[Association between heavy metal mixed exposure and neonatal birth weight in pregnancy].

The impact of prenatal exposure to a mixture of heavy metals on birth weight in newborns has been a topic of ongoing interest. In this study, 258 mothers and infants from the New Hampshire Birth Cohort Study (NHBCS) were selected as the study subjects, and the concentrations of seven heavy metals in the placenta, including Aluminum (Al), Cobalt (Co), Chromium (Cr), Nickel (Ni), Plumbum (Pb), Selenium (Se) and Arsenic (As) were collected. And the birth weight of newborns, the relevant covariates of mothers and newborns were collected. Three analytical methods, Weighted Quantile Sum (WQS) regression, Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) were employed. After adjusting for maternal gestational age, pre-pregnancy BMI, smoking status, education level, parity, gestational age and newborn gender, the combined three methods showed that the total effect of mixed exposure of seven heavy metals on birth weight was negative. Specifically, the WQS analysis revealed that Se had the greatest impact on birth weight, followed by Al. The QGC results showed that the heavy metal associated with the reduction of birth weight was mainly Se and Al in female and male infants, respectively. The BKMR analysis demonstrated a negative combined effect of the seven heavy metals on birth weight in both male and female infants, with Se having the highest posterior inclusion probabilities (PIPs) for female infants (0.45), and Al having the highest PIPs for male infants (0.64) after stratification by gender. In summary, mixed exposure to heavy metals during pregnancy was associated with a decrease in newborn birth weight. Furthermore, there are gender effects with Se and Al associated with decreased birth weight in female and male infants, respectively. These findings provide a theoretical basis for the development of public health policies aimed at preventing adverse pregnancy outcomes and improving the health of newborns.

[????The diagnostic performance of the combination of ASL and TOF MRA for the cerebral arteriovenous shunt].

Objective: To evaluate the diagnostic performance of the combination of arterial spin labeling (ASL) and time of flight MR angiography (TOF MRA) for intracranial arteriovenous shunt (AVS) detection. Methods: A total of 39 patients with known or suspected with cerebrovascular malformations underwent digital subtraction angiography (DSA) and ASL/TOF MRA imaging in Department of neurosurgery and radiology and nuclear medicine, Xuanwu Hospital from May 1, 2020 to October 31, 2020 were retrospectively analyzed. Patients were divided into either acute cerebral hemorrhage group (n=13) or non-acute cerebral hemorrhage group (n=26) based on the signs of bleeding on imaging findings. According to history of treatment, those patients were divided into treated (n=11) and untreated (n=28) subgroups. The determination of the presence of AVS on images was judged by two radiologists in a blinded and randomized order fashion. The diagnostic performance of ASL or TOF MRA for AVS were evaluated in overall, acute cerebral hemorrhage subgroup and treated subgroup by using the area under receiver operating curve (AUC) with DSA as the reference standard, respectively. The κ coefficients were calculated to determine the interobserver agreement. Results: Among 39 patients, 29 patients were confirmed with AVS by DSA while 10 patients with no AVS. Interobserver agreement was good-excellent (κ=0.83-1.00). In patients with AVM, the detection rates for AVS of ASL or TOF MRA were 93.1% and 86.2% respectively, while the detection rates of the combination of ASL and TOF MRA were 100%. The AUC of ASL, TOF MRA and their combination for diagnosis of AVS in overall were 0.966 (95%CI: 0.909-1.00), 0.914 (95%CI: 0.825-1.00) and 0.983 (95%CI:0.943-1.00), respectively. The AUC of ASL, TOF MRA and their combination for AVS in acute cerebral hemorrhage subgroup were 1(95%CI:1.00-1.00), 0.833(95%CI:0.611-1.00), 1(95%CI:1.00-1.00), respectively. Conclusion: Combination of ASL and TOF MRA can be a non-invasive thchnique for the detection of AVS.

Prevention of hypoxic pulmonary hypertension by hypoxia-inducible expression of p27 in pulmonary artery smooth muscle cells.

Hypoxia-induced proliferation of pulmonary artery smooth muscle cells (SMCs) is important in the development of hypoxic pulmonary hypertension (HPH). We constructed a lentivirial vector containing a smooth muscle-specific promoter and six copies of hypoxia response element to co-drive the expression of p27, the key cyclin-dependent kinase inhibitor that blocks the G1 to S phase transition in cell cycle progression, in pulmonary artery SMCs in hypoxia. Then in vivo we examined the prevention effects of the vector on HPH in mice and in vitro the specificity on the hypoxia-inducible expression of p27 in pulmonary artery SMCs. Hypobaric hypoxia for 4 weeks resulted in significant increases in the right ventricular systolic pressure, the ratio of right ventricle to left ventricle plus septal weight and the muscularization of pulmonary vessels in mice. Administration of the vector before hypoxia significantly prevented the effects of hypoxia. In vitro, the vector exhibited hypoxic inducibility and relatively specific expression in pulmonary artery SMCs, inhibited the hypoxia-induced proliferation of pulmonary artery SMCs and arrested more cells at G0/G1 phase. These results demonstrate that the hypoxia-inducible p27 expression prevents the development of HPH in mice.

[Comparison of inhibitory effects of three natriuretic peptides on the proliferation of pulmonary artery smooth muscle cells of rats].

The inhibitory effects of atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) and vasonatrin peptide (VNP) on the proliferation of pulmonary artery smooth muscle cells (PASMCs) were compared in rats. Total protein and OD value of MTT were detected in cultured rat PASMCs to examine the influence of the three peptides on PASMC proliforation induced by phorbol 12-myristate 13-acetate (PMA). The results show that PMA (10( 9) 10( 7) mol/L) increased and VNP (10( 8) 10( 6) mol/L), ANP and CNP (10( 7) 10( 6) mol/L) decreased the total protein and OD value in a dose-dependent manner (P<0.05). The data above suggest that PMA stimulates the proliferation of PASMCs while the three peptides inhibit the proliferation induced by PMA. Of the three peptides VNP has the strongest inhibitory effect.

[Vasonatrin peptide attenuates hypoxia-induced increase in [Ca(2+)] (i) of culured rat cardiac fibroblasts].

The purpose of this work was to test the hypothesis that vasonatrin peptide (VNP) can attenuate the growth-promoting effect by hypoxia in cardiac fibroblasts of cultured neonatal rats. Cultured fibroblasts were divided into four groups: control group, hypoxia group, VNP group and VNP+hypoxia group. The growth of cardiac fibroblasts was observed using MTT method and the incorporation of (3)H-TdR, and the effect of VNP on the intracellular level of Ca(2+) was measured by means of interactive laser cytometry. It was found that hypoxia (2% - 3%) increased significantly the MTT optical density (OD) of cardiac fibroblasts (P<0.05 vs control group), but the increase was greatly attenuated in the VNP (10(- 6)mol/L) group and also the incorporation of (3)H-TdR in cardiac fibroblasts (P<0.05 vs hypoxia group). VNP (10(- 6)mol/L) also decreased the intracellular level of Ca(2+) which was increased by hypoxia (P<0.05) as compared with control and hypoxia group. These findings demonstrate that VNP can attenuate the hypoxia-induced growth-promoting effect in cardiac fibroblasts, which may be associated with the elevation of intracellular Ca(2+).

[Comparison of sensitivity of mental load assessment indexes].

Objective. To compare the sensitivities of indexes used in the assessment of mental load. Method. Twenty five indexes belonging to primary task performance, additional task performance, subjective rate and psychophysiological measure were recorded during performance of 11 different difficult tasks. Result. It showed that tracking error (ER), reaction time (RT), correct rate (CR), category scale (CS), multistage evaluation scale (MES), multi-dimensional scale (MDS), latency of P3 (LAT), inter beat interval (IBI), inter respiration interval (IRI) and blink rate (BR) were significantly different among the various tasks. CS, MES and MDS were more sensitive to the total load; ER, LAT, IBI and IRI were more sensitive to the load of primary task, while RT and CR to that of additional task and BR to the visual load. Conclusion. It demonstrated that the sensitivities of the various indexes are different and the information are limited. Multi-indexes may be preferred for mental load assessment.

Multiple RGS proteins alter neural G protein signaling to allow C. elegans to rapidly change behavior when fed.

Regulators of G protein signaling (RGS proteins) inhibit heterotrimeric G protein signaling by activating G protein GTPase activity. Many mammalian RGS proteins are expressed in the brain and can act in vitro on the neural G protein G(o), but the biological purpose of this multiplicity of regulators is not clear. We have analyzed all 13 RGS genes in Caenorhabditis elegans and found that three of them influence the aspect of egg-laying behavior controlled by G(o) signaling. A previously studied RGS protein, EGL-10, affects egg laying under all conditions tested. The other two RGS proteins, RGS-1 and RGS-2, act as G(o) GTPase activators in vitro but, unlike EGL-10, they do not strongly affect egg laying when worms are allowed to feed constantly. However, rgs-1; rgs-2 double mutants fail to rapidly induce egg-laying behavior when refed after starvation. Thus EGL-10 sets baseline levels of signaling, while RGS-1 and RGS-2 appear to redundantly alter signaling to cause appropriate behavioral responses to food.

Binding of ATP to the fructose-2,6-bisphosphatase domain of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase leads to activation of its 6-phosphofructo-2-kinase.

To understand the mechanism by which the activity of the 6-phosphofructo-2-kinase (6PF-2K) of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is stimulated by its substrate ATP, we studied two mutants of the enzyme. Mutation of either Arg-279, the penultimate basic residue within the Walker A nucleotide-binding fold in the bisphosphatase domain, or Arg-359 to Ala eliminated the activation of the chicken 6PF-2K by ATP. Binding analysis by fluorescence spectroscopy using 2'(3')-O-(N-methylanthraniloyl)-ATP revealed that the kinase domains of these two mutants, unlike that of the wild type enzyme, showed no cooperativity in ATP binding and that the mutant enzymes possess only the high affinity ATP binding site, suggesting that the ATP binding site on the bisphosphatase domain represents the low affinity site. This conclusion was supported by the result that the affinity of ATP for the isolated bisphosphatase domain is similar to that for the low affinity site in the wild type enzyme. In addition, we found that the 6PF-2K of a chimeric enzyme, in which the last 25 residues of chicken enzyme were replaced with those of the rat enzyme, could not be activated by ATP, despite the fact that the ATP-binding properties of this chimeric enzyme were not different from those of the wild type chicken enzyme. These results demonstrate that activation of the chicken 6PF-2K by ATP may result from allosteric binding of ATP to the bisphosphatase domain where residues Arg-279 and Arg-359 are critically involved and require specific C-terminal sequences.

Intrathymic delta selection events in gammadelta cell development.

The major pathway of gammadelta cell development is shown to be regulated by in-frame rearrangements at the T cell receptor (TCR) delta locus. Such "delta selection" occurs at or around the same point in thymocyte development as selection for in-frame rearrangements at the TCRbeta locus. However, there are at least two major differences with beta selection: first, delta selection commonly involves selection on the cognate TCR chain, gamma, suggesting that there is no "preTgamma" chain of major biological significance; second, most gammadelta-selected thymocytes differentiate rather than proliferate. Nonetheless, some delta selection events seemingly facilitate thymocyte expansion, similar to alphabeta T cell development. In these cases, TCRgamma selection is less obvious. Furthermore, the capacity of individual gamma chains to facilitate gammadelta selection is shown to vary with developmental age. The results further clarify early T cell development at the beta selection/delta selection stage and place clear constraints on models of cell fate determination.

Expression of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in Escherichia coli.

Chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was expressed in E. coli by using a pET3a T7 RNA polymerase-based expression system and was purified to homogeneity. The kinase and bisphosphatase of the expressed bifunctional enzyme had kinetic properties identical to those of the native chicken liver enzyme. However, the kinase activity of the chicken liver enzyme was 7-fold higher, while the bisphosphatase activity was 50 percent lower than those of the rat liver enzyme. Cys-256 of the rat liver bisphosphatase domain is not conserved in the chicken liver enzyme. A site-directed mutation was engineered at Cys-256 of the rat liver enzyme and the results indicate that the variation of this residue is not responsible for the difference in fructose-2,6-bisphosphatase activity between the rat and chicken liver enzymes. It is postulated that the difference in the kinase/bisphosphatase activity ratios of these two enzymes results from differences in their NH2-terminal regions.