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Choriocarcinoma (CC) is a malignant trophoblastic tumor that occurs in women of childbearing age. Its cure rate could be over 90% following single drug or multidrug chemotherapy with methotrexate, 5-fluorouracil and etc. Chemoresistance is the main cause of treatment failure in CC, and the mechanisms have yet to be elucidated. Most of the previous works on the chemoresistance of CC focused on the transcript and protein levels, and much less attention was put on the metabolic level. In this study, the metabolomic phenotypes of two lines of CC cell, methotrexate-resistant cell (JEG3R) and methotrexate-sensitive cell (JEG3), as well as the medium extracts, were investigated using an NMR-based metabonomics method. The results showed that the chemoresistance of CC was likely related to disturbed glucose metabolism. Glucitol accumulation was observed only in the JEG3R cell line, suggesting the involvement of aldose reductase in the development of chemoresistance. In addition, methotrexate chemoresistance was also associated with lactate accumulation and stimulated alanine synthesis to fuel the Krebs cycle. The levels of amino acids, nucleotides and phosphocholine in the resistant line showed significant differences from the non-resistant line, and positive correlations with the proliferation rate of CC. This study provided insights into the chemoresistance of CC from the metabolism aspect.

Gut microbiota is important for human health. The complex relationship between intestinal flora and bile acid profile has been studied previously. However, few previous studies have determined the profile and functions of bile acids in different intestinal segments, and whether they are related to the distribution of intestinal flora. In this paper, we measured the distribution of bile acids in different intestinal segments of male and female C57BL/6 mice with ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QqQ-MS) based targeted metabonomics analysis and nuclear magnetic resonance (NMR) based untargeted metabonomics analysis. Gender difference in distributions of bile acids were observed, which was more evident in the lower parts of intestine than in the upper part of intestine, especially in the cecum segment. This might be related to the abundance of gut microflora in different intestine segments. This study provided metabolic phenotypes of bile acids in mice of different genders, and demonstrated their interactions with gut microbiota.

The combination of doxorubicin and paclitaxel is widely used in clinical cancer therapy. Due to enhanced permeation and retention effects of nanomaterials in tumor tissues, nanocarriers with good biocompatibility have been designed to encapsulate doxorubicin/paclitaxel, and used to facilitate delivery of the drugs to achieve better therapeutic outcome. In this study, NMR-based metabonomic analyses were used to study the metabolic profiles in spleen tissues of normal healthy mice and of 4T1 tumor-bearing mice, which were treated with either saline, or doxorubicin/paclitaxel in their free forms, or doxorubicin/paclitaxel encapsulated in nanocarriers. The results demonstrated that treatment with the free forms of doxorubicin/paclitaxel remitted tumor-induced disturbances in gut microbiota, while treatment with nanocarrier-encapsulated doxorubicin/paclitaxel alleviated increased glucose and fumarate metabolism associated with tumor bearing. In contrast, tumor-related splenomegaly and metabolic alterations in amino acids, organic acids, nucleic acids and choline, both attributable to immune responses of the spleen, were not ameliorated by drug treatment. This could also be due to the fact that the treatment period was too short to have any significant effects. This work provided metabolic phenotypical information of the spleen tissues in 4T1 tumor-bearing mice, and helped to understand the metabolic impacts of drug delivery systems on the spleen.

This paper introduces a numerical approach for the fractional-order Rössler chaotic systems and gives error analysis. The effectiveness of the present method is determined by comparing the numerical results of the high-precision difference scheme and predictor-correctors scheme. Some complex dynamical behaviors for the fractional-order Rössler chaotic systems are shown. [ABSTRACT FROM AUTHOR]

In order to stop and reverse land degradation and curb the loss of biodiversity, the United Nations 2030 Agenda for Sustainable Development proposes to combat desertification. In this paper, a fractional vegetation–water model in an arid flat environment is studied. The pattern behavior of the fractional model is much more complex than that of the integer order. We study the stability and Turing instability of the system, as well as the Hopf bifurcation of fractional order α , and obtain the Turing region in the parameter space. According to the amplitude equation, different types of stationary mode discoveries can be obtained, including point patterns and strip patterns. Finally, the results of the numerical simulation and theoretical analysis are consistent. We find some novel fractal patterns of the fractional vegetation–water model in an arid flat environment. When the diffusion coefficient, d, changes and other parameters remain unchanged, the pattern structure changes from stripes to spots. When the fractional order parameter, β , changes, and other parameters remain unchanged, the pattern structure becomes more stable and is not easy to destroy. The research results can provide new ideas for the prevention and control of desertification vegetation patterns. [ABSTRACT FROM AUTHOR]

For a bus transit system with peak and normal periods, we derived an approximated formulated solution, to provide a patchwork for a published paper. Based on the same numerical example of the original model, our approximated solution attains the minimum cost within 0.3% to indicate that our approximated formulated solution is a good supplementary tool to estimate the optimal solution., Author(s): Yu-Lan Wang [1]; Ming-Li Chen (corresponding author) [2]; Scott Shu-Cheng Lin [3] 1. Introduction Researchers developed models to mimic real-world phenomena, and then tried to apply their results from [...]

The blood‐retinal barrier (BRB), homeostasis, neuronal integrity, and metabolic processes are all directly influenced by Müller cells, the most important retinal glial cells. We isolated primary Müller cells from Sprague–Dawley (SD) neonatal rats and treated them with glucose at varying doses. CCK‐8 was used to quantify cellular viability, and a TUNEL assay was performed to detect cell apoptosis. ELISA, immunofluorescence, and western blotting were used to assess cAMP/PKA/CREB signaling, Kir4.1, AQP4, GFAP, and VEGF levels, respectively. H&E staining was used to examine histopathological alterations in diabetic retinopathy (DR)‐affected retinal tissue in rats. As glucose concentration increases, gliosis of Müller cells became apparent, as evidenced by a decline in cell activity, an increase in apoptosis, downregulation of Kir4.1 level, and overexpression of GFAP, AQP4, and VEGF. Treatments with low, intermediate, and high glucose levels led to aberrant activation of cAMP/PKA/CREB signaling. Interestingly, blocking cAMP and PKA reduced high glucose‐induced Müller cell damage and gliosis by a significant amount. Further in vivo results suggested that cAMP or PKA inhibition significantly improved edema, bleeding, and retinal disorders. Our findings showed that high glucose exacerbated Müller cell damage and gliosis via a mechanism involving cAMP/PKA/CREB signaling. [ABSTRACT FROM AUTHOR]

Chaotic systems arise everywhere in control theory and nonlinear vibration. This paper uses a high-precision numerical approach for capturing chaotic attractors of the fractional EI Ni ñ o chaotic systems. The numerical results indicate that some of the chaotic attractors of fractional-order systems are topologically equivalent to those discovered in the integer-order systems, and some unusual attractors of fractional EI Ni ñ o chaotic systems are found by using the present method. [ABSTRACT FROM AUTHOR]