Asymptotic Properties of Solutions to Third-Order Nonlinear Neutral Differential Equations

The aim of this work is to discuss asymptotic properties of a class of third-order nonlinear neutral functional differential equations. The results obtained extend and improve some related known results. Two examples are given to illustrate the main results

Is exponential gravity a viable description for the whole cosmological history?

Here we analysed a particular type of $F(R)$ gravity, the so-called exponential gravity which includes an exponential function of the Ricci scalar in the action. Such term represents a correction to the usual Hilbert-Einstein action. By using Supernovae Ia, Barionic Acoustic Oscillations, Cosmic Microwave Background and $H(z)$ data, the free parameters of the model are well constrained. The results show that such corrections to General Relativity become important at cosmological scales and at late-times, providing an alternative to the dark energy problem. In addition, the fits do not determine any significant difference statistically with respect to the $\Lambda$CDM model. Finally, such model is extended to include the inflationary epoch in the same gravitational Lagrangian. As shown in the paper, the additional terms can reproduce the inflationary epoch and satisfy the constraints from Planck data.Comment: 20 pages, 6 figures, analysis extended, version published in EPJ

Temozolomide and Pazopanib Combined with FOLFOX Regressed a Primary Colorectal Cancer in a Patient-derived Orthotopic Xenograft Mouse Model.

PurposeThe goal of the present study was to determine the efficacy of temozolomide (TEM) and pazopanib (PAZ) combined with FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) on a colorectal cancer patient-derived orthotopic xenograft (PDOX) mouse model.Materials and methodsA colorectal cancer tumor from a patient previously established in non-transgenic nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice in order to label the tumor stromal cells with GFP. Then labeled tumors were orthotopically implanted into the cecum of nude mice. Mice were randomized into four groups: Group 1, untreated control; group 2, TEM + PAZ; group 3, FOLFOX; group 4, TEM + PAZ plus FOLFOX. Tumor width, length, and mouse body weight were measured weekly. The Fluor Vivo imaging System was used to image the GFP-lableled tumor stromal cells in vivo. H&E staining and immunohistochemical staining were used for histological analysis.ResultsAll three treatments inhibited tumor growth as compared to the untreated control group. The combination of TEM + PAZ + FOLFOX regressed tumor growth significantly more effectively than TEM + PAZ or FOLFOX. Only the combination of TEM + PAZ + FOLFOX group caused a decrease in body weight. PAZ suppressed lymph vessels density in the colorectal cancer PDOX mouse model suggesting inhibition of lymphangiogenesis.ConclusionOur results suggest that the combination of TEM + PAZ + FOLFOX has clinical potential for colorectal cancer patient

Establishment of an isotope dilution LC-MS/MS method revealing kinetics and distribution of co-occurring mycotoxins in rats

An isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with a fast sample preparation using homemade clean-up cartridges was developed for simultaneous determination of co-occurring mycotoxins exemplified with aflatoxin B1 (AFB1) and T-2 toxin (T-2) in representative biomatrices of rat plasma, heart, liver, kidney, spleen, lung and brain in a total run time of 7 min. The established approach using stable internal standards of [C-13(17)]-AFB1 and [C-13(24)]-T-2 was extensively validated by determining the specificity, linearity (R-2 >= 0.9990), sensitivity (lower limit of quantitation at 0.05 ng mL(-1)), accuracy (70.9-107.7%), precision (RSD = 70.8%). Based on this methodological advance, the subsequent kinetics and tissue distribution after oral administration of 0.5 mg kg(-1) b.w. of both AFB1 and T-2 in rats were thoroughly studied. As revealed, both AFB1 and T-2 were rapidly eliminated with the half-life time (t(1/2)) in plasma of 8.44 +/- 4.02 h and 8.12 +/- 4.05 h, respectively. Moreover, AFB1 accumulated in all organs where the highest concentration was observed in liver (1.34 mu g kg(-1)), followed by kidney (0.76 mu g kg(-1)). Notably, only low levels of T-2 were observed in spleen (0.70 mu g kg(-1)) and in liver (0.15 mu g kg(-1)). The achieved data as supporting evidence would substantially promote the practical application of the proposed LC-MS/MS method for in vivo toxicokinetics and toxicity studies of co-occurring mycotoxins imitating natural incidence in rat system

MAU-Net: Mixed attention U-Net for MRI brain tumor segmentation

Computer-aided brain tumor segmentation using magnetic resonance imaging (MRI) is of great significance for the clinical diagnosis and treatment of patients. Recently, U-Net has received widespread attention as a milestone in automatic brain tumor segmentation. Following its merits and motivated by the success of the attention mechanism, this work proposed a novel mixed attention U-Net model, i.e., MAU-Net, which integrated the spatial-channel attention and self-attention into a single U-Net architecture for MRI brain tumor segmentation. Specifically, MAU-Net embeds Shuffle Attention using spatial-channel attention after each convolutional block in the encoder stage to enhance local details of brain tumor images. Meanwhile, considering the superior capability of self-attention in modeling long-distance dependencies, an enhanced Transformer module is introduced at the bottleneck to improve the interactive learning ability of global information of brain tumor images. MAU-Net achieves enhancing tumor, whole tumor and tumor core segmentation Dice values of 77.88/77.47, 90.15/90.00 and 81.09/81.63% on the brain tumor segmentation (BraTS) 2019/2020 validation datasets, and it outperforms the baseline by 1.15 and 0.93% on average, respectively. Besides, MAU-Net also demonstrates good competitiveness compared with representative methods

The Effects of Jiang-Zhi-Ning and Its Main Components on Cholesterol Metabolism

To examine how Jiang-Zhi-Ning (JZN) regulates cholesterol metabolism and compare the role of its four main components. We established a beagle model of hyperlipidemia, fed with JZN extract and collected JZN-containing serum 0, 1, 2, 4, and 6 h later. Human liver cells Bel-7402 were stimulated with 10% JZN-containing serum as well as the four main components of JZN and Atorvastatin. The mRNA expression of LDL receptor (LDL-R), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoAR), cytochrome P450 7A1 (CYP7A1), and acetyl-Coenzyme A acetyltransferase 2 (ACAT2) was measured by real-time PCR. LDL-R surface expression and LDL-binding and internalization were examined by flow cytometry. The results showed that JZN-containing serum significantly increased the mRNA expression of LDL-R, HMG-CoAR, and CYP7A1 in Bel-7402 cells. All the four components significantly increased the mRNA and protein expression of LDL-R and HMG-CoAR and decreased the mRNA and protein expression of ACAT2 in Bel-7402 cells. Hyperinand chrysophanol also markedly increased the mRNA expression of CYP7A1. Stimulation with stilbene glycosidesignificantly increased the surface expression of LDL-R and the binding and internalization of LDL. In conclusion, JZN and its four components have close relationship with the process of cholesterol metabolism, emphasizing their promising application as new drug candidates in the treatment of hyperlipidemia

No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs) is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family