Liquid biopsy in ovarian cancer in China and the world: current status and future perspectives

Ovarian cancer (OC) is the eighth most common cancer in women, but the mild, non-specific clinical presentation in early stages often prevents diagnosis until progression to advanced-stage disease, contributing to the high mortality associated with OC. While serum cancer antigen 125 (CA-125) has been successfully used as a blood-borne marker and is routinely monitored in patients with OC, CA-125 testing has limitations in sensitivity and specificity and does not provide direct information on important molecular characteristics that can guide treatment decisions, such as homologous recombination repair deficiency. We comprehensively review the literature surrounding methods based on liquid biopsies, which may provide improvements in sensitivity, specificity, and provide valuable additional information to enable early diagnosis, monitoring of recurrence/progression/therapeutic response, and accurate prognostication for patients with OC, highlighting applications of this research in China

Dental tissue proportions in fossil orangutans from mainland Asia and Indonesia

Orangutans (Pongo) are the only great ape genus with a substantial Pleistocene and Holocene fossil record, demonstrating a much larger geographic range than extant populations. In addition to having an extensive fossil record, Pongo shows several convergent morphological similarities with Homo, including a trend of dental reduction during the past million years. While studies have documented variation in dental tissue proportions among species of Homo, little is known about variation in enamel thickness within fossil orangutans. Here we assess dental tissue proportions, including conventional enamel thickness indices, in a large sample of fossil orangutan postcanine teeth from mainland Asia and Indonesia. We find few differences between regions, except for significantly lower average enamel thickness (AET) values in Indonesian mandibular first molars. Differences between fossil and extant orangutans are more marked, with fossil Pongo showing higher AET in most postcanine teeth. These differences are significant for maxillary and mandibular first molars. Fossil orangutans show higher AET than extant Pongo due to greater enamel cap areas, which exceed increases in enamel-dentine junction length (due to geometric scaling of areas and lengths for the AET index calculation). We also find greater dentine areas in fossil orangutans, but relative enamel thickness indices do not differ between fossil and extant taxa. When changes in dental tissue proportions between fossil and extant orangutans are compared with fossil and recent Homo sapiens, Pongo appears to show isometric reduction in enamel and dentine, while crown reduction in H. sapiens appears to be due to preferential loss of dentine. Disparate selective pressures or developmental constraints may underlie these patterns. Finally, the finding of moderately thick molar enamel in fossil orangutans may represent an additional convergent dental similarity with Homo erectus, complicating attempts to distinguish these taxa in mixed Asian faunas

Activation of Wnt signaling reduces high-glucose mediated damages on skin fibroblast cells

Objective(s): High-glucose (HG) stress, a mimic of diabetes mellitus (DM) in culture cells, alters expression of a large number of genes including Wnt and NF-κB signaling-related genes; however, the role of Wnt signaling during HG-mediated fibroblast damage and the relationship between Wnt and NF-κB signaling have not been understood. In this study, we aimed to investigate the ffects of Wnt signaling on HG-mediated damages. Materials and Methods: Wnt3a was treated to HG-stressed human primary foreskin fibroblasts and the levels of Wnt signaling markers and cell proliferation were monitored. In addition, Wnt3a and NF-κB signaling inhibitor were assisted to analyze the relationship between two pathways. Results: The results indicated that HG treatment repressed β-catenin level, and Wnt3a treatment increased the levels of β-catenin and FZD8 as well as cell proliferation. RNA-seq based transcriptome analysis identified 207 up-regulated and 200 down-regulated genes upon Wnt3a supply. These altered genes are distributed into 20 different pathways. In addition, gene ontology (GO) analysis indicates that 20 GO terms are enriched. Wnt signaling genes were further verified by qRT-PCR and the results were similar with RNA-seq assay. Since NF-κB signaling negatively regulates Wnt marker gene expression, Bay117082, a typical NF-κB signaling inhibitor and Wnt3a were supplemented for testing β-catenin and phosphorylated IκBα (p-IκBα), respectively. Conclusion: HG positively inhibits Wnt signaling, and signaling activation via supplementation of Wnt3a rescued the defect caused by HG. NF-κB signaling negatively regulates accumulation of β-catenin, but Wnt signaling has no effects on IκBα activation

Development and Validation of LC-MS/MS Method for Determination of Ondansetron in rat Plasma and its Application

A selective and sensitive liquid chromatography-mass spectrometry (LC–MS) method for determination of ondansetron in rat plasma was developed and validated. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation, and chromatography involved Agilent SB-C18 column (2.1 x 150 mm, 5 μm) using 0.1 % formic acid in water and acetonitrile as a mobile phase with gradient elution. Detection involved positive ion mode electrospray ionization (ESI), and multiple reaction monitoring (MRM) mode was used for quantification of target fragment ions m/z 294.0→169.7 for ondansetron and m/z 326.0→291.0 for midazolam (internal standard, IS). The assay was linear over the range of 5–1000 ng/mL for ondansetron, with a lower limit of quantitation (LLOQ) of 5 ng/mL for ondansetron. Intra- and inter-day precisions were less than 14 % and the accuracies were in the range of 94.7-113.5 % for ondansetron. This developed method was successfully applied for the determination of ondansetron in rat plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer

The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-α-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of α-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the α-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future

Determination of ramosetron in rat plasma by LC-ESI-MS and its application

A sensitive and simple liquid chromatography/electrospray mass spectrometry (LC-ESI-MS) method for determination of ramosetron in rat plasma using one-step protein precipitation was developed and validated. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographically separation was achieved on an SB-C18 (2.1 mm × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as the mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; selected ion monitoring (SIM) mode was used to quantification using target fragment ions m/z 280 for ramosetron and m/z 326 for the IS. Calibration plots were linear over the range of 10-1000 ng/mL for ramosetron in rat plasma. Lower limit of quantification (LLOQ) for Ramosetron was 10 ng/mL. Mean recovery of ramosetron from plasma was in the range of 88.5-92.8 %. CV of intra-day and inter-day precision were both less than 15 %. This method is simple and sensitive enough to be used in pharmacokinetic study for determination of ramosetron in rat plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Combustion reactivity of ilmenite with coal volatiles under steam gasification atmosphere

学位記番号：理工博甲6

TiAVox: Time-aware Attenuation Voxels for Sparse-view 4D DSA Reconstruction

Four-dimensional Digital Subtraction Angiography (4D DSA) plays a critical role in the diagnosis of many medical diseases, such as Arteriovenous Malformations (AVM) and Arteriovenous Fistulas (AVF). Despite its significant application value, the reconstruction of 4D DSA demands numerous views to effectively model the intricate vessels and radiocontrast flow, thereby implying a significant radiation dose. To address this high radiation issue, we propose a Time-aware Attenuation Voxel (TiAVox) approach for sparse-view 4D DSA reconstruction, which paves the way for high-quality 4D imaging. Additionally, 2D and 3D DSA imaging results can be generated from the reconstructed 4D DSA images. TiAVox introduces 4D attenuation voxel grids, which reflect attenuation properties from both spatial and temporal dimensions. It is optimized by minimizing discrepancies between the rendered images and sparse 2D DSA images. Without any neural network involved, TiAVox enjoys specific physical interpretability. The parameters of each learnable voxel represent the attenuation coefficients. We validated the TiAVox approach on both clinical and simulated datasets, achieving a 31.23 Peak Signal-to-Noise Ratio (PSNR) for novel view synthesis using only 30 views on the clinically sourced dataset, whereas traditional Feldkamp-Davis-Kress methods required 133 views. Similarly, with merely 10 views from the synthetic dataset, TiAVox yielded a PSNR of 34.32 for novel view synthesis and 41.40 for 3D reconstruction. We also executed ablation studies to corroborate the essential components of TiAVox. The code will be publically available.Comment: 10 pages, 8 figure

Onboard guidance system design for reusable launch vehicles in the terminal area energy management phase

A terminal area energy management (TAEM) guidance system for an unpowered reusable launch vehicle (RLV) is proposed in this paper. The mathematical model representing the RLV gliding motion is provided, followed by a transformation of extracting the required dynamics for reference profile generation. Reference longitudinal profiles are conceived based on the capability of maximum dive and maximum glide that a RLV can perform. The trajectory is obtained by iterating the motion equations at each node of altitude, where the angle of attack and the flight-path angle are regarded as regulating variables. An onboard ground-track predictor is constructed to generate the current range-to-go and lateral commands online. Although the longitudinal profile generation requires pre-processing using the RLV aerodynamics, the ground-track prediction can be executed online. This makes the guidance scheme adaptable to abnormal conditions. Finally, the guidance law is designed to track the reference commands. Numerical simulations demonstrate that the proposed guidance scheme is capable of guiding the RLV to the desired touchdown conditions