Changes in Chemical Composition of Flaxseed Oil during Thermal-Induced Oxidation and Resultant Effect on DSC Thermal Properties

To investigate the changes in chemical composition of flaxseed oil during thermal-induced oxidation and the resultant effect on thermal properties, samples with different oxidation levels were obtained by being heated at 180 °C for two hours and four hours. The oxidation degree was evaluated using peroxide value (PV), extinction coefficient at 232 nm and 268 nm (K232 and K268), and total polar compounds (TPC). Using chromatography, the fatty acid profile and triacylglycerol (TAG) profile were examined. Differential scanning calorimetry (DSC) was used to determine the crystallization and melting profiles. Thermal-induced oxidation of flaxseed oil led to a significant increase (p 232, K268, and TPC, but the relative content of linolenic acid (Ln) and LnLnLn reduced dramatically (p Ton) of the crystallization curve was highly correlated with K232, TPC, and the relative content of LnLnLn (p Toff) of the melting curve was highly correlated with the relative content of most fatty acids (p < 0.05). This finding provides a new way of rapid evaluation of oxidation level and changes of chemical composition for flaxseed oils using DSC

DRMC: A Generalist Model with Dynamic Routing for Multi-Center PET Image Synthesis

Multi-center positron emission tomography (PET) image synthesis aims at recovering low-dose PET images from multiple different centers. The generalizability of existing methods can still be suboptimal for a multi-center study due to domain shifts, which result from non-identical data distribution among centers with different imaging systems/protocols. While some approaches address domain shifts by training specialized models for each center, they are parameter inefficient and do not well exploit the shared knowledge across centers. To address this, we develop a generalist model that shares architecture and parameters across centers to utilize the shared knowledge. However, the generalist model can suffer from the center interference issue, \textit{i.e.} the gradient directions of different centers can be inconsistent or even opposite owing to the non-identical data distribution. To mitigate such interference, we introduce a novel dynamic routing strategy with cross-layer connections that routes data from different centers to different experts. Experiments show that our generalist model with dynamic routing (DRMC) exhibits excellent generalizability across centers. Code and data are available at: https://github.com/Yaziwel/Multi-Center-PET-Image-Synthesis.Comment: This article has been early accepted by MICCAI 2023,but has not been fully edited. Content may change prior to final publicatio

Numerical Simulation Investigation on Parameter Optimization of Deep-Sea Mining Vehicles

Abstract The four-track walking mining vehicle can better cope with the complex terrain of cobalt-rich crusts on the seabed. To explore the influence of different parameters on the obstacle-crossing ability of mining vehicles, this paper took a certain type of mine vehicle as an example and establish a mechanical model of the mine vehicle. Through this model, the vehicle’s traction coefficient variation could be analyzed during the obstacle-crossing process. It also reflected the relationship between the obstacle-crossing ability and the required traction coefficient. Many parameters were used for this analysis including the radius of the guide wheel radius, ground clearance of the driving wheel, the dip angle of the approaching angular and the position of centroid. The result showed that the ability to cross the obstacles requires adhesion coefficient as support. When the ratio between obstacle height and ground clearance of the guide wheel was greater than 0.7, the required adhesion coefficient increased sharply. The ability to cross obstacles will decrease, if the radius of the guide wheel increases, the height of the driving wheel increases or the dip angle of the approaching angular increases. It was most beneficial to cross the obstacle when the ratio of the distance between the center of mass and the front driving wheel to the wheelbase is between 0.45‒0.48. The results of this paper could provide reference for structural parameter design and performance research for mining vehicles

Marine-Steroid Derivative 5α-Androst-3β, 5α, 6β-triol Protects Retinal Ganglion Cells from Ischemia–Reperfusion Injury by Activating Nrf2 Pathway

High intraocular pressure (IOP)-induced retinal ischemia leads to acute glaucoma, which is one of the leading causes of irreversible visual-field loss, characterized by loss of retinal ganglion cells (RGCs) and axonal injury in optic nerves (ONs). Oxidative stress and the inflammatory response play an important role in the ischemic injury of retinal and optic nerves. We focus on 5&alpha;-androst-3&beta;, 5&alpha;, 6&beta;-triol (TRIOL), a synthetic neuroactive derivative of natural marine steroids 24-methylene-cholest-3&beta;, 5&alpha;, 6&beta;, 19-tetrol and cholestane-3&beta;, 5&alpha;, 6&beta;-triol, which are two neuroactive polyhydroxysterols isolated from the soft coral Nephthea brassica and the gorgonian Menella kanisa, respectively. We previously demonstrated that TRIOL was a neuroprotective steroid with anti-inflammatory and antioxidative activities. However, the potential role of TRIOL on acute glaucoma and its underlying mechanisms remains unclear. Here, we report TRIOL as a promising neuroprotectant that can protect RGCs and their axons/dendrites from ischemic&ndash;reperfusion (I/R) injury in an acute intraocular hypertension (AIH) model. Intravitreal injection of TRIOL significantly alleviated the loss of RGCs and the damage of axons and dendrites in rats and mice with acute glaucoma. As NF-E2-related factor 2 (Nrf2) is one of the most critical regulators in oxidative and inflammatory injury, we further evaluated the effect of TRIOL on Nrf2 knockout mice, and the neuroprotective role of TRIOL on retinal ischemia was not observed in Nrf2 knockout mice, indicating that activation of Nrf2 is responsible for the neuroprotection of TRIOL. Further experiments demonstrated that TRIOL can activate and upregulate Nrf2, along with its downstream hemeoxygenase-1 (HO-1), by negative regulation of Kelch-like ECH (Enoyl-CoA Hydratase) associated Protein-1 (Keap1). In conclusion, our study shed new light on the neuroprotective therapy of retinal ischemia and proposed a promising marine drug candidate, TRIOL, for the therapeutics of acute glaucoma

Non-O1/O139 Vibrio cholerae causes severe intestinal disease in bullfrogs (Rana catesbeiana)

Abstract Bullfrogs (Rana catesbeiana) are amphibians with high economic value, but in recent years, bullfrog farming has encountered serious threats of bacterial diseases, and the “bullfrog economy” is facing a continuous decline. In this study, the dominant strain was isolated from diseased bullfrogs in a bullfrog farm in Nanning, Guangxi, and based on its morphological, physiological, and biochemical characteristics and analysis of 16S rRNA gene sequences, the strain was identified as a non-O1/O139 group Vibrio cholerae and named TC1. Three virulence factors were identified in this strain, including hemolysin, outer membrane protein, and toxin-coregulated pili. Drug susceptibility testing showed that the strain resisted gentamicin, florfenicol, nitrofural, oxytetracycline, neomycin, penicillin, amoxicillin, doxycycline, and sulfamonomethoxine. The results of artificial infection experiments showed that TC1 caused serious pathologies such as abdominal swelling and anal prolapse in bullfrogs, especially severe intestinal bleeding. Histopathological observations revealed that the bullfrog intestine exhibited obvious pathological lesions. These results provide an essential epidemiological basis for controlling V. cholerae infections in aquatic animals and demonstrate the promise of bullfrogs as an amphibian model for studying the pathogenesis of V. cholerae

Synthesis of taurine–fluorescein conjugate and evaluation of its retina-targeted efficiency in vitro

In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F–Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F–Tau. The cellular uptake of F–Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F–Tau compared with fluorescein. As compared with fluorescein, F–Tau showed little toxicity, and was retained longer by cells in uptake experiments. F–Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P<0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina

Directly targeting ASC by lonidamine alleviates inflammasome-driven diseases

Abstract Background Dysregulated activation of the inflammasome is involved in various human diseases including acute cerebral ischemia, multiple sclerosis and sepsis. Though many inflammasome inhibitors targeting NOD-like receptor protein 3 (NLRP3) have been designed and developed, none of the inhibitors are clinically available. Growing evidence suggests that targeting apoptosis-associated speck-like protein containing a CARD (ASC), the oligomerization of which is the key event for the assembly of inflammasome, may be another promising therapeutic strategy. Lonidamine (LND), a small-molecule inhibitor of glycolysis used as an antineoplastic drug, has been evidenced to have anti-inflammation effects. However, its anti-inflammatory mechanism is still largely unknown. Methods Middle cerebral artery occlusion (MCAO), experimental autoimmune encephalomyelitis (EAE) and LPS-induced sepsis mice models were constructed to investigate the therapeutic and anti-inflammasome effects of LND. The inhibition of inflammasome activation and ASC oligomerization by LND was evaluated using western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) in murine bone marrow-derived macrophages (BMDMs). Direct binding of LND with ASC was assessed using molecular mock docking, surface plasmon resonance (SPR), and drug affinity responsive target stability (DARTS). Results Here, we find that LND strongly attenuates the inflammatory injury in experimental models of inflammasome-associated diseases including autoimmune disease-multiple sclerosis (MS), ischemic stroke and sepsis. Moreover, LND blocks diverse types of inflammasome activation independent of its known targets including hexokinase 2 (HK2). We further reveal that LND directly binds to the inflammasome ligand ASC and inhibits its oligomerization. Conclusions Taken together, our results identify LND as a broad-spectrum inflammasome inhibitor by directly targeting ASC, providing a novel candidate drug for the treatment of inflammasome-driven diseases in clinic