Abstract Background: The pandemic of the coronavirus disease 2019 (COVID-19) has brought a global public health crisis. However, the pathogenesis underlying COVID-19 are barely understood. Methods: In this study, we performed proteomic analyses of airway mucus obtained by bronchoscopy from severe COVID-19 patients. In total, 2351 and 2073 proteins were identified and quantified in COVID-19 patients and healthy controls, respectively. Results: Among them, 92 differentiated expressed proteins (DEPs) (46 up-regulated and 46 down-regulated) were found with a fold change > 1.5 or < 0.67 and a p-value < 0.05, and 375 proteins were uniquely present in airway mucus from COVID-19 patients. Pathway and network enrichment analyses revealed that the 92 DEPs were mostly associated with metabolic, complement and coagulation cascades, lysosome, and cholesterol metabolism pathways, and the 375 COVID-19 only proteins were mainly enriched in amino acid degradation (Valine, Leucine and Isoleucine degradation), amino acid metabolism (beta-Alanine, Tryptophan, Cysteine and Methionine metabolism), oxidative phosphorylation, phagosome, and cholesterol metabolism pathways. Conclusions: This study aims to provide fundamental data for elucidating proteomic changes of COVID-19, which may implicate further investigation of molecular targets directing at specific therapy.
The system of derivative action plays an important role in prote cting a company and its shareholders interests.The plaintiff in a derivative suit shoul d be confined to the company's shareholders, and those who uncovered have ri ght to conduct a derivative act,no matter how long and how many they interests shoul d be accused as defendant in a derivative suit ,not limited to the company 's con trolling shareholders and directors.In a derivative suit ,a company should not p lay as a kind of independent litigant particepants, and it should remain neutral.
Background: The pandemic of the coronavirus disease 2019 (COVID-19) has brought a global public health crisis. However, the pathogenesis underlying COVID-19 are barely understood.Methods: In this study, we performed proteomic analyses of airway mucus obtained by bronchoscopy from severe COVID-19 patients. In total, 2351 and 2073 proteins were identified and quantified in COVID-19 patients and healthy controls, respectively.Results: Among them, 92 differentiated expressed proteins (DEPs) (46 up-regulated and 46 down-regulated) were found with a fold change > 1.5 or < 0.67 and a p-value < 0.05, and 375 proteins were uniquely present in airway mucus from COVID-19 patients. Pathway and network enrichment analyses revealed that the 92 DEPs were mostly associated with metabolic, complement and coagulation cascades, lysosome, and cholesterol metabolism pathways, and the 375 COVID-19 only proteins were mainly enriched in amino acid degradation (Valine, Leucine and Isoleucine degradation), amino acid metabolism (beta-Alanine, Tryptophan, Cysteine and Methionine metabolism), oxidative phosphorylation, phagosome, and cholesterol metabolism pathways.Conclusions: This study aims to provide fundamental data for elucidating proteomic changes of COVID-19, which may implicate further investigation of molecular targets directing at specific therapy.Funding Statement: This work was supported by grants from the National Key R&D Program of China (2016YFC0903700), the National Natural Science Foundation of China (81520108001 and 81770043), and grant specific for COVID-19 study from Guangzhou Institute of Respiratory Health.Declaration of Interests: The authors have no conflict of interest to declare.Ethics Approval Statement: All the procedures were approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (No. 2020-65). Verbal informed consent were obtained from all participants because the family members were in quarantine.
On the basis of the disputes about the nature of the right stipulated in article 286 of Law of the People's Republic of China on Contract, this paper advances the concept of the priority of special creditor's rights, and compares the differences among the priority of special creditor's rights, legal hypothecation and legal right of lien. By observing the civil codes of France and Japan and the relevant stipulations in China, the paper induces the kinds of the priority of special creditor's rights, and studies their respective legal features, effectiveness, the idea and the fundamental principle of enacting the priority of special creditor's rights. This paper then shows clearly the insufficiency of the relevant stipulations of China. In the end, the paper offers proposal about how to improve of the legislation covering the system of the priority of special creditor's rights.
Two functional input pathways for protons have been characterized in the heme−copper oxidases: the D-channel and the K-channel. These two proton-conducting channels have different functional roles and have been defined both by X-ray crystallography and by the characterization of site-directed mutants. Whereas the entrance of the D-channel is well-defined as D132I (subunit I; Rhodobacter sphaeroides numbering), the entrance of the K-channel has not been clearly defined. Previous mutagenesis studies of the cytochrome bo3 quinol oxidase from Escherichia coli implicated an almost fully conserved glutamic acid residue within subunit II as a likely candidate for the entrance of the K-channel. The current work examines the properties of mutants of this conserved glutamate in the oxidase from R. sphaeroides (E101III,A,C,Q,D,N,H) and residues in the immediate vicinity of E101II. It is shown that virtually any substitution for E101II, including E101IID, strongly reduces oxidase turnover (to 8−29%). Furthermore, the low steady-state activity correlates with an inhibition of the rate of reduction of heme a3 prior to the reaction with O2. These are phenotypes expected of K-channel mutants. It is concluded that the predominant entry point for protons going into the K-channel of cytochrome oxidase is the surface-exposed glutamic acid E101II in subunit II.
Abstract Recently, Guo and Tang independently established some q -supercongruences from Rahman’s quadratic transformation. In this paper, by applying the method of creative microscoping devised by Guo and Zudilin together with Rahman’s quadratic transformation again, we provide proofs for eight conjectures on q -supercongruences proposed by Guo and by Tang.
Background: COPD is a type of chronic bronchitis and/or emphysema accompanied by airflow obstruction. At present, the understanding of the genetic basis in COPD patients is still limited. Objective: We aimed to identify rare genetic variations contributing to the development of COPD. Methods: Five COPD pedigrees were selected for whole genome sequencing and bioinformatics analysis. Patients and controls were recruited and categorized into COPD and non-COPD groups based on lung function, inclusive and exclusive criteria. The genotypes association study were performed to validate the SNP sites. PCR, Western Blot, Small interfering RNA, immunoprecipitation and the lentiviral gene expression vector were used to explore the function of the genes and SNPs. Results: Four SNPs locating in four different genes were identified to be associated with COPD by WGS and association study. Only two of the 4 genes, Cbl-b and SREK1, are expressed in the lung. Cigarette Smoking Extract(CSE) significantly upregulated the Cbl-b expression but not SREK1 in 16HBE cells.siCbl-b destructed the downregulation or upregulation of MMP9 and TIMP1 caused by CSE exposure. Cbl-b(1396A) over-expression vector induced a greater decrease of TIMP1 and increase of MMP9 in 16HBE cells than GFP vector. The protein regulation was obstructed when incubated with Cbl-b(1396T) vector. Cbl-b(1396T) vector also showed a weaker interaction between Cbl-b and TIMP1 than Cbl-b(1396A) overexpression vector. Conclusion: we firstly demonstrated that the functional SNP (rs61758360T>C) locateing on Cbl-b contributed, at least partially, to decrease COPD susceptibility likely via decreasing the binding ability of Cbl-b with TIMP1.
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