pregnancy, while the unexposed group (N = 493,496) included women who were pregnant during the same calendar months in 2015-2019. Cumulative exposure was calculated based on days exposed to different levels of emergency responses with different weighting. Generalized linear regression models were applied to estimate the associations of lockdown exposure with gestational length and risk of PTB (< 37 weeks). RESULTS: The exposed group had a shorter mean gestational length than the unexposed group (38.66 vs 38.74 weeks: adjusted ß = - 0.06 week [95%CI, - 0.07, - 0.05 week]). The exposed group also had a higher risk of PTB (5.7% vs 5.3%; adjusted OR = 1.08 [95%CI, 1.05, 1.11]). These associations seemed to be stronger when exposure occurred before or during the 23rd gestational week (GW) than during or after the 24th GW. Similarly, higher cumulative lockdown exposure was associated with a shorter gestational length and a higher risk of PTB. CONCLUSIONS: The COVID-19 lockdown measures were associated with a slightly shorter gestational length and a moderately higher risk of PTB. Early and middle pregnancy periods may be a more susceptible exposure window.
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COVID-19/epidemiologia , Exposição Materna/estatística & dados numéricos , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , China/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Quarentena , Adulto JovemRESUMO
The development of a polar-view Kirkpatrick-Baez microscope, fielded in the upper polar zone of the Shenguang-III laser fusion facility, is presented. With this microscope, the resolving power of polar-direction X-ray imaging diagnostics is improved, to the 3 ~5 µm scale. The microscope is designed for implosion asymmetry studies, with response energy points at 1.2 keV, 3.5 keV, and 8 keV. A biperiodic multilayer scheme is adopted to accommodate multiple implosion stages. We present the overall optical system design, target aiming scheme, characteristic composite imaging diagnostic experiments and initial results. The inertial-driven quasi-one-dimensional spherical implosions were observed from orthogonal directions with a convergence ratio of ~14.4. Fine features of the stagnating hot spot core are also resolved.
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α-Thalassemia (α-thal) is a very common single gene hereditary disease caused by large deletions or point mutations of the α-globin gene cluster in tropical and subtropical regions of the world. Here, we report for the first time, a novel large α-thal deletion in a Chinese family from Jiangsu Province, People's Republic of China (PRC), which removes almost the entire α2 and α1 genes from the α-globin gene cluster. Thus, it was named the Jiangsu deletion (- -JS) on the α-globin gene cluster causing α0-thal. Heterozygotes for this deletion showed an α-thal trait phenotype with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels. The sequencing results showed that a 2538 bp deletion (NG_000006.1: g.35801_38338) existed in this novel genotype on the basis of -α4.2 (leftward), indicating a deletion of about 6.8 kb from the α-globin cluster. In addition, a 29 bp sequence was inserted into the deletion during the recombination events that led to this deletion. Through pedigree analysis, we knew that the proband inherited the novel allele from his mother.
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Sequência de Bases , Diagnóstico Pré-Natal , Deleção de Sequência , alfa-Globinas/genética , Talassemia alfa , Feminino , Humanos , Masculino , Gravidez , Talassemia alfa/diagnóstico , Talassemia alfa/genéticaRESUMO
Background: Individual metal levels are potential risk factors for the development of preeclampsia (PE). However, understanding of relationship between multiple metals and PE remains elusive. Purpose: The purpose of this study was to explore whether eight metals [zinc (Zn), manganese (Mn), copper (Cu), nickel (Ni), lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg)] in serum had a certain relationship with PE. Methods: A study was conducted in Dongguan, China. The concentrations of metals in maternal serum were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Data on various factors were collected through a face-to-face interview and hospital electronic medical records. The unconditional logistic regression model, principal component analysis (PCA) and Bayesian Kernel Machine Regression (BKMR) were applied in our study. Results: The logistic regression model revealed that the elevated levels of Cu, Pb, and Hg were associated with an increased risk of PE. According to PCA, principal component 1 (PC1) was predominated by Hg, Pb, Mn, Ni, Cu, and As, and PC1 was associated with an increased risk of PE, while PC2 was predominated by Cd and Zn. The results of BKMR indicated a significant positive cumulative effect of serum metals on PE risk, with Ni and Cu exhibiting a significant positive effect. Moreover, BKMR results also revealed the nonlinear effects of Ni and Cd. Conclusion: The investigation suggests a potential positive cumulative impact of serum metals on the occurrence of PE, with a particular emphasis on Cu as a potential risk factor for the onset and exacerbation of PE. These findings offer valuable insights for guiding future studies on this concern.
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Arsênio , Mercúrio , Metais Pesados , Pré-Eclâmpsia , Feminino , Humanos , Metais Pesados/análise , Cádmio , Teorema de Bayes , Chumbo , Arsênio/análise , Zinco , Níquel , ManganêsRESUMO
Steroid hormone imbalance is believed to increase the odds of developing PE. Bisphenol A (BPA) and its substitutes (e.g., bisphenol S (BPS) and bisphenol F (BPF)) have estrogen-like effects, and its exposure may be related to the development of preeclampsia (PE). To explore the effects of bisphenol exposure on maternal serum steroid hormones and the potential mediating role of steroid hormones in the association between bisphenol exposure and developing PE, concentrations of bisphenols and steroid hormones in serum samples of 383 pregnant women were examined before delivery (including 160 PE cases and 223 control cases). Multivariable logistic and linear models were used to explore the associations of maternal serum bisphenols concentrations with both maternal steroid hormones and PE risk. Mediation modeling was employed to evaluate the mediating role of steroid hormones in the association between bisphenols and PE. Results showed that maternal serum BPS concentrations were positively associated with testosterone (T) concentrations. The mediation analyses suggested that approximately 10.17â¯% of the associations between BPS concentrations and the development of PE might be mediated by maternal T. In conclusion, maternal exposure to BPS during pregnancy is linked to higher maternal T concentrations, which might increase the odds of developing PE. T might mediate the association between BPS exposure and the development of PE.
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Compostos Benzidrílicos , Fenóis , Pré-Eclâmpsia , Sulfonas , Testosterona , Humanos , Feminino , Fenóis/sangue , Gravidez , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/induzido quimicamente , Compostos Benzidrílicos/sangue , Adulto , Sulfonas/sangue , Testosterona/sangue , Exposição Materna/efeitos adversos , Estudos de Casos e Controles , Adulto JovemRESUMO
Exposure to environmental heavy metals may pose a risk factor for developing preeclampsia (PE) modified through intervention. This case-control study aimed to investigate the association between serum heavy metal concentrations and PE in pregnant women and whether hormones served as mediating factors in the impact of heavy metals on PE. From October 2020 to 2022, 160 patients with PE and 160 pregnant women with normal deliveries were recruited at Dongguan Songshan Lake Central Hospital. Serum concentrations of manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), ß-human chorionic gonadotropin (ß-hCG), progesterone (P), estradiol (E2), testosterone (T), cortisol (Cort), and cortisone (Cor) were measured. Logistic, restricted cubic splines, weighted quantile sum and multivariate linear regression models were employed to account for different aspects and explore the relationships among heavy metals, hormones, and PE. Mediation model analysis was performed to assess the role of hormones in mediation. The median concentrations of Mn, E2, and Cort were lower in the PE group than in the control group. The median concentrations of Cu, Zn, ß-hCG, and T were higher in the PE than in the control. Mn, E2, and Cort showed negative associations with PE, while Cu, Zn, ß-hCG, and T demonstrated positive associations, as determined through logistic regression. Mn, Cu, and Zn displayed linear dose-response relationships with PE. Zn and Cu had high weights in the positive association model of mixed heavy metal exposure with PE. The mediation analysis revealed that serum E2, P, T, Cort, and Cort/Cor might be potential mediators of the association between heavy metals (Mn, Cu, and Zn) and PE.
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Metais Pesados , Pré-Eclâmpsia , Feminino , Metais Pesados/sangue , Humanos , Pré-Eclâmpsia/sangue , Gravidez , Adulto , Estudos de Casos e Controles , Estradiol/sangue , Poluentes Ambientais/sangue , Hormônios/sangue , Progesterona/sangue , Adulto Jovem , Hidrocortisona/sangue , Exposição Ambiental , Testosterona/sangueRESUMO
Background: During the special period of the global spread of COVID-19, pregnant women are sensitive groups to the impacts of COVID-19 epidemic. However, the effects of lockdown measures implemented in response to the COVID-19 on fetal birthweight remain unclear. Objectives: This study investigated the associations of COVID-19 lockdown with birth weight in Chinese population. Methods: We collected 730,153 data of participants from hospitals of five cities in the south of China, we defined the time period of level I response (1/23-2/24/2020) as level I lockdown, and women who were pregnant during level I lockdown as the exposure group. Women who were pregnant during the same calendar month from 2015 to 2019 were defined as the unexposed group. We quantitatively estimate the individual cumulative exposure dose by giving different weights to days with different emergency response levels. Generalized linear regression models were used to estimate the association between COVID-19 lockdown exposure with birth weight and risk of low birth weight (<2,500â g) and macrosomia (>4,000â g). Results: The birth weight of the exposed group is heavier than the unexposed group (3,238.52 vs. 3,224.11â g: adjusted ß = 24.39â g [95% CI: 21.88, 26.91â g]). The exposed group had a higher risk of macrosomia (2.8% vs. 2.6%; adjusted OR = 1.17 [95% CI: 1.12, 1.22]). More obvious associations were found between COVID-19 lockdown and macrosomia in women who experienced the lockdown in their early pregnancy. Women who experienced the lockdown at their 4-7 weeks of pregnancy showed statistically significant heavier birth weight than unexposed group (after adjustment): ß = 1.28 (95% CI: 1.11, 1.46) g. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown in all pregnant women and birth weight, after divided into four groups, Q1: ß = 32.95 (95% CI: 28.16, 37.75)â g; Q2: ß = 18.88 (95% CI: 14.12, 23.64)â g; Q3: ß = 19.50 (95% CI: 14.73, 24.28)â g; Q4: ß = 21.82 (95% CI: 17.08, 26.56)â g. However, there was no statistically significant difference in the risk of low birth weight between exposed and unexposed groups. Conclusions: The COVID-19 lockdown measures were associated with a heavier birth weight and a higher risk of macrosomia. Early pregnancy periods may be a more susceptible exposure window for a heavier birth weight and a higher risk of macrosomia. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown and birth weight. The government and health institutions should pay attention to the long-term health of the infants born during the COVID-19 lockdown period, and follow up these mothers and infants is necessary.
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INTRODUCTION: The health effects of ambient ozone have been investigated in many previous studies. However, the effects of long-term exposure to ambient ozone on the incidence of cardiovascular disease (CVD) remain inconclusive. OBJECTIVES: To estimate the associations of long-term exposure to maximum daily 8-hours average ozone (MDA8 O3) with the incidence of total CVD, heart disease, hypertension, and stroke. METHODS: This was a prospective cohort study, and the data was obtained from the China Health and Retirement Longitudinal Survey (CHARLS) implemented during 2011-2018 and the China Family Panel Studies (CFPS) implemented during 2010-2018. We applied a Cox proportional hazards regression model to evaluate the associations of MDA8 O3 with total CVD, heart disease, hypertension, and stroke risks, and the corresponding population-attributable fractions (PAF) attributable to MDA8 O3 were also calculated. All analyses were conducted by R software. RESULTS: The mean MDA8 O3 concertation of all included participants in the CHARLS and CFPS were 51.03 part per billion (ppb) and 51.15â¯ppb, respectively. In the CHARLS including 18,177 participants, each 10â¯ppb increment in MDA8 O3 concentration was associated with a 31% increase [hazard ratio (HR)â¯=â¯1.31, 95% confidence interval (CI): 1.22-1.42] in the risk of incident heart disease, and the corresponding population-attributable fractions (PAF) was 13.79% [10.12%-17.32%]. In the CFPS including 30,226 participants, each 10â¯ppb increment in MDA8 O3 concentration was associated with an increase in the risk of incident total CVD (1.07 [1.02-1.13]), and hypertension (1.10 [1.03-1.18]). The PAFs of total CVD, and hypertension attributable to MDA8 O3 were 3.53% [0.82%-6.16%], and 5.11% [1.73%-8.38%], respectively. Stratified analyses showed greater associations in males, urban areas, and Southern China. CONCLUSIONS: Long-term exposure to MDA8 O3 may increase the incidence of CVD. Therefore, the policies that control O3 and related precursors are persistently needed.
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Preeclampsia (PE) is a pregnancy-specific disorder, which is one of the leading causes of maternal, fetal, and neonatal death, particularly in developing countries. Arsenic (As), which is commonly found in soil and groundwater, has been associated with various complications of pregnancy, such as spontaneous abortion, hypertension, and stillbirth. Hence, the study was used to explore the relationship between PE and blood concentration of As in this study. Blood concentration of As during pregnancy was measured by inductively coupled plasma mass spectrometry (ICP-MS). The results shown that the mean blood concentration of As was gradually increased from the control group to the severe PE group (P < 0.0001). Elevated blood concentration of As was associated with the prevalence of PE (OR = 12.81, 95% CI: 2.43-67.39 and 27.55, 1.75-433.43 for middle and high vs. low). Furthermore, elevated blood concentration of As was associated with the severity of PE. Additionally, we observed that blood concentration of As was associated with the hypoproteinemia (P = 0.001, rs = 0.37). Blood concentration of As was negatively corelated with the mean corpuscular volume (MCV) (P = 0.040, rs = - 0.23) and positively corelated with the mean corpuscular hemoglobin concentration (MCHC) (P = 0.044, rs = 0.23). Overall, our results indicated that the blood concentration of As can significantly predict the occurrence of PE. Additionally, we provided evidence that blood concentration of As may affect the occurrence of hypoproteinemia. These findings may provide some ideas for the prevention of PE and pregnancy complications.
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Aborto Espontâneo , Arsênio , Hipoproteinemia , Pré-Eclâmpsia , Feminino , Sangue Fetal , Humanos , Recém-Nascido , GravidezRESUMO
BACKGROUND: Mercury (Hg) is a highly toxic substance, and its harmful effects on maternal and infant health have been reported. Yet, the associations of Hg exposure with preeclampsia (PE) and adverse birth outcomes are not well understood. OBJECTIVE: The aim of this study was to investigate the potential effects of maternal Hg exposure on PE and birth outcomes. METHODS: We conducted a case-control study with 84 participants in China. Logistic models were used to estimate odds ratios for PE risk and birth outcomes according to maternal blood Hg levels, adjusting for potential confounding factors. RESULTS: Elevated blood Hg levels were associated with increased risks of mild PE (aOR, 7.03; 95% CI, 1.61, 30.62; P < 0.01) and severe PE (aOR, 47.55; 95% CI, 5.27, 429.05; P < 0.05). We also found that increased blood Hg levels were associated with low birth weight (aOR, 1.12; 95% CI, 1.00, 1.25; P < 0.05) and preterm birth (PTB) (aOR, 1.22; 95% CI, 1.08, 1.38; P < 0.05). CONCLUSIONS: Our study provided evidence that elevated blood Hg levels were significantly associated with an increased risk of PE. In addition, our findings support that increased blood Hg levels might be associated with low birth weight and PTB.
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Mercúrio , Pré-Eclâmpsia , Nascimento Prematuro , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , GravidezRESUMO
Importance: The ongoing pandemic of COVID-19 is still affecting our life, but the effects of lockdown measures on gestational diabetes mellitus (GDM) in pregnant women remain unclear. Aim: To investigate the association between COVID-19 lockdown and GDM. Subjects and Methods: Medical records of 140844 pregnant women during 2015-2020 were extracted from 5 hospitals in Guangdong Province, China. Pregnant women who underwent the COVID-19 Level I lockdown (1/23 - 2/24/2020) during pregnancy were defined as the exposed group (N=20472) and pregnant women who underwent the same calendar months during 2015-2019 (1/23 - 2/24) were defined as the unexposed group (N=120372). Subgroup analyses were used to explore the potential susceptible exposure window of COVID-19 lockdown on GDM. Cumulative exposure is quantitatively estimated by assigning different weights to response periods with different exposure intensities. A logistic regression model was used to estimate the association between COVID-19 lockdown exposure and GDM. Results: The rates of GDM in the exposed and unexposed groups were 15.2% and 12.4%, respectively. The overall analyses showed positive associations (odds ratio, OR=1.22, 95%CI: 1.17, 1.27) between lockdown exposure and GDM risk in all pregnant women. More pronounced associations were found in women who underwent the COVID-19 lockdown in their first four months of pregnancy, and the adjusted OR values ranged from 1.24 (95%CI: 1.10, 1.39) in women with 5-8 gestational weeks (GWs) to 1.35 (95%CI: 1.20, 1.52) with < 5 GWs. In addition, we found a positive exposure-response association of cumulative lockdown exposure with the risk of GDM. Conclusions: The COVID-19 lockdown was associated with an increased risk of GDM, and the first four months of pregnancy may be the window for sensitive exposure.
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COVID-19 , Diabetes Gestacional , COVID-19/epidemiologia , China/epidemiologia , Controle de Doenças Transmissíveis , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Gravidez , GestantesRESUMO
BACKGROUND: Recurrent pregnancy loss (RPL) refers to two or more consecutive spontaneous abortion before 24 weeks of gestation, representing 1% of couples of childbearing age. Epigenetic factors including dysregulation of DNA methylation of some genes may play a role in RPL. OBJECTIVE: To identify RPL related genes modulated by DNA methylation expressed in decidua and blood. METHODS: Three decidua samples each from RPL patients and normal controls were recruited to perform genome-wide bisulfite sequencing (GWBS) and transcriptome sequencing. Based on the above results, 22.52 kb of differential methylation regions (DMRs) from 17 genes were verified by bisulfite sequencing PCR at specific region (Hi-MethylSeq) in another 15 decidua (7RPL vs. 8 Controls) and 13 blood (5RPL vs. 8 Controls) samples. RESULTS: 23 genes showed significantly differential cytosine methylation status and distinct expression level between PRL patients and healthy controls synergistically. Three signaling pathways were found to be shared between genes with both hypomethylated differential methylation regions (DMR) and upregulated differential gene expression (DGE). The results from Hi-MethylSeq showed that the hypermethylation of SGK1 in both blood and decidua samples in RPL patients, which was consistent to its lower expression in endometrium reported earlier. SGK3 and CREB5 also showed modulated methylation level in RPL decidua. CONCLUSION: Our finding supported that aberrant methylation of SGK1 and CREB5 could be a cause of the dysregulation of these gens in the endometrium, which is one of cause of reproductive failure. The function of SGK3 in reproduction system deserves further investigation.
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Aborto Habitual/genética , Metilação de DNA , Aborto Habitual/metabolismo , Adulto , Proteína A de Ligação a Elemento de Resposta do AMP Cíclico/genética , Decídua/metabolismo , Feminino , Genoma Humano , Humanos , Proteínas Imediatamente Precoces/genética , Gravidez , Proteínas Serina-Treonina Quinases/genética , RNA-Seq , Adulto JovemRESUMO
In inertial confinement fusion, quantitative and high-spatial resolution ([Formula: see text]m) measurements of the X-rays self-emitted by the hotspot are critical for studying the physical processes of the implosion stagnation stage. Herein, the 8 ± 0.39-keV monochromatic X-ray distribution from the entire hotspot is quantitatively observed in 5-[Formula: see text]m spatial resolution using a Kirkpatrick-Baez microscope, with impacts from the responses of the diagnosis system removed, for the first time, in implosion experiments at the 100 kJ laser facility in China. Two-dimensional calculations along with 2.5% P2 drive asymmetry and 0.3 ablator self-emission are congruent with the experimental results, especially for the photon number distribution, hotspot profile, and neutron yield. Theoretical calculations enabled a better understanding of the experimental results. Furthermore, the origins of the 17.81% contour profile of the deuterium-deuterium hotspot and the accurate Gaussian source approximation of the core emission area in the implosion capsule are clarified in detail. This work is significant for quantitatively exploring the physical conditions of the hotspot and updating the theoretical model of capsule implosion.
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Background: Previous studies have demonstrated the embryotoxicity and fetotoxicity of thallium (Tl). However, the effects of prenatal exposure to Tl on birth weight and placental weight and the mediating role of placental weight in the association of Tl with birth weight remain unclear. Methods: We recruited 2,748 participants from the ongoing Prenatal Environment and Offspring Health Cohort (PEOH Cohort) study, which was initiated in 2016 in Guangzhou, China. The Tl concentrations in maternal urine samples collected during the first and third trimester were determined by inductively coupled plasma mass spectrometry. Birth weight and placental weight were extracted from maternal medical records. Results: Pregnant women exposed to the highest tertile of Tl in the first trimester (ß = -42.7 g, 95% CI: -82.3, -3.1 g) and third trimester (ß = -50.6 g, 95% CI: -99.0, -2.3 g) had babies with lower birth weights than those exposed to the lowest tertile. We also found significant negative associations of exposure to Tl concentrations in the first and third trimester with placental weight. Mediation analyses showed that 50.3% (95% CI: 15.9, 79.2%) and 33.5% (95% CI: 1.3, 80.3%) of the effects of Tl exposure in the first and third trimester on birth weight were mediated by decreased placental weight. Conclusion: Our results suggest that prenatal exposure to Tl is negatively associated with birth weight and that this association may be mediated by decreased placental weight.
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Efeitos Tardios da Exposição Pré-Natal , Tálio , Peso ao Nascer , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Exposição Materna/efeitos adversos , Placenta , Gravidez , Estudos ProspectivosRESUMO
To study the effects of chunk mixing, the implosion experiments using capsules filled with deuterated foam (CDF capsule) were carried out on the Shenguang laser facility. Three types of the CDF capsules, namely the capsules without Au dopant, with micrometer Au dopant, and with atomic Au dopant, were used in the experiments. The neutron yields, the size, and the emission intensity of the hotspots were measured. The CDF capsules without Au dopant produced the highest neutron yield and the largest hotspot size at the time of peak emission. The capsules with micrometer or atomic Au dopant showed similar reduced neutron yield and hotspot size. The time-resolved hotspot emissions showed different behaviors between different capsules. One-dimensional simulations were carried out to understand the implosion dynamics of the CDF capsule without Au dopant, and to provide the thermodynamic conditions that the Au dopant would experience during the implosion. The effects of Au dopant were then discussed qualitatively.