Ambient outdoor air pollutants and sex ratio of singletons born after in vitro fertilization: the effect of single blastocyst transfer.

OBJECTIVE(#br)To evaluate the impact of air pollution on the sex ratio in singletons after IVF treatment and to evaluate the influence of the number of and the developmental stage of transferred embryos on the sex ratio.(#br)DESIGN(#br)Retrospective cohort study.(#br)SETTING(#br)University-affiliated IVF unit.(#br)PATIENT(S)(#br)A total of 7,004 singletons born after fresh transfer or frozen-thawed embryo transfer (FET) between January 2013 and December 2017.(#br)INTERVENTION(S)(#br)None.(#br)MAIN OUTCOME MEASURE(S)(#br)Male-to-female ratio in live-born singletons.(#br)RESULT(S)(#br)The estimated medians (interquartile range) of particle matter (PM)10, PM2.5, CO, NO2, O3, and SO2 at the IVF site were 51.4 (39.5-64.6), 27.7 (20.7-37.4), 0.62 (0.5-0.72), 32.5 (25.4-40.1), 79.6 (63.3-96.6), and 11.9 (9.3-15.9) μg/m3, respectively. Multivariate analysis indicated that SO2 was the only pollutant clearly associated with sex ratio. In singletons from single blastocyst transfer (SBT), as indicated by the generalized additive model, the SO2 concentration and sex ratio showed an inverted-U-shape association. In singletons after non-SBT, a monotonic decreasing in the sex ratio was observed with increased SO2 concentration. Compared with the referent category (SO2 < 7.57 μg/m3), the sex ratio at the 5th decile of SO2 (10.81-11.94 μg/m3) was increased by 2.1-fold (95% confidence interval [CI], 1.3-3.14) after adjusting covariates. In singletons born from non-SBT, the sex ratio significantly decreased only in the 9th (odds ratio = 0.69; 95% CI, 0.53-0.90) and 10th (OR = 0.74, 95% CI, 0.56-0.98) deciles.(#br)CONCLUSION(S)(#br)Low concentrations of SO2 showed an association with increased sex ratio in singletons of SBT, while in singletons born from another ET system the sex ratios did not show an association at low concentrations of SO2

Interferon gamma (IFN-γ) disrupts energy expenditure and metabolic homeostasis by suppressing SIRT1 transcription

Chronic inflammation impairs metabolic homeostasis and is intimately correlated with the pathogenesis of type 2 diabetes. The pro-inflammatory cytokine IFN-γ is an integral part of the metabolic inflammation circuit and contributes significantly to metabolic dysfunction. The underlying mechanism, however, remains largely unknown. In the present study, we report that IFN-γ disrupts the expression of genes key to cellular metabolism and energy expenditure by repressing the expression and activity of SIRT1 at the transcription level. Further analysis reveals that IFN-γ requires class II transactivator (CIITA) to repress SIRT1 transcription. CIITA, once induced by IFN-γ, is recruited to the SIRT1 promoter by hypermethylated in cancer 1 (HIC1) and promotes down-regulation of SIRT1 transcription via active deacetylation of core histones surrounding the SIRT1 proximal promoter. Silencing CIITA or HIC1 restores SIRT1 activity and expression of metabolic genes in skeletal muscle cells challenged with IFN-γ. Therefore, our data delineate an IFN-γ/HIC1/CIITA axis that contributes to metabolic dysfunction by suppressing SIRT1 transcription in skeletal muscle cells and as such shed new light on the development of novel therapeutic strategies against type 2 diabetes

A Highly Sensitive XNA-Based RT-qPCR Assay for the Identification of ALK, RET, and ROS1 Fusions in Lung Cancer

Lung cancer is often triggered by genetic alterations that result in the expression of oncogenic tyrosine kinases. Specifically, ALK, RET, and ROS1 chimeric receptor tyrosine kinases are observed in approximately 5–7%, 1–2%, and 1–2% of NSCLC patients, respectively. The presence of these fusion genes determines the response to tyrosine kinase inhibitors. Thus, accurate detection of these gene fusions is essential in cancer research and precision oncology. To address this need, we have developed a multiplexed RT-qPCR assay using xeno nucleic acid (XNA) molecular clamping technology to detect lung cancer fusions. This assay can quantitatively detect thirteen ALK, seven ROS1, and seven RET gene fusions in FFPE samples. The sensitivity of the assay was established at a limit of detection of 50 copies of the synthetic template. Our assay has successfully identified all fusion transcripts using 50 ng of RNA from both reference FFPE samples and cell lines. After validation, a total of 77 lung cancer patient FFPE samples were tested, demonstrating the effectiveness of the XNA-based fusion gene assay with clinical samples. Importantly, this assay is adaptable to highly degraded RNA samples with low input amounts. Future steps involve expanding the testing to include a broader range of clinical samples as well as cell-free RNAs to further validate its applicability and reliability

Does prolonged pituitary down-regulation with gonadotropin-releasing hormone agonist improve the live-birth rate in in vitro fertilization treatment?

Xiamen City [3502z20111006]Objective: To evaluate the effects of a prolonged duration of gonadotropin-releasing hormone agonist (GnRH-a) in pituitary down-regulation for controlled ovarian hyperstimulation (COH) on the live-birth rate in nonendometriotic women undergoing in vitro fertilization and embryo transfer (IVF-ET). Design: Retrospective cohort study. Setting: University-affiliated hospital. Patient(s): Normogonadotropic women undergoing IVF. Intervention(s): Three hundred seventy-eight patients receiving a prolonged pituitary down-regulation with GnRH-a before ovarian stimulation and 422 patients receiving a GnRH-a long protocol. Main Outcome Measure(s): Live-birth rate per fresh ET. Result(s): In comparison with the long protocol, the prolonged down-regulation protocol required a higher total dose of gonadotropins. A lower serum luteinizing hormone (LH) level on the starting day of gonadotropin and the day of human chorionic gonadotropin (hCG) and a fewer number of oocytes and embryos were observed in the prolonged down-regulation protocol. However, the duration of stimulation and number of high-quality embryos were comparable between the two groups. A statistically significantly higher implantation rate (50.27% vs. 39.69%), clinical pregnancy rate (64.02% vs. 56.87%) and live-birth rate per fresh transfer cycle (55.56% vs. 45.73%) were observed in the prolonged protocol. Conclusion(s): Prolonged down-regulation in a GnRH-a protocol might increase the live-birth rates in normogonadotropic women. (C) 2014 by American Society for Reproductive Medicine

A novel XNA-based Luminex assay to detect UBA1 somatic mutations associated with VEXAS syndrome.

OBJECTIVES: Patients with VEXAS syndrome carry mutations of UBA1 gene coding for the E1 enzyme. The three most frequent mutations are p.M41T(122T&nbsp;&gt;&nbsp;C), p.M41V (c.121A&nbsp;&gt;&nbsp;G), and p.M41L (c.121A&nbsp;&gt;&nbsp;C) in codon 41 of exon 3. Currently, sanger sequencing was mainly used to detect these mutations, which has low sensitivity and low throughput. There is a need of high sensitivity, simple and high throughput method to characterize patients with VEXAS syndrome. METHODS: Based on our proprietary XNA technology, we have developed a QClamp® Plex platform to detect eight mutations in a single reaction using the Luminex xMap technology. The assay sensitivity, specificity and precision were subsequently evaluated. Furthermore, the reference interval and clinical sensitivity/specificity were estimated using clinical healthy/positive DNA samples and the sanger sequencing method was used for comparison. RESULTS: With spiking synthetic mutant DNA in wildtype GM24385&nbsp;cell line DNA, this assay can detect UBA1 mutations with a detection limit of variant allele frequency (VAF) at 0.1-5%. Our assay shows 100% concordance with Sanger sequencing results when used for analyzing 15 positive and 19 negative clinical samples. CONCLUSIONS: The QClamps® Plex UBA1 Mutation Detection Assay is a quicker, simpler, and more sensitive assay that can accurately detect the UBA1 mutations even at early stages with low mutation frequency

A novel XNA-based Luminex assay to detect UBA1 somatic mutations associated with VEXAS syndrome

Objectives: Patients with VEXAS syndrome carry mutations of UBA1 gene coding for the E1 enzyme. The three most frequent mutations are p.M41T(122T > C), p.M41V (c.121A > G), and p.M41L (c.121A > C) in codon 41 of exon 3. Currently, sanger sequencing was mainly used to detect these mutations, which has low sensitivity and low throughput. There is a need of high sensitivity, simple and high throughput method to characterize patients with VEXAS syndrome. Methods: Based on our proprietary XNA technology, we have developed a QClamp® Plex platform to detect eight mutations in a single reaction using the Luminex xMap technology. The assay sensitivity, specificity and precision were subsequently evaluated. Furthermore, the reference interval and clinical sensitivity/specificity were estimated using clinical healthy/positive DNA samples and the sanger sequencing method was used for comparison. Results: With spiking synthetic mutant DNA in wildtype GM24385 cell line DNA, this assay can detect UBA1 mutations with a detection limit of variant allele frequency (VAF) at 0.1–5%. Our assay shows 100% concordance with Sanger sequencing results when used for analyzing 15 positive and 19 negative clinical samples. Conclusions: The QClamps® Plex UBA1 Mutation Detection Assay is a quicker, simpler, and more sensitive assay that can accurately detect the UBA1 mutations even at early stages with low mutation frequency

Seminal Plasma Metals Concentration with Respect to Semen Quality

The aim of the current study was to assess relationships between multiple metals burden in human seminal plasma and semen quality parameters. Levels of five metals (lead, manganese, copper, arsenic, and selenium) in human seminal plasma were determined by inductively coupled plasma mass spectrometry (ICP-MS), and the correlations between the metal concentrations and semen parameters (sperm concentration, sperm motility rate, and sperm morphology) were analyzed. The activities of acid phosphatase (ACP) and of alpha-glucosidase in human seminal plasma were also determined. Of the 100 subjects, 21 had fertility problems according to the World Health Organization criteria and were designated as "abnormal group." Significant inverse correlations were found between the concentrations of Cu, As, Pb, and the sperm concentrations (r (Cu) = -0.312, P (Cu) = 0.029; r (As) = -0.328, P (As) = 0.021; r (Pb) = -0.377, P (Pb) = 0.008). Moreover, the Cu, Mn, and Se concentrations were significantly higher in the abnormal group than that in the normal group (P (Cu) = 0.024, P (Mn) = 0.002, P (Se) = 0.002). The ACP activity was significantly higher in the normal group than that in the abnormal group (P = 0.021). We also found a significantly negative correlation between alpha-glucosidase activity and the levels of As (r = -0.367, P = 0.023). These findings provide evidence for relationships between human semen quality and metal exposures. These relationships are consistent with animal data, but additional human and mechanistic studies are needed.Fundamental Research Funds for the Central Universities [2010121024]; National Foundation for fostering talents of basic science [J1030626

Response of net primary productivity to precipitation exclusion in a savanna ecosystem

Declines in precipitation are expected to affect plant performance and ecosystem carbon uptake. The response of ecosystem productivity to declines in precipitation and potential underlying mechanisms have been well studied in many biomes; however, little is known about the role of declines in precipitation and the involved mechanisms in savanna ecosystems. In a 4-year field precipitation manipulation experiment, we simulated four levels of precipitation exclusion (control, 30%, 50% and 70%) to assess the effects of declines in precipitation on net primary productivity (NPP) in a savanna ecosystem in southwestern China. NPP was strongly correlated with soil water content during the experimental period. Precipitation exclusion significantly decreased the NPP of the entire vegetation including trees, shrubs, perennials and litterfall but significantly increased the NPP of annuals. Our results suggested that precipitation exclusion can reduce the productivity of savannas and that plant functional types differ in sensitivity to precipitation exclusion. These findings imply that future declines in precipitation in savanna regions may negatively impact carbon accumulation and may induce shifts in plant functional types to buffer the effects of declines in precipitation on productivity and stabilize ecosystem function in savannas