Functional Nucleic Acid Nanoparticle-Based Resonance Scattering Spectral Probe

Highly sensitive and selective resonance Rayleigh scattering (RRS) and surface enhanced resonance Raman scattering (SERRS) spectral detection technique are developed by combining the functional nucleic acid including aptamer and DNAzyme, and nanoparticle such as gold/silver (NG/NS) aggregation and catalysis reaction. The recent progress of resonance scattering spectral technologies including RRS and SERRS are reviewed in this paper.     

Vero细胞和脊髓灰质炎病毒在无血清条件下的培养探究

目的：探索Vero细胞和脊髓灰质炎病毒在无血清条件下的最佳培养条件,为无血清培养Vero细胞生产脊髓灰质炎疫苗奠定基础。方法选择直接适应（直降组）和序贯适应（驯化组）两种无血清培养方法,观察Vero细胞和脊髓灰质炎病毒在无血清条件下的生长情况,并检测脊髓灰质炎病毒及其病毒滴度。结果 Vero细胞在两种无血清条件下均生长良好,其中驯化组细胞生长速度更接近对照组。以脊髓灰质炎病毒Sabin株Ⅰ型分别感染直降组、驯化组和对照组细胞的病毒滴度平均值分别为8．94、8．81和8．94 LgCCID50/mL;Ⅱ型病毒滴度平均值分别为8．84、8．25和7．94 LgCCID50/mL;Ⅲ型病毒滴度平均值分别为8．91、8．57和8．63 LgCCID50/mL;且3组的变异系数（ CV）均小于10％。结论 Vero细胞在无血清条件下生长良好,无血清培养的Vero 细胞可用作脊髓灰质炎疫苗生产的基质。     

Cancer Risks in Parents Who had a Child with a Congenital Malformation

Cancer risk in parents may be related to congenital malformations (CMs) in their children if they share genetic susceptibility or environmental exposure that may be teratogenic and carcinogenic. We conducted a population‐based cohort study based on Danish register data. We identified 795,607 mothers and 781,424 fathers who had all their children between 1977 and 2007 in Denmark. Information on CM was obtained from the Danish Hospital Registry and information on cancer was obtained from the Danish Cancer Registry. Parents were followed from the birth of their first child until the diagnosis of cancer, death, emigration, or December 31, 2007. We used Cox regression models to estimate hazard ratios (HRs) for cancer including cancer in specific organs in mothers and fathers. Overall, 75,701 (9.5%) mothers and 72,724 (9.3%) fathers had at least one child diagnosed with CMs within the first year of life. Neither mothers (HR = 1.04; 95% CI: 0.99–1.04) nor fathers (HR = 1.03; 95% CI: 0.98–1.09) who had a child with a CM had a higher overall risk of cancer. Mothers (HR = 0.76, 95% CI: 0.58–1.00) or fathers (HR = 0.89, 95% CI: 0.66–1.19) who had a child with a chromosomal malformation had a lower overall cancer risk. The findings also showed a higher risk for some specific types of cancer in parents who had children with a CM in the specific system. Some, or perhaps all, of these findings may be due to chance caused by multiple comparisons. We present all results on paper or online to provide clues for further research and to avoid publication bias.     

Design,synthesis and biological evaluation of novel 1H-1,2,4-triazole,benzothiazole and indazole-based derivatives as potent FGFR1 inhibitors viafragment-based virtual screening

Abstract

Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC₅₀ = 15.0?nM) and modest anti-proliferative activity (IC₅₀ = 785.8?nM). Through two rounds of optimisation, the indazole derivative 9?u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC₅₀ = 3.3?nM) and cellular activity (IC₅₀ = 468.2?nM). Moreover, 9?u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1.     

Evaluation of urinary 1-hydroxypyrene,S-phenylmercapturic acid,trans,trans-muconic acid, 3-methyladenine, 3-ethyladenine, 8-hydroxy-2′-deoxyguanosine and thioethers as biomarkers of exposure to cigarette smoke

The objective was to evaluate the utility of urinary 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (S-PMA), trans,trans-muconic acid (t,t-MA), 3-methyladenine (3-MeAd), 3-ethyladenine (3-EtAd), 8-hydroxy-2′-deoxyguanosine (8-OHdG) and thioethers as biomarkers for assessing the exposure in adult smokers who switched from smoking conventional cigarettes to candidate potential reduced exposure products (PREP) or who stopped smoking. Two electrically heated smoking systems (EHCSS) were used as prototype cigarettes that have significant reductions in a number of mainstream smoke constituents as measured by smoking machines relative to those from conventional cigarettes. Urine samples were collected from a randomized, controlled, forced-switching study in which 110 adult smokers of a conventional cigarette brand (CC1) were randomly assigned to five study groups. The groups included the CC1 smoking group, a lower-tar conventional cigarette (CC2) smoking group, EHCSS1 group, EHCSS2 group and a no smoking group that were monitored for 8 days. Biomarkers were measured at baseline and day 8. The daily excretion levels of these biomarkers were compared among the groups before and after switching, and the relationships between the daily excretion levels of these biomarkers and cigarette smoking-related exposure were investigated using Pearson product-moment correlation and multiple regression analyses. It was concluded that under controlled study conditions: (1) 1-OHP, S-PMA and t,t-MA are useful biomarkers that could differentiate exposure between smoking conventional and EHCSS cigarettes or between smoking conventional cigarettes and no smoking; between S-PMA and t,t-MA, the former appeared to be more sensitive; (2) 3-MeAd could only differentiate between smoking conventional cigarettes and no smoking; the results for 3-EtAd were not conclusive because contradictory results were observed; (3) 8-OHdG had a questionable association with smoking and therefore the utility of this biomarker for smoking-related exposure could not be established; and (4) urinary excretion of thioethers as a biomarker lacked sensitivity to demonstrate a clear dose–response relationship in conventional cigarette smokers, although it could differentiate the excretion levels between those subjects who smoked a conventional cigarette and those who stopped smoking.     

Five-Year Change in Intraocular Pressure Associated with Changes in Arterial Blood Pressure and Body Mass Index. The Beijing Eye Study

Purpose

To examine a potential association between longitudinal changes in intraocular pressure (IOP), arterial blood pressure and body mass index (BMI) in a population-based setting.

Methods

The longitudinal population-based Beijing Eye Study included 2355 subjects with an age of 45+ years who were examined in 2006 and in 2011. The participants underwent a detailed ophthalmic examination including tonometry and measurement of arterial blood pressure and BMI.

Results

Data on IOP, arterial blood pressure and BMI measured in 2006 and in 2011 were available for 2257 (95.8%) subjects with a mean age of 59.5±9.7 years. The mean change in IOP was −1.25±2.26 mm Hg, mean change in mean blood pressure −7.4±12.1 mmHg, and mean change in BMI was 0.01±2.04 kg/m². In multivariate analysis, the 5-year change in IOP was significantly associated with a higher change in mean blood pressure (P<0.001; standardized regression coefficient Beta:0.11; regression coefficient B:0.02; 95% confidence interval (CI):0.01,0.03) after adjusting for younger age (P<0.001;Beta:−0.18;B:−0.04;95% CI:−0.05,−0.03), shorter body stature (P = 0.002;Beta:−0.06;B:−0.06;95% CI:−0.03,−0.01), thicker central corneal thickness (P<0.001;Beta:0.19;B:0.02;95% CI:0.01,0.02), deeper anterior chamber depth (P = 0.01;Beta:0.05;B:0.33;95% CI:0.07,0.60), and lower intraocular pressure at baseline (P<0.001;Beta:−0.56;B:−0.42;95% CI:−0.45,−0.39). If the analysis included only longitudinal parameters, the change in IOP was significantly associated with a higher change in mean arterial blood pressure (P<0.001;Beta:0.10;B:0.02;95% CI:0.01,0.03) and a higher change in body mass index (P<0.04;Beta:0.04;B:0.04;95% CI:0.01,0.09).

Conclusions

In the 5-year follow-up of our population-based sample, a change in IOP was associated with a corresponding change in arterial blood pressure and with a corresponding change in body mass index. These longitudinal data support the notion of a physiological relationship between arterial blood pressure, intraocular pressure and body mass index. These findings may be of interest for the discussion of the pathogenesis of glaucomatous optic neuropathy.     

JcLEA,a Novel LEA-Like Protein from Jatropha curcas,Confers a High Level of Tolerance to Dehydration and Salinity in Arabidopsis thaliana

Jatropha curcas L. is a highly drought and salt tolerant plant species that is typically used as a traditional folk medicine and biofuel crop in many countries. Understanding the molecular mechanisms that underlie the response to various abiotic environmental stimuli, especially to drought and salt stresses, in J. curcas could be important to crop improvement efforts. In this study, we cloned and characterized the gene for a late embryogenesis abundant (LEA) protein from J. curcas that we designated JcLEA. Sequence analyses showed that the JcLEA protein belongs to group 5, a subgroup of the LEA protein family. In young seedlings, expression of JcLEA is significantly induced by abscisic acid (ABA), dehydration, and salt stress. Subcellular localization analysis shows that that JcLEA protein is distributed in both the nucleus and cytoplasm. Moreover, based on growth status and physiological indices, the overexpression of JcLEA in transgenic Arabidopsis plants conferred increased resistance to both drought and salt stresses compared to the WT. Our data suggests that the group 5 JcLEA protein contributes to drought and salt stress tolerance in plants. Thus, JcLEA is a potential candidate gene for plant genetic modification.