Prediction of Mechanical Behaviours of FRP-Confined Circular Concrete Columns Using Artificial Neural Network and Support Vector Regression: Modelling and Performance Evaluation.

The prediction and control of the mechanical behaviours of fibre-reinforced polymer (FRP)-confined circular concrete columns subjected to axial loading are directly related to the safety of the structures. One challenge in building a mechanical model is understanding the complex relationship between the main parameters affecting the phenomenon. Artificial intelligence (AI) algorithms can overcome this challenge. In this study, 298 test data points were considered for FRP-confined circular concrete columns. Six parameters, such as the diameter-to-fibre thickness ratio (D/t) and the tensile strength of the FRP (ffrp) were set as the input sets. The existing models were compared with the test data. In addition, artificial neural networks (ANNs) and support vector regression (SVR) were used to predict the mechanical behaviour of FRP-confined circular concrete columns. The study showed that the predictive accuracy of the compressive strength in the existing models was higher than the peak compressive strain for the high dispersion of material deformation. The predictive accuracy of the ANN and SVR was higher than that of the existing models. The ANN and SVR can predict the compressive strength and peak compressive strain of FRP-confined circular concrete columns and can be used to predict the mechanical behaviour of FRP-confined circular concrete columns.

VLM catecholaminergic neurons control tumor growth by regulating CD8+ T cells.

It is known that tumor growth can be influenced by the nervous system. It is not known, however, if tumors communicate directly with the central nervous system (CNS) or if such interactions may impact tumor growth. Here, we report that ventrolateral medulla (VLM) catecholaminergic (CA) neurons in the mouse brain are activated in tumor-bearing mice and the activity of these neurons significantly alter tumor growth in multiple syngeneic and spontaneous mouse tumor models. Specific ablation of VLM CA neurons by a dopamine-ß-hydroxylase (DBH) promotor-activated apoptosis-promoting caspase-3 in Dbh-Cre mice as well as inhibition of these neurons by a chemogenetic method slowed tumor progression. Consistently, chemogenetic activation of VLM CA neurons promoted tumor growth. The tumor inhibition effect of VLM CA neuron ablation is mitigated in Dbh-Cre;Rag1-/- mice, indicating that this regulatory effect is mediated by the adaptive immune system. Specific depletion of CD8+ T cells using an anti-CD8+ antibody also mitigated the tumor suppression resulting from the VLM CA neuron ablation. Finally, we showed that the VLM CA neuronal ablation had an additive antitumor effect with paclitaxel treatment. Collectively, our study uncovered the role of VLM CA neurons in the mouse brain in controlling tumor growth in the mouse body.

Novel Abs targeting the N-terminus of fibroblast growth factor 19 inhibit hepatocellular carcinoma growth without bile-acid-related side-effects.

Hepatocellular carcinoma (HCC) is a common and particularly fatal form of cancer for which very few drugs are effective. The fibroblast growth factor 19 (FGF19) has been viewed as a driver of HCC development and a potential Ab target for developing novel HCC therapy. However, a previously developed anti-FGF19 Ab disrupted FGF19's normal regulatory function and caused severe bile-acid-related side-effects despite of having potent antitumor effects in preclinical models. Here, we developed novel human Abs (G1A8 and HS29) that specifically target the N-terminus of FGF19. Both Abs inhibited FGF19-induced HCC cell proliferation in vitro and significantly suppressed HCC tumor growth in mouse models. Importantly, no bile-acid-related side effects were observed in preclinical cynomolgus monkeys. Fundamentally, our study demonstrates that it is possible to target FGF19 for anti-HCC therapies without adversely affecting its normal bile acid regulatory function, and highlights the exciting promise of G1A8 or HS29 as potential therapy for HCC.

Effects of macamides on endurance capacity and anti-fatigue property in prolonged swimming mice.

CONTEXT: Lepidium meyenii Walp. (Brassicaceae), most commonly known as "maca", has been used as a food or folk medicine to improve vitality in Peru. Previous research demonstrated that lipid-soluble extract from maca improved swimming endurance capacity. Macamides are considered the typical lipid-soluble markers for maca and proved to have several pharmacological properties, such as improving sexual performance and neuroprotective activies. OBJECTIVE: The present study investigates the effects of macamides on endurance capacity and anti-fatigue property in prolonged swimming mice. MATERIALS AND METHODS: The Balb/c mice were divided into seven groups: a control group, low-dose groups of N-benzyllinoleamide, N-benzyloleamide, and N-benzylpalmitamide, high-dose groups of these macamides. The macamides groups received the commercial products (12 and 40 mg/kg, ig), while the control group received vehicle for 21 d. On the 14th day, the mice were given the weight-loaded swimming test. On the 21st day, the mice were sacrificed immediately after 90 min swimming, and some biochemical parameters were measured. RESULTS AND DISCUSSION: Compared with the control group, exhaustive swimming time was significantly prolonged in high-dose group of N-benzyloleamide (p < 0.05); the levels of lactic acid (LD), blood ammonia (BA), and lactate dehydrogenase (LDH) were significantly decreased (p < 0.05), whereas the levels of liver glycogen (LG) and non-esterified fatty acid (NEFA) were significantly increased (p < 0.05) in high-dose group of N-benzyloleamide. The malondialdehyde (MDA) contents in the brain, muscle, and liver were significantly decreased (p < 0.05), whereas superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities in the brain, muscle, and liver were significantly increased in high-dose group of N-benzyloleamide (p < 0.05). CONCLUSION: The results indicate that N-benzyloleamide has pharmaceutical property against exercise-induced fatigue, and this effect can be explained by the modulated energy metabolism and improved antioxidant status.