Stacking Transformation-Triggered Circularly Polarized Luminescence Reversion in γ-Cyclodextrins-Pyrene Co-Assembly.

Considerable attention has been directed towards cyclodextrins (CDs) in the creation of co-assembled CPL-active materials, owing to their intrinsic chiral host cavities and synergistic host-guest interactions. However, achieving reversed CPL emission regulation with single-handedness CDs moiety poses a significant challenge. In this study, we have devised a series of γ-CD-based host-guest complexes comprising dual pyrene imidazolium derivatives with multiple linkers, which exhibit reversed circularly polarized emission. We have uncovered that the transformation of excimer stacking within γ-CD/pyrene complexes contributes to the inverted CPL emissions originating from a single-handed chiral host. This research elucidates the phenomenon of (+)- and (-)-circularly polarized excimer emission (CPEE) within γ-CD, arising from right- and left-handed stacking conformations, respectively.

Proteomics and metabolomics profiling reveal panels of circulating diagnostic biomarkers and molecular subtypes in stable COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease with high morbidity and mortality, especially in advanced patients. We aimed to develop multi-omics panels of biomarkers for the diagnosis and explore its molecular subtypes. METHODS: A total of 40 stable patients with advanced COPD and 40 controls were enrolled in the study. Proteomics and metabolomics techniques were applied to identify potential biomarkers. An additional 29 COPD and 31 controls were enrolled for validation of the obtained proteomic signatures. Information on demographic, clinical manifestation, and blood test were collected. The ROC analyses were carried out to evaluate the diagnostic performance, and experimentally validated the final biomarkers on mild-to-moderate COPD. Next, molecular subtyping was performed using proteomics data. RESULTS: Theophylline, palmitoylethanolamide, hypoxanthine, and cadherin 5 (CDH5) could effectively diagnose advanced COPD with high accuracy (auROC = 0.98, sensitivity of 0.94, and specificity of 0.95). The performance of the diagnostic panel was superior to that of other single/combined results and blood tests. Proteome based stratification of COPD revealed three subtypes (I-III) related to different clinical outcomes and molecular feature: simplex COPD, COPD co-existing with bronchiectasis, and COPD largely co-existing with metabolic syndrome, respectively. Two discriminant models were established using the auROC of 0.96 (Principal Component Analysis, PCA) and 0.95 (the combination of RRM1 + SUPV3L1 + KRT78) in differentiating COPD and COPD with co-morbidities. Theophylline and CDH5 were exclusively elevated in advanced COPD but not in its mild form. CONCLUSIONS: This integrative multi-omics analysis provides a more comprehensive understanding of the molecular landscape of advanced COPD, which may suggest molecular targets for specialized therapy.

Gene Expression Trajectories from Normal Nonsmokers to COPD Smokers and Disease Progression Discriminant Modeling in Response to Cigarette Smoking.

Background: Cigarette smoking (CS) is considered to the predominant risk factor contributing to the etiopathogenesis of chronic obstructive pulmonary disease (COPD); meanwhile, genetic predisposition likely plays a role in determining disease susceptibility. Objectives: We aimed to investigate gene expression trajectories from normal nonsmokers to COPD smokers and disease progression discriminant modeling in response to cigarette smoking. Methods: Small airway epithelial samples of human with different smoking status using fiberoptic bronchoscopy and corresponding rat lung tissues following 0, 3, and 6 months of CS exposure were obtained. The expression of the significant overlapping genes between human and rats was confirmed in 16HBE cells, rat lung tissues, and human peripheral PBMC using qRT-PCR. Binary logistic regression analysis was carried out to establish discrimination models. Results: The integrated bioinformatic analysis of 8 human GEO datasets (293 individuals) and 9 rat transcriptome databases revealed 13 overlapping genes between humans and rats in response to smoking exposure during COPD progression. Of these, 5 genes (AKR1C3/Akr1c3, ERP27/Erp27, AHRR/Ahrr, KCNMB2/Kcnmb2, and MRC1/Mrc1) were consistently identified in both the human and rat and validated by qRT-PCR. Among them, ERP27/Erp27, KCNMB2/Kcnmb2, and MRC1/Mrc1 were newly identified. On the basis of the overlapping gene panel, discriminant models were established with the receiver operating characteristic curve (AUC) of 0.98 (AKR1C3/Akr1c3 + ERP27/Erp27) and 0.99 (AHRR/Ahrr + KCNMB2/Kcnmb2) in differentiating progressive COPD from normal nonsmokers. In addition, we also found that DEG obtained from each expression profile dataset was better than combined analysis as more genes could be identified. Conclusion: This study identified 5 DEG candidates of COPD progression in response to smoking and developed effective and convenient discriminant models that can accurately predict the disease progression.

Gut Microbial Metabolite Trimethylamine N-Oxide Aggravates Pulmonary Hypertension.

Trimethylamine N-oxide (TMAO), a metabolite derived from intestine microbial flora, enhances vascular inflammation in a variety of cardiovascular diseases, and the bacterial communities associated with TMAO metabolism are higher in pulmonary hypertension (PH) patients. The effects of TMAO on PH, however, have not been elucidated. In the present study, circulating TMAO was found to be elevated in intermediate to high-risk PH patients when compared with healthy control or low-risk PH patients. In monocrotaline-induced rat PH models, circulating TMAO was elevated; and reduction of TMAO using 3,3-dimethyl-1-butanol (DMB) significantly decreased right ventricle systolic pressure and pulmonary vascular muscularization in both monocrotaline-induced rat PH and hypoxia-induced mouse PH models. RNA sequencing of rat lungs revealed that DMB treatment significantly suppressed the pathways involved in cytokine-cytokine receptor interaction and in cytokine and chemokine signaling. Protein-protein interaction analysis of the differentially expressed transcripts regulated by DMB showed five hub genes with a strong connectivity of proinflammatory cytokines and chemokines, including Kng1, Cxcl1, Cxcl2, Cxcl6, and Il6. In vitro, TMAO significantly increased the expression of Kng1, Cxcl1, Cxcl2, Cxcl6, and Il6 in bone-marrow-derived macrophage. Also, TMAO-treated conditioned medium from macrophage increased the proliferation and migration of pulmonary artery smooth muscle cells, but TMAO treatment did not change the proliferation or migration of pulmonary artery smooth muscle cells. In conclusion, our study demonstrates that TMAO is increased in severe PH, and the reduction of TMAO decreases pulmonary vascular muscularization and alleviates PH by suppressing the macrophage production of chemokines and cytokines.

Proteomic profiling reveals a distinctive molecular signature for critically ill COVID-19 patients compared with asthma and chronic obstructive pulmonary disease.

OBJECTIVE: The mortality rate for critically ill COVID-19 cases was more than 80%. Nonetheless, research about the effect of common respiratory diseases on critically ill COVID-19 expression and outcomes is scarce. DESIGN: We performed proteomic analyses on airway mucus obtained by bronchoscopy from patients with severe COVID-19, or induced sputum from patients with chronic obstructive pulmonary disease (COPD), asthma, and healthy controls. RESULTS: Of the total identified and quantified proteins, 445 differentially expressed proteins (DEPs) were found in different comparison groups. In comparison with COPD, asthma, and controls, 11 proteins were uniquely present in COVID-19 patients. Apart from DEPs associated with COPD versus controls and asthma versus controls, there was a total of 59 DEPs specific to COVID-19 patients. Finally, the findings revealed that there were 8 overlapping proteins in COVID-19 patients, including C9, FGB, FGG, PRTN3, HBB, HBA1, IGLV3-19, and COTL1. Functional analyses revealed that most of them were associated with complement and coagulation cascades, platelet activation, or iron metabolism, and anemia-related pathways. CONCLUSIONS: This study provides fundamental data for identifying COVID-19-specific proteomic changes in comparison with COPD and asthma, which may suggest molecular targets for specialized therapy.

Novel Magnet and Thermoresponsive Chemosensory Electrospinning Fluorescent Nanofibers and Their Sensing Capability for Metal Ions.

Novel multifunctional switchable chemosensors based on fluorescent electrospun (ES) nanofibers with sensitivity toward magnetism, temperature, and mercury ions (Hg2+) were prepared using blends of poly(N-isopropylacrylamide)-co-(N-methylolacrylamide)-co-(Acrylic acid), the fluorescent probe 1-benzoyl-3-[2-(2-allyl-1,3-dioxo-2,3-dihydro-1Hbenzo[de]isoquinolin-6-ylamino)-ethyl]-thiourea (BNPTU), and magnetite nanoparticles (NPs), and a single-capillary spinneret. The moieties of N-isopropylacrylamide, N-methylolacrylamide, acrylic acid, BNPTU, and Iron oxide (Fe3O4) NPs were designed to provide thermoresponsiveness, chemical cross-linking, Fe3O4 NPs dispersion, Hg2+ sensing, and magnetism, respectively. The prepared nanofibers exhibited ultrasensitivity to Hg2+ (as low as 10-3 M) because of an 80-nm blueshift of the emission maximum (from green to blue) and 1.6-fold enhancement of the emission intensity, as well as substantial volume (or hydrophilic to hydrophobic) changes between 30 and 60 °C, attributed to the low critical solution temperature of the thermoresponsive N-isopropylacrylamide moiety. Such temperature-dependent variations in the presence of Hg2+ engendered distinct on⁻off switching of photoluminescence. The magnetic ES nanofibers can be collected using a magnet rather than being extracted through alternative methods. The results indicate that the prepared multifunctional fluorescent ES nanofibrous membranes can be used as naked eye sensors and have the potential for application in multifunctional environmental sensing devices for detecting metal ions, temperature, and magnetism as well as for water purification sensing filters.