Impaired colonic motility in high-glycemic diet-induced diabetic mice is associated with disrupted gut microbiota and neuromuscular function

Background: Similar to the high-fat diet (HFD), the high-glycemic diet (HGD) contributes to the development and progression of type 2 diabetes mellitus (T2DM). However, the effect of HGD on gastrointestinal motility in T2DM and its u nderlying mechanisms remain unclear. Methods: Thirty C57BL/6J mice were randomly designated into the normal-feeding diet (NFD) group, HFD group, and HGD group. The plasma glucose, plasma insulin, and gastrointestinal motility were examined. Meanwhile, the tension of isolated colonic smooth muscle rings was calculated, and the gut microbiota was analyzed by 16s rDNA high-throughput sequencing. Result: After 16 weeks of HGD feeding, obesity, hyperglycemia, insulin resistance, and constipation were observed in HGD mice. Autonomic contraction frequency of the colonic neuromuscular system and electrical field stimulation-induced contractions were reduced in HGD mice. On the contrary, neuronal nitric oxide synthase activity and neuromuscular relaxation were found to be enhanced. Finally, gut microbiota analysis revealed that Rhodospirillaceae abundance significantly increased at the family level in HGD mice. At the genus level, the abundance of Insolitispirillum increased remarkably, whereas Turicibacter abundance decreased significantly in HGD mice. Conclusion: HGD induced constipation in obese diabetic mice, which we speculated that it may be related to neuromuscular dysmotility and intestinal microbiota dysbiosis

Patchouli alcohol improved diarrhea-predominant irritable bowel syndrome by regulating excitatory neurotransmission in the myenteric plexus of rats

Background and Purpose: Irritable bowel syndrome (IBS) is usually associated with chronic gastrointestinal disorders. Its most common subtype is accompanied with diarrhea (IBS-D). The enteric nervous system (ENS) modulates major gastrointestinal motility and functions whose aberration may induce IBS-D. The enteric neurons are susceptible to long-term neurotransmitter level alterations. The patchouli alcohol (PA), extracted from Pogostemonis Herba, has been reported to regulate neurotransmitter release in the ENS, while its effectiveness against IBS-D and the underlying mechanism remain unknown.Experimental Approach: In this study, we established an IBS-D model in rats through chronic restraint stress. We administered the rats with 5, 10, and 20 mg/kg of PA for intestinal and visceral examinations. The longitudinal muscle myenteric plexus (LMMP) neurons were further immunohistochemically stained for quantitative, morphological, and neurotransmitters analyses.Key Results: We found that PA decreased visceral sensitivity, diarrhea symptoms and intestinal transit in the IBS-D rats. Meanwhile, 10 and 20 mg/kg of PA significantly reduced the proportion of excitatory LMMP neurons in the distal colon, decreased the number of acetylcholine (Ach)- and substance P (SP)-positive neurons in the distal colon and restored the levels of Ach and SP in the IBS-D rats.Conclusion and Implications: These findings indicated that PA modulated LMMP excitatory neuron activities, improved intestinal motility and alleviated IBS-induced diarrheal symptoms, suggesting the potential therapeutic efficacy of PA against IBS-D

Robust Graph Meta-Learning via Manifold Calibration with Proxy Subgraphs

Graph meta-learning has become a preferable paradigm for graph-based node classification with long-tail distribution, owing to its capability of capturing the intrinsic manifold of support and query nodes. Despite the remarkable success, graph meta-learning suffers from severe performance degradation when training on graph data with structural noise. In this work, we observe that the structural noise may impair the smoothness of the intrinsic manifold supporting the support and query nodes, leading to the poor transferable priori of the meta-learner. To address the issue, we propose a new approach for graph meta-learning that is robust against structural noise, called Proxy subgraph-based Manifold Calibration method (Pro-MC). Concretely, a subgraph generator is designed to generate proxy subgraphs that can calibrate the smoothness of the manifold. The proxy subgraph compromises two types of subgraphs with two biases, thus preventing the manifold from being rugged and straightforward. By doing so, our proposed meta-learner can obtain generalizable and transferable prior knowledge. In addition, we provide a theoretical analysis to illustrate the effectiveness of Pro-MC. Experimental results have demonstrated that our approach can achieve state-of-the-art performance under various structural noises

Effect of Pyrite on the Leaching Kinetics of Pitchblende in the Process of Acid In Situ Leaching of Uranium

In the process of acid in situ leaching of sandstone uranium ore, pyrite, which is a common associated mineral of pitchblende, would inevitably participate in the reaction. Therefore, it is important to study the influence of pyrite on the leaching kinetics of pitchblende. In this study, we compared the difference leaching rates of pitchblende in the systems of sulfuric acid–hydrogen peroxide, sulfuric acid–hydrogen peroxide–pyrite and sulfuric acid–pyrite and studied the influence of temperature and pyrite quantity on the leaching rate of pitchblende. The results show that the leaching process of pitchblende follows the shrinking particle model controlled by a chemical reaction, and the apparent activation energy Ea of the leaching reaction is (3.74 ± 0.40) × 10 kJ/mol. Pyrite itself cannot promote the dissolution of pitchblende; however, it can promote the leaching of pitchblende in the presence of an oxidizer. Increasing the quantity of pyrite in a certain range can increase the leaching rate of pitchblende, and the reaction order of pyrite is 0.36

Exosomes of endothelial progenitor cells repair injured vascular endothelial cells through the Bcl2/Bax/Caspase-3 pathway

Abstract The main objective of this study is to evaluate the influence of exosomes derived from endothelial progenitor cells (EPC-Exo) on neointimal formation induced by balloon injury in rats. Furthermore, the study aims to investigate the potential of EPC-Exo to promote proliferation, migration, and anti-apoptotic effects of vascular endothelial cells (VECs) in vitro. The underlying mechanisms responsible for these observed effects will also be thoroughly explored and analyzed. Endothelial progenitor cells (EPCs) was isolated aseptically from Sprague–Dawley (SD) rats and cultured in complete medium. The cells were then identified using immunofluorescence and flow cytometry. The EPC-Exo were isolated and confirmed the identities by western-blot, transmission electron microscope, and nanoparticle analysis. The effects of EPC-Exo on the rat carotid artery balloon injury (BI) were detected by hematoxylin and eosin (H&E) staining, ELISA, immunohistochemistry, immunofluorescence, western-blot and qPCR. LPS was used to establish an oxidative damage model of VECs. The mechanism of EPC-Exo repairing injured vascular endothelial cells was detected by measuring the proliferation, migration, and tube function of VECs, actin cytoskeleton staining, TUNEL staining, immunofluorescence, western-blot and qPCR. In vivo, EPC-Exo exhibit inhibitory effects on neointima formation following carotid artery injury and reduce the levels of inflammatory factors, including TNF-α and IL-6. Additionally, EPC-Exo downregulate the expression of adhesion molecules on the injured vascular wall. Notably, EPC-Exo can adhere to the injured vascular area, promoting enhanced endothelial function and inhibiting vascular endothelial hyperplasia Moreover, they regulate the expression of proteins and genes associated with apoptosis, including B-cell lymphoma-2 (Bcl2), Bcl2-associated x (Bax), and Caspase-3. In vitro, experiments further confirmed that EPC-Exo treatment significantly enhances the proliferation, migration, and tube formation of VECs. Furthermore, EPC-Exo effectively attenuate lipopolysaccharides (LPS)-induced apoptosis of VECs and regulate the Bcl2/Bax/Caspase-3 signaling pathway. This study demonstrates that exosomes derived from EPCs have the ability to inhibit excessive carotid intimal hyperplasia after BI, promote the repair of endothelial cells in the area of intimal injury, and enhance endothelial function. The underlying mechanism involves the suppression of inflammation and anti-apoptotic effects. The fundamental mechanism for this anti-apoptotic effect involves the regulation of the Bcl2/Bax/Caspase-3 signaling pathway

Changes in Gut Microbiota Composition Associated with the Presence of Enteric Protist Blastocystis in Captive Forest Musk Deer (Moschus Berezovskii)

10.1128/spectrum.02269-21MICROBIOLOGY SPECTRUM10

Hydrogen Generation from Hydrolysis and Methanolysis of Guanidinium Borohydride

Metal-catalyzed hydrolysis and methanolysis of guanidinium borohydride (C­(NH₂)₃BH₄ or GBH) for hydrogen generation are reported. GBH is comparatively stable in water with only 0.3 equiv of H₂ liberated in 24 h at 25 °C while it reacts vigorously with methanol, releasing more than 3.2 equiv of H₂ within only 17 min. Even at 0 °C, there was still nearly 2.0 equiv of H₂ released after 2 h, but no H₂ liberation was observed for hydrolysis under the same conditions. Various metal chlorides were adopted to enhance the reaction kinetics of the hydrolysis and methanolysis, of which CoCl₂ exhibits the highest activity in both cases. With the addition of 2.0 mol % CoCl₂ at 25 °C, the methanolysis of GBH could generate 4 equiv of H₂ within 10 min with a maximum hydrogen generation rate of 9961.5 mL·min^<b>–</b>1·g^<b>–</b>1 while only 1.8 equiv of H₂ was obtained under the same conditions at a maximum hydrogen generation rate of 692.3 mL·min^<b>–</b>1·g^<b>–</b>1 for hydrolysis. Compared with hydrolysis, methanolysis of GBH possesses much faster reaction kinetics, rendering it an advantage for hydrogen generation, especially at subzero areas. It was proposed that the faster reaction kinetics of methanolysis of BH₄^– containing compounds is ascribed to the more electron donating methoxy group than that of hydroxyl group. Moreover, a comparison between hydrolysis and methanolysis of GBH indicates that the loss of the first H from BH₄^– controls the hydrolysis kinetics instead of the cleavage of the O–H bond