Combining Metagenomics, Network Pharmacology and RNA-Seq Strategies to Reveal the Therapeutic Effects and Mechanisms of Qingchang Wenzhong Decoction on Inflammatory Bowel Disease in Mice.

Background: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that lacks effective treatments. Qingchang Wenzhong Decoction (QCWZD) is a clinically effective herbal prescription that has been proven to attenuate intestinal inflammation in IBD. However, its molecular mechanism of action has not been clearly elucidated. Purpose: We aimed to probe the mechanism of QCWZD for the treatment of IBD. Methods: The dextran sulfate sodium (DSS)-induced mouse model of IBD was used to identify the molecular targets involved in the mechanism of action of QCWZD. Metagenomics sequencing was utilized to analyze the differences in gut microbiota and the functional consequences of these changes. Network pharmacology combined with RNA sequencing (RNA-seq) were employed to predict the molecular targets and mechanism of action of QCWZD, and were validated through in vivo experiments. Results: Our results demonstrated that QCWZD treatment alleviated intestinal inflammation and accelerated intestinal mucosal healing that involved restoration of microbial homeostasis. This hypothesis was supported by the results of bacterial metagenomics sequencing that showed attenuation of gut dysbiosis by QCWZD treatment, especially the depletion of the pathogenic bacterial genus Bacteroides, while increasing the beneficial microorganism Akkermansia muciniphila that led to altered bacterial gene functions, such as metabolic regulation. Network pharmacology and RNA-seq analyses showed that Th17 cell differentiation plays an important role in QCWZD-based treatment of IBD. This was confirmed by in vivo experiments showing a marked decrease in the percentage of CD3+CD4+IL-17+ (Th17) cells. Furthermore, our results also showed that the key factors associated with Th17 cell differentiation (IL-17, NF-κB, TNF-α and IL-6) in the colon were significantly reduced in QCWZD-treated colitis mice. Conclusion: QCWZD exerted beneficial effects in the treatment of IBD by modulating microbial homeostasis while inhibiting Th17 cell differentiation and its associated pathways, providing a novel and promising therapeutic strategy for the treatment of IBD.

Novel insights into macrophage immunometabolism in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH.

Study on the Electrical Insulation Properties of Modified PTFE at High Temperatures.

During the operation of multi-electric aircraft, the polytetrafluoroethylene (PTFE) material used to insulate the aviation cable is subjected to a high electric field while working under the extreme conditions of high temperatures for a long time, which can easily cause a partial discharge and even flashover along the surface, which seriously threaten the safe operation of the aircraft. In this paper, the electrical insulation properties of PTFE were regulated via modification by the magnetron sputtering of TiO2 under high temperatures, and modified PTFE with different sputtering times was prepared. The direct current (DC) surface discharge, surface flashover, and electric aging characteristics of modified PTFE were studied under the condition of 20~200 °C, and the mechanisms by which modification by sputtering of TiO2 and high temperature influence the insulation properties were analyzed. The results show that the surface discharge intensity increases with the increase in temperature, the modification by sputtering of TiO2 can significantly inhibit the partial discharge of PTFE, and the flashover voltage first increases and then decreases with the increase in the modification time. The modification by magnetron sputtering can effectively increase the surface potential decay rate of the PTFE, increase the shallow trap energy density, effectively avoid charge accumulation, inhibit the partial discharge phenomenon, and improve the surface electrical insulation and anti-aging properties.

How to improve the diagnosis of neoplastic transformation of gastric hyperplastic polyps in the context of autoimmune gastritis?: A case report and lierature review.

RATIONALE: Gastric hyperplastic polyp (GHP) commonly arises in the abnormal background mucosa, which makes it easy to be misdiagnosed and missed, and has a potential risk of malignant transformation over time. Here, we present a case of neoplastic transformation of GHP in a context of autoimmune gastritis (AIG). PATIENT CONCERNS: In 2020, a 67-year-old woman was admitted for endoscopic review 6 years after gastric polyp resection, the histological diagnosis of gastric polyp was neoplastic transformation of GHP as before. The patient had undergone multiple polypectomies at the same part. Then histological examination revealed that partial epithelial hyperplasia and dysplasia, and the neoplastic areas were interlaced with normal mucosa. DIAGNOSES AND INTERVENTIONS: We further found that the background diagnosis was AIG. These results supported the diagnosis of neoplastic transformation of GHP in a context of AIG. With the doubt of missed diagnose, we retrospectively analyzed the medical history in 2014, 2015 and 2016, confirmed the presence of AIG. Unfortunately, serological tests and special treatment were not performed. OUTCOMES: The correct diagnosis was eventually confirmed in 2020, which enables patients to receive normal treatment and monitoring, and avoids further deterioration of the disease. LESSONS: The purpose of this case report is to increase clinical awareness of neoplastic transformation of GHP in a context of AIG, and hope promise for early diagnosis and treatment.

Effects of Mechanical Stress on Insulation Structure and Performance of HV Cable.

Mechanical stresses generated during manufacturing and laying process of high voltage cables can result in degradation of insulation properties, affecting the stable operation of the transmission system. Traditional test methods for testing the effect of mechanical stress on the insulation properties of polyethylene still have some shortcomings to be explored and it is able to explain the changes of the insulation properties of polyethylene under mechanical stress from a microscopic perspective. In order to further study the effect of stress on the insulation properties of polyethylene, microstructural changes, the breakdown field strength, conductivity and charge distribution of polyethylene at different elongation rates are investigated by a combination of experimental and molecular dynamics simulations. The results show that the increase in stress leads to a decrease in crystallinity and microcrystalline size of the material decrease. The untwisting and orientation of the polyethylene molecular chains during the stretching process can create cavities, resulting in an uneven sample distribution and thickness reduction, leading to a reduction in the breakdown field strength. Meanwhile, some crystal regions are transformed into amorphous regions. The loose amorphous regions facilitate the directional migration of carriers, resulting in the increase of conductivity. When the elongation ratio is smaller, the distance between the molecular chains increases and the trap depth of the specimen becomes shallower. This facilitates the migration of ions and electrons and increases the rate of decay of the surface potential. When the stretch is further increased, new traps are created by broken molecular chains to limit the movement of charges, decreasing the decay rate of the surface potential and reducing the insulation properties of the polyethylene. Meanwhile, the molecular dynamics model of semi-crystalline polyethylene was developed to observe the microstructure and energy changes during the stretching process. The conclusions in terms of tensile tests were verified from a microscopic perspective.

Study on Surface Discharge Characteristics of GO-Doped Epoxy Resin-LN2 Composite Insulation.

Superconducting power lead equipment for epoxy insulation, such as high-temperature superconducting DC power or liquefied natural gas energy pipelines, as well as high-temperature superconducting cables, has long been used in extreme environments, from liquid nitrogen temperatures to normal temperatures. It is easy to induce surface discharge and flashover under the action of strong electric field, which accelerates the insulation failure of current leads. In this paper, two-dimensional nano-material GO was used to control the electrical properties of epoxy resins. The DC surface discharge and flashover characteristics of the prepared epoxy resin-GO composite insulation materials were tested at room temperature with liquid nitrogen. The surface discharge mechanism of the epoxy resin-GO composite insulation materials was analyzed. The experimental results show that the insulation properties of epoxy composites doped with GO changed. Among them, the surface flashover voltage of 0.05 wt% material is the best, which can inhibit the discharge phenomenon and improve its insulation properties in extreme environments, from room temperature to liquid nitrogen temperature. It is found that the development process of surface discharge of composite insulating materials under liquid nitrogen is quite different from that under room temperature. Before critical flashover, the repetition rate and amplitude of surface discharge remain at a low level until critical flashover. Furthermore, the voltage of the first flashover is significantly higher than that of the subsequent flashover under the action of the desorption gas on the surface of the composite insulating material and the gasification layer produced by the discharge. Given that the surface flashover voltage of 0.05 wt% epoxy composite is the best, the research and analysis of 0.05 wt% composite is emphasized. In the future design of superconducting power lead insulation, the modification method of adding GO to epoxy resin can be considered in order to improve its insulation performance.

The role of Akkermansia muciniphila in inflammatory bowel disease: Current knowledge and perspectives.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, is a chronic relapsing gastrointestinal inflammatory disease mediated by dysregulated immune responses to resident intestinal microbiota. Current conventional approaches including aminosalicylates, corticosteroids, immunosuppressive agents, and biological therapies are focused on reducing intestinal inflammation besides inducing and maintaining disease remission, and managing complications. However, these therapies are not curative and are associated with various limitations, such as drug resistance, low responsiveness and adverse events. Recent accumulated evidence has revealed the involvement of mucin-degrading bacterium Akkermansia muciniphila (A. muciniphila) in the regulation of host barrier function and immune response, and how reduced intestinal colonisation of probiotic A. muciniphila can contribute to the process and development of inflammatory bowel diseases, suggesting that it may be a potential target and promising strategy for the therapy of inflammatory bowel disease. In this review, we summarise the current knowledge of the role of A. muciniphila in IBD, especially focusing on the related mechanisms, as well as the strategies based on supplementation with A. muciniphila, probiotics and prebiotics, natural diets, drugs, and herbs to promote its colonisation in the gut, and holds promise for A. muciniphila-targeted and -based therapies in the treatment of inflammatory bowel disease.

Molecular Dynamics Simulation of Cracking Process of Bisphenol F Epoxy Resin under High-Energy Particle Impact.

The current lead insulation of high-temperature superconductivity equipment is under the combined action of large temperature gradient field and strong electric field. Compared with a uniform temperature field, its electric field distortion is more serious, and it is easy to induce surface discharge to generate high-energy particles, destroy the insulation surface structure and accelerate insulation degradation. In this paper, the degradation reaction process of bisphenol F epoxy resin under the impact of high-energy particles, such as O3-, HO-, H3O+ and NO+, is calculated based on ReaxFF simulation. According to the different types of high-energy particles under different voltage polarities, the micro-degradation mechanism, pyrolysis degree and pyrolysis products of epoxy resin are analyzed. The results show that in addition to the chemical reaction of high-energy particles with epoxy resin, their kinetic energy will also destroy the molecular structure of the material, causing the cross-linked epoxy resin to pyrolyze, and the impact of positive particles has a more obvious impact on the pyrolysis of epoxy resin.

Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice.

Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/ß-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.

Inhibition Effect of Graphene Nanoplatelets on Electrical Degradation in Silicone Rubber.

Silicone rubber (SIR) is widely used as an insulation material in high voltage cable accessories. Electrical tree is a typical electrical degradation and is easily initiated because of the distorted electric field. In this study, graphene nanoplatelets at contents of 0.001-0.010 wt % (0.00044-0.00436 vol %) were added into SIR to improve the electrical tree inhibiting ability. Scanning electron microscopy, conductivity and surface potential decay tests were conducted to analyze the characteristics of graphene/SIR nanocomposites. The typical electrical treeing experiment was employed to observe the electrical tree inhibition of graphene in SIR. The results show that graphene nanoplatelets were well dispersed in SIR. The conductivity was higher after the addition of graphene nanoplatelets, and the trap distribution was affected by graphene nanoplatelets. The tree was changed from a bush-branch structure to a bush structure after the addition of graphene. Tree inception voltage improved and reached the highest mean value at 0.003 wt %. The tree length was inhibited at 0.001 to 0.007 wt % and the lowest tree length occurred at 0.005 wt %.