Search

Introduction: Females with haemophilia A (HA [FHAs]) and HA carriers (HACs) have an increased risk of bleeding and complications compared to the general population. Aim: To examine the characteristics, billed annualised bleed rates (ABRb), costs and healthcare resource utilisation for males with HA (MHAs), FHAs and HACs in the United States. Methods: Data were extracted from the IBM® MarketScan® Research Databases (Commercial and Medicaid) for claims during the index period (July 2016 to September 2018) and analysed across MHAs, FHAs and HACs. Results: Dual diagnosis females (DDFs; both HA and HAC claims) were grouped as a separate cohort. MHAs were generally younger than females (all cohorts) by up to 19 years (Commercial) and 23 years (Medicaid). ABRb >0 was more frequent in females. Factor VIII claims were higher for MHAs versus female cohorts. Joint‐related health issues were reported for 24.4 and 25.6% (Commercial) and 29.3 and 26.6% (Medicaid) of MHAs and FHAs, respectively; lower rates were reported in the other two cohorts. Heavy menstrual bleeding claims occurred for approximately a fifth (Commercial) to a quarter (Medicaid) of female cohorts. All‐cause emergency department and inpatient visits in FHAs and DDFs were similar to, or more frequent than, those in MHAs; bleed‐related inpatient visits were infrequent. In MHAs (Commercial), mean all‐cause total costs ($214,083) were higher than in FHAs ($40,388), HACs ($15,647) and DDFs ($28,320) with similar trends for Medicaid patients. Conclusions: FHAs and HACs may be undermanaged and undertreated. Further research is needed to fully understand these cohorts' bleeding rates, long‐term complications and costs. [ABSTRACT FROM AUTHOR]

Gas generation-based immunoassay is considered an attractive biosensing platform for the detection of biomarkers by incorporating the target recognition event with a catalyzed gas-generating reaction. Herein, an optical gas pressure sensor based on a silver/polydimethylsiloxane (Ag/PDMS) bilayer system was designed as a signal transducer to read the concentration of the detection target alpha-fetoprotein (AFP) quantitatively. In this proposed pressure-based assay, silicon dioxide (SiO2) nanospheres decorated with platinum (Pt) nanoparticles were coupled to detect antibodies by covalent linkage, and the captured antibodies were conjugated with magnetic beads via streptavidin-biotin interaction, simultaneously. When the AFP was loaded, the Pt-catalyzed hydrogen peroxide (H2O2) decomposition reaction was triggered to induce a significant increase in the reflectance signal of the Ag/PDMS bilayer gas pressure sensor (BGPS) due to a "wrinkled–specular" transition of the Ag film's surface. Under optimal conditions, the pressure-based biosensor exhibited a broad linear detection range from 0.05 to 132 ng mL−1 with a limit of detection (LOD) of 0.016 ng mL−1 for AFP, which satisfies the requirements for the clinical detection of AFP. Besides, the high specificity and detection accuracy of our Ag/PDMS BGPS also proved its feasibility for practical diagnosis. [ABSTRACT FROM AUTHOR]

Background: Alcohol septal ablation (ASA) has been proven to reverse left ventricular (LV) remodeling in hypertrophic cardiomyopathy (HCM). However, there are no studies on the effect of sex on LV remodeling after ASA. We aimed to investigate whether sex differences affect the process of LV remodeling and outcome after ASA. Methods: A total of 107 patients with obstructive HCM (54 men and 53 women, mean age 51 ± 8 years) were recruited. Cardiovascular magnetic resonance (CMR) was performed at baseline and 16 months after ASA. The extent of late gadolinium enhancement (LGE) was measured. Results: Women had a higher indexed LV mass and smaller indexed LV end-systolic volumes than men at the time of ASA. After ASA, both men and women exhibited a regression of LV mass, and the percentage of mass regression was greater in men than women (15.3% ± 4.3% vs. 10.7% ± 1.8%, p < 0.001). In multivariable analysis, male sex, higher reduction of LV outflow tract (LVOT) gradient and lower baseline LV mass index were independently associated with greater LV mass regression after ASA. Kaplan–Meier analysis showed significantly higher cardiovascular events in women than in men (p = 0.015). Female sex [hazard ratio (HR) 3.913, p = 0.038] and LV mass preablation (HR, 1.019, p = 0.010) were independent predictors of cardiovascular outcomes. Conclusions: Males with HCM had favorable reverse remodeling with greater LV mass regression post-ASA than female patients. This favorable LV reverse remodeling might provide a mechanistic explanation for the survival advantage in men. Highlights: Female patients with HCM showed worse LV remodeling with a higher indexed LV mass and a smaller indexed LV end-diastolic volume (measured by CMR) at the time of ASA. Both men and women exhibited the LV reverse remodeling, however, men experienced more favorable LV reverse remodeling than women after ASA. The overall percentage of the LVM index regression was greater among men than women. Women with HCM had worse relative composite endpoint than men. Sex and LV mass preablation were independent predictors of cardiovascular outcomes. Sex appears to be a significant modifier in HCM patients receiving ASA treatment and highlighted the need for a different approach to women with HCM, such as improving women's awareness of diagnosis and follow-up management as well as earlier referral for advanced therapies (e.g., septal reduction therapy and ICD implantation). [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC. Methods: The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model. Results: In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3β/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo. Conclusions: Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the outcomes of total knee arthroplasty (TKA) in patients with a prior femoral or tibial fracture, and identify the risk factors for surgical site complications and reoperations. Methods: Seventy‐one TKAs performed in 71 patients with a prior tibial or femoral fracture between January 2005 and December 2016 were reviewed retrospectively. Forty males (40 knees) and 31 females (31 knees) were included. The mean age at the time of TKA was 59.2 (range, 29–83) years. Outcomes were assessed using the Knee Society score before surgery and at the final follow‐up visit. The patients' satisfaction rates were evaluated. Complications and reoperations were recorded by clinical and radiographic assessment. Logistic regression analysis was used to identify the risk factors for surgical site complications and reoperations. Results: The median follow‐up period was 4.7 (range, 3.2–7.1) years. The median knee range of motion increased from 90° preoperatively to 110° at the latest follow‐up. The Knee Society knee score and function score improved from 35 (30, 40) and 40 (30, 50) to 90 (82, 93) and 90 (65, 100), respectively. The degree of overall satisfaction after TKA surgery was very satisfied in 41 patients, satisfied in 20 patients, neutral in four patients, dissatisfied in four patients, and very dissatisfied in two patients. The overall satisfaction (very satisfied and satisfied) rate was 85.9% (61 knees). Twelve knees (16.9%) had 19 surgical site complications. Six knees (8.3%) underwent reoperations, including one revision due to periprosthetic joint infection, one debridement and implant retention for superficial infection, two debridements for delayed wound healing, one open reduction and internal fixation for supracondylar fracture, and one re‐fixation and bone grafting for hardware failure after a combined femoral shaft osteotomy and TKA. Preoperative patella baja was diagnosed in 12 knees, and was identified as a risk factor for surgical site complications and reoperations. Conclusions: TKA for post‐fracture osteoarthritis significantly relieved pain and improved function, but the incidence of surgical site complications and reoperations was high. Preoperative patella baja was a risk factor for surgical site complications and reoperations. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prognostic value of circulating tumor cells (CTCs) in nasopharyngeal carcinoma (NPC). Methods: Cox's proportional hazards regression models were used to identify whether CTCs was a poor prognostic factor for NPC. Chi-square tests were used to analyze and compare the distribution characteristics of CTCs in NPC. ROC curve was used to estimate the cut-off point of CTCs. Kaplan-Meier survival analyses were used to observe the prognostic value of CTCs alone and in combined with Epstein-Barr Virus DNA (EBV-DNA). Results: CTCs was confirmed to be an independent risk factor for poor prognosis of NPC by Cox's regression models that enrolled 370 NPC cases and took age, gender, EBV-DNA and CTCs as variables. The proportion of CTCs in stage IV NPC was statistically different from that in stage III; the cut-off point of CTCs between stage IV (288 cases) and stage III (70 cases) NPC estimated by ROC curve was 0.5. The prognosis of advanced NPC patients became worse with the increase of CTCs count. The combined detection of CTCs and EBV-DNA could better predict the prognosis of NPC compared with the single detection of EBV-DNA. [ABSTRACT FROM AUTHOR]

Quantitative analyses of potential radionuclide contaminants in solid wastes (e.g. calcium fluoride sludge) generated by the nuclear industry are essential for clearance or reutilization of these wastes. In order to measure trace uranium isotopes in calcium fluoride sludge, a total sample dissolution method was developed utilizing lithium metaborate fusion and anion exchange chromatography combined with a triple quadrupole ICP-MS/MS instrument. The method was validated using calcium fluoride sludge spiked with known amounts of uranium isotopes. All measured results were in good agreement with the expected values, demonstrating the feasibility of the method for the determination of trace uranium isotopes. The minimum detectable activities of 234U, 235U and 238U were determined to be 0.15 mBq (0.65 pg), 0.67 μBq (8.38 pg) and 0.014 mBq (1.13 ng), respectively. A key finding was that the sensitivity of uranium (750 Mcps ppm−1) with He at a flow rate of 8.5 mL min−1 was 5 times that achieved by ICP-MS/MS without the collision gas. The investigation of the mechanism of He collision would provide a novel and optimal method to simultaneously improve the sensitivity and suppress interference for the analysis of ultra-low level heavy radionuclides (e.g., uranium, plutonium, and americium) combined with reaction gasses (e.g., CO2, O2, and NH3). [ABSTRACT FROM AUTHOR]

• Pu tracer is successfully applied to evaluate soil erosion in the Loess Plateau. • Both of natural grassland and artificial forest rehabilitation were effective. • Artificial forest is superior for reducing soil erosion in the short-term. • Natural grass rehabilitation is better for inhibiting soil erosion in the long-term. Soil erosion is a critical threat to the agriculture and ecosystem in the Chinese Loess Plateau area. Ecological rehabilitation has been applied in large area for reduction of the soil erosion. Six soil depth profiles were collected from Nanxiaohegou watershed in the Loess Plateau in northwest China and analyzed for the activity concentrations of plutonium isotopes. The measured 240Pu/239Pu atomic ratios in all these samples (0.186±0.017) showed that the global fallout was the dominant source of plutonium in this region. An exponential decline of 239,240Pu activity concentrations with depth was observed in most of soil profiles. The total inventory of 239,240Pu in the reference site was calculated to be 110 Bq/m2, agreeing well with the reported total fallout value in this latitude. The soil erosion rates were estimated by comparison with the reference site to be 538–941 t/km2/yr in the most of sites. While an excessive inventory of 239,240Pu (186 Bq/m2) compared to the reference site was observed in one site in the base area, indicating a significant accumulation of soil occurred in this area. The soil erosion depths were estimated to be 2.4–4.6 cm in most of sites during 1963–2016, which can be classified as minor erosion. Compared with the erosion rates in the Nanxiaohegou watershed in 1963–2012 which was estimated by other methods, it is suggested that the natural grass is better for long-term ecological restoration, especially in slope area. [ABSTRACT FROM AUTHOR]

In order to measure trace plutonium and its isotopes ratio ( 240 Pu/ 239 Pu) in environmental samples with a high uranium, an analytical method was developed using radiochemical separation for separation of plutonium from matrix and interfering elements including most of uranium and ICP-MS for measurement of plutonium isotopes. A novel measurement method was established for extensively removing the isobaric interference from uranium ( 238 U 1 H and 238 UH 2 + ) and tailing of 238 U, but significantly improving the measurement sensitivity of plutonium isotopes by employing NH 3 /He as collision/reaction cell gases and MS/MS system in the triple quadrupole ICP-MS instrument. The results show that removal efficiency of uranium interference was improved by more than 15 times, and the sensitivity of plutonium isotopes was increased by a factor of more than 3 compared to the conventional ICP-MS. The mechanism on the effective suppress of 238 U interference for 239 Pu measurement using NH 3 -He reaction gases was explored to be the formation of UNH + and UNH 2 + in the reactions of UH + and U + with NH 3 , while no reaction between NH 3 and Pu + . The detection limits of this method were estimated to be 0.55 fg mL -1 for 239 Pu, 0.09 fg mL −1 for 240 Pu. The analytical precision and accuracy of the method for Pu isotopes concentration and 240 Pu/ 239 Pu atomic ratio were evaluated by analysis of sediment reference materials (IAEA-385 and IAEA-412) with different levels of plutonium and uranium. The developed method were successfully applied to determine 239 Pu and 240 Pu concentrations and 240 Pu/ 239 Pu atomic ratios in soil samples collected in coastal areas of eastern China. [ABSTRACT FROM AUTHOR]

There is a growing demand for the determination of actinides in soil and sediment samples for environmental monitoring and tracing, radiological protection, and nuclear forensic reasons. A total sample dissolution method based on lithium metaborate fusion, followed by sequential column chromatography separation, was developed for simultaneous determination of Pu, Am and Cm isotopes in large-size environmental samples by alpha spectrometry and mass spectrometric techniques. The overall recoveries of both Pu and Am for the entire procedure were higher than 70% for large-size soil samples. The method was validated using 20 g of soil samples spiked with known amounts of 239 Pu and 241 Am as well as the certified reference materials IAEA-384 (Fangataufa Lagoon sediment) and IAEA-385 (Irish Sea sediment). All the measured results agreed very well with the expected values. [ABSTRACT FROM AUTHOR]

Aims: To compare adherence and persistence to oral antidiabetic drugs (OAD) between patients who are new users of second generation antipsychotics (SGA) versus new users of other depression therapies in adults with type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD).Methods: Adults 18-64 years with previously-treated T2DM and MDD (past OAD and SSRI/SNRI use) who are new users of SGA or non-SGA therapies (bupropion, lithium, mirtazapine, thyroid hormone, tricyclic antidepressant) were identified in the 2009-2015 MarketScan® Commercial Claims and Encounters database. Multivariate regression models were used to determine the odds of a ≥10% decline in OAD adherence over 180- and 365-days, and time to OAD discontinuation, adjusting for differences between groups.Results: A total of 8664 (21.5% SGA), 8311 (22.1% SGA), and 17,524 (21.3% SGA) patients met inclusion criteria for the 180-day adherence, 365-day adherence, and persistence cohorts, respectively. Over 180-days, 16.6% of SGA and 13.3% of non-SGA initiators had a ≥10% decline in OAD adherence (adjusted odds ratio [OR] = 1.41, 95% CI 1.21-1.63). Over 365-days, 22.3% of SGA and 18.9% of non-SGA initiators had a ≥ 10% decline (OR = 1.34, 95% CI 1.17-1.53). Time to OAD discontinuation was similar between groups (adjusted hazard ratio = 1.03, 95% CI 0.94-1.12).Conclusion: Use of SGA was associated with a 1.3-1.4 times higher odds of a ≥10% decline in OAD adherence. Adherence to OAD is critical for optimal diabetes control and reductions in this magnitude may impact A1C. Close monitoring of OAD adherence after SGA initiation is warranted. [ABSTRACT FROM AUTHOR]

Sargassum polycystum C. Agardh, a brown alga that is widely distributed in tropical areas, has significant economic value by virtue of its use as food, traditional medicine, animal fodder, and chemical products in Asian countries. In order to explore suitable conditions for the aquaculture of this alga, we used 9-10 cm long branches of S. polycystum to assess the effects of various environmental factors, including temperature, salinity, and irradiance upon the relative growth rate (RGR), photosynthetic pigment content, and chlorophyll fluorescence characteristics of this species. Data showed that S. polycystum exhibited a relatively broad tolerance to various environmental conditions, and grew well in different conditions of temperature, salinity, and irradiance, ranging from 15 to 25 °C, 20-40 PSU, and 10-80 μmol photons·m−2·s−1. The maximum RGR of S. polycystum occurred at 23 °C, 32 PSU, and 20-80 μmol photons·m−2·s−1 (P < 0.05). Temperature had a significant effect (P < 0.05) upon RGR and the chlorophyll fluorescence characteristics of S. polycystum, and lower temperature (10 °C) led to rapid reductions in the maximal photochemical quantum yield of photosystem II (Fv/Fm) and non-photochemical quenching (NPQ) values. Salinity exhibited a relatively weak effect upon the growth of S. polycystum, and the plant was able to survive at salinities from 16 to 40 PSU; during a two-week cultivation period, significant differences in RGR were not observed among different salinity conditions until 2 weeks of cultivation. Chlorophyll a and carotenoid content of S. polycystum decreased as irradiance increased (P < 0.05), and photo-inhibition occurred under higher levels of irradiance (> 80 μmol photons·m−2·s−1). These physiological data provide valuable data related to the successful cultivation of S. polycystum under controlled conditions. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to estimate the association between use of second generation antipsychotics (SGAs) and type 2 diabetes (T2DM) among commercially insured children and young adults 6-24 years compared to users of non-SGA psychotropic medications.Methods: Using the Truven MarketScan Commercial Claims and Encounters Database, new users of SGA and non-SGA psychotropic medications (anxiolytics, antidepressants, hypnotics, and mood stabilizers) between July 1, 2009 and December 31, 2013 who were 6-24 years of age and had continuous coverage ≥180 days before their index date (i.e., date of first fill of SGA or non-SGA psychotic) were identified. SGA users were propensity score (PS) matched to non-SGA psychotropic users at a 1:1 ratio. Individuals were followed until diabetes diagnosis, discontinuation or switch from index medication, end of continuous coverage, or end of the study period. The Cox proportional hazards model was used to estimate the hazard ratio (HR) for incident T2DM for SGA users compared to non-SGA users.Results: A total of 45,289 SGA users and 932,336 non-SGA psychotropic users met inclusion criteria. In the PS matched sample, there were 102,028 patient-years of follow-up and median time to event was 202 days for SGA users (n = 43,407) and 290 days for non-SGA psychotropic users (n = 43,407). A total of 141 SGA users (33 cases per 10,000 patient-years) and 110 of the non-SGA psychotropic users (18 cases per 10,000 patient-years) developed T2DM. The SGA users had a 1.7 times higher risk of T2DM (HR 1.71, 95% confidence intervals [CI] 1.33-2.20) compared to non-SGA psychotropic users.Conclusion: Risk of T2DM should be considered when evaluating the risk/benefit of SGA use among children and young adults. Future studies aimed at evaluating risk factors, diabetes prevention strategies, and effective management of the long-term consequences of T2DM in this vulnerable population are needed. [ABSTRACT FROM AUTHOR]

Speciation analysis of long-lived I in seawater can provide useful information on the source of water masses. This paper presents an improved method for speciation analysis of I based on coprecipitation of iodide as AgI with AgSO and AgCl. By adding a small amount of I carrier, the separation efficiency of iodine species and the accuracy and precision of I measurement are remarkably improved. I species in depth profiles of seawater from the Antarctic were analyzed for investigation of water circulation in the Antarctic. [ABSTRACT FROM AUTHOR]

The low-thrust trajectory optimization with complicated constraints must be considered in practical engineering. In most literature, this problem is simplified into a two-body model in which the spacecraft is subject to the gravitational force at the center of mass and the spacecraft's own electric propulsion only, and the gravity assist (GA) is modeled as an instantaneous velocity increment. This paper presents a method to solve the fuel-optimal problem of low-thrust trajectory with complicated constraints in a full ephemeris model, which is closer to practical engineering conditions. First, it introduces various perturbations, including a third body's gravity, the nonspherical perturbation and the solar radiation pressure in a dynamic equation. Second, it builds two types of equivalent inner constraints to describe the GA. At the same time, the present paper applies a series of techniques, such as a homotopic approach, to enhance the possibility of convergence of the global optimal solution. [ABSTRACT FROM AUTHOR]

Porcine interleukin-6 gene and CpG sequences were used as immunoadjuvants to enhance the immune responses of newborn piglets to Pseudorabies attenuated vaccine (PAV). The titer of specific antibodies to PAV, the proliferation of lymphocytes and induced IL-2 activities were all examined to identify the immune response of the piglets. The results showed that the immune responses with CpG ODN and porcine interleukin-6 gene were significantly stronger than routine immunities. The data suggests that porcine IL-6 and CpG motifs could be employed as effective immunoadjuvants to raise the humoral and cellular responses of newborn piglets to Pseudorabies attenuated vaccine. [ABSTRACT FROM AUTHOR]

Studies high frequency mitotic gene conversion in genetic hybrids of the oomycete Phytophthora sojae. Main factor affecting the ability of microbial populations to respond to novel challenges from the environment; Frequency of gene conversion after vegetative passaging and sexual reproduction; High frequency changes to homozygosity in F[sub 1] progeny of P6497 x P7076.

[Display omitted] • U-PSresin was synthesized to use for separation and detection of U(VI). • U-PSresin shows good irradiation and thermal stability. • U-PSresin is demonstrated a highly sensitive detection efficiency of U(VI). • U-PSresin is proved to be used for continuous measurement of U(VI). It is extremely significant to monitor the radioactive uranium during the process of nuclear energy mining and disposal because of its high levels of chemical and radiological toxicity. In this work, a novel uranium plastic scintillator resin (U-PSresin) was successfully synthesized by suspension polymerization and used to rapidly enrich and determine uranium by Liquid Scintillation Counting (LSC). The U-PSresin shows excellent irradiation stability, extremely appropriate adsorption capacity of U(VI) (9.35 mg/g), which is convenient for the accurate measurement of LSC. Meanwhile, U-PSresin has a deviation of less than 5 % in adsorption and measurement repeatability and can be utilized to accurately measure more than 1 mg of natural uranium after enrichment. For different types of spiked water samples, the measurement deviation of U-PSresin is less than 15 %. This work demonstrates that U-PSresin can selectively enrich and quantitatively measure uranium in an aqueous environment, showcasing its significant potential in nuclear emergency scenarios and environmental monitoring. [ABSTRACT FROM AUTHOR]

Tumor-derived extracellular vesicles (TEVs) have emerged as promising sources of diagnostic and prognostic biomarkers for nasopharyngeal carcinoma (NPC). However, the lack of high-sensitivity analytic methods for ultratrace membrane proteins on TEVs hamper their clinical application of TEVs. Herein, by combining aptamers that specifically bind to protein targets on TEVs, PCR-based exponential amplification and CRISPR/Cas12a real-time DNA detection, we developed a novel technique, termed the aptamer-CRISPR/Cas12a assay, to detect CD109+ and EGFR+ TEVs from cell lines and complex biofluids. The platform enables highly sensitive detection of CD109+ and EGFR+ TEVs at as low as 100 particles/mL with a linear range spanning 6 orders of magnitude (102-108 particles/mL), which was found to be sufficient to effectively detect TEV proteins directly in low-volume (50 μl) samples. Furthermore, clinical serum sample analysis verified that the combination of serum CD109+ and EGFR+ TEV levels yielded high diagnostic accuracy, with an AUC of 0.934 (95% CI: 0.868–1.000), a sensitivity of 84.1% and a specificity of 85.0%, in discriminating NPC from healthy controls. Moreover, the dramatic decrease in both biomarkers in responders after radiotherapy indicated their potential roles in radiotherapy surveillance. Given that the aptamer-CRISPR/Cas12a assay rapidly and conveniently detects ultralow concentrations of CD109+ and EGFR+ TEVs directly in serum, it could be useful in NPC diagnosis and prognosis. Image 1 • A novel approach, called the aptamer-CRISPR/Cas12a assay, was developed. • A highly sensitive, specific and cost-effective method to measure EV surface protein. • Serum CD109+ and EGFR+ EVs as new biomarkers in NPC. • Provided possibility of CRISPR/Cas12a to detect trace surface proteins on EVs. [ABSTRACT FROM AUTHOR]

The long-lived anthropogenic 129I released from human nuclear activities has been widely employed as an effective oceanographic tracer to investigate circulation of water masses in marine environment. Depth profiles of seawater collected from the Amundsen Sea Polynya, Antarctica were analyzed for total 129I and 127I, as well as their species of iodide and iodate. The measured 129I concentrations ((1.15–3.43) × 106 atoms/L) and 129I/127I atomic ratios ((0.53–1.19) × 10−11) indicate that anthropogenic 129I has not only reached the Antarctic surface marine environment but also the deep water due to a strong vertical mixing of water masses. The Circumpolar Deep Water (CDW) flowed southward along continental shelf towards the ice shelf zone (74.25°S) at a depth of 1025 m and then migrated upward and northward to the polynya and finally to the sea ice zone (71.95°S). The maximum upwelling depth of the CDW was around 200 m in the polynya. The source of 129I− in the polynya is predominantly the intrusion of source waters rather than the in-situ reduction of iodate by phytoplankton, implying a considerably slow reduction process of iodate to iodide in this region. Image 1 • Anthropogenic 129I has not only reached the Antarctic surface water but also the deep water with a depth of at least 1025 m. • The transport pathway of CDW was firstly investigated in the Amundsen Sea Polynya, and its maximum upwelling depth was around 200 m. • The reduction of iodate to iodide in the polynya might be a relatively slow process. [ABSTRACT FROM AUTHOR]

Introduction: Intracranial hemorrhage (ICH), a serious complication in persons with hemophilia A (PWHA), causes high rates of mortality and morbidity. Identified ICH risk factors from patient data spanning 1998– 2008 require reassessment in light of changes in the current treatment landscape. Aim and methods: PWHA identified in the ATHNdataset were evaluated retrospectively to assess incidence of ICH and determine the association between ICH risk and key characteristics using time-to-event analyses (Cox proportional-hazards models, survival curves, and sensitivity analyses). Results: Over a median follow-up time of 10.7 patient-years, 135 of 7837 PWHA over 2 years of age in the ATHNdataset (1.7%) experienced an ICH. Stratification by prophylaxis status and inhibitor status resulted in an incidence rate (IR) ratio (IRR) (IR+/IR−) of 0.63 (95% confidence interval [CI], 0.43– 0.94; P=0.020) and 1.76 (95% CI, 0.97– 3.20; P=0.059), respectively. Characteristics associated with greater risk of developing ICH include being aged 2– 12 years; being covered by Medicaid; having had HIV, hepatitis C, or hypertension; and never having received factor VIII or prophylactic treatment. In multivariable analysis with interaction, the estimated hazard ratio for PWHA never receiving prophylaxis was 7.67 (95% CI, 2.24– 26.30), which shrunk to 2.03 (95% CI, 1.30– 9.12) in bootstrapping analysis and 3.09 in the highest-penalty ridge-regression analysis but was still significant. Inhibitor status was found not to be statistically associated with ICH in all analyses. Conclusion: These results align with previous studies demonstrating that prophylaxis confers a protective effect against ICH. Previously, inhibitor positivity had been shown to increase risk for ICH; however, this study did not corroborate those findings. [ABSTRACT FROM AUTHOR]

Transuranium elements such as Np, Pu and Am, are considered to be the most important radioactive elements in view of their biological toxicity and environmental impact. Concentrations of 237Np, Pu isotopes and 241Am in two sediment cores collected from Peter the Great Bay of Japan Sea were determined using radiochemical separation combined with inductively coupled plasma mass spectrometry (ICP-MS) measurement. The 239,240Pu and 241Am concentrations in all sediment samples range from 0.01 Bq/kg to 2.02 Bq/kg and from 0.01 Bq/kg to 1.11 Bq/kg, respectively, which are comparable to reported values in the investigated area. The average atomic ratios of 240Pu/239Pu (0.20 ± 0.02 and 0.21 ± 0.01) and 241Am/239+240Pu activity ratios (3.32 ± 2.76 and 0.45 ± 0.17) in the two sediment cores indicated that the sources of Pu and Am in this area are global fallout and the Pacific Proving Grounds through the movement of prevailing ocean currents, and no measurable release of Np, Pu and Am from the local K-431 nuclear submarine incident was observed. The extremely low 237Np/239Pu atomic ratios ((2.0–2.5) × 10−4) in this area are mainly attributed to the discrepancy of their different chemical behaviors in the ocean due to the relatively higher solubility of 237Np compared to particle active plutonium isotopes. It was estimated using two end members model that 23% ± 6% of transuranium radionuclides originated from the Pacific Proving Grounds tests, and the rest (ca. 77%) from global fallout. [Display omitted] • Distribution of transuranium radionuclides in the sediment cores were investigated. • The contribution of transuranium from PPG was estimated to be 23 ± 6 %. • No measurable release of transuranium from K-431 incident was observed. • 237Np/239Pu atomic ratio might be unsuitable for the source identification. [ABSTRACT FROM AUTHOR]

The leaves of many plants are red during particular stages of their lives, but the adaptive significance of leaf colouration is not yet clearly understood. In order to reveal whether anthocyanins play a similar role (i.e. antioxidants) in different seasonal contexts, this study investigated species with red young leaves in the subtropical forest of Dinghushan biosphere reserve (South China) during summer and winter and compared group leaf characteristics between the two seasons. Of 62 total species, 33 exhibited red young leaves in summer only, 6 in winter only, and 23 in both seasons. The anthocyanins extracted from most of these species had an absorption peak at ~530 nm. Frequency distribution analysis showed that the species containing anthocyanins at levels ranging from 0.02 to 0.04 μmol cm−2 occurred most frequently in summer or winter. Based on conditional grouping of the species, no significant variation was observed in the average anthocyanin contents and antioxidant abilities between summer and winter; the flavonoid content in summer was 2-fold that in winter, whereas the anthocyanin:flavonoid ratio in summer was only half that in winter. Moreover, a positive correlation between anthocyanins and flavonoids was found in summer. Therefore, it is less likely for anthocyanins to serve as antioxidants in summer than winter, because such a function in summer leaves is readily replaced by other flavonoids. [ABSTRACT FROM AUTHOR]

A rapid analytical method for sequential separation and determination of the most significant α- and β-emitting radionuclidic impurities in 99Tc radiopharmaceutical raw material is presented. Successive HTiO co-precipitation steps were first conducted for effective removal of 99Tc to avoid its spectral interference on the determination of β-emitting nuclides by liquid scintillation counting. A sequential chromatographic method was applied for simultaneous separation and purification of actinide and lanthanide isotopes. A series of K99TcO4 solution spiked with known quantities of 238Pu, 239Pu, 241Pu, 237Np, 241Am, 244Cm and 147Pm were analyzed for method evaluation, demonstrating that the method would meet the analytical requirements for radionuclidic impurity evaluation of K99TcO4 raw material. [ABSTRACT FROM AUTHOR]

Background: Lumacaftor/ivacaftor was approved by the Food and Drug Administration (FDA) as a combination treatment for Cystic Fibrosis (CF) patients who are homozygous for the F508del mutation. The objective of this study was to assess the cost-effectiveness of lumacaftor/ivacaftor combination for the treatment of CF homozygous for F508del CF Transmembrane Conductance Regulator (CFTR) mutation.Methods: A Markov-state transition model following a cohort of 12 year-old CF patients homozygous for F508del CFTR mutation in the United States (US) over two, four, six, eight and ten years from a payer's perspective was developed using TreeAge Pro 2016. Markov states included: mild (percentage of predicted forced expiratory volume in 1 s or FEV1 > 70%), moderate (FEV1 40-70%), severe (FEV1 < 40%) disease, post-transplant, and death. Pulmonary exacerbation and lung transplant were included as transition states. All the input parameters were estimated from the literature. A 1-year cycle length and 3% discount rate were applied. To assess uncertainty in long-term treatment effects, several scenarios were modelled: 100% long-term effectiveness (base-case), defined as improvement in FEV1 in the first year followed by no annual FEV1 decline and a constant reduction in pulmonary exacerbations throughout, 75%, 50%, 25% and 0% (worst case) long-term effectiveness, where treatment effects were intermediate from the second year of treatment until the end of the time horizon. Other scenarios included changing the starting age of the cohort to 6 and 25 years. Primary outcome included incremental cost-effectiveness ratio (ICER) in terms of cost per quality adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to determine uncertainty.Results: Under the base-case, Lumacaftor/ivacaftor resulted in higher QALYs (7.29 vs 6.84) but at a very high cost ($1,778,920.88) compared to usual care ($116,155.76) over a 10-year period. The ICER for base-case and worst-case scenarios were $3,655,352 / QALY, and $8,480,265/QALY gained, respectively. In the base-case, lumacaftor/ivacaftor was cost-effective at a threshold of $150,000/QALY-gained when annual drug costs were lower than $4153. The results were not substantially affected by the sensitivity analyses.Conclusions: The intervention produces large QALY gains but at an extremely high cost, resulting in an ICER that would not typically be covered by any insurer. Lumacaftor/ivacaftor's status as an orphan drug complicates coverage decisions. [ABSTRACT FROM AUTHOR]

Background: While lung cancer patient outcomes are well-recognized to vary as a function of patient sex, there has been insufficient research regarding the relationship between patient sex and EGFR(Epidermal growth factor receptor) response efficacy. The present study therefore sought to identify novel sex-related biomarkers of bevacizumab/erlotinib (BE) responses in non-small cell lung cancer (NSCLC) patients. Methods: The exon array data in the Gene Expression Omnibus (GEO) dataset were analyzed in order to identify patterns of mRNA and lncRNA expression associated with BE resistance in NSCLC. These differentially expressed (DE) lncRNAs and mRNAs were identified via DE Analysis Filtering. These DE mRNAs were then assessed for their potential functional roles via pathway enrichment analyses, with overlapping functions possibly associated with the BE resistance. The mRNAs in these overlapping groups were then assessed for their correlations with patient survival, and lncRNA-mRNA co-expression networks were generated for each patient subset. A protein-protein interaction (PPI) network was also generated based upon these DE mRNAs. Results: In females we identified 172 DE lncRNAs and 1766 DE mRNAs associated with BE responses, while in males we identified 78 DE lncRNAs and 485 DE mRNAs associated with such responses. Based on the overlap between these two datasets, we identified a total of 37 GO functions and 18 pathways associated with BE responses. Co-expression and PPI networks suggested that the key lncRNAs and mRNAs associated with these BE response mechanisms weredifferent in the male and female patients. Conclusions: This work is the first to conduct a global profiling of the relationship between lncRNA and mRNA expression patterns, patient sex, and BE responses in individuals suffering from NSCLC. Together these results suggest that the integrative lncRNA-mRNA expression analyses may offer invaluable new therapeutic insights that can guide the tailored treatment of lung cancer in order to ensure optimal BE responses. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, there has been increased focus on individualizing treatment for persons with hemophilia including pharmacokinetic‐guided (PK) dosing. Aims: In this retrospective study clinical outcomes before and after PK‐guided prophylaxis were examined. Materials and methods: Eight Haemophilia Treatment Centres from the United States participated in the study and included 132 patients classified into two cohorts: those undergoing a PK‐assessment for product switch (switchers) or to optimize treatment (non‐switchers). Subset analyses for the two most common products and patients with dosing per prescription label were included for annual bleeding rates (ABR), mean weekly consumption outcomes, and annualized cost of prophylaxis. Results: The most common products before and after index date were octocog alfa, rurioctocog alfa pegol, and efmoroctocog alfa. Seventy‐four (56%) patients were identified as switchers and 58 (44%) patients were classified as non‐switchers. The majority of patients (78.0%) experienced either a decrease in ABR post‐index or maintained 0 ABR during pre‐ and post‐index time periods, with similar proportions identified in both switchers (77.0%) and non‐switchers (79.3%) populations. Non‐switchers were identified as having no significant change in cost of therapy, while switchers experienced increased cost of therapy driven by higher price of extended half‐life products. Within subset analyses, patients receiving rurioctocog alfa pegol and efmoroctocog alfa had mean ABR under 1 after index date. Conclusion: PK‐guided prophylaxis has the potential to improve clinical outcomes without increase in cost of therapy for patients maintaining product and can aid in maintaining effective protection against bleeds in those switching product. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the frequency of oral glucose tolerance test (OGTT) on patients suffering from symptomatic cerebrovascular diseases.

A method using solvent extraction following a preconcentration of iodine by evaporation was developed for separation of iodine in waters associated with coalbed methane (CBM) for the determination of 129I using accelerator mass spectrometry, for exploration of CBM resources. The 129I/127I ratios in water samples collected in a CBM field have been determined using the developed method to be (1.6–2.4) × 10–11, which are 2–3 orders of magnitudes lower than that of environmental samples in Xi'an, but 2 orders of magnitude higher than the procedure blank of (1.5–2.1) × 10–13, confirming no measurable crossover contamination during sample analysis and slightly input of modern water in the CBM water. [ABSTRACT FROM AUTHOR]

Background: Elevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC).Methods: YKL-40 was detected in ESCC cell lines and tissues by real-time RT-PCR, Western blotting and ELISA. YKL-40 protein expression was determined in 20 ESCC tumor tissues using immunohistochemistry. Serum YKL-40 was measured by ELISA in 126 healthy donors, 59 patients with benign esophageal diseases and 150 patients with ESCC. Serum CEA, CYFRA21-1 and SCCA were determined by electrochemiluminescence.Results: YKL-40 mRNA and protein were observed in ESCC cancer cell lines, tissues and cell culture media, respectively. YKL-40 expression was observed in 17 of 20 ESCC samples (85%). Serum YKL-40 concentration was significantly elevated in patients with ESCC (Range: 6.95-502.10 ng/ml) compared with patients with benign diseases (Range: 1.21-429.30 ng/ml; P = 0.038) and healthy controls (Range: 2.56-132.26 ng/ml; P < 0.001). ROC curves demonstrated that serum YKL-40 has a sensitivity of 72.70%, a specificity of 84.13% and an AUC of 0.874 for the diagnosis of ESCC, which was superior to CEA (Sen: 8.00%; Spe: 96.80%, AUC = 0.652), CYFRA21-1 (Sen: 40.00%; Spe: 92.06%, AUC = 0.746) and SCCA (Sen: 32.67%; Spe: 94.44%, AUC = 0.789). The YKL-40 and SCCA combination was better for diagnosing ESCC (Sen: 82.00%, Spe: 79.37%, PPV: 82.55 and NPV: 78.74; AUC = 0.917) than the YKL-40 and CEA combination (Sen: 74.00%, Spe: 83.20%, PPV: 84.09 and NPV: 72.73; AUC = 0.877), the YKL-40 and CYFRA21-1 combination (Sen: 82.00%, Spe: 77.78%, PPV: 81.46% and NPV: 78.40%; AUC = 0.897) or the CEA, CYFRA21-1 and SCCA combination (Sen: 56.67%, Spe: 84.80%, PPV: 81.73 and NPV: 61.99; AUC = 0.831). Associations between serum YKL-40 levels and the clinic characteristics of ESCC were not significant, with the exception of age (p = 0.001).Conclusions: ESCC tumor cells and tissues express YKL-40. Serum YKL-40 may be a potential biomarker for ESCC. Serum YKL-40 in combination with SCCA significantly increases the sensitivity of detecting ESCC. [ABSTRACT FROM AUTHOR]

In the crystal structure of the title compound, C15H12Cl2O2, the chloro-substituted benzene rings are not parallel; the other rings are nearly parallel and the molecules stack in layers parallel to these rings. There are two molecules in the asymmetric unit. [ABSTRACT FROM AUTHOR]

A novel method for the determination of 99Tc in water samples was developed using stable Re as a chemical yield tracer and TiCl 3 as a reducing agent. The influences of several experimental parameters, including TiCl 3 concentration, HCl concentration and reaction time, on the reduction of TcO 4 − and ReO 4 − as well as Ti(OH) 3 -TcO 2 -ReO 2 co-precipitation were investigated. Tc(VII) and Re(VII) retained on TK200 resin were effectively eluted by 5 mL of 1 mol/L NH 4 SCN, which can be directly mixed with the scintillation cocktail for liquid scintillation counting. The results show that the chemical behaviors of Tc and Re are very consistent in the whole procedure. The decontamination factors of potential interferences from β-emitting nuclides mainly released from nuclear fuel reprocessing plants were also evaluated, and the minimum detectable activity concentration was calculated to be 0.08 Bq/L for 99Tc in water samples with a counting time of 2 h. [Display omitted] • Re as a non-isotopic tracer was used for measuring 99Tc in 1 L water sample. • TiCl 3 was first used as a reducing agent. • TcO 4 − and ReO 4 − were eluted from TK200 resin using 5 mL of 1 mol/L NH 4 SCN, which can be directly used for LSC measurement. • The MDA was estimated to be 0.08 Bq/L for 99Tc with a counting time of 2 h. [ABSTRACT FROM AUTHOR]

To reveal effects of elevated atmospheric CO2 on tolerance to the herbicide glyphosate in the populations of goosegrass (Eleusine indica) known to have resistance to this herbicide, two biotypes of goosegrass, a resistant (R) and a susceptible (S) biotype, were analyzed after exposed to ambient (400 μmol mol-1) and elevated CO2 (800 μmol mol-1) for 25 d. The results showed that elevated CO2 had little effect on growth of both biotypes. At elevated CO2, shoot biomass of R biotype was statistically lower than of S biotype (P<0.5). The dose-response analysis showed that glyphosate tolerance was reduced by 60% in R biotype exposed to elevated Co2 while it was slightly increased in S biotype. Elevated Co2 also had more adverse effects on photosynthetic capacity of R biotype than S biotype. As a result, maximum rate of net photosynthesis (Amax) and carboxylation efficiency (CE) under elevated CO2 in R biotype were significantly lower than in S biotype (P<0.5). These results indicate that elevated atmospheric Co2 can lead to a compromise in glyphosate tolerance of R biotype associated with poor photosynthetic characteristics, and thus will affect weed management involved with herbicide resistance in prospective agricultural systems. © 2015 Friends Science Publishers [ABSTRACT FROM AUTHOR]

Plasmonic nanostructures offer an enticing prospect in many applications, ranging from lasing to biosensing, due to their unrivaled light concentration beyond the diffraction limit. However, this promise is substantially undercut by the intrinsically high losses in metals. Here, an experimental ultra‐high‐Q plasmon resonance with a linewidth down to 2 nm (Q‐factor ≈ 350) and a resonance intensity of 51% in an ultrasmooth gold nanogroove array is reported. Such an experimental ultranarrow resonance arises from two key factors. First, a geometrical‐induced coupling between the Fabry–Pérot and Wood's anomaly modes significantly suppresses the groove array's radiative damping. Second, an ultrasmooth gold surface fabricated by template stripping minimizes its surface scattering and grain boundary scattering. Benefiting from this ultranarrow resonance, a figure of merit (FOM) of 284 and an FOM* of 617 in refraction index (RI) sensing under normally incident detection are demonstrated, the former of which is the record FOM in all reported broad‐RI‐range plasmonic RI sensors. The array is further demonstrated as a surface thickness sensor for detecting mercaptocarboxylic acids with the surface sensitivity of 0.18 nm/CH2, which suggests that the array is a promising platform for thickness detection of surface analytes and label‐free biomedical sensing. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel extractant resin DtBuCH18C6@CG-71 was successfully prepared with simple and low-cost method. • DtBuCH18C6@CG-71 exhibited remarkable separation ability of Sr(II) even in high concentration HNO 3 (3–12 mol/L). • DtBuCH18C6@CG-71 possessed great acid, irradiation and thermal resistance stability. • DtBuCH18C6@CG-71 can adeptly sequesters and recovers Sr(II) from wastewater via an automated separation system. Effective removal of radioactive 90Sr is crucial for both management of spent nuclear fuel and recovery of radioactive strontium resources, while it's still a great challenge due to the presence of high acid levels and intense radiation. Herein, a novel porous resin (DtBuCH18C6@CG-71) were synthesized by introducing 4′,4″(5″)-di- tert -butyldicyclohexano-18-crown-6 onto CG-71 resin using vacuum impregnation. The DtBuCH18C6@CG-71 resin maintains superior adsorption abilities in extreme conditions, including high acid resistance (3–12 mol/L HNO 3), substantial γ-irradiation (200 kGy 60Co), and elevated temperatures (50–100 ℃). Impressively, even when exposed to a high concentration of matrix ions (59 elemental ions), the Sr(II) adsorption ratio onto DtBuCH18C6@CG-71 resin remains near 100 % even in highly acidic condition, which performance outpaces most of commercial resins. Dynamic column tests using an automated separation system further confirmed the superior ability of DtBuCH18C6@CG-71 in term of extracting Sr(II) from wastewater. Given its impressive features, cost-effectiveness, and scalability, DtBuCH18C6@CG-71 resin holds promising potential for 90Sr disposal in nuclear wastewater. [ABSTRACT FROM AUTHOR]

Zexieyin formula (ZXYF) has been identified to have therapeutic actions of atherosclerosis (AS). It's unknown that whether ZXYF has therapeutic potential of atherosclerosis (AS) with cognitive impairment (CI) and its underlying mechanisms. To elucidate therapeutic effect of ZXYF for AS with CI as well as its underlying mechanisms in AS with CI mice model. To establish AS with CI model, we fed ApoE−/− mice with high-fat diet (HFD) for 8 weeks. Oil red O staining (ORO) and Hematoxylin-eosin staining (HE) were used to detect aortic plaque area. Morris water maze (MWM) and Y-maze were used to measure cognitive function and cognitive improvement after administration of ZXYF and atorvastatin (ATO). Network pharmacology was used to screen for potential mechanisms for improving cognitive function. Western blot was used to detect expressions of MAPK, Aβ and synaptic proteins in hippocampus. HFD caused and accelerated the AS in ApoE−/− mice, while it was easier able to produce CI than normal mice. Administration of ZXYF or ATO for 8 weeks significantly reduced aortic plaque area in ORO and HE tests, and improved cognitive abilities in MWM and Y-maze tests. Network pharmacology results showed that MAPK or synaptic proteins were highly associated with CI. HFD contributed to abnormal expressions of MAPK (pERK, pP38, pJNK), NF-kB, synaptic proteins (PSD95, synapsin1) and β-amyloid (Aβ) in hippocampus, which were all reversed by ZXYF. However, ERK and PSD95 expressions were not reversed by ATO in hippocampus. ZXYF mitigated AS, further alleviating CI by modulating MAPK signaling, relating to synaptic proteins enhancing and Aβ protein decreasing in the hippocampus. This study firstly lit up the new clinical application of ZXYF, which might promote the use of ZXYF in AS and CI patients. [Display omitted] • Long-term HFD caused atherosclerosis with cognitive impairment only in ApoE−/− mice but not in WT mice. • Zexieyin formula mitigated atherosclerosis to relieve cognitive impairment by modulating MAPK signaling, synaptic proteins and β-amyloid in hippocampus. • This study firstly shed light on clinical application of Zexieyin formula for the treatment of comorbidities such as atherosclerosis with cognitive impairment in patients. [ABSTRACT FROM AUTHOR]

Rapid bioassay method for plutonium in urine samples are employed to assess the possible internal dose resulting from exposure to plutonium in the event of a radiological and nuclear emergency. In this work, a rapid method for the determination of plutonium isotopes (239Pu and 240Pu) in large volume of urine samples was developed using tandem quadrupole ICP-MS combined with a high-efficiency sample introduction system (APEX-Ω). The mixture gases of NH 3 and He was employed to effectively eliminate the tailing of 238U and the uranium hydride ions (238U1H+and 238U1H 2 +) and significantly improve the measurement sensitivity of plutonium. The method was validated by analyzing urine samples spiked with known amounts of 239Pu and 240Pu ranging from 1 to 60 fg. The detection limits for the method were estimated to be 0.83 fg for 239Pu, 0.14 fg for 240Pu in 1 L of urine. [Display omitted] • Tandem quadrupole ICP-MS was utilized to measure Pu isotopes in large volume of urine samples. • The interference of 238U (0.23 cps) would be much less a concern at 4.0 mL min−1 NH 3 and 3.0 mL min−1 He. • The detection limits of 239Pu (0.83 fg/L) and 240Pu (0.14 fg/L) are suitable for Pu routine analysis of urine. [ABSTRACT FROM AUTHOR]

Introduction: High mortality rates in patients with chronic kidney disease‐mineral and bone disorder (CKD‐MBD) receiving maintenance hemodialysis are largely due to cardiovascular (CV) events. Methods: We evaluated associations between MBD parameters, fibroblast growth factor 23 (FGF23) concentrations, and clinically adjudicated CV events from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. Patients enrolled in EVOLVE, who had not experienced any study endpoints between randomization and week 20 with evaluable baseline and week 20 values for key laboratory parameters (parathyroid hormone, calcium, phosphate, and FGF23), were assessed. We used adjusted Cox proportional hazards regression models to estimate relative risk of outcomes (primary composite, all‐cause mortality, and CV events) based on FGF23 and MBD parameters. Laboratory values were modeled with linear terms and using natural cubic splines with two degrees of freedom. Findings: For the primary endpoint, patients assessed (N = 2309) were followed up over a mean duration of 3.1 years, during which 1037 CV events (497 deaths, 540 nonfatal events) occurred. Adjusted models showed an association between FGF23 and the risk of CV events. Hazard ratio per log unit of FGF23 at week 20 was 1.09 [95% CI: 1.03–1.16], and the hazard ratio per log unit change in FGF23 from week 0 to week 20 was 1.09 [95% CI: 1.00–1.17]. Discussion: Our data highlight FGF23 as an independent CV risk factor and potential biomarker and therapeutic target for patients with CKD‐MBD receiving maintenance hemodialysis. [ABSTRACT FROM AUTHOR]

Background: Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants.Methods: A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks.Results: The total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96-1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28-296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000-1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment.Conclusions: Repeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g. Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073 ; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500 . [ABSTRACT FROM AUTHOR]

Coumarin is an allelochemical that is widely present in the plant kingdom and has great potential for weed control. However, its mechanisms of action remain largely unknown. This study employed metabolomic and transcriptomic analyses along with evaluations of amino acid profiles and related physiological indicators to investigate how coumarin inhibits the germination and seedling growth of Eleusine indica by modifying metabolic pathways. At 72 h of germination at 50 and 100 mg L−1 coumarin, E. indica had lower levels of soluble sugar and activities of amylases and higher levels of starch, O 2 −, H 2 O 2 , auxin (IAA) and abscisic acid (ABA) compared to the control. Metabolomic analysis demonstrated that coumarin treatments had a significant impact on the pathways associated with amino acid metabolism and transport and aminoacyl-tRNA biosynthesis. Exposure to coumarin induced significant alterations in the levels of 19 amino acids, with a decrease in 15 of them, including Met, Leu and γ-aminobutyric acid (GABA). Additionally, transcriptomic analysis showed that coumarin significantly disrupted several essential biological processes, including protein translation, secondary metabolite synthesis, and hormone signal transduction. The decrease in TCA cycle metabolite (cis-aconitate, 2-oxoglutarate, and malate) contents was associated with the suppression of transcription for related enzymes. Our findings indicate that the inhibition of germination and growth in E. indica by coumarin involves the suppression of starch conversion to sugars, modification of the amino acid profile, interference of hormone signalling and the induction of oxidative stress. The TCA cycle appears to be one of the most essential pathways affected by coumarin. • The mechanisms of coumarin to inhibit seed germination were investigated in Eleusine indica. • Seed germination of Eleusine indica were sensitive to coumarin. • Exposure to coumarin induced significant alteration in the amino acid profile. • The metabolites and genes related to the TCA cycle was dramatically affected by coumarin. [ABSTRACT FROM AUTHOR]

• A highly efficient adsorbent was prepared and used for the treatment of uranium wastewater. • MXene/PAO hydrogel beads exhibit outstanding adsorption capacity under different conditions. • MXene/PAO hydrogel beads have excellent practicality coupling through columns. • Adsorption mechanism under F− conditions is the coordination of MXene and amidoxime to uranium complexes. The treatment of radioactive wastewater is crucial to ensure the safe and rapid development of nuclear energy. However, efficient disposal of uranium wastewater containing high concentrations of fluoride ions (F−) generated during uranium enrichment and conversion poses a formidable and pressing challenge. In this study, we successfully synthesized MXene/PAO hydrogel beads (MPH beads) by self-assembling two-dimensional Ti 3 C 2 T x MXene nanosheets with amidoxime through ionic cross-linking. MPH beads exhibited exceptional uranium adsorption capacity (625 mg/g), remarkable adsorption selectivity, and good reusability. Notably, MPH beads demonstrated a maximum uranium adsorption capacity of 400 mg/g in an aqueous solution containing 8000 ppm F−. Furthermore, MPH beads showed favorable F− resistance and were able to remove>95% of U(Ⅵ) even after being immersed in an extreme environment for 15 days. Additionally, MPH beads achieved a high U(Ⅵ) recovery of 98.2% from real environment water samples using dynamic column experiments, showcasing their excellent application performance. The efficient U(Ⅵ) adsorption and anti-fluoride effect were mainly attributed to the combined complexation between the C(NH 2) = N-OH, C-Ti-OH groups and U(Ⅵ), as demonstrated by experiments, characterization, and DFT calculations. Our study highlights the significant potential of MPH beads in the treatment of uranium from radioactive wastewater, especially wastewater with high concentrations of F−. [ABSTRACT FROM AUTHOR]

The successful development of photosynthetic organs is the basis of plant growth and community development. To reveal photo-acclimation to high irradiance in tree species during the course of leaf development and plant succession of subtropical forests, photosynthetic efficiency and photoprotective compounds were analyzed in young and mature leaves of three mid-successional tree species ( Castanopsis fissa , Castanopsis chinensis and Schima superba ) and three late-successional tree species ( Machilus chinensis , Cryptocarya chinensis and Cryptocarya concinna ), grown in 100% full sunlight (FL) or 30% of FL (low light, LL). Young leaves of the two species groups exhibited lower chlorophyll (Chl) content, Rubisco content, net photosynthetic rate ( P n ), carboxylation efficiency ( CE ), effective photochemical yield ( Φ PSII ), photorespiratory electron flow ( J O ), but higher dark respiration ( R d ), and ratios of carotenoids/chlorophylls (Car/Chl), anthocyanins/chlorophylls (Anth/Chl), flavonoids/chlorophylls (Flav/Chl), phenols/chlorophylls (Phen/Chl) and total antioxidant capacity/chlorophylls (TAC/Chl) than those of mature leaves, regardless of growth irradiance. Young leaves of both species groups demonstrated a higher flexibility of Anth/Chl, Flav/Chl, Phen/Chl and TAC/Chl in response to different light conditions than mature leaves. Flav/Chl in young leaves of late-successional group was remarkably higher than that of mid-successional group under the same light conditions. There was a negative correlation between antioxidant-dependent photoprotective potential and photosynthetic efficiency in young and mature leaves of the six tree species grown under either FL or LL. Our results explain partial mechanisms that lie behind the replacement of communities in subtropical forests: highly integrated photoprotective potential allows young leaves of shade-tolerant late-successional species to develop smoothly into mature organs under high irradiance. [ABSTRACT FROM AUTHOR]

The abundance of phenolic compounds (including anthocyanins) in leaves is associated with photosynthetic performance, but the regulatory mechanism is unclear. Schima superba Gardn. et Champ. and Cryptocarya concinna Hance. which exhibit distinct anthocyanin accumulation patterns, are dominant tree species in the early- and late-successional stages, respectively, of subtropical forests in China. RNA-seq and analyses of phenolic concentrations, antioxidant capacity and photosynthetic characteristics were performed on young and mature leaves of these two species under contrasting light conditions. The high-light-acclimated young leaves of S. superba and C. concinna and low-light-acclimated young leaves of C. concinna were red. These red leaves had higher ratios of electron transport rate to gross photosynthesis (ETR: P gross) and total antioxidant capacity to chlorophyll (TAC:Chl) than did the green leaves, regardless of light conditions. In addition, the red leaves had a higher expression level of the UDP-glucose:flavonoid 3-O-glucosyltransferase (UFGT) gene than did the green leaves, irrespective of light conditions. Total antioxidant capacity was positively correlated with flavonoid content in C. concinna leaves and with total phenolic content in leaves of both species under both high and low light. Consistent with the measurements of photosynthetic performance and flavonoids:Chl ratio, photosynthesis-related genes were extensively downregulated and flavonoid-pathway-related genes were extensively upregulated in young leaves relative to mature leaves. Under high and low light, both non-photochemical quenching and TAC:Chl, which serve as different types of photoprotective tools, were enhanced in young leaves of S. superba, whereas only TAC:Chl was enhanced in young leaves of C. concinna. Our results indicate that the biosynthesis of phenolic compounds in young leaves is likely enhanced by an imbalance between photosynthetic electron supply and demand and that flavonoids play a larger role in meditating photoprotection in late-successional species than in early-successional ones. [ABSTRACT FROM AUTHOR]

Tumor-derived exosomes (TEXs) are extracellular vesicles that are continuously released into the blood by tumor cells and carry specific surface markers of the original tumor cells. Substantial evidence has implicated TEXs as attractive diagnostic markers for cancer. However, the detection of TEXs in blood at an early tumor stage is challenging due to their very low concentration. Here, we established a method called PLA-RPA-TMA assay that allows TEXs to be detected with high sensitivity and specificity. Based on two proximity ligation assay (PLA) probes that recognize a biomarker on a TEX, we generated a unique surrogate DNA signal for the specific biomarker, which was synchronously amplified twice by recombinase polymerase amplification (RPA) coupled with transcription-mediated amplification (TMA), and then the products of the RPA-TMA reaction were quantitatively detected using a gold nanoparticle-based colorimetric assay. We established proof-of-concept evidence for this approach using TEXs from nasopharyngeal carcinoma (NPC) cells, with a detection limit of 10 2 particles/mL, and reported the measurement of plasma Epstein-Barr virus latent membrane protein 1 (LPM1)-positive (LMP1 + , accuracy: 0.956) and epidermal growth factor receptor (EGFR)-positive (EGFR + , accuracy: 0.906) TEXs as potent early diagnostic biomarkers for NPC. [ABSTRACT FROM AUTHOR]

WNT-ß-catenin-TCF pathway is involved in carcinogenesis and foetal development. As a member of the WNT gene family, Wnt8A encodes secreted signalling proteins and responds to many biological processes. However, similar research on the effects of genetic variations of Wnt8A gene on growth traits is lacking. Therefore, in this study, polymorphisms of Wnt8A were detected in 396 animals from Chinese Qinchuan cattle using DNA pool sequencing and PCR-RFLP methods. Four novel single-nucleotide polymorphisms (SNPs) of Wnt8A gene were identified, including three mutations in introns (g.T-445C, g.G244C and g.G910A) and one in exon (g.T4922C). Additionally, we examined the associations of four SNPs with growth traits. The results revealed that SNP2 (g.G244C) was significantly associated with shoulder height, hip height, body length, hip width, and body weight ( $$P < 0.05$$ ). SNP3 (g.G910A) also displayed notable effects on hip width ( $$P < 0.05$$ ). Meanwhile, the haplotype combination CC-GC-GA-CC was strongly associated with heavier, taller and longer animals ( $$P < 0.05$$ ). These results show that the Wnt8A gene may be a potential candidate gene, and the SNPs could be used as molecular markers in early marker-assisted selection in beef cattle breeding programmes. [ABSTRACT FROM AUTHOR]

Temperatures are expected to fluctuate widely under climate change but little is known about how extreme temperatures might affect the physiology and performance of invasive compared to native plant species. In this study, we evaluated the effects of high (40/35°C) and low (10/5°C) temperature regimes on the growth and photosynthesis of the invasive Asteraceae species Bidens alba and its native congener B. biternata using a growth chamber experiment. Results showed that invasive B. alba had significantly greater total biomass and relative growth rate, accompanied by higher net photosynthetic rate (Pn), than native B. biternata at both low and high temperature extremes. The reduction in Pn for B. alba was mainly caused by stomatal limitations, but for B. biternata it was caused by non-stomatal factors, indicating that greater damage to physiological processes may occur in native B. biternata under both low and high temperature stress. Higher cyclic electron flow around photosystem I in invasive B. alba than in native B. biternata under extreme temperatures might alleviate the negative effect of temperature extremes to photosynthetic and thus promote its photosynthetic efficiency. To conclude, the invasive B. alba has both greater cold and heat tolerance than its native congener B. biternata, suggesting that the invader may outperform native species under future extreme temperature conditions. [ABSTRACT FROM AUTHOR]

Background. The pretreatment albumin and globulin ratio (AGR) was an inflammation-associated factor which was related to the overall survival in various malignancies. The aim of this study was to evaluate the prognostic value of AGR in patients with gastric cancer. Method. This retrospective study included 862 cases pathologically diagnosed with gastric cancer. All patients were randomly divided into the testing group (431 cases) and validation group (431 cases). The relationships of AGR with clinicopathologic characteristics and prognosis were analyzed by Kaplan-Meier and Cox regression methods. Results. In the testing group, the median overall survival was 26.90 months and the cutoff value of AGR was 1.50 based on R language. Kaplan-Meier analysis showed that lower AGR was correlated with poorer overall survival. Multivariate analysis demonstrated that AGR was an independent prognostic factor for overall survival (HR: 0.584, 95% CI = 0.351–0.973, and p = 0.039). In the validation group, the median overall survival was 24.10 months. Lower AGR (≤1.50) also had a significantly poorer overall survival by Kaplan-Meier analysis. According to multivariate analysis, the AGR was also confirmed to be an independent prognostic factor for overall survival (HR: 0.578, 95% CI = 0.373–0.897, and p = 0.015). Conclusions. Our study suggested that the pretreatment AGR could be a prognostic biomarker for overall survival in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The insulin-like growth factor (IGF) system plays an important role in the development and progression of cancer. However, little is known about the expression of the IGF system components and their clinicopathological significance and prognostic value in nasopharyngeal carcinoma (NPC).Methods: IGF system components (IGF-1, IGF-2, IGF-1SR, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-6) were quantified from the plasma of NPC patients and healthy individuals using the RayBio Human Cytokine Antibody Array. IGFBP-1 and IGF-1 mRNA levels were quantified by real-time qPCR, and protein expression was detected by western blot in nine NPC cell lines and four immortalized nasopharyngeal epithelial (NPE) cell lines. Tissue-specific expression of IGFBP-1 and IGF-1 was detected by immunohistochemistry in paraffin-embedded NPC tissues. ELISA analysis was used to measure the serum levels of IGFBP-1 and IGF-1 in 142 NPC patients and 128 healthy controls and determine potential correlation with clinicopathological parameters.Results: Significantly higher levels of circulating IGFBP-1 and lower levels of IGF-1 and IGF-2 were detected in NPC patients compared to healthy controls by Cytokine Antibody Array analyses (P = 0.034, 0.012, 0.046, respectively). IGFBP-1 expression was detected in the majority of NPC cell lines, but not in NPE cell lines, and was shown to localize to the nucleus of tumour cells, in contrast to the cytoplasmic staining observed in normal cells. Importantly, IGFBP-1 expression was stronger in NPC tumour tissues compared to peritumoural tissues. In contrast, IGF-1 expression was weak or absent in NPC and NPE cell lines, with the exception of the EBV-infected C666 cell line, and was found to be expressed at lower levels in tumour tissues compared to tumour-adjacent normal tissue. Levels of serum IGFBP-1 were shown to be significantly higher in patients with NPCs compared to healthy control individuals (55.23 ± 41.25 μg/L vs. 32.08 ± 29.73 μg/L, P < 0.001), whereas serum levels of IGF-1 were significantly lower in NPC patients compared to healthy controls (98.14 ± 71.48 μg/L vs. 164.01 ± 92.08 μg/L, P = 0.001). Consistently, the IGFBP-1/IGF-1 serum ratio was shown to be significantly higher in NPC patients compared to healthy control individuals (P = 0.002). Serum levels of IGFBP-1 and the IGFBP-1/IGF-1 ratio significantly correlated with age (P = 0.020; P = 0.016), WHO histological classification (P = 0.044; P = 0.048), titre of EA (EB Virus Capsid Antigen-IgA) and NPC (P = 0.015; P = 0.016). In contrast, higher IGFBP-1 serum levels and IGFBP-1/IGF-1 ratio significantly correlated with poor RFS (P = 0.046; P = 0.037) and OS (P = 0.038; P = 0.009). Multivariate analysis revealed that the IGFBP-1/IGF-1 ratio, but not serum IGFBP-1 level, represents an independent risk factor for poor RFS (P = 0.044) and OS (P = 0.035).Conclusions: A higher IGFBP-1/IGF-1 serum ratio is significantly associated with poor prognosis in NPC patients. [ABSTRACT FROM AUTHOR]

In this paper, the effects of Al doping and equibiaxial strain on monolayer h-BN were investigated by first-principles calculations. The results show that with tensile strain applied, the structure of the material is more stable, while the structural stability of the material decreases when compressive strain is applied. When the monolayer h-BN is doped with Al, the band gap decreases, and the higher the doped Al concentration, the lower the band gap. Equibiaxial strain is very effective for band gap tuning of monolayer h-BN. The optical calculation results show that the peaks of dielectric function and optical constant of the material decrease after Al doping, and the peaks decrease with the increase of Al concentration. When the strain is tensile, the optical properties of the material will be red-shifted as a whole, and the optical properties of the material will be blue-shifted when compressive strain is applied. After the monolayer h-BN was doped with two Al atoms and a strain of −9% was applied, the optical properties of the material were significantly affected. Our study provides some theoretical implications for the application of monolayer h-BN in the field of spintronic devices and optoelectronic devices. • The effect of equbiaxial strain and Al doping on monolayer h-BN were investigated. • Using first principles based on density functional theory. • Compared with the compression strain, the structure of the material is more stable under the tensile strain. • Band gap decreases with increasing Al doping concentration. • Optical properties of the material are red-shifted with tensile strain and blue-shifted with compressive strain. [ABSTRACT FROM AUTHOR]

Objective Chinese crude drug Mori Cortex Radicis (the root cortex of Morus species) has been used as a folk medicine to treat hypertension, diabetes, as well as in expectorant, diuretic agents. This investigation aims to study the anti-hyperlipidemia effects of Mori Cortex Radicis (MCR) extracts in hyperlipidemic rat models and the potential therapeutic activities of compounds isolated from the extracts. Materials and methods The effects of MCR on hypolipidemic parameters were investigated using Wistar rats induced by high-lipid emulsion. Sixty healthy Wistar rats were randomly divided into 6 groups: normal group, hyperlipidaemia model group, simvastatin, and high-, medium- and low-dose MCR extracts. After four weeks, body weight, total cholesterol (TC), triglycerides (TG), high and low-density lipoproteins (HDL, LDL), as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured. To further investigation, four major active compounds were isolated from extracts through high performance liquid chromatography (HPLC) and their diacylglycerol acyltransferase 1 (DGAT1) inhibitory activity was evaluated. Results MCR dose-dependently reduced serum TC, TG, LDL-C, inhibited the activity of ALT, AST, and increased HDL-C. Furthermore, in vitro biochemistry tests revealed that four active isolates showed moderate inhibitory activity against DGAT1 with IC 50 values ranging from 62.1±1.2 to 99.3±2.3 µM. Conclusions The results demonstrated that MCR could effectively ameliorate hyperlipidaemia and inhibit DGAT1 that a key enzyme closely related to hyperlipidaemia and type 2 diabetes. It may provide a new pharmacological basis for treating hyperlipidaemia and related diseases using MCR. [ABSTRACT FROM AUTHOR]