The Dynamic Changes in the Composition and Diversity of Vaginal Microbiota in Women of Different Pregnancy Periods.

The vaginal microbiota undergoes subtle changes during pregnancy, which may affect different pregnancy responses. This study used the Illumina MiSeq high-throughput sequencing method to analyze the 16S rRNA gene amplicons of pregnant women and the vaginal microbiota structure of pregnant women at different pregnancy periods. There were a total of 15 pregnant women, with 45 samples were taken from these women, within half a year before becoming pregnant, in the last trimester, and 42 days postpartum. Before and after pregnancy, the female vaginal microbiota was mainly composed of Firmicutes, followed by Actinobacteriota and Proteobacteria. The abundance of Lactobacillus was relatively high. The α-diversity and microbial abundance were relatively low, and there was no significant difference in microbial composition between the two. After childbirth, the diversity and abundance of women's vaginal bacterial communities were higher, with a decrease in the number of Firmicutes and a higher abundance of Actinobacteria, Proteobacteria, and Bacteroidota. There was a significant difference in the microbial community structure before and after pregnancy. This study showed that the microbiota structure of the vagina of pregnant women was similar to before pregnancy, but after childbirth, there were significant changes in the microbiota of the vagina, with a decrease in the number of probiotics and an increase in the number of harmful bacteria, increasing the risk of illness.

A Theoretical Study on the Spatiotemporal Variation in the Temperature Field in Linings of High-Water-Temperature Tunnels.

On the basis of the theory of unsteady heat conduction, discrete equations for the unsteady temperature field in the secondary linings of high-water-temperature tunnels when considering the hydration heat of lining concrete were derived and established. Spatiotemporal variation in the temperature field of tunnel linings was revealed through the analysis of numerical examples. Research demonstrates that the temperature of the secondary lining within a thickness range of approximately 15 cm near the tunnel clearance decreases sharply under the condition that the lining thickness is 35 cm. The higher the temperature on the lining's outer surface, the more drastically the lining temperature decreases. When considering the hydration heat of lining concrete, the lining temperature increases to a certain extent after a sudden drop, reaching stability after approximately 20 h, and the lining temperature is approximately 1-2 °C higher than that without taking concrete hydration heat into account. The temperature difference between the tunnel lining's core and its inner and outer surfaces is positively and negatively correlated with the temperature of the secondary lining's outer surface, respectively. When the temperature of the secondary lining's outer surface is not higher than 65 °C, the temperature difference between the tunnel lining's core and its inner and outer surfaces is less than 20 °C. Conversely, it partially or completely exceeds 20 °C, in which case an insulation method is recommended to utilize to prevent thermal cracks in secondary linings triggered via a high temperature difference.

New insights into the ambivalent role of YAP/TAZ in human cancers.

Hippo signaling was first identified in Drosophila as a key controller of organ size by regulating cell proliferation and anti-apoptosis. Subsequent studies have shown that this pathway is highly conserved in mammals, and its dysregulation is implicated in multiple events of cancer development and progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) (hereafter YAP/TAZ) are the downstream effectors of the Hippo pathway. YAP/TAZ overexpression or activation is sufficient to induce tumor initiation and progression, as well as recurrence and therapeutic resistance. However, there is growing evidence that YAP/TAZ also exert a tumor-suppressive function in a context-dependent manner. Therefore, caution should be taken when targeting Hippo signaling in clinical trials in the future. In this review article, we will first give an overview of YAP/TAZ and their oncogenic roles in various cancers and then systematically summarize the tumor-suppressive functions of YAP/TAZ in different contexts. Based on these findings, we will further discuss the clinical implications of YAP/TAZ-based tumor targeted therapy and potential future directions.

Large-Scale Model Test on Water Pressure Resistance of Lining Structure of Water-Rich Tunnel.

In order to solve the problem of testing the water pressure resistance of lining structures of water-rich tunnels and the difficulty of implementing the existing model tests, a large-scale model test method was proposed relying on the New Yuanliangshan Tunnel threatened by high pressure and rich water. This method creatively transformed the external water pressure of the lining structure into internal water pressure, and the conversion coefficient of water resistance of lining under different sizes and loading modes was obtained by numerical calculation. Results showed that the ultimate water pressure resistance of the lining structure under an external uniformly distributed water pressure and local water pressure was 1.44 and 0.67 times of that obtained from the large-scale model tests, respectively. By conducting the large-scale model tests and combining with the conversion coefficient, the water pressure resistance of the actual tunnel lining could be obtained. Research indicated that water pressure resistance of K2.0 (bearing water pressure of 2.0 MPa) type lining at the transition section of karst caves and K3.0 (bearing water pressure of 3.0 MPa) type lining at the section of karst caves of the New Yuanliangshan Tunnel was 3.33 MPa and not less than 4.36 MPa, respectively, and the high reliability of the large-scale model tests was verified by numerical calculation, implying that the model test method could be extended to similar tunnel projects.

Spraying sorbitol-chelated calcium affected foliar calcium absorption and promoted the yield of peanut (Arachis hypogaea L.).

The prevalent use of foliar calcium fertilizers in peanut production is inorganic, but calcium absorbed from the foliar has poor availability. Sorbitol-chelated calcium is a novel organic foliar calcium fertilizer that has rarely been studied for application in peanut production. To explore whether calcium absorption and peanut yields can be affected by foliar application of sorbitol-chelated calcium, this study conducted two field experiments using Virginia peanut (Huayu-22) in 2020 and 2021. The five spray treatments included: deionized water (CK), sorbitol (Sor), calcium nitrate (CaN), a mixture of sorbitol and calcium nitrate (SN), and sorbitol-chelated calcium (SC). The yield of peanuts treated with sorbitol-chelated calcium was increased by 12.31-16.63%, 10.22-11.83%, 6.31-9.69%, and 4.18-6.99% compared to the CK, Sor, CaN, and SN treatments, respectively. Sorbitol-chelated calcium had the lowest contact angle due to the wetting effect of sorbitol, which promoted calcium absorption by leaves. Sorbitol-chelated calcium improved the leaf calcium concentration by 13.12-19.32% and kernel calcium concentration by 6.49-8.15% compared to the CK treatment. Foliar fertilization increased the calcium concentration of each subcellular fraction of leaves and changed the distribution of calcium in mesophyll cells. This change was directly observed by transmission electron microscopy. Additionally, spraying sorbitol alone obtained similar effects to spraying calcium nitrate alone, indicating that the benefits of sorbitol itself were not negligible. The results of the principal component and correlation analysis showed that the increase in calcium concentrations and the change in calcium distribution improved the pod traits of the peanut, thus affecting the peanut yield. The above results showed that from the perspective of calcium absorption and distribution, sorbitol-chelated calcium is a more effective foliar calcium fortifier for peanuts and effectively improves peanut yields.

Individual dynamic prediction and prognostic analysis for long-term allograft survival after kidney transplantation.

BACKGROUND: Predicting allograft survival is vital for efficient transplant success. With dynamic changes in patient conditions, clinical indicators may change longitudinally, and doctors' judgments may be highly variable. It is necessary to establish a dynamic model to precisely predict the individual risk/survival of new allografts. METHODS: The follow-up data of 407 patients were obtained from a renal allograft failure study. We introduced a landmarking-based dynamic Cox model that incorporated baseline values (age at transplantation, sex, weight) and longitudinal changes (glomerular filtration rate, proteinuria, hematocrit). Model performance was evaluated using Harrell's C-index and the Brier score. RESULTS: Six predictors were included in our analysis. The Kaplan-Meier estimates of survival at baseline showed an overall 5-year survival rate of 87.2%. The dynamic Cox model showed the individual survival prediction with more accuracy at different time points (for the 5-year survival prediction, the C-index = 0.789 and Brier score = 0.065 for the average of all time points) than the static Cox model at baseline (C-index = 0.558, Brier score = 0.095). Longitudinal covariate prognostic analysis (with time-varying effects) was performed. CONCLUSIONS: The dynamic Cox model can utilize clinical follow-up data, including longitudinal patient information. Dynamic prediction and prognostic analysis can be used to provide evidence and a reference to better guide clinical decision-making for applying early treatment to patients at high risk.

Analysis of serum fatty acid, amino acid, and organic acid profiles in gestational hypertension and gestational diabetes mellitus via targeted metabolomics.

This study aimed to characterize metabolite differences and correlations between hypertensive disorders of pregnancy (HP) and gestational diabetes mellitus (GDM) using univariate, multivariate analyses, RF, and pathway analyses in a cross-sectional study. Dietary surveys were collected and targeted metabolomics was applied to measure levels of serum fatty acids, amino acids, and organic acids in 90 pregnant women at 24-28 weeks gestation at the First Affiliated Hospital of Harbin Medical University. Principal components analysis (PCA) and partial least squares-discriminatory analysis (PLS-DA) models were established to distinguish HP, GDM, and healthy, pregnant control individuals. Univariate and multivariate statistical analyses and Random Forest (RF) were used to identify and map co-metabolites to corresponding pathways in the disease states. Finally, risk factors for the disease were assessed by receiver operating characteristics (ROC) analysis. Dietary survey results showed that HP and GDM patients consumed a high-energy diet and the latter also consumed a high-carbohydrate and high-fat diet. Univariate analysis of clinical indices revealed HP and GDM patients had glycolipid disorders, with the former possessing more severe organ dysfunction. Subsequently, co-areas with significant differences identified by basic discriminant analyses and RF revealed lower levels of pyroglutamic acid and higher levels of 2-hydroxybutyric acid and glutamic acid in the GDM group. The number of metabolites increased in the HP group as compared to the healthy pregnant control group, including pyroglutamic acid, γ-aminobutyric acid (GABA), glutamic acid, oleic acid (C18:1), and palmitic acid (C16:0). ROC curves indicated that area under curve (AUC) for pyroglutamic acid in the GDM group was 0.962 (95% CI, 0.920-1.000), and the AUC of joint indicators, including pyroglutamic acid and GABA, in the HP group was 0.972 (95% CI, 0.938-1.000). Collectively, these results show that both GDM and HP patients at mid-gestation possessed dysregulated glucose and lipid metabolism, which may trigger oxidative stress via glutathione metabolism and biosynthesis of unsaturated fatty acids.

A well-defined hierarchically porous metal-organic framework and its application in separation and purification of steviol glycosides.

The separation and removal of stevioside from natural product steviol glycosides to obtain high-purity rebaudioside A is of great significance for the application of steviol glycosides in food, medicine, and other fields. Here, in order to explore the adsorbent pore structure suitable for the separation of stevioside and rebaudioside A, a hierarchically porous amino-functionalized metal-organic framework (HP-NH2 -MIL-53) with an appropriate and narrow pore size distribution was prepared using a modulator-induced defect-formation strategy. The results showed that the hierarchically porous structure with micropores and mesopores increased the specific surface area and exposed amino groups compared with original metal organic framework (NH2 -MIL-53), and the maximum adsorption capacity of HP-NH2 -MIL-53 for stevioside and rebaudioside A was 233.89 mg/g. The narrow pore size distribution close to 3.80 nm promoted the screening effect, resulting in a maximum adsorption selectivity of 4.13. This work proves that when the pore size of the adsorbent is between 1.41 and 3.80 nm, it has a certain pore size screening effect on stevioside and rebaudioside A, and the hierarchically porous metal-organic frameworks provide a pre-design idea of adsorbent structure for the separation of natural products with molecular weight of 800-1000 Da.

Human Decidual Mesenchymal Stem Cells Obtained From Early Pregnancy Improve Cardiac Revascularization Postinfarction by Activating Ornithine Metabolism.

BACKGROUND: Compared with bone marrow mesenchymal stem cells (BMSCs), decidual mesenchymal stem cells (DMSCs) are easy to obtain and exhibit excellent angiogenic effects, but their role in cell transplantation after myocardial infarction (MI) remains unclear. METHODS: BMSCs and DMSCs were harvested from healthy donors. The effects of both cell types on angiogenesis were observed in vitro. Metabonomics analysis was performed to compare different metabolites and screen critical metabolic pathways. A murine model of acute myocardial infarction (AMI) was established, which was randomized into five groups (control, BMSC, DMSC, DMSC + ODCshRNA and BMSC + ODC consisting of 50 animals, equally divided into each group). The therapeutic effect of DMSCs on MI in rats was assessed based on neovascularization and cardiac remodeling. RESULTS: DMSCs exhibited a better angiogenic effect on human umbilical vein endothelial cells (HUVECs) than BMSCs in vitro. In addition, ornithine metabolism, which is associated with vascularization, was significantly increased in DMSCs. The transplantation of DMSCs in the rat MI model significantly enhanced angiogenesis of the infarct border area and improved cardiac remodeling and dysfunction postinfarction compared with BMSCs. Furthermore, inhibition of ornithine metabolism by silencing ornithine decarboxylase (ODC) in DMSCs partly abolished the benefits of DMSC transplantation. CONCLUSION: Compared with BMSCs, DMSCs exhibited better efficacy in improving revascularization and heart remodeling post-MI via the activation of ODC-associated ornithine metabolism.

Evaluation of the effect of antibiotics on gut microbiota in early life based on culturomics, SMRT sequencing and metagenomics sequencing methods.

Symbiotic gut microbiota in early life plays a vital role in human health, and changes in its communication and function are associated with various complex disorders. In this study, we analyzed the gut flora communication of 6 infants at 4 months of age and determined the disturbances related to antibiotic treatment. By the culturomics and Single Molecule Real-time sequencing methods, a total of 6234 strains were divided into 16 genera and 45 species. The alpha diversity of culturable microorganisms in amoxicillin-treated infants was significantly less than that in healthy infants (p <0.05), as indicated by Chao 1, observed species and Faith's PD index. According to metagenomics, the dominant genus and species were Bifidobacterium and B. longum in the healthy group. After treatment with amoxicillin, the dominant genus and species shifted to Enterococcus and E. faecium. Based on the functional annotation of metagenomics, amoxicillin affected the metabolic function of the gut microbiome by activating carbohydrate and lipid metabolism and inhibiting amino acid metabolism. Besides, the intake of antibiotics in early life increased the risk of neurodegenerative disease, virus infectious disease and antimicrobial resistance. The Antibiotic Resistance Genes Database annotation result indicated that the abundance of drug-resistance genes in the antibiotic group was higher than that in the healthy group. These genes were associated with resistance to bacitracin, most of which were associated with K. pneumonia. These findings can provide guidance in the clinic on the proper usage of antibiotics.

Synthesis and antitumor evaluation of (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole as potential PI3K/AKT/mTOR signaling pathway inhibitors.

In an attempt to search for new natural product-based antitumor agents, a series of novel (aryl)methyl-amine derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary bioassay showed that compounds 5r and 5s presented certain inhibitory activity against cancer cells, weak cytotoxic activity against normal cells, and inhibitory activity against PI3K/AKT/mTOR signaling pathway. The binding modes and the binding site interactions between the active compounds and the target proteins were predicted preliminarily by the molecular docking method.

Impact of Lead Exposure on Thyroid Status and IQ Performance among School-age Children Living Nearby a Lead-Zinc Mine in China.

BACKGROUND: Lead exposure is one of the most concerning public health problems worldwide, particularly among children. Yet the impact of chronic lead exposure on the thyroid status and related intelligence quotient performance among school-age children remained elusive. OBJECTIVE: The aim of this study was to evaluate the influence of lead exposure on the thyroid hormones, amino acid neurotransmitters balances, and intelligence quotient (IQ) among school-age children living nearby a lead-zinc mining site. Other factors such as rice lead levels, mothers' smoking behavior, and diet intake were also investigated. METHODS: A total of 255 children aged 7-12 years old were recruited in this study. Blood lead level (BLL), thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH), and amino acid neurotransmitters such as glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) were measured using graphite furnace atomic absorption spectroscopy (GFAAS), chemiluminescence immunoassay, high performance liquid chromatography (HPLC). Raven's standard progressive matrices (SPM) and the questionnaire were used to determine IQ and collect related influence factors. RESULTS: The average BLL of children was 84.8 µg/L. The occurrence of lead intoxication (defined as the BLL ≥ 100 µg/L) was 31.8%. Serum TSH levels and IQ of lead-intoxicated children were significantly lower than those without lead toxicity. The GABA level of girls with the lead intoxication was higher than those with no lead-exposed group. Correlation analyses revealed that BLL were inversely associated with the serum TSH levels (R= -0.186, p < 0.05), but positively related with IQ grades (R = 0.147, p < 0.05). Moreover, BLL and Glu were inversely correlated with IQ. In addition, this study revealed four factors that may contribute to the incidence of lead intoxication among children, including the frequency of mother smoking (OR = 3.587, p < 0.05) and drinking un-boiled stagnant tap water (OR = 3.716, p < 0.05); eating fresh fruits and vegetables (OR = 0.323, p < 0.05) and soy products regularly (OR = 0.181, p < 0.05) may protect against lead intoxication. CONCLUSION: Lead exposure affects the serum TSH, GABA levels and IQ of school-aged children. Developing good living habits, improving environment, increasing the intake of high-quality protein and fresh vegetable and fruit may improve the condition of lead intoxication.

Evidence for the existence of CD34+ angiogenic stem cells in human first-trimester decidua and their therapeutic for ischaemic heart disease.

Stem cell transplantation is nearly available for clinical application in the treatment of ischaemic heart disease (IHD), where it may be joined traditional methods (intervention and surgery). The angiogenic ability of seed cells is essential for this applicability. The aim of this study was to reveal the presence of CD34+ angiogenic stem cells in human decidua at the first trimester and to use their strong angiogenic capacity in the treatment of IHD. In vitro, human decidual CD34+ (dCD34+ ) cells from the first trimester have strong proliferation and clonality abilities. After ruling out the possibility that they were vascular endothelial cells and mesenchymal stem cells (MSCs), dCD34+ cells were found to be able to form tube structures after differentiation. Their angiogenic capacity was obviously superior to that of bone marrow mesenchymal stem cells (BMSCs). At the same time, these cells had immunogenicity similar to that of BMSCs. Following induction of myocardial infarction (MI) in adult rats, infarct size decreased and cardiac function was significantly enhanced after dCD34+ cell transplantation. The survival rate of cells increased, and more neovasculature was found following dCD34+ cell transplantation. Therefore, this study confirms the existence of CD34+ stem cells with strong angiogenic ability in human decidua from the first trimester, which can provide a new option for cell-based therapies for ischaemic diseases, especially IHD.

Study on the Methods of Separation and Detection of Chelates.

The separation and purification techniques of chelates can improve the accuracy of detecting results of the chelation rate. As a quantitative indicator of metal ion chelates, the chelation rate can not only reflect the completion of chelation but also determine the amount of metal ions in different forms. The determination of chelation rate can help to determine the suitable chelating reaction conditions, make theoretical basis for the fertilizer efficiency, analyze the stability of chelating fertilizers and study the action mechanism of trace elements. In our study, the methods of separation free metal ions from mixture were reviewed first, including gel filtration chromatography, organic solvent precipitation, ion exchange chromatography, membrane separation and high performance liquid chromatography. Then, the qualitative analysis methods of chelates were introduced briefly, including chemical identification, infrared spectroscopy, ultraviolet spectroscopy. A detailed overview of the quantitative determination methods of chelates were also shown, such as ethylenediaminetetraacetic acid titration, chemical titration, atomic absorption spectrometry, inductively coupled plasma atomic emission spectrometry, inductively coupled plasma mass spectrometry, spectrophotometric, chemical modified electrode. In addition, the merits and demerits of chelated rate determination methods of various determination methods were analyzed, and summarized the applicability of various methods, which provided a theoretical basis for optimizing chelating process, characterizing the structure of chelates and analyzing the mechanism of chelating fertilizer. The current methods of measuring chelation rate were also summarized and prospected.

Pyrethroid pesticide residues in the global environment: An overview.

Pyrethroids are synthetic organic insecticides with low mammalian toxicity that are widely used in both rural and urban areas worldwide. After entering the natural environment, pyrethroids circulate among the three phases of solid, liquid, and gas and enter organisms through food chains, resulting in substantial health risks. This review summarized the available studies on pyrethroid residues since 1986 in different media at the global scale and indicated that pyrethroids have been widely detected in a range of environments (including soils, water, sediments, and indoors) and in organisms. The concentrations and detection rates of agricultural pyrethroids, which always contain α-cyanogroup (α-CN), such as cypermethrin and fenvalerate, decline in the order of crops > sediments > soils > water. Urban pyrethroids (not contain α-CN), such as permethrin, have been detected at high levels in the indoor environment, and 3-phenoxybenzoic acid, a common pyrethroid metabolite in human urine, is frequently detected in the human body. Pyrethroid pesticides accumulate in sediments, which are a source of pyrethroid residues in aquatic products.

Characteristics and source distribution of air pollution in winter in Qingdao, eastern China.

To characterize air pollution and determine its source distribution in Qingdao, Shandong Province, we analyzed hourly national air quality monitoring network data of normal pollutants at nine sites from 1 November 2015 to 31 January 2016. The average hourly concentrations of particulate matter <2.5 µm (PM2.5) and <10 µm (PM10), SO2, NO2, 8-h O3, and CO in Qingdao were 83, 129, 39, 41, and 41 µg m-3, and 1.243 mg m-3, respectively. During the polluted period, 19-26 December 2015, 29 December 2015 to 4 January 2016, and 14-17 January 2016, the mean 24-h PM2.5 concentration was 168 µg m-3 with maximum of 311 µg m-3. PM2.5 was the main pollutant to contribute to the pollution during the above time. Heavier pollution and higher contributions of secondary formation to PM2.5 concentration were observed in December and January. Pollution pathways and source distribution were investigated using the HYbrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model and potential source contribution function (PSCF) and concentration weighted trajectory (CWT) analyses. A cluster from the west, originating in Shanxi, southern Hebei, and west Shandong Provinces, accounted for 44.1% of the total air masses, had a mean PM2.5 concentration of 134.9 µg m-3 and 73.9% trajectories polluted. This area contributed the most to PM2.5 and PM10 levels, >160 and 300 µg m-3, respectively. In addition, primary crustal aerosols from desert of Inner Mongolia, and coarse and fine marine aerosols from the Yellow Sea contributed to ambient PM. The ambient pollutant concentrations in Qingdao in winter could be attributed to local primary emissions (e.g., coal combustion, vehicular, domestic and industrial emissions), secondary formation, and long distance transmission of emissions.

The risk of missed abortion associated with the levels of tobacco, heavy metals and phthalate in hair of pregnant woman: A case control study in Chinese women.

To assess the association between exposure to the tobacco, heavy metals and phthalate on early pregnancy and missed abortion.42 women with missed abortion and 57 matched controls (women with normal pregnancies) were recruited between March and May 2012, from the Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangxi Medical University and the People Hospital of Guangxi Zhuang Autonomous Region. The questionnaire survey was carried on to learn about the basic conditions, as well as smoking history of all participants. The levels of tobacco, heavy metal, and phthalate exposure were compared between the 2 groups by measuring nicotine, cocaine, cadmium (Cd), manganese (Mn), plumbum (Pb) and dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), di-2-ethyl hexyl phthalate (DEHP) in the hair samples.Out results showed that significant differences in age (P = .042), premarital examination (P = .041), passive smoking (P = .021), and heavy metal exposure (P = .022) were found in the case group compared to the control. In addition, the concentration of nicotine (P = .037), cotinine (P = .018), Cd (P = .01), Pb (P = .038) and DEHP (P = .001) in the hair were significantly higher in the case group. Furthermore, logistic analysis revealed that age [Odds Ratio (OR) 1.172, 95% confidence interval (CI) 1.036-1.327], Cd (OR 8.931, 95% CI 2.003-39.811), Cotinine (OR 4.376, 95% CI 1.159-16.531), DEHP (OR 1.863, 95% CI 1.103-3.146) were important factors contributing to the missed abortion (P < .05).It was demonstrated that high gestational age, passive smoking, heavy metals, and the phthalate exposure were the risk factors for missed abortion, while the premarital health examination was a protective factor. Avoiding these harmful substances before getting pregnant and during the early stages of pregnancy, might help prevent missed abortions.

Human papillomavirus 16 E6 modulates the expression of host microRNAs in cervical cancer.

OBJECTIVE: Human papillomavirus (HPV) infection is a prerequisite of developing cervical cancer, approximately half of which are associated with HPV type 16. There are reports that HPV can disturb the expression pattern of host miRNAs, but its mechanism is not well understood. MATERIALS AND METHODS: In this study, we scanned 11 tumorigenesis related miRNAs in Hela cells that were overexpressed with HPV type 16 E6 protein. RESULTS: We found the expression of miR-21 was upregulated by HPV type 16 E6 protein and meanwhile, the expression of miR-27a and miR-218 was downregulated. Furthermore, we identified that miR-21 overexpression could promote Hela and U2OS cells proliferation by targeting phosphatase-tensin homolog (PTEN), the result of which can be rescued by miR-21 inhibitor. In addition, E6 overexpression could also promote Hela cell migration and invasion. CONCLUSION: Our results indicate that HPV infection and subsequent transformation take place through complex regulatory patterns of gene expression in the host cells, part of which are regulated by the E6 protein.

Blood lead level and its relationship to essential elements in preschool children from Nanning, China.

OBJECTIVE: Our study aimed to assess the distribution of blood lead level and its relationship to essential elements in preschool children in an urban area of China. DESIGN AND METHODS: A total of 6741 children aged 0- to 6-year-old were recruited. Levels of lead, zinc, copper, iron, calcium, and magnesium in whole blood samples were determined using atomic absorption spectrometry. RESULTS: The mean blood lead level (BLL) and the prevalence of BLL≥10µg/dl (5.26±4.08µg/dl and 6.84%, respectively) increased with age gradually, and there was a gender-difference for blood lead, copper, zinc and iron levels. Compared with the group of children who had BLLs<5µg/dl, the groups of 5≤BLLs<10µg/dl and 10≤BLLs<15µg/dl showed higher blood zinc, iron and magnesium levels, and a lower blood calcium level. A positive correlation of lead with zinc, iron and magnesium, and a negative correlation of lead with calcium were found in the group of children with BLL<5µg/dl. CONCLUSION: Age- and gender-differences were found when assessing the BLL and intoxication prevalence in preschool children. Metabolic disorder of essential elements was found even with a low level of lead exposure.

TSP50 depends on its threonine protease activity and its interactions with TNF-α-induced NF-κB for its role in human cervical tumorigenesis.

Testes-specific protease 50 (TSP50) has threonine activity and has homology to serine proteases. TSP50 protein, which is encoded by a possible proto-oncogene, is overexpressed in cervical tumor tissues. Through overexpression experiments using both TSP50 and a TSP50 mutant (TSP50 T310A), it is clear that this protein may play an important role in carcinogenesis and progression of cervical tumor. However, the mechanism underlying how TSP50 modulates cancer cell growth is still unclear. To examine the difference in TSP50 expression in cervical carcinoma tissues and in paracarcinoma tissues, we detected TSP50 mRNA and protein in ten paired tissues from patients with cervical cancer. To determine whether TSP50's threonine protease activity is crucial for its effects on tumor formation, we generated a mutant version of TSP50 (T310A). Via overexpression and silencing experiments, we identified a role for TSP50 in cell proliferation and migration. Furthermore, we examined the signaling pathway of TNF-α-induced NFκB activation to explain the mechanism by which TSP50 participates in tumorigenesis. Similarly, we found that all these effects could be abolished by the TSP50 T310A mutation. Our results suggest that the threonine 310 residue within TSP50 helps modulate its role in cervical tumorigenesis and indicates that TSP50's role in tumorigenesis may be dependent on its interaction with TNF-α-induced NF-κB.