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Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.
Annexin A2 (ANXA2) is reported to be associated with cancer development. To investigate the roles ANXA2 plays during the development of cancer, the RNAi method was used to inhibit the ANXA2 expression in caco2 (human colorectal cancer cell line) and SMMC7721 (human hepatocarcinoma cell line) cells. The results showed that when the expression of ANXA2 was efficiently inhibited, the growth and motility of both cell lines were significantly decreased, and the development of the motility relevant microstructures, such as pseudopodia, filopodia, and the polymerization of microfilaments and microtubules were obviously inhibited. The cancer cell apoptosis was enhanced without obvious significance. The possible regulating pathway in the process was also predicted and discussed. Our results suggested that ANXA2 plays important roles in maintaining the malignancy of colorectal and hepatic cancer by enhancing the cell proliferation, motility, and development of the motility associated microstructures of cancer cells based on a possible complicated signal pathway.
Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.
G-protein-coupled receptor 142 (GPR142) belongs to rhodopsin family. GPR142 and GPR119, both Gq-coupled receptors, are expressed in pancreatic β cells of pancreas; their activation eventually leads to triggering of insulin secretion. In this paper, through a systems and synthetic biology approach, the effect of a common hit compound has been investigated in GPR142 and GPR119 pathways. This hit that has the potential to be developed as a lead for nanodrug was obtained through high-throughput virtual screening. The hit compound was further docked with nanoparticles (GOLD, SPION, and CeO2). The probable effect of this potential hit on insulin secretion in type 2 diabetes and its dynamic behavior was explored. Kinetic simulation was performed for cross-validation of its role in both the pathways. This study opens up a probable avenue in therapy of type 2 diabetes through regulation of GPR142 and GPR119 receptors. The biological circuit constructed may further have an application as a modulator to control the up- and downregulation of the biochemical pathway and can be implemented as sensors or nanochips for therapy.
Research suggests an association between metabolic disorders, such as type 2 diabetes mellitus (T2DM), and schizophrenia. However, the risk of metabolic disorders in the unaffected siblings of patients with schizophrenia remains unclear.
Using the Taiwan National Health Insurance Research Database, 3135 unaffected siblings of schizophrenia probands and 12,540 age-/sex-matched control subjects were included and followed up to the end of 2011. Individuals who developed metabolic disorders during the follow-up period were identified.
The unaffected siblings of schizophrenia probands had a higher prevalence of T2DM (3.4% vs. 2.6%, p = 0.010) than the controls. Logistic regression analyses with the adjustment of demographic data revealed that the unaffected siblings of patients with schizophrenia were more likely to develop T2DM (odds ratio [OR]: 1.39, 95% confidence interval [CI]: 1.10–1.75) later in life compared with the control group. Moreover, only female siblings of schizophrenia probands had an increased risk of hypertension (OR: 1.47, 95% CI: 1.07–2.01) during the follow-up compared with the controls.
The unaffected siblings, especially sisters, of schizophrenia probands had a higher prevalence of T2DM and hypertension compared with the controls. Our study revealed a familial link between schizophrenia and T2DM in a large sample. Additional studies are required to investigate the shared pathophysiology of schizophrenia and T2DM.
Bipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.
Among the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.
FDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.
Our study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.
Nanosize SiCp (n-SiCp) reinforced Mg–9Al matrix composites (Mg–9Al–xSiC, x = 2.5, 5, 7.5, 10 wt%) with nearly full densification are fabricated by the semisolid powder hot pressing technique assisted with ultrasonic. The effect of SiC nanoparticle contents on microstructures and mechanical properties of the composites is systematically investigated. Grain size and density of Mg–9Al–xSiC composites and morphology of bonding interfacial between the n-SiCp and matrix are found to be greatly dependent on the n-SiCp contents, resulting in the strength and ductility of the composites increase first and then decrease as the increase of n-SiCp contents. As the SiCp content increasing to 7.5 wt%, superior mechanical properties with the yield strength of 191 MPa, ultimate tensile strength of 248 MPa, and elongation to failure of 5.3% are achieved. The improved mechanical properties could be attributed to grain boundary strengthening, Orowan strengthening, and load transfer strengthening.
A high power laser system was used to drive the ignition of inertial confinement fusion (ICF), of which the high energy, the uniform focal spot, the accurate laser waveform, and the synchronization between the laser beams are key parameters. To accomplish this, global laser characteristics control should be assured, which was the main purpose of the injection laser system. In this paper, the key technological progress involved in the improvement of the performance of the injection laser of SG-II is reported, including frequency domain control, time domain control, near-field spatial shaping, pre-amplifier technology, and the optical parametric chirped pulse amplification pump source.
An optically addressed liquid crystal modulator for wavefront control of 1053 nm laser beam is reported in this paper. Its working principle, control method and spatial phase modulation capability are mainly introduced. A new method of measuring the relationship between gray level and phase retardation is proposed. The rationality of the curve is further confirmed by designing special experiments. According to the curve, several spatial phase distributions have been realized by this home-made device. The results show that, not only the maximum phase retardation is larger than
for 1053 nm wavelength, but also the control accuracy is high. Compared with the liquid crystal on silicon type spatial light modulator, this kind of modulator has the advantages of generating smooth phase distribution and avoiding the black-matrix effect.
Several studies have suggested that higher carotenoid levels may be beneficial for atherosclerosis patients, but few studies have examined this relationship in the Chinese population. This cross-sectional study examined the association between the levels of carotenoids in diet and serum and carotid intima–media thickness (IMT) in Chinese adults aged 50–75 years in Guangzhou, China. Dietary intake was assessed using a FFQ. HPLC was used to assay the serum concentrations of α-carotene, β-carotene, lutein+zeaxanthin, β-cryptoxanthin and lycopene. The IMT at the common carotid artery (CCA) and bifurcation of the carotid artery was measured by B-mode ultrasound. A total of 3707 and 2947 participants were included in the analyses of dietary and serum carotenoids. After adjustment for demographic, socio-economic and lifestyle factors, all the serum carotenoids levels except lycopene were found to be inversely associated with the IMT at the CCA and bifurcation (Ptrend<0·001 to 0·013) in both men and women. The absolute mean differences in the IMT between the subjects in the extreme quartiles of serum carotenoid levels were 0·034 mm (α-carotene), 0·037 mm (β-carotene), 0·032 mm (lutein+zeaxanthin), 0·030 mm (β-cryptoxanthin), 0·015 mm (lycopene) and 0·035 mm (total carotenoids) at the CCA; the corresponding values were 0·025, 0·053 0·043, 0·050, 0·011 and 0·042 mm at the bifurcation. The favourable associations were also observed between dietary carotenoids (except lycopene) and the CCA IMT. In conclusion, elevated carotenoid levels in diet and serum are associated with lower carotid IMT values (particular at the CCA) in Chinese adults.
Attention-deficit hyperactivity disorder (ADHD) increases the risk of suicidal behaviours through psychiatric comorbidities; however, a significant direct association has not been observed between ADHD and suicide attempts.
To evaluate the risk of suicide attempt in adolescents and young adults with ADHD.
Using a nationwide, population-based insurance claims database, this longitudinal cohort study enrolled 20 574 adolescents and young adults with ADHD and 61 722 age- and gender-matched controls between 2001 and 2009. Any suicide attempt was identified from enrolment to 31 December 2011. The association between ADHD medications and the likelihood of suicide attempt was assessed.
ADHD was an independent risk factor for any suicide attempt (hazard ratio = 3.84, 95% CI = 3.19–4.62) and repeated suicide attempts (hazard ratio = 6.52, 95% CI = 4.46–9.53). Subgroup analyses of men, women, adolescents and young adults demonstrated the same trend. Methylphenidate or atomoxetine treatment did not increase the risk of suicide attempt or repeated suicide attempts. Long-term methylphenidate treatment was associated with a significantly decreased risk of repeated suicide attempts in men (hazard ratio = 0.46, 95% CI = 0.22–0.97).
ADHD was a risk factor for suicide attempt and a stronger predictor of repeated suicide attempts, independent of comorbidities. Further investigation is warranted to explore the mechanism underlying the association between ADHD and suicidal behaviours.
Apathy is a condition characterized by a lack of motivation that manifests in emotional, behavioral, and cognitive domains. Although previous studies have indicated that apathy is associated with frontal lesions, few studies have focused on the different subdomains of apathy, and no in vivo human biochemical data have been obtained to examine the neurochemical changes related to apathy in patients with Alzheimer's disease (AD). Thus, we investigated the frontal neurochemical alterations related to apathy among patients with AD using proton magnetic resonance spectroscopy (1H MRS).
Apathy was assessed through the Apathy Evaluation Scale (AES). 1H MRS was performed to measure neurochemical metabolite levels in the anterior cingulate region and right orbitofrontal region. Associations between neurochemical metabolites and the total score and subscores of each domain of the AES were analyzed.
Altogether, 36 patients completed the study. Patients with lower N-acetylaspartate/creatine ratios (NAA/Cr) in the anterior cingulate region demonstrated higher total apathy scores (β = −0.56, p = 0.003) with adjustments for age, gender, educational level, dementia severity, and depression severity. In a further analysis, a lower NAA/Cr in the anterior cingulate region was associated with all subdomains of apathy, including cognition (β = −0.43, p = 0.028), behavior (β = −0.55, p = 0.002), and emotion (β = −0.50, p = 0.005). No statistically significant associations were discovered in the right orbitofrontal region.
Our results suggest that apathy, in each of its cognitive, behavioral, or emotional subdomains is associated with brain neurochemical alterations in the anterior cingulate region. Abnormal neuronal integrity over the anterior cingulate cortex may exhibit a central role in causing all aspects of apathy in patients with AD.
We experimentally investigate the generation of above-threshold harmonics completely from argon atoms on an excited state using mid-infrared femtosecond laser pulses. The highly nonlinear dependences of the observed signal on the pulse energy and polarization of the probe laser pulses indicate its nonperturbative characteristic.
The purpose of this paper was to examine whether glaucoma could be a non-memory manifestation of Alzheimer's disease in older people.
We conducted a population-based, retrospective, case-control study to analyze the database of the Taiwan National Health Insurance Program. There were 1,351 subjects ≥65 years old with newly diagnosed Alzheimer's disease as the cases, and 5,329 subjects without any type of dementias as the controls during 2000–2011. The odds ratio (OR) and 95% confidence interval (CI) for the risk of Alzheimer's disease associated with glaucoma was estimated by the multivariable unconditional logistic regression model.
After controlling for confounders, the multivariable logistic regression model demonstrated that the adjusted OR of Alzheimer's disease was 1.50 in subjects with glaucoma (95% CI 1.19, 1.89), compared to subjects without glaucoma.
Older people with glaucoma are associated with 1.5-fold increased odds of Alzheimer's disease in Taiwan. Glaucoma may be a non-memory manifestation of Alzheimer's disease in older people. Further research is needed to confirm this issue.
A “RE-free” and I-phase-containing Mg–8Sn-based alloy system was developed and successfully fabricated through the equal channel angular pressing (ECAP) process. The influence of the Zn/Al mass ratio on the microstructures and mechanical properties of the as-ECAPed Mg–8Sn–(5,6,7)Zn–2(wt%)Al alloys was investigated using an optical microscope, an X-ray diffractometer, a scanning electron microscope, a transmission electron microscope, and a universal testing machine. Grain size, dynamic recrystallization behavior, and texture were found to be greatly affected by the Zn/Al mass ratio. Furthermore, the ultimate tensile strength (250 MPa) and elongation (14.5%) of the alloy with a Zn/Al mass ratio of 3 were considerably increased compared to those of the as-ECAPed alloys with Zn/Al ratios of 2.5 and 3.5 (ultimate tensile strength and elongation of 215 MPa and 13% and 184 MPa and 10%, respectively). This significant enhancement was attributed to extensive grain boundary strengthening, precipitation strengthening, and higher work hardening capacity as well as texture randomization. The strength and ductility of the as-ECAPed alloys are also discussed in terms of the I-phase and Mg2Sn formation.
The early Cambrian Period was a key interval in Earth history with regard to changes in both ocean chemistry and animal evolution. Although increasing ocean ventilation has been widely assumed to have played a key role in the rapid appearance, diversification and spatial colonization of early animals, this relationship is in fact not firmly established. Here, we report a high-resolution Fe-C-S-Al-Ti geochemical study of the lower Cambrian Wangjiaping section from an outer-shelf setting of the Yangtze Sea of South China. Iron speciation data document a redox transition from dominantly euxinic to ferruginous conditions during Cambrian Age 3 (c. 521–514 Ma). Interpretation of coexisting pyrite sulphur isotope (δ34Spy) records from Wangjiaping reveals relatively high marine sulphate availability at Wangjiaping. Furthermore, Wangjiaping section shows lower δ34Spy (‒2.1±5.3‰) and lower TOC (2.4±1.1%) values but higher positive correlation (R2 = 0.66, p < 0.01) between TOC and Fepy/FeHR relative to deeper sections reported previously, suggesting that euxinia developed at Wangjiaping in response to increasing marine productivity and organic matter-sinking fluxes. Our reconstructed redox conditions and fossils at Wangjiaping in comparison with previously well-studied strata in the inner-shelf Xiaotan and Shatan sections suggest that planktonic and benthic planktonic trilobites with bioturbation appeared in the oxic water columns, whereas only planktonic trilobites without bioturbation occurred within the anoxic (even euxinic) water columns during Cambrian Age 3. This finding indicates that spatial heterogeneity of redox conditions in the shelves had an important effect on early animal distribution in the Yangtze Block.
We report on a systematic experimental study on the fluorescence spectra produced from a femtosecond laser filament in air under a high electric field. The electric field alone was strong enough to create corona discharge (CD). Fluorescence spectra from neutral and ionic air molecules were measured and compared with pure high-voltage CD and pure laser filamentation (FIL). Among them, high electric field assisted laser FIL produced nitrogen fluorescence more efficiently than either pure CD or pure FIL processes. The nonlinear enhancement of fluorescence from the interaction of the laser filament and corona discharging electric field resulted in a more efficient ionization along the laser filament zone, which was confirmed by the spectroscopic measurement of both ionization-induced fluorescence and plasma-scattered 800 nm laser pulses. This is believed to be the key precursor process for filament-guided discharge.
Stable isotopic analysis of carbon and nitrogen in human and faunal remains has been widely used to reconstruct prehistoric diets and environmental changes. Isotopic analysis of plant remains allows for a more extensive consideration of paleodiets and can potentially provide information about the environment in which the crops were grown. This paper reports the results of δ13C and δ15N analyses performed on modern and charred archaeological foxtail millet samples collected from the western part of the Chinese Loess Plateau. The δ13C mean value of modern samples is lower than that of ancient samples. There is a significant difference between grain and leaf δ15N values. These results challenge the standard assumption in isotope studies that the nitrogen isotope signals of the different part of plants consumed by humans and animals are the same. The 3–5‰ difference between human and animal δ15N values is always regarded as an indicator of whether human diets contained considerable animal protein. The difference between grain and leaf δ15N values makes this assumption problematic in a foxtail millet-dominated society.
Previous evidence has shown positive associations between post-traumatic
stress disorder (PTSD) and hypertension, dyslipidaemia and diabetes
mellitus, which are all risk factors for stroke, but the role of PTSD in
the subsequent development of stroke is still unknown.
To investigate the temporal association between PTSD and the development
Identified from the Taiwan National Health Insurance Research Database,
5217 individuals aged 18 years, with PTSD but with no history of stroke,
and 20 868 age- and gender-matched controls were enrolled between 2002
and 2009, and followed up until the end of 2011 to identify the
development of stroke.
Individuals with PTSD had an increased risk of developing any stroke
(hazard ratio (HR) 3.37, 95% CI 2.44–4.67) and ischaemic stroke (HR =
3.47, 95% CI 2.23–5.39) after adjusting for demographic data and medical
comorbidities. Sensitivity tests showed consistent findings (any stroke
HR = 3.02, 95% CI 2.13–4.28; ischaemic stroke HR = 2.89, 95% CI
1.79–4.66) after excluding the first year of observation.
Individuals with PTSD have an increased risk of developing any stroke and
ischaemic stroke. Further studies are required to investigate the
In order to identify the density and material type, high energy protons, electrons, and heavy ions are used to radiograph dense objects. The particles pass through the object, undergo multiple coulomb scattering, and are focused onto an image plane by a magnetic lens system. A modified beam line at the Institute of Modern Physics of the Chinese Academy of Sciences has been developed for heavy-ion radiography. It can radiograph a static object with a spatial resolution of about 65 µm (1 σ). This paper presents the heavy-ion radiography facility at the Institute of Modern Physics, including the beam optics, the simulation of radiography by Monte Carlo code and the experimental result with 600 MeV/u carbon ions. In addition, dedicated beam lines for proton radiography which are planned are also introduced.