Towards Understanding {10-11}-{10-12} Secondary Twinning Behaviors in AZ31 Magnesium Alloy during Fatigue Deformation.

Tensile-compression fatigue deformation tests were conducted on AZ31 magnesium alloy at room temperature. Electron backscatter diffraction (EBSD) scanning electron microscopy was used to scan the microstructure near the fatigue fracture surface. It was found that lamellar {10-11}-{10-12} secondary twins (STs) appeared inside primary {10-11} contraction twins (CTs), with a morphology similar to the previously discovered {10-12}-{10-12} STs. However, through detailed misorientation calibration, it was determined that this type of secondary twin is {10-11}-{10-12} ST. Through calculation and analysis, it was found that the matrix was under compressive stress in the normal direction (ND) during fatigue deformation, which was beneficial for the activation of primary {10-11} CTs. The local strain accommodation was evaluated based on the geometric compatibility parameter (m') combined with the Schmid factor (SF) of the slip system, leading us to propose and discuss the possible formation mechanism of this secondary twin. The analysis results indicate that when the local strain caused by basal slip at the twin boundaries cannot be well transmitted, {10-11}-{10-12} STs are activated to coordinate the strain, and different loading directions lead to different formation mechanisms. Moreover, from the microstructure characterization near the entire fracture surface, we surmise that the presence of such secondary twins is not common.

Correlation of Great Chinese Famine Exposure During Early Life to Prevalence of Kidney Stone in Adulthood.

Background: The Great Chinese Famine, as the famine of 1959-1961 was often known. Famine exposure during early life was proven to be associated with some kidney diseases but has not been studied with kidney stone. We aimed to investigate the relationship between exposure to the Great Chinese Famine in early life and the incidence of kidney stone in adulthood. Methods: From 1 January 2017 to 31 December 2018, a total of 19,658 eligible adults were recruited in a cross-sectional survey who were born between 1 October 1952 and 30 September 1964 in Guangdong, China. Participants were separated into kidney stone and none-kidney stone groups based on kidney stone status. According to birth data, participants were divided into non-exposed, fetal-exposed, early-, mid-, and late-childhood-exposed groups. Multivariate logistic regression, subgroup analysis and interaction test were used to estimate the odds ratios (ORs) and confidence intervals (CIs) between famine exposure and kidney stone. Results: In total, 19,658 (12,246 female, mean age 59.31 ± 3.68 years) subjects were enrolled, and 3219 (16.38%) participants with kidney stone. The prevalence of kidney in none-, fetal-, early-, mid-, and late-childhood-exposed groups were 645 (14.9%), 437 (15.9%), 676 (16.3%), 743 (17.0%), and 718 (17.6%), respectively (P<0.001). When compared with the unexposed group, the fully adjusted ORs for kidney stone from fetal-exposed, early-, mid- to late-childhood-exposed groups were 1.37 (95% CI: 1.13, 1.68, P=0.002), 1.98 (95% CI: 1.45, 2.72, P<0.001), 2.94 (95% CI: 1.96, 4.42, P<0.001), and 3.48 (95% CI: 2.11, 5.72, P<0.001), respectively (P for trend<0.001). Subgroup analyses revealed no interactions between the famine effect on kidney stones and body mass index, gender, smoking status, history of diabetes or hypertension (all P for interaction >0.05). Conclusion: This study found that exposure to the Great Chinese Famine during early life was independently associated with the increased incidence of kidney stone in adulthood.

Association between sedentary behavior and depression in US adults with chronic kidney disease: NHANES 2007-2018.

BACKGROUND: Depression increases the risk of adverse clinical outcomes in patients with chronic kidney disease. Physical activity has been shown to improve depressive symptoms in this population, but the relationship of sedentary behavior with depression has not been studied. In this study, we examined the relationship between sedentary behavior and depression in patients with chronic kidney disease. METHODS: This cross-sectional study included 5,205 participants aged ≥ 18 years with chronic kidney disease participating in the 2007-2018 National Health and Nutrition Examination Survey. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Recreation activity, work activity, walking or cycling for transportation, and sedentary behavior were measured using the Global Physical Activity Questionnaire. A series of weighted logistic regression models were used to investigate the aforementioned relationship. RESULTS: The prevalence of depression among US adults with chronic kidney disease was 10.97% in our study. In addition, sedentary behavior was strongly associated with higher levels of depressive symptoms, as measured by the PHQ-9 (P < 0.001). In the fully adjusted model, we found that compared with participants who had shorter durations of sedentary behavior, participants who had the highest durations of sedentary behavior had 1.69 times (odd ratio 1.69, 95% confidence interval: 1.27, 2.24) greater risk of being clinically depressed. After adjusting for confounding factors, subgroup analyses showed that the association between sedentary behavior and depression still existed in all stratifications. CONCLUSION: We found an association between longer duration of sedentary behavior and more severe depression in US adults with chronic kidney disease; however, prospective studies with larger sample sizes are still needed to confirm the effects of sedentary behavior on depression in the chronic kidney disease population.

Role of oral and gut microbiota in childhood obesity.

Childhood obesity not only causes damage to children's respiratory, cardiovascular, endocrine, motor, and other systems but also is a significant risk factor for metabolic diseases such as obesity in adulthood, which has become one of the serious public health problems worldwide. The etiology and pathogenesis of obesity are complex. In addition to genetic and lifestyle factors, recent studies have found that the microbes in the digestive tract play a crucial role in the occurrence and development of obesity. Among them, the gut microbiota has been confirmed to be one of the important pathogenic factors of obesity, which can mediate the occurrence and development of obesity by interfering with the balance of host energy metabolism and inducing low-grade chronic inflammation throughout the host. Targeting the gut microbiota to treat obesity through various methods such as fecal microbiota transplantation, dietary intervention, and probiotic supplementation has become a research hotspot in obesity treatment. In addition, the oral microbiota is also considered closely related to the occurrence and development of obesity due to its regulatory effect on the balance of gut microbiota. Exploring the relationship between oral and gut microbiota and childhood obesity elucidates the pathogenesis and treatment concepts of childhood obesity from a new perspective. It may provide new methods for the prevention and treatment of childhood obesity in the future.

Influence of Environmental Factors on Salivary Microbiota and Their Metabolic Pathway: Next-Generation Sequencing Approach.

The current study aimed to investigate the effect of periodontitis and long-term heavy metal (HM) exposure on the salivary microbiome. The patients were divided into four groups as Wu Wei control (WWC) group involved healthy individuals, Wu Wei periodontitis (WWP) patients having periodontitis, Jing Chang with metal pollution periodontally healthy individuals (JCP), and Kuang periodontitis (KP). The most abundant bacteria identified at the phylum level in the WWC group were Bacteroides, Firmicutes, and Fusobacteria. Firmicutes were observed in a significantly higher proportion in the KP group than in the WWC, WWP, and JCP. At the genus level, the WWC has major dominating bacterial genera (such as Leptotrichia, Neisseria, and Fusobacterium) which were similar to WWP and KP group. The significant difference (p < 0.05) was found in alpha diversity while in beta diversity, the significant (p = 0.005) results were found among the four groups. The correlation of oral microbiota revealed that HMs present in the soil (Cr, Ni, and Cu) are associated with the growth of Capnocytophaga, Selenomonas, Aggregatibacter, and Campylobacter. The bacterial functions in the KP group were higher in translation and nucleotide metabolism than in the WWP group. This demonstrated that long-term exposure to HMs can influence the salivary microbiota which can alter the functioning, and diversity of bacteria.

Association between serum Klotho concentration and all-cause and cardiovascular mortality among American individuals with hypertension.

Background and aims: Evidence indicates that serum Klotho concentration is associated with mortality in patients with chronic kidney disease (CKD). However, evidence on this association among people with hypertension is scarce. Therefore, we aimed to examine the association between serum Klotho concentration and all-cause and cardiovascular mortality in American patients with hypertension. Methods and results: We included 6,778 participants with hypertension from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. A Cox proportional hazard model was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs). The correlation between serum Klotho concentration and mortality was determined using restricted cubic spline and piecewise linear regression analyses. During 36,714 person-years of follow-up, 575 deaths were documented. Lower serum Klotho concentration was associated with increased all-cause mortality, but not cardiovascular mortality after multivariate adjustment. According to spline analysis, the correlation between serum Klotho concentration and all-cause mortality was non-linear (P < 0.001), and the threshold value was 574 pg/mL. The HR below the threshold point was 0.79 (95% CI: 0.67-0.93); no significant difference was found above the threshold point. Conclusion: Higher serum Klotho concentration was associated with lower all-cause mortality, but not cardiovascular mortality in patients with hypertension with or without chronic renal impairment.

The Relationship Between Famine Exposure During Early Life and Left Ventricular Hypertrophy in Adulthood.

Background: Although the evidence was still limited, some studies suggested that childhood malnutrition might affect cardiac function and structure in adulthood. To address the knowledge gap, this study investigated if the Great Chinese Famine exposure during early life had affected left ventricular hypertrophy (LVH). Methods: This research was a cross-sectional study. It included participants who had cardiac ultrasound assessments and were born in Guangdong, China, from 1 October 1952 to 30 September 1964. They were classified according to their exposure period to famine, namely, no exposure, fetal-, early-, mid-, and late childhood. Multivariate logistic regression and subgroup analysis have been conducted to determine the odds ratio (OR) and confidence intervals (CIs) between famine exposure and LVH. Results: This research included 2,543 participants, 1,612 women, their mean age was 59.07 ± 3.65 years, and 704 participants had LVH. LVH prevalence was 122 (23.6%), 87 (25.1%), 133 (27.3%), 184 (29.2%), and 178 (31.7%), in non-, fetal-, early-, mid-, and late-childhood exposed groups, respectively (p = 0.031), while in the non-exposed group, the ORs for developing carotid plaque as a result of fetal, early-, mid- to late-childhood exposure were 1.08 (95% CI: 0.76, 1.59, p = 0.619), 1.24 (95% CI: 1.03, 1.79, p = 0.031), 1.49 (95% CI: 1.10, 2.01, p = 0.009), and 1.64 (95% CI: 1.25, 2.18, p = 0.001), respectively (p for trend = 0.003). There was no interactive effect between gender, obesity, or hypertension history with how the famine influenced LVH, as the subgroups analyses demonstrated (all p for interaction > 0.05). Conclusion: This research has demonstrated the potential relationship between Great Chinese Famine exposure during childhood and LVH in adults.

A Non-Linear Association of High-Density Lipoprotein Cholesterol with All-Cause and Cause-Specific Mortality in Diabetic Patients.

BACKGROUND: The association between high-density lipoprotein cholesterol (HDL-C) and the risk of death among people with diabetes remains to be verified. METHODS: This was a nationwide, population-based cohort study in United States. A total of 6549 diabetes patients were included from the National Health and Nutrition Examination Surveys (NHANES). HDL-C concentration was divided into quintiles, and the lowest risk group (Q4: 1.32 to 1.53 mmol/L) was used as reference. Multivariate Cox proportional hazards models and restrictive cubic curves were performed to estimate hazard ratios (HRs) with 95% confidence interval (CI) for all-cause and cause-specific mortality. RESULTS: During a median follow-up of 82.36 ± 50.11 months, 1546 (23.61%) cases of all-cause, 389 (5.94%) cardiovascular and 262 (4.00%) cancer mortality have occurred, respectively. After adjusting for potential covariates, a U-shaped association was found between HDL-C and all-cause mortality (minimum mortality risk at 1.37 mmol/L); the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration <0.96 mmol/L (HR: 1.30; 95% CI: 1.09, 1.56; P=0.0046) and with HDL-C concentration ≥1.55 mmol/L (HR: 1.20; 95% CI: 1.00, 1.44; P=0.0481) than participants with HDL-C concentrations ranging from 1.32 to 1.53mmol/L. Nonlinear associations of HDL-C levels with both cardiovascular and cancer mortality were also observed. CONCLUSION: A non-linear association was observed association of HDL-C with all-cause, cardiovascular and cancer mortality among diabetic patients.

Visit-to-Visit Variability in Total Cholesterol Correlates with the Progression of Renal Function Decline in a Chinese Community-Based Hypertensive Population.

BACKGROUND: Studies have demonstrated that cholesterol variability is an independent predictor of cerebrovascular and cardiovascular events. OBJECTIVE: This study aimed to investigate the association of visit-to-visit variability in total cholesterol (TC) with kidney decline in a Chinese community-based population. METHODS: We assessed intraindividual variability in TC among 6,465 hypertensive participants and correlated the results with endpoints. TC variability was measured using standard deviation (SD), average successive variability (ASV), coefficient of variation (CV), and variability independent of the mean (VIM). The endpoint of this study was progression of renal function decline defined as a decrease in estimated glomerular filtration rate (eGFR) ≥30% and to a level <60 mL/min/1.73 m2 during follow-up if the baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR ≥50% during follow up if the baseline eGFR was <60 mL/min/1.73 m2. RESULTS: After a median follow-up of 27 months, 13.5% (n = 877) of the participants experienced progression of renal function decline. In the multivariable-adjusted Cox model, each 1-SD increase in TC variability (by SD) increased the risk of renal function decline by 11% (HR = 1.11; 95% CI 1.034-1.197; p = 0.004); this was independent of the baseline eGFR, mean follow-up TC levels, and the lipid-lowering therapy. Similar results were found for the 3 other measures of variability, i.e., ASV, CV, and VIM. CONCLUSION: In subjects with hypertension, visit-to-visit variability in TC is an independent predictor of renal function decline.

Expression of organic anion transporting polypeptide 1c1 and monocarboxylate transporter 8 in the rat placental barrier and the compensatory response to thyroid dysfunction.

Thyroid hormones (THs) must pass from mother to fetus for normal fetal development and require the expression of placental TH transporters. We investigate the compensatory effect of placental organic anion transporting polypeptide 1c1 (Oatp1c1) and monocarboxylate transporter 8 (Mct8) on maternal thyroid dysfunction. We describe the expressions of these two transporters in placental barriers and trophoblastic cell populations in euthyroidism and thyroid dysfunction resulting from differential iodine nutrition at gestation day (GD) 16 and 20, that is, before and after the onset of fetal thyroid function. Immunohistochemistry revealed that in the blood-placenta barrier, these two TH transporters were strongly expressed in the villous interstitial substance and were weakly expressed in trophoblast cells. Levels of Oatp1c1 protein obviously increased in the placental fetal portion during maternal thyroid deficiency at GD16. Under maternal thyroid deficiency after the production of endogenous fetal TH, quantitative PCR analysis revealed down-regulation of Oatp1c1 occurred along with up-regulation of Mct8 in trophoblast cell populations isolated by laser capture microdissection (LCM); this was consistent with the protein levels in the fetal portion of the placenta. In addition, decreased D3 mRNA at GD16 and increased D2 mRNA on two gestational days were observed in trophoblast cells with thyroid dysfunction. However, levels of Oatp1c1 mRNA at GD16 and D3 mRNA at GD20 were too low to be detectable in trophoblast cells. In conclusion, placental Oatp1c1 plays an essential compensatory role when the transplacental passage of maternal THs is insufficient at the stage before the fetal TH production. In addition, the coordinated effects of Oatp1c1, Mct8, D2 and D3 in the placental barrier may regulate both transplacental TH passage and the development of trophoblast cells during thyroid dysfunction throughout the pregnancy.

Thyroid dysfunction during late gestation is associated with excessive iodine intake in pregnant women.

CONTEXT: Adequate iodine intake during pregnancy is essential for both the synthesis of maternal thyroid hormones and the maintenance of normal fetal brain development. Scant evidence is available on the effects of excessive iodine intake during pregnancy. OBJECTIVE: The study assesses the relationship between iodine nutritional status and thyroid function of pregnant women with excessive iodine intake during late gestation. DESIGN AND PARTICIPANTS: A cross-sectional study of 384 pregnant women was carried out in Tianjin and Haixing from April to October in 2010. MAIN OUTCOME MEASURES: Morning urine samples and blood samples were obtained from all subjects. Serum levels of free T(3), free T(4), and sensitive TSH and urinary iodine concentration were measured. RESULTS: The median urinary iodine concentration of pregnant women with excessive iodine intake was significantly higher than those with adequate iodine intake (P < 0.001). The prevalence of thyroid disease, especially subclinical hypothyroidism, in pregnant women with excessive iodine intake was significantly higher than in those with adequate iodine intake (P < 0.05). Subclinical hypothyroidism was the most frequent pattern of thyroid disease for pregnant women and those with positive or negative thyroid autoantibodies. Living with high water iodine content and having urinary iodine concentration higher than 250 µg/liter are associated risk factors for subclinical hypothyroidism in pregnant women (OR(1) = 41.822, OR(2) = 6.202; P < 0.05, where OR(1) is the odds ratio for living with high water iodine content and hypothyroidism and OR(2) is the odds ratio for urinary iodine concentration >250 µg/liter and hypothyroidism). CONCLUSIONS: Excessive iodine intake during late pregnancy may lead to maternal thyroid dysfunction, particularly subclinical hypothyroidism. The appropriate measurements should be performed to monitor the onset of hypothyroidism in pregnant women with excessive iodine intake.

Adipose tissue-derived stem cells embedded with eNOS restore cardiac function in acute myocardial infarction model.

This study assessed the potential therapeutic efficacy of endothelial NO syntheses (eNOS)-expressing adipose tissue-derived stem cells (ADSCs) on infarcted hearts. We isolated CD29+, CD44+, CD45- cells from adipose tissue. Multipotent property of ADSCs was characterized by induction to differentiate into myogenic, neurogenic, and endothelic lineages. We hypothesized that combination of eNOS over-expression and transplantation of ADSCs could restore NO bioavailability and improve cardiac function in infarcted hearts. Here with several lines of experimental evidences, we demonstrated that ADSCs with eNOS overexpression induced eNOS expression in host endothelial cells and vascular smooth muscle cells, both in vitro and in vivo. This effect was possibly mediated by calcium signal. Transplantation of ADSCs with eNOS embedded showed great therapeutic efficacy in reduction of infarcted size, compared with normal ADSC. Results of this study suggest that ADSCs could be an attractive vehicle for the exogenous eNOS expression into heart after infarction, which is beneficial to restoration of cardiac function. Paracrine effect by mobilizing the host endothelial cells and smooth muscle cells may be the mechanism underlying the therapeutic effect.

Trimester- and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals.

OBJECTIVE: The importance of diagnosis and treatment of thyroid dysfunction during pregnancy has been widely recognized. We therefore established trimester- and method-specific reference intervals for thyroid testing in pregnant women according to the NACB recommended criteria. Several factors can affect the setting of reference intervals, in particular manufacturer's methodology, euthyroid definition and iodine status. DESIGN: Cross-sectional dataset analysis. SUBJECTS: Five hundred and five normal pregnant women at different stages of gestation were rigorously selected for setting reference intervals. All were healthy, iodine sufficient, euthyroid and negative for both serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). MEASUREMENTS: Thyrotrophin (TSH), total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3) and anti-TPOAb and anti-TgAb were measured using the Bayer ADVIA Centaur system. Iodine content in drinking water, salt and urine was determined by national standard methods. The 2·5th and 97·5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. RESULTS: All participants had long-term consumption of iodized salt and median urinary iodine of 150-200 µg/l during each three trimester. The reference intervals for the first, second and third trimesters were, respectively, TSH 0·03-4·51, 0·05-4·50 and 0·47-4·54 mIU/l and FT4 11·8-21·0, 10·6-17·6 and 9·2-16·7 pmol/l. The manufacturer's method, euthyroid definition and iodine status may influence TSH and FT4 reference intervals. Alterations in thyroid hormone concentrations during pregnancy differed at different stage of gestation and to those of a nonpregnant state. CONCLUSIONS: The trimester- and method-based reference intervals for thyroid tests during pregnancy are clinically appropriate. Some variables should be controlled when establishing reference intervals.

Type 1 iodothyronine deiodinase activity and mRNA expression in rat thyroid tissue with different iodine intakes.

BACKGROUND: Type 1 deiodinase (D1) plays an important role in the metabolism of thyroid hormone and has close relationship with thyroid function. In this study we explore the effects of iodine intake on D1 activity and its mRNA expression and its possible mechanism. METHODS: Forty-eight Wistar rats were randomly divided into six groups with 8 in each: low iodine (LI), normal iodine (NI), five-fold iodine (HI(5)), ten-fold iodine (HI(10)), fifty-fold iodine (HI(50)), one hundred-fold iodine (HI(100)) group. Three months, six months and twelve months after admistration of potassium iodate, they were sacrificed and thyroids were excised. The expression of D1 mRNA in the thyroid tissue was determined by RT-PCR and D1 activity was analyzed by (125)I-rT3 as substrate. The thyroid hormone was measured with radioimmunoassay method. RESULTS: Compared with NI group, D1 mRNA expression in LI groups slightly decreased, and D1 activity greatly increased. Both T(3) and T(4) in thyroid tissue significantly decreased, but the T(3)/T(4) ratio increased. D1 mRNA expression decreased in all HI groups, and D1 activity was significantly lower in HI groups. There was a tendency of decrease in D1 activity with increased doses of iodine intakes. There was no significant difference in T(4) in thyroid tissue between HI groups and NI group, but a tendency of decrease in T(3) level was found in all HI groups. CONCLUSIONS: In the case of iodine deficiency, D1 activity increased greatly in order to convert more T(4) to T(3). Excess iodine can inhibit both D1 mRNA expression and its activity to protect organism from being injured by excessive T(3).

[Meta-analysis on the relationship between children's intelligence and factors as iodine deficiency, supplement iodine and excessive iodine].

OBJECTIVE: To estimate the role and extent of iodine deficiency, iodine supplement and iodine excess on mental development of children. METHODS: Meta-analysis was applied to study 128 independent items from 63 published and non-published papers and reports. The standards of references collected included: age of sample declared by references was 5 - 15; belong to comparison study; children lived in iodine deficiency disorders (IDD) and iodine excess areas; no difference of social economic and culture development level between the study group and the control group. RESULTS: Sixty-seven percent and 79% of the reports mainly involved severe IDD areas respectively. Hunter test of each studies, i.e. iodine deficiency, iodine supplement and excessive iodine group had not discovered statistic difference at the level of alpha = 0.05. The weighted average ES of damage affecting on children's intelligence by iodine deficiency achieved 0.69, which was equivalent to a marked drop in 10.4 IQ points [95% confidence interval (CI): 9.9 - 10.9] when comparing with the children living under non-IDD. The weighted average ES of protective effect on children's intelligence by iodine supplement reached 0.81, which meant that the IQ of children born after correction of iodine deficiency increased 12.2 points (95% CI: 11.5 - 12.9) in comparison with those born at least one year before the correction of iodine deficiency. Most of the references about the relationship between iodine excess and intelligence were gathered from proceedings, while the others were from journals. They location were in some areas of Shandong, Hebei, Shanxi and Inner Mongolia. The mean ES of the role of iodine excess on intelligence was 0.21, which was corresponding to 3.2 IQ points (95% CI: 2.5 - 4.0). CONCLUSION: 1) Iodine deficiency played a role of intermediate strength compared with other causes in delaying brain development making children to be at least 10 IQ points loss in IDD areas. 2) Effective iodine supplement plays a remarkable strengthening role in promoting brain development and can cause 12 IQ points increase for children who were born after the correction of iodine status. 3) Iodine excess has not shown significant important role in children's intelligence.