Gut microbiota and chronic obstructive pulmonary disease: a Mendelian randomization study

BackgroundA growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut microbiota and COPD remains unclear. As a result, we used a two-sample Mendelian randomization (MR) method to investigate the connection between gut microbiota and COPD in this study.MethodsThe largest available genome-wide association study (GWAS) of gut microbiota was obtained from the MiBioGen consortium. Summary-level dataset for COPD were obtained from the FinnGen consortium. The main analysis method for determining the causal link between gut microbiota and COPD was inverse variance weighted (IVW). Subsequently, pleiotropy and heterogeneity tests were performed to determine the reliability of the results.ResultsIVW method identified 9 bacterial taxa nominally associated with the risk of COPD. Class Actinobacteria (p = 0.020), genus Allisonella (p = 0.024), genus Coprococcus2 (p = 0.002) and genus Oscillospira (p = 0.018) were protective against COPD. In addition, order Desulfovibrionales (p = 0.011), family Desulfovibrionaceae (p = 0.039), family Peptococcaceae (p = 0.020), family Victivallaceae (p = 0.012) and genus Marvinbryantia (p = 0.017) were associated with a higher risk of COPD. No pleiotropy or heterogeneity were found.ConclusionAccording to the findings of this MR analysis, a causal relationship exists between certain gut microbiota and COPD. New insights into the mechanisms of COPD mediated by gut microbiota are provided

Epidemiology and survival of patients with central nervous system solitary fibrous tumors: A population-based analysis

BackgroundThe objective of this study was to determine population-based estimates of the epidemiology and prognosis of central nervous system solitary fibrous tumors (cSFTs).MethodsWe extracted the data of patients diagnosed with cSFTs between 2004 and 2018 from the Surveillance, Epidemiology, and End Results database. We analyzed the distribution of patients according to their demographic and clinical characteristics. Binary logistic regression analysis was performed to predict which patients would be diagnosed with malignant cSFT. Possible prognostic indicators were analyzed by multivariable Cox proportional hazards models.ResultsA total of 650 cases were included. The majority of patients were diagnosed at 50-59 years old, and the median age at diagnosis was 55 years. A total of 13.4% of the tumors were located in the spinal canal, and 24% of the tumors were benign. Most of the tumors were larger than 3 cm, but distant metastasis was rare. Tumor resection was the first choice of treatment for these patients, and total resection was achieved in 51.1%. Radiation therapy after surgery was also administered to 42.3% of the patients. The median survival was 57 months. Intracranial tumors and tumors with distant metastasis tended to be malignant. The results of the log-rank test showed that the patients who underwent total resection had better overall survival (OS), but the effect of radiation therapy after surgery was not significant.ConclusioncSFT is a rare and aggressive type of tumor. Tumor resection is the first choice for treatment, and radiation therapy after surgery does not improve OS. Patients older than 60 years of age who are diagnosed with intracranial tumors, malignant tumors and distant metastasis have worse OS outcomes than their counterparts

Interferon-γ-Induced Intestinal Epithelial Barrier Dysfunction by NF-κB/HIF-1α Pathway

Interferon-? (IFN-?) plays an important role in intestinal barrier dysfunction. However, the mechanisms are not fully understood. As hypoxia-inducible factor-1 (HIF-1) is a critical determinant response to hypoxia and inflammation, which has been shown to be deleterious to intestinal barrier function, we hypothesized that IFN-? induces loss of barrier function through the regulation of HIF-1α activation and function. In this study, we detected the expressions of HIF-1α and tight junction proteins in IFN-?-treated T84 intestinal epithelial cell line. IFN-? led to an increase of HIF-1α expression in time- and dose-dependent manners but did not change the expression of HIF-1?. The IFN-?-induced increase in HIF-1α was associated with an activation of NF-?B. Treatment with the NF-?B inhibitor, pyrolidinedithiocarbamate (PDTC), significantly suppressed the activation of NF-?B and the expression of HIF-1α. In addition, IFN-? also increased intestinal epithelial permeability and depletion of tight junction proteins; inhibition of NF-?B or HIF-1α prevented the increase in intestinal permeability and alteration in tight junction protein expressions. Interestingly, we demonstrated that a significant portion of IFN-? activation NF-kB and modulation tight junction expression is mediated through HIF-1α. Taken together, this study suggested that IFN-? induced the loss of epithelial barrier function and disruption of tight junction proteins, by upregulation of HIF-1α expression through NF-?B pathway.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140108/1/jir.2013.0044.pd

Direct transformation of-alkane into all-conjugated polyene via cascade dehydrogenation

Selective C(sp$^{3}$) −H activation is of fundamental importance in processing alkane feedstocks to produce high-value-added chemical products. By virtue of an on-surface synthesis strategy, we report selective cascade dehydrogenation of n-alkane molecules under surface constraints, which yields monodispersed all-trans conjugated polyenes with unprecedented length controllability. We are also able to demonstrate the generality of this concept for alkyl-substituted molecules with programmable lengths and diverse functionalities, and more importantly its promising potential in molecular wiring

MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma

ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy. Inhibiting ATG4B in combination with radiotherapy in treating mice with intracranial GBM xenograft markedly slows tumor growth and provides a significant survival benefit. Our work describes an MST4-ATG4B signaling axis that influences GBM autophagy and malignancy, and whose therapeutic targeting enhances the anti-tumor effects of radiotherapy., • MST4 kinase regulates the growth, sphere formation, and tumorigenicity of GBM cells • MST4 stimulates autophagy by activating ATG4B through phosphorylation of ATG4B S383 • Radiation increases MST4 expression and ATG4B phosphorylation, inducing autophagy • Inhibiting ATG4B enhances the anti-tumor effects of radiotherapy in GBM PDX models , Huang et al. show that radiation induces MST4 expression and that MST4 phosphorylates ATG4B at serine 383, which increases ATG4B activity and autophagic flux. Inhibition of ATG4B reduces autophagy and tumorigenicity of glioblastoma (GBM) cells and improves the impact of radiotherapy on GBM growth in mice

He-Jie-Shen-Shi Decoction as an Adjuvant Therapy on Severe Coronavirus Disease 2019: A Retrospective Cohort and Potential Mechanistic Study

Combination therapy using Western and traditional Chinese medicines has shown notable effects on coronavirus disease 2019 (COVID-19). The He-Jie-Shen-Shi decoction (HJSS), composed of Bupleurum chinense DC., Scutellaria baicalensis Georgi, Pinellia ternata (Thunb.) Makino, Glycyrrhiza uralensis Fisch. ex DC., and nine other herbs, has been used to treat severe COVID-19 in clinical practice. The aim of this study was to compare the clinical efficacies of HJSS combination therapy and Western monotherapy against severe COVID-19 and to study the potential action mechanism of HJSS. From February 2020 to March 2020, 81 patients with severe COVID-19 in Wuhan Tongji Hospital were selected for retrospective cohort study. Network pharmacology was conducted to predict the possible mechanism of HJSS on COVID-19-related acute respiratory distress syndrome (ARDS). Targets of active components in HJSS were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases. The targets of COVID-19 and ARDS were obtained from GeneCards and Online Mendelian Inheritance in Man databases. The key targets of HJSS in COVID-19 and ARDS were obtained based on the protein–protein interaction network (PPI). Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) was conducted to predict the pathways related to the targets of HJSS in COVID-19 and ARDS. A “herb-ingredient-target-pathway” network was established using Cytoscape 3.2.7. Results showed that the duration of the negative conversion time of nucleic acid was shorter in patients who received HJSS combination therapy. HJSS combination therapy also relieved fever in patients with severe COVID-19. Network pharmacology analysis identified interleukin (IL) 6, tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), catalase (CAT), mitogen-activated protein kinase (MAPK) 1, tumor protein p53 (TP53), CC-chemokine ligand (CCL2), MAPK3, prostaglandin-endoperoxide synthase 2 (PTGS2), and IL1B as the key targets of HJSS in COVID-19-related ARDS. KEGG analysis suggested that HJSS improved COVID-19-related ARDS by regulating hypoxia-inducible factor (HIF)-1, NOD-like receptor, TNF, T cell receptor, sphingolipid, PI3K-Akt, toll-like receptor, VEGF, FoxO, and MAPK signaling pathways. In conclusion, HJSS can be used as an adjuvant therapy on severe COVID-19. The therapeutic mechanisms may be involved in inhibiting viral replication, inflammatory response, and oxidative stress and alleviating lung injury. Further studies are required to confirm its clinical efficacies and action mechanisms

Research on Dynamic Analysis and Mitigation Strategies of Supply Chains under Different Disruption Risks

Due to the globalization of supply and production, supply chain management has tightened the connection between upstream and downstream enterprises. Although this modern strategy has significantly improved the efficiency of enterprises, the increasingly complex relationship between nodes also makes the supply chain system more vulnerable and unstable. As a result, the interruption of any node location in the supply chain will spread to other nodes via their diffusion, which could cause irreparable damage to the entire supply chain. Therefore, under this realistic background, only by quantitatively analyzing the specific impact on the supply chain of interruption events in different locations we can formulate active and effective mitigation strategies to achieve the effective recovery of node enterprises from interruption accidents. In this study, the system dynamics method was used to simulate the changes in inventory level, order accumulation, and profit level caused by disruption of supply, production, and sales of different node companies. The results show that the closer the node enterprise to the interruption source, the greater the risk of loss. Due to the conduction effect of the supply chain system, the risk spreads to other node enterprises. Based on the above results, corresponding mitigation strategies for enterprises to cope with different node interruptions are proposed to improve the overall efficiency and operational capabilities of the enterprise

Molecular Simulation Study on the Microscopic Structure and Mechanical Property of Defect-Containing sI Methane Hydrate

The study of changes in the related mechanical property and microscopic structure of methane hydrate during the decomposition process are of vital significance to its exploitation and comprehensive utilization. This paper had employed the molecular dynamics (MD) method to investigate the influence of defects on the microscopic structure and mechanical property of the sI methane hydrate system, and to discover the mechanical property for the defect-containing hydrate system to maintain its brittle materials. Moreover, the stress-strain curve of each system was analyzed, and it was discovered that the presence of certain defects in the methane hydrate could promote its mechanical property; however, the system mechanical property would be reduced when the defects had reached a certain degree (particle deletion rate of 9.02% in this study). Besides, the microscopic structures of the sI methane hydrate before and after failure were analyzed using the F3 order parameter value method, and it was found that the F3 order parameters near the crack would be subject to great fluctuations at the time of failure of the hydrate structure. The phenomenon and conclusions drawn in this study provide a basis for the study of the microscopic structure and mechanical characteristics of methane hydrate

Monomeric compounds from traditional Chinese medicine: New hopes for drug discovery in pulmonary fibrosis

Pulmonary fibrosis (PF) is a chronic and irreversible pulmonary disease, and can lead to decreased lung function, respiratory failure and even death. The pathogenesis research and treatment strategy of PF significantly lag behind the medical progress and clinical needs. The treatment of this disease remains a thorny clinical problem, and the effective therapeutic drugs are still limited. Monomeric compounds from traditional Chinese medicine own various biological activities and high safety. They play a broad part in treating diseases and is also a candidate drug for preventing and treating PF. In this paper, we reviewed the mechanism of action and potential value of various anti-PF monomeric compounds from traditional Chinese medicine. These monomeric compounds can attenuate inflammatory response, oxidative stress, epithelial mesenchymal transformation and other processes of lung through many signaling pathways, and inhibit the activation and differentiation of fibroblasts, thus contributing to the treatment of PF. This review can provide new ideas for the development of anti-PF drugs in high efficiency with low toxicity