Circ_0068481 Affects the Human Pulmonary Artery Smooth Muscle Cells' Progression by miR-361-3p/KLF5 Axis.

BACKGROUND: Uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). In this work, we defined the precise part of circ_0068481 in PASMC proliferation and migration induced by hypoxia. We hypothesized that circ_0068481 enhanced hypoxia-induced PASMC proliferation, invasion, and migration through the microRNA (miR)-361-3p/Krüppel-like factor 5 (KLF5) pathway. METHODS: Human PASMCs (hPASMCs) were exposed to hypoxic (3% O2) conditions. Circ_0068481, miR-361-3p, and KLF5 levels were gauged by qRT-PCR and western blot. Cell viability, proliferation, invasion, and migration were detected by XTT, EdU incorporation, transwell, and wound-healing assays, respectively. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were performed to confirm the direct relationship between miR-361-3p and circ_0068481 or KLF5. RESULTS: Circ_0068481 expression was increased in the serum of PAH patients and hypoxia-induced hPASMCs. Downregulation of circ_0068481 attenuated hypoxia-induced promotion in hPASMC proliferation, invasion, and migration. Circ_0068481 directly targeted miR-361-3p, and miR-361-3p downregulation reversed the inhibitory effects of circ_0068481 silencing on hypoxia-induced hPASMC proliferation, invasion, and migration. KLF5 was a direct miR-361-3p target, and miR-361-3p upregulation mitigated hypoxia-induced hPASMC proliferation, invasion, and migration by inhibiting KLF5 expression. Moreover, circ_0068481-induced KLF5 expression by binding to miR-361-3p in hypoxic hPASMCs. CONCLUSIONS: Circ_0068481 knockdown ameliorated hypoxia-induced hPASMC proliferation, invasion, and migration at least in part through the miR-361-3p/KLF5 axis.

Effects of intermittent fasting on cardiometabolic risk factors in patients with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Evidence showed that intermittent fasting may have beneficial effects on metabolic syndrome. However, the results are controversial and indefinite. This study intends to investigate and assess the effects of intermittent fasting (IF) on cardiometabolic risk factors in patients with metabolic syndrome. METHODS AND STUDY DESIGN: We searched PubMed, Web of Science, Embase, and Cochrane Library databases up to July 31, 2022. Primary outcomes included body mass index, fat mass, fat free mass, body weight, blood pressure, the homeostasis model assessment of insulin resistance (IR), fasting blood glucose, fasting insulin, and lipid profiles. RESULTS: Of 4997 retrieved records, 6 met the inclusion criteria. The meta-analysis showed that IF can significantly reduce BMI (mean difference=-1.56 kg/m2, 95% CI: -2.62 to -0.51), fat mass (mean difference=-1.35%, 95% CI: -2.03 to -0.67), fat free mass (mean difference=-0.63%, 95% CI: -1.22 to -0.04), body weight (mean difference=-2.49 kg, 95% CI: -3.11 to -1.88), waist circumference (mean difference=-3.06 cm, 95% CI: -4.21 to -1.92), and HOMA-IR (mean difference=-0.62, 95% CI: -0.84 to -0.40) compared with non-fasting. However, no statistical difference was found in the SBP, DBP, TC, TG, LDL-C, HDL-C, fasting blood glucose, and fasting insulin comparing fasting and non-fasting group. Subgroup analyses suggested that study duration and sample size may be the source of heterogeneity for LDL-C. Sensitivity analysis indicated that our results are reliable and robust. CONCLUSIONS: IF could be used for patients with metabolic syndrome. Further studies with a larger sample size are needed to verify the effectiveness and safety of IF in patients with metabolic syndrome.

Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms.

Identification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. Various NGS based in-house developed and commercial myeloid neoplasm panels have been integrated into routine clinical practice. However, some genes frequently mutated in myeloid malignancies are particularly difficult to sequence with NGS panels (e.g., CEBPA, CARL, and FLT3). We report development and validation of a 48-gene NGS panel that includes genes that are technically challenging for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies ≥5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n = 2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9-99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n = 2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms even in technically challenging genes.

Protective effect of fermented Diospyros lotus L. extracts against the high glucose-induced apoptosis of MIN6 cells.

Date plum persimmon (Diospyros lotus L.) is a fruit crop from the Ebenaceae family. Its microorganism-fermented extract (DPEML) was shown to exhibit a hypoglycemic effect in our previous work. Here, we investigated the effects of DPEML fermented by Microbacterium flavum YM18-098 and Lactobacillus plantarum B7 on the high glucose-induced apoptosis of MIN6 cells and explored its potential cell protective mechanisms. DPEML ameliorated the apoptosis of MIN6 cells cultured under high glucose conditions, thereby improving cell viability. DPEML upregulated the Bcl-2/Bax mRNA ratio to obstruct an intrinsic apoptotic pathway and concomitantly downregulated the expression of the apoptosis-linked proteins, AIF, and Cyt-C, in high glucose-induced MIN6 cells. Furthermore, DPEML promoted the insulin secretion of MIN6 cells grown under chronically high-glucose conditions by upregulating Ins mRNA expression. In summary, our study suggested that DPEML is a promising functional food for the development of therapeutics for the treatment of Type 2 diabetes mellitus. PRACTICAL APPLICATIONS: We investigated the effects of DPEML fermented by Microbacterium flavum YM18-098 and Lactobacillus plantarum B7 on the high glucose-induced apoptosis of MIN6 cells and explored its potential cell protective mechanisms. DPEML ameliorated the apoptosis of MIN6 cells cultured under high glucose conditions, thereby improving cell viability. DPEML upregulated the Bcl-2/Bax mRNA ratio to obstruct an intrinsic apoptotic pathway and concomitantly downregulated the expression of the apoptosis-linked proteins, AIF and Cyt-C, in high glucose-induced MIN6 cells. Furthermore, DPEML promoted the insulin secretion of MIN6 cells grown under chronically high-glucose conditions by upregulating Ins mRNA expression. We suggested that DPEML is a promising functional food for the development of therapeutics for the treatment of Type 2 diabetes mellitus.

Separation, identification, and molecular docking of tyrosinase inhibitory peptides from the hydrolysates of defatted walnut (Juglans regia L.) meal.

Defatted walnut meal protein was hydrolyzed using alcalase to yield tyrosinase inhibitory peptides. After separation by ultrafiltration and Sephadex G-25, the fraction with the highest tyrosinase inhibitory activity was identified using liquid chromatography-tandem mass spectrometry and 606 peptides were obtained. Then, molecular docking was used to screen for tyrosinase inhibitory peptides and to clarify the theoretical interaction mechanism between the peptides and tyrosinase. A peptide with the sequence Phe-Pro-Tyr (FPY, MW: 425.2 Da) was identified and the synthesized peptide inhibited tyrosine monophenolase and diphenolase with IC50 values of 1.11 ± 0.05 and 3.22 ± 0.09 mM, respectively. The inhibition of tyrosinase by FPY was competitive and reversible. Good stability of FPY toward digestion was observed in an in vitro gastrointestinal digestion simulation experiment. These results indicated that FPY can be used as a potential tyrosinase inhibitor in the food, medicine, and cosmetics industries.

Effect of WeChat consultation group on residents staying at home in Sichuan and Chongqing regions during the Coronavirus Disease 2019 (COVID-19) outbreak in China: a cross-sectional study.

BACKGROUND: After the outbreak of Coronavirus in Wuhan, Hubei, in 2019, the disease rapidly spread to other parts of China as well as outside of China. Since the pandemic outbreak, the general public has been responsive to the national call to stay at home in quarantine. However, since doubts and anxiety related to the disease have been detected in the general public, in this study, we established the WeChat platform "Coronavirus Disease 2019 Voluntary Assistance Group in Sichuan and Chongqing regions" in January 2020, which was committed to providing professional consultation and psychological counseling services for residents in Sichuan and Chongqing during the Coronavirus Disease 2019 outbreak. Our aim was to analyze the consultation practices of residents in the WeChat assistance group and provide a reference for the similar "non-contact" voluntary service platforms aiming to implement consultations during the late pandemic period. METHODS: A cross-sectional study was conducted using the records containing the consultation content from the WeChat assistance groups in Sichuan and Chongqing between January 30 and March 1, 2020. Data on consultation content, changes in a number of consultation items, answers, knowledge on popular science, and expert advice were summarized, and the Pareto chart was used to analyze the primary and secondary factors of consultation content. RESULTS: The constituent ratio of "respiratory symptoms, masks, and disinfection" in consultation content ranked as the top three factors. Cumulatively, they occupied 49.77% of the content, thus resulting as the primary factors in the consultation content. The number of consultation items suddenly increased from 10 on the first day to 116 on the 7th day, resulting in a 1060% increased rate. There were 151 consultation factors, among which 130 (86.1%) were related to the Coronavirus Disease 2019, and 21 (13.9%) were unrelated to the Coronavirus Disease 2019. CONCLUSION: WeChat groups may be used as an effective means for providing assistance services for the public during the Coronavirus Disease 2019 outbreak.

Pooling of Upper Respiratory Specimens Using a SARS-CoV-2 Real-time RT-PCR Assay Authorized for Emergency Use in Low-Prevalence Populations for High-Throughput Testing.

BACKGROUND: Nucleic acid amplification testing is a critical tool for addressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Specimen pooling can increase throughput and conserve testing resources but requires validation to ensure that reduced sensitivity does not increase the false-negative rate. We evaluated the performance of a real-time reverse transcription polymerase chain reaction (RT-PCR) test authorized by the US Food and Drug Administration (FDA) for emergency use for pooled testing of upper respiratory specimens. METHODS: Positive specimens were selected from 3 prevalence groups, 1%-3%, >3%-6%, and >6%-10%. Positive percent agreement (PPA) was assessed by pooling single-positive specimens with 3 negative specimens; performance was assessed using Passing-Bablok regression. Additionally, we assessed the distributions of RT-PCR cycle threshold (Ct) values for 3091 positive specimens. RESULTS: PPA was 100% for the 101 pooled specimens. There was a linear relationship between Ct values for pooled and single-tested specimens (r = 0.96-0.99; slope ≈ 1). The mean pooled Ct shifts at 40 cycles were 2.38 and 1.90, respectively, for the N1 and N3 targets. The median Cts for 3091 positive specimens were 25.9 (N1) and 24.7 (N3). The percentage of positive specimens with Cts between 40 and the shifted Ct was 1.42% (N1) and 0.0% (N3). CONCLUSIONS: Pooled and individual testing of specimens positive for SARS-CoV-2 demonstrated 100% agreement, which demonstrates the viability of pooled specimens for SARS-COV-2 testing using a dual-target RT-PCR system. Pooled specimen testing can help increase testing capacity for SARS-CoV-2 with a low risk of false-negative results.

Expression patterns of intermediate filament proteins desmin and lamin A in the developing conduction system of early human embryonic hearts.

Since embryonic heart development is a complex process and acquisition of human embryonic specimens is challenging, the mechanism by which the embryonic conduction system develops remains unclear. Herein, we attempt to gain insights into this developmental process through immunohistochemical staining and 3D reconstructions. Expression analysis of T-box transcription factor 3, cytoskeleton desmin, and nucleoskeleton lamin A protein in human embryos in Carnegie stages 11-20 showed that desmin is preferentially expressed in the myocardium of the central conduction system compared with the peripheral conduction system, and is co-expressed with T-box transcription factor 3 in the central conduction system. Further, lamin A was first expressed in the embryonic ventricular trabeculations, where the terminal ramifications of the peripheral conduction system develop, and extended progressively to all parts of the central conduction system. The uncoupled spatiotemporal distribution pattern of lamin A and desmin indicated that the association of cytoskeleton desmin and nucleoskeleton lamin A may be a late event in human embryonic heart development. Compared with model animals, our data provide a direct morphological basis for understanding the arrhythmogenesis caused by mutations in human DES and LMNA genes.

Isl-1 positive pharyngeal mesenchyme subpopulation and its role in the separation and remodeling of the aortic sac in embryonic mouse heart.

BACKGROUND: Second heart field cells and neural crest cells have been reported to participate in the morphogenesis of the pharyngeal arch arteries (PAAs); however, how the PAAs grow out and are separated from the aortic sac into left and right sections is unknown. RESULTS: An Isl-1 positive pharyngeal mesenchyme protrusion in the aortic sac ventrally extends and fuses with the aortic sac wall to form a midsagittal septum that divides the aortic sac. The aortic sac division separates the left and right PAAs to form independent arteries. The midsagittal septum dividing the aortic sac has a different expression pattern from the aortic-pulmonary (AP) septum in which Isl-1 positive cells are absent. At 11 days post-conception (dpc) in a mouse embryo, the Isl-1 positive mesenchyme protrusion appears as a heart-shaped structure, in which subpopulations with Isl-1+ Tbx3+ and Isl-1+ Nkx2.5+ cells are included. CONCLUSIONS: The aortic sac is a dynamic structure that is continuously divided during the migration from the pharyngeal mesenchyme to the pericardial cavity. The separation of the aortic sac is not complete until the AP septum divides the aortic sac into the ascending aorta and pulmonary trunk. Moreover, the midsagittal septum and the AP septum are distinct structures.

Septation of the Intrapericardial Arterial Trunks in the Early Human Embryonic Heart.

BACKGROUND: Outflow tract (OFT) septation defects are a common cause of congenital heart disease. Numerous studies have focused on the septation mechanism of the OFT, but have reported inconsistent conclusions. This study, therefore, aimed to investigate the septation of the aortic sac and the OFT in the early embryonic human heart. METHODS: Serial sections of 27 human embryonic hearts from Carnegie stage (CS) 10 to CS19 were immunohistochemically stained with antibodies against α-smooth muscle actin (α-SMA) and myosin heavy chain. RESULTS: At CS10-CS11, the OFT wall was an exclusively myocardial structure that was continuous with the aortic sac at the margin of the pericardial cavity. From CS13 onward, the OFT was divided into nonmyocardial and myocardial portions. The cushion formed gradually, and its distal border with the OFT myocardium was consistently maintained. The aortic sac between the fourth and sixth aortic arch arteries was degenerated. At CS16, the α-SMA-positive aortopulmonary septum formed and fused with the two OFT cushions, thus septating the nonmyocardial portion of the OFT into two arteries. At this stage, the cushions were not fused. At CS19, the bilateral cushions were fused to septate the myocardial portion of the OFT. CONCLUSIONS: Data suggest that the OFT cushion is formed before the aortopulmonary septum is formed. Thus, the OFT cushion is not derived from the aortopulmonary septum. In addition, the nonmyocardial part of the OFT is septated into the aorta and pulmonary trunk by the aortopulmonary septum, while the main part of the cushion fuses and septates the myocardial portion of the OFT.

Identification of circulating microRNAs as diagnostic biomarkers for ovarian cancer:A pooled analysis of individual studies.

BACKGROUND: Circulating microRNAs (miRNAs) are proposed as promising non-invasive diagnostic biomarkers for many cancers. However, the diagnostic value of circulating miRNAs in ovarian cancer is inconsistent in different studies. Thus we performed this meta-analysis to systematically evaluate the diagnostic value of circulating miRNAs in ovarian cancer. METHODS: Eligible studies that were published prior to 30 June 2017 were searched from the PubMed, EMBASE, Cochrane Library, and Chinese National Knowledge Infrastructure. All analyses were performed using STATA 12.0 software. A bivariate regression was used to calculate pooled diagnostic accuracy estimates. RESULTS: A total of 36 studies from 16 publications were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating miRNAs for ovarian cancer diagnosis were 0.76 (95% confidence intervals (CI): 0.69, 0.81), 0.81 (95% CI 0.74, 0.87), 4.00 (95% CI 2.70, 5.30), 0.30(95% CI 0.24, 0.37) and 13.00 (95% CI 9.00, 19.00), respectively. The area under the summary receiver operating characteristic curve was 0.85 (95% CI 0.82, 0.88). Subgroup analyses showed that multiple miRNA assays yielded better diagnostic characteristics than a single miRNA assay, and plasma miRNAs were better than serum miRNAs for ovarian cancer detection. CONCLUSION: Circulating miRNAs, especially the combination of multiple circulating miRNAs, are promising biomarkers for the diagnosis of ovarian cancer. However, further large-scale prospective studies are necessary to validate the applicability of the miRNAs in the early detection of ovarian cancer.

Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

OBJECTIVE: The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. METHODS: The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. RESULTS: BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. CONCLUSION: Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP.

Y chromosome polymorphisms may contribute to an increased risk of male-induced unexplained recurrent miscarriage.

The present study aims to explore the relationship between the Y chromosome polymorphisms (1qh+, inv(9), 9qh+, 16qh+, group D/G, Yqh- and Yqh+) and the risk of unexplained recurrent miscarriage (URM). A total of 507 couples with URM were recruited as case group and 465 healthy couples as control group. The Y chromosome polymorphisms of the male individuals were analysed with the G-banding technique, and the results of the chromosome G-banding analysis were determined using the International Naming Standards of Human Genetics (ISCN). Logistic regression analysis was used to analyse the risk factors for URM. The detection rate of Y chromosome polymorphisms in the case group (12.03%) was higher than that in the control group (2.15%). Y chromosome polymorphisms were detected at significantly higher rates in the case group than in the control group. Using the normal Y chromosomes in individuals of the case group as reference, the partners of their counterparts were more likely to experience miscarriage. The couples who were Y chromosome-polymorphism carriers had shorter gestational age, increased frequency of URM and longer average interval between pregnancies. The results of logistic regression analysis revealed that Y chromosome polymorphisms, shorter gestational age, a higher frequency of miscarriage and longer pregnancy interval were independent risk factors for URM. Y chromosome polymorphisms may be associated with the risk of URM and may play an important role in the development of URM.

[Study of IR Property of Glow Discharge Polymer (GDP)].

To achieve the object of NIF ignition , it is required to prepare high density fuel targets . For DD layer, IR-layering can be used to improve its surface roughness. In this paper, glow discharge polymer (GDP) flat films and capsules were synthesized. The IR absorptive properties of GDP were thoroughly studied by using infrared spectrometer and microscopy while the extinction coefficients of GDP flat film at specific wavelengths were obtained. By comparing absorption properties of flat films and capsules, it is found that thermal treatments can lower the OH content of GDP and thus improve IR layering of DD ice. Finally, the needed IR power of integration sphere were estimated by using data obtained for future DD layering experiments in this paper. The results have laid a solid foundation for the implementation of DD IR layering.

Transcatheter closure of ventricular septal defect in patients with aortic valve prolapse and mild aortic regurgitation: feasibility and preliminary outcome.

OBJECTIVE: To evaluate the feasibility, safety and efficacy of transcatheter closure of ventricular septal defect (VSD) in patients with aortic valve prolapse (AVP) and mild aortic regurgitation (AR). METHODS: Between January 2008 and July 2014, transcatheter closure of VSD was attempted in 65 patients. RESULTS: The total intermediate closure successful rate in all subjects was 96.9%. During the perioperative period, no death, major bleeding, pericardial tamponade, occluder dislodgement, residual shunt or hemolysis occurred. Two procedures had been forced to suspend due to significant aggregation of device related aortic regurgitation, three cases of transient complete left bundle branch block occurred but did not sustain. At 1-year follow-up, no patients had residual shunts and complications. Furthermore, grade of residual AR were relieved in 61.9% (39/63) cases and degree of AVP were ameliorated in 36.5% (23/63) patients; CONCLUSIONS: Transcatheter closure VSD in selected patients with AVP and mild AR is technically feasible and highly effective. Long term safety and efficacy needs to be assessed.

Spatial and seasonal variations of the air pollution index and a driving factors analysis in china.

In this study, the daily air pollution index (API) of 110 cities based on ground monitoring was conducted on the 2011 data set from the Ministry of Environmental Protection of China. The pollutant concentrations, seasonal variations, and spatial autocorrelations were evaluated. The results show that the major principal pollutants in China are inhalable particles. In addition, the total number of clean days (API ≤ 50) is apparently smaller in the northern cities than in the southern cities as a result of fuel utilization and large-scale organized central heating. Seasonally, air pollution is most severe in winter and is caused by low-frequency rainfall, strong northwest winds, dry climate, and high energy consumption; this is followed by spring, which is a season of frequent sandstorms. According to spatial autocorrelation analysis, clusters with high API value agglomeration (High-High clusters) are mainly concentrated in the middle and northern parts of China, whereas clusters with low API agglomeration (Low-Low clusters) are principally concentrated in the southern parts of China due to a favorable climate and abundant rainfall. Meteorological data, including wind speed and temperature, have great impacts on API. The air quality effects of industrial structure, energy use, urban greening, and traffic congestion were also analyzed. With the ecological function of purifying the air, industries that use natural resources and urban greening could help to reduce API, whereas secondary industry and gas use, which have a positive coefficient, increase the API value. The risk of exposure to poor air quality is largest in the winter, smallest in the summer, and remains relatively unchanged in the spring and autumn.

Second heart field and the development of the outflow tract in human embryonic heart.

The second heart field (SHF) is indicated to contribute to the embryonic heart development. However, less knowledge is available about SHF development of human embryo due to the difficulty of collecting embryos. In this study, serial sections of human embryos from Carnegie stage 10 (CS10) to CS16 were stained with antibodies against Islet-1 (Isl-1), Nkx2.5, GATA4, myosin heavy chain (MHC) and α-smooth muscle actin (α-SMA) to observe spatiotemporal distribution of SHF and its contribution to the development of the arterial pole of cardiac tube. Our findings suggest that during CS10 to CS12, SHF of the human embryo is composed of the bilateral pharyngeal mesenchyme, the central mesenchyme of the branchial arch and splanchnic mesoderm of the pericardial cavity dorsal wall. With development, SHF translocates and consists of ventral pharyngeal mesenchyme and dorsal wall of the pericardial cavity. Hence, the SHF of human embryo shows a dynamic spatiotemporal distribution pattern. The formation of the Isl-1 positive condense cell prongs provides an explanation for the saddle structure formation at the distal pole of the outflow tract. In human embryo, the Isl-1 positive cells of SHF may contribute to the formation of myocardial outflow tract (OFT) and the septum during different development stages.

Gossypol exhibits a strong influence towards UDP-glucuronosyltransferase (UGT) 1A1, 1A9 and 2B7-mediated metabolism of xenobiotics and endogenous substances.

Gossypol, the polyphenolic constituent isolated from cottonseeds, has been used as a male antifertility drug for a long time, and has been demonstrated to exhibit excellent anti-tumor activity towards multiple cancer types. The toxic effects of gossypol limit its clinical utilization, and enzyme inhibition is an important facet of this. In the present study, in vitro human liver microsomal incubation system supplemented with UDPGA was used to investigate the inhibition of gossypol towards UGT1A1, 1A9 and 2B7-mediated metabolism of xenobiotics and endogenous substances. Estradiol, the probe substrate of UGT1A1, was selected as representative endogenous substance. Propofol (a probe substrate of UGT1A9) and 3'-azido-3'-deoxythimidine (AZT, a probe substrate of UGT2B7) were employed as representative xenobiotics. The results showed that gossypol noncompetitively inhibits UGT-mediated estradiol-3-glucuronidation and propofol O-glucuronidation, and the inhibition kinetic parameters (K(i)) were calculated to be 34.2 and 16.4 µM, respectively. Gossypol was demonstrated to exhibit competitive inhibition towards UGT-mediated AZT glucuronidation, and the inhibition kinetic parameter (K(i)) was determined to be 14.0 µM. All these results indicated that gossypol might induce metabolic disorders of endogenous substances and alteration of metabolic behaviour of co-administered xenobiotics through inhibition of UGTs' activity.

Bioaccessibility and risk assessment of cadmium from uncooked rice using an in vitro digestion model.

Cadmium (Cd)-contaminated rice is one of the most important sources of cadmium exposure in the general population from some Asian countries. This study was conducted to assess cadmium exposure from uncooked rice in rural mining areas based on the bioaccessible fraction of cadmium using an in vitro digestion model. The biotoxic effects of cadmium in uncooked rice from mining areas were much higher than those in the control area, based not only on their higher total concentration (52.49 vs. 7.93 µg kg(-1)), but also on their higher bioaccessibility (16.94% vs. 2.38%). In the mining areas, the bioaccessible fraction of cadmium in uncooked rice has a significant positive correlation with the total concentration of cadmium in rice and there was quarterly unsafe rice to the public in the mining areas. The results indicated that the in vitro digestion model could be a useful and economical tool for providing the solubilization or bioaccessibility of uncooked rice in the mining area. The results could be helpful in conducting future experiments of cooked rice in the vitro model.

[Remediation Pb, Cd contaminated soil in lead-zinc mining areas by hydroxyapatite and potassium chloride composites].

The composite agents containing potassium chloride (KCl) and Hydroxyapatite (HA) were used to remediate the lead and cadmium contaminated soil in Fenghuang lead-zinc mining-smelting areas, Hunan province. The objective of this study was to identify and evaluate the influence of Cl- to the fixing efficiency of Pb and Cd by HA. Two types of contaminated soil (HF-1, HF-2) were chosen and forty treatments were set by five different Hydroxyapatite (HA) dosages and four different Cl- dosages. The toxicity characteristic leaching procedure (TCLP) was used to evaluate the results. It showed that HA could efficiently fix the Pb and Cd from TCLP form. The maximum Pb-fixing efficiency and Cd-fixing efficiency of two types of soil were 83.3%, 97.27% and 35.96%, 57.82% when the HA: Pb: KCl molar ratio was 8: 1: 2. Compared to the fixing efficiency without KCl, KCl at the KCl: Pb molar ratio of 2 improved Pb-fixing efficiency and Cd-fixing efficiency by 6.26%, 0.33% and 7.74%, 0.83% respectively when the HA: Pb molar ratio was 8. Generally, Cl- can improve the Pb/Cd-fixing efficiency in heavy metal contaminated soil by Hydroxyapatite.