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Bronchial asthma is a heterogeneous disease with complex pathological mechanisms representing different phenotypes, including severe asthma. The airway epithelium is a major site of complex pathological changes in severe asthma due, in part, to activation of inflammatory and immune mechanisms in response to noxious agents. Current imaging procedures are unable to accurately measure epithelial and airway remodeling. Damage of airway epithelial cells occurs is linked to specific phenotypes and endotypes which provides an opportunity for the identification of biomarkers reflecting epithelial, and airway, remodeling. Identification of patients with more severe epithelial disruption using biomarkers may also provide personalised therapeutic opportunities and/or markers of successful therapeutic intervention. Here, we review the evidence for ongoing epithelial cell dysregulation in the pathogenesis of asthma, the sentinel role of the airway epithelium and how understanding these molecular mechanisms provides the basis for the identification of candidate biomarkers for asthma prediction, prevention, diagnosis, treatment and monitoring. [ABSTRACT FROM AUTHOR]

The molecular mechanics method (MM3) is used to study the surface chemistry of diamond. The structure and energetics of clean and hydrogenated diamond are determined and this leads to the understanding of some gas-surface reactions involving hydrogen and diamond (100) surface. However, the model generated by the MM3 method is found to limited in application since the force field is accurate only near chemically significant minima in the potential.

A cluster of patients with coronavirus disease 2019 (COVID-19) underwent repeated positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA tests after they were discharged from the hospital. We referred to them as re-positive (RP) patients in this study. We aimed to describe the clinical characteristics of these patients in a retrospective cohort study. After being treated for COVID-19, the patients underwent 14 days of quarantine following their discharge from the Huangshi Hospital of Traditional Chinese Medicine and the Huangshi Hospital of Youse. Two additional sequential SARS-CoV-2 RNA tests were performed at the end of quarantine. The median age of the 368 patients was 51 years, and 184 (50%) patients were female. A total of 23 RP patients were observed at follow-up. Using multivariate Cox regression analysis, risk factors associated with RP included a higher ratio of lymphocyte/white blood cell on admission (adjusted HR 7.038; 95% CI, 1.911–25.932; P = 0.0034), lower peak temperature during hospitalization (adjusted HR, 0.203; 95% CI, 0.093–0.443; P<0.0001), and the presence of comorbidities, particularly hypertension or chronic diseases in the respiratory system (adjusted HR, 3.883; 95% CI, 1.468–10.273; P = 0.0063). Antivirus treatment with arbidol was associated with a lower likelihood of re-positive outcomes (adjusted HR, 0.178; 95% CI, 0.045–0.709; P = 0.0144). [ABSTRACT FROM AUTHOR]

Osteosarcoma is one of the most common primary malignant tumors of the bone and tends to develop in teenage years. Although multitreatments for the diagnosis and therapy of osteosarcoma have been developed, there are still needs of new methods to prevent and treat the osteosarcoma. Here, we performed bioinformatic analysis to screen for the key genes, molecules, and pathways involved in osteosarcoma survival. Four microarray data sets (GSE99671, GSE87624, GSE65071, and GSE28423), which include data from human bone and osteosarcoma samples, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed mRNAs and miRNAs were identified. Kyoto Encyclopedia of Genes and Genomes enriched pathways, miRNA-mRNA target, gene/disease relationship, and overall survival was elucidated using related websites and software according to bioinformatic analysis protocols. We found three critical genes miR-29c, blood vessel epicardial substance (BVES), and proteasome 20S subunit beta 2 (PSMB2) through the GEO database and predicting miRNA-mRNA target. Among these genes, BVES and PSMB2 presented a high expression level in osteosarcoma based on GSE99671 and GSE87624 data sets, while miR-29c showed a low expression level in osteosarcoma based on GSE65071 and GSE28423 data sets. Furthermore, we found that the high expression level of miR-29c and BVES associated with better prognosis, while highly expressed PSMB2 associated with poor prognosis. The abnormally expressed mRNAs and miRNAs, which were identified by integrated bioinformatic analysis, provided insights into the molecular mechanisms of osteosarcoma. Notably, we found three critical genes that could be used as novel therapeutic targets for preventing or diagnosing osteosarcoma. Finally, PSMB2 may be the target of miR-29c. [ABSTRACT FROM AUTHOR]

Background: No formal diagnostic criteria for progressive pseudo‐rheumatoid dysplasia (PPD) are available because of insufficient clinical data, which results in that PPD is often misdiagnosed with other diseases. Whole exome sequencing (WES) and Sanger sequencing were employed to reveal the novel mutations on CCN6 of five patients with PPD from China in order to increase the clinical data of PPD. Methods: Four suspected PPD pedigrees containing five patients in total were collected from 1998 to 2018 in our medical center. The phenotypes of each suspected PPD case were recorded in detail, and peripheral blood samples were collected for subsequent sequencing. Genomic DNA was extracted from peripheral blood samples, and Agilent liquid phase chip capture system was utilized for efficient enrichment of whole exome region DNA. After acquiring raw sequenced reads of whole exome region, bioinformatics analysis was completed in conjunction with reference or genome sequence (GRCh37/hg19). Sanger sequencing was performed to identify the results of WES. Results: In total, four novel PPD‐related mutation sites in CCN6 gene were identified including (CCN6):c.643 + 2T>C, (CCN6):c.1064_1065dupGT(p.Gln356ValfsTer33), (CCN6):c.1064G > A), and exon4:c.670dupA:p.W223fs. Conclusion: Our findings increase the clinical data of PPD including the CCN6 mutation spectrum, the clinical symptoms and signs. Moreover, the study highlights the utility of WES in reaching definitive diagnoses for PPD. [ABSTRACT FROM AUTHOR]

The biological functions of lipocalin-1 (LCN1) are involved in innate immune responses and act as a physiological scavenger of potentially harmful lipophilic molecules. However, the relevance of LCN1 with cancer is rarely concerned currently. The aim of this study is to address the relevance of LCN1 with BRCA by bioinformatics. In this study, we found that the expressions of LCN1 increased significantly in various cancerous tissues, including BRCA, compared with their adjacent normal tissues through the TIMER database. Furthermore, UALCAN database analysis showed that the expression of LCN1 increased gradually from stage 1 to stage 4 and was upregulated in BRCA patients with different races and subtypes compared with that in the normal. In addition, those patients with perimenopause and postmenopause status displayed higher LCN1 expression. Importantly, LCN1 genetic alterations, including copy number amplification, deep deletion, and missense mutation, could be found, and the alteration frequency showed difference in various invasive BRCA through cBioPortal database. Moreover, a positive correlation between LCN1 somatic copy number alterations and immune cell enrichments was revealed in basal like BRCA by GISTIC 2.0. Finally, analysis on prognostic value of LCN1 by Kaplan–Meier plotter showed that low LCN1 expression correlated with poor prognosis for relapse-free survival in all types of BRCA, overall survival in luminal B BRCA, distant metastasis free survival in human epithelial growth factor receptor-2 (HER2) positive BRCA, and postprogression survival (PPS) in luminal A BRCA. But high LCN1 expression also displayed poor prognosis for PPS in HER2 positive BRCA. The results together verified the significance of LCN1 in BRCA, suggesting that it may be a potential biomarker for BRCA diagnosis. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of cancer-associated mortality among women worldwide, and the prevalence and mortality rates associated with this disease are high in Western countries. The melanoma-associated antigen (MAGE) family proteins are well-known tumor-specific antigens; this family includes >60 proteins that serve an important part in cell cycle withdrawal, neuronal differentiation and apoptosis. The aim of the present study was to identify a biomarker within the MAGE family that is specific for breast cancer. In the present study, the prognostic role of MAGE mRNA expression was investigated in patients with breast cancer using the Kaplan-Meier plotter database. The prognostic value of MAGE members in the different intrinsic subtypes of breast cancer was further investigated, as well as the clinicopathological features of the disease. The results of the present study indicated that patients with breast cancer that had high mRNA expression levels of MAGEA5, MAGEA8, MAGEB4 and MAGEB6 had an improved relapse-free survival, whereas those with high mRNA expression levels of MAGEB18 and MAGED4 did not. These results suggested that MAGEA5, MAGEA8, MAGEB4 and MAGEB6 may have roles as tumor suppressors in the occurrence and development of breast cancer, whereas MAGEB18 and MAGED4 may possess carcinogenic potential. MAGED2, MAGED3 and MAGEF1 had different effects depending on the type of breast cancer. In particular, high MAGEC3 mRNA expression was associated with worse RFS in lymph node-positive breast cancer, but with improved RFS in lymph node-negative breast cancer. In patients with wild-type TP53 and patients with different pathological grades of breast cancer, MAGEE2, MAGEH1 and MAGEL2 were more worthy of attention as potential prognostic factors. The results of the present study may help to elucidate the role of MAGE family members in the development of breast cancer, and may promote further research that identifies MAGE-targeting reagents for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To explore novel related genes and potential biomarkers of pancreatic neuroendocrine tumors (PanNETs). Materials and Methods: Two data sets from ICGC and two from the NCBI GEO database were used to identify the differentially expressed genes (DEGs) in PanNETs. The common DEGs among the four sources were analyzed; furthermore, the relationship of these gene expression patterns with different PanNET grades, their mutation status and corresponding impact on prognosis, the interaction network, and the relationship with three known PanNET genes (ATRX, DAXX, and MEN1) were analyzed by two other GEO data and cBioPortal database. Finally, the expressions of novel DEGs were validated in Chinese PanNET tissues by RT-qPCR. Results: Five new DEGs (ABCC8, PCSK2, IL13RA2, KLKB1, and PART1) and one confirmed DEG-ISL1 were identified. The mutation counts of DEGs increased with the tumor grade increasing from G1 to G3, and PanNET patients present vascular invasion or are deceased. These DEG expression patterns in PanNETs are quite different from that of pancreatic ductal adenocarcinoma and are related to A–D–M (ATRX–DAXX–MEN1) mutation. ABCC8 and KLKB1 are co-occurrence with the A–D–M axis in PanNETs. Importantly, patients with DEG mutations have a lower survival rate. RT-qPCR verification results of KLKB1 (P < 0.01), IL13RA2 (P < 0.01), ABCC8 (P < 0.01), and PART1 (P < 0.0001) expressions in Chinese PanNET tissues are consistent with our database analysis, which were significantly up-regulated. However, the expression of PCSK2 (P < 0.01) was contrary to our bioinformatics analysis, which was significantly down-regulated, suggesting that the expression trend of PCSK2 may be different among different races. These results indicated that these five genes may play an important role in the occurrence and progression of PanNETs. Conclusion: Five novel common DEGs identified are related to the development and prognosis of PanNETs and may serve as specific biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

We have investigated the surface chemistry of coadsorbed hydrogen and halogen atoms on Ge(100), produced by dissociative chemisorption of HCl and HBr, by temperature-programmed desorption. The initial sticking probability S0 for HCl decreases from 0.6 at a substrate temperature of 270 K to 0.05 at 400 K, indicative of a precursor state to adsorption. For HBr S0 is constant at 0.7 over the same temperature range. A fraction f of adsorbed hydrogen atoms desorb associatively as H2 near 570 K, while the remaining (1-f) H atoms recombine with adsorbed halogen atoms and desorb as the hydrogen halide (HX) near 580–590 K. The activation energies for desorption of H2, HCl, and HBr are all approximately 40 kcal/mol. For both HCl and HBr f is 0.7 at low initial coverage and decreases slightly to 0.6 at saturation. The fraction f of adsorbed halogen atoms left on the surface following the competitive desorption of H2 and HX desorb as the dihalides GeCl2 and GeBr2 near 675 and 710 K, respectively. Desorption of H2, HCl, and HBr occurs with near-first-order kinetics, similar to the behavior of hydrogen adsorbed alone, which we attribute to preferential pairing induced by the π bond on unoccupied Ge dimers. We introduce and solve a generalized doubly occupied dimer model incorporating competitive pairing of H+H, H+X, and X+X on Ge dimers to explain the near-first-order kinetics. The model quantitatively accounts for both the desorption kinetics and the relative yields of H2 and HX with pairing energies of ≊3 kcal/mol. Implications of the present results for surface thermochemistry, chemical vapor deposition, and atomic layer epitaxy of Ge and Si(100)2×1 surfaces are discussed. [ABSTRACT FROM AUTHOR]

Evidence is presented that π-bonding is present in the surface dimers on clean Si(100)–(2×1) and, as a consequence, that hydrogen atoms preferentially pair on surface dimer atoms even at low coverage. We propose a simple lattice gas model in order to calculate the equilibrium distribution of doubly- and singly-occupied dimers as a function of coverage and temperature, and show that even a very conservative estimate of the enthalpy difference between hydrogen on doubly- and singly-occupied dimers can explain the observed first-order desorption kinetics. [ABSTRACT FROM AUTHOR]

We show by temperature-programmed desorption that hydrogen desorbs from Ge(100)2×1 near 570 K with near-first-order kinetics, similar to the behavior of hydrogen on Si(100)2×1. The near-first-order desorption kinetics are attributed to pairing on surface dimers induced by the π bond on unoccupied dimer atoms, and a pairing energy of 5±1 kcal/mol is inferred. However, a comparison between the pairing energies for H atoms on Ge(100) and Si(100) with the electronic structure of the respective clean surfaces indicates that estimates of the π bond strength based on the surface band structure do not correlate with the propensity for pairing. [ABSTRACT FROM AUTHOR]

Oxygen exchange at a highly oriented La[sub 0.5]Sr[sub 0.5]CoO[sub 3-δ] thin film prepared on (100) surfaces of an yttria-stabilized zirconia single crystal by pulsed-laser deposition was studied with ac impedance spectroscopy under various temperatures and oxygen partial pressures. Three distinctive features observed in the impedance spectra were assigned to contributions from the ionic conduction of the electrolyte, oxide ion transfer across the electrode/electrolyte interface, and the oxygen exchange on the film surface. An equivalent circuit model was proposed to analyze the impedance results, from which the surface chemical exchange coefficients, k[sub chem], were derived as a function of temperature and oxygen partial pressure. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]