Reduced Tolerogenic Program Death-Ligand 1-Expressing Conventional Type 1 Dendritic Cells Are Associated with Rapid Decline in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized, at least in part, by autoimmunity through amplified T helper 1 and 17 (Th1 and Th17) immune responses. The loss of immune tolerance controlled by programmed death-ligand 1 (PD-L1) may contribute to this. OBJECTIVES: We studied the tolerogenic role of PD-L1+ dendritic cells (DCs) and their subtypes in relation to specific T cell immunity and the clinical phenotypes of COPD. METHODS: We used flow cytometry to analyze PD-L1 expression by the DCs and their subtypes in the peripheral blood mononuclear cells (PBMCs) from normal participants and those with COPD. T cell proliferation and the signature cytokines of T cell subtypes stimulated with elastin as autoantigens were measured using flow cytometry and enzyme-linked immunosorbent assays (ELISA), respectively. MEASUREMENT AND MAIN RESULTS: A total of 83 participants were enrolled (normal, n = 29; COPD, n = 54). A reduced PD-L1+ conventional dendritic cell 1 (cDC1) ratio in the PBMCs of the patients with COPD was shown (13.7 ± 13.7%, p = 0.03). The decrease in the PD-L1+ cDC1 ratio was associated with a rapid decline in COPD (p = 0.02) and correlated with the CD4+ T cells (r = -0.33, p = 0.02). This is supported by the NCBI GEO database accession number GSE56766, the researchers of which found that the gene expressions of PD-L1 and CD4, but not CD8 were negatively correlated from PBMC in COPD patients (r = -0.43, p = 0.002). Functionally, the PD-L1 blockade enhanced CD4+ T cell proliferation stimulated by CD3/elastin (31.2 ± 22.3%, p = 0.04) and interleukin (IL)-17A production stimulated by both CD3 (156.3 ± 54.7, p = 0.03) and CD3/elastin (148 ± 64.9, p = 0.03) from the normal PBMCs. The PD-L1 blockade failed to increase IL-17A production in the cDC1-depleted PBMCs. By contrast, there was no significant change in interferon (IFN)-γ, IL-4, or IL-10 after the PD-L1 blockade. Again, these findings were supported by the NCBI GEO database accession number GSE56766, the researchers of which found that only the expression of RORC, a master transcription factor driving the Th17 cells, was significantly negatively correlated to PD-L1 (r = -0.33, p = 0.02). CONCLUSIONS: Circulating PD-L1+ cDC1 was reduced in the patients with COPD, and the tolerogenic role was suppressed with susceptibility to self-antigens and linked to rapid decline caused by Th17-skewed chronic inflammation.

Prediction value of neutrophil and eosinophil count at risk of COPD exacerbation.

INTRODUCTION: Predicting acute exacerbations (AEs) in chronic obstructive pulmonary disease (COPD) is crucial. This study aimed to identify blood biomarkers for predicting COPD exacerbations by inflammatory phenotypes. MATERIALS AND METHODS: We analyzed blood cell counts and clinical outcomes in 340 COPD patients aged 20-90 years. Patients were categorized into eosinophilic inflammation (EOCOPD) and non-eosinophilic inflammation (N-EOCOPD) groups. Blood cell counts, eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) were calculated. Linear and logistic regression models assessed relationships between health outcomes and blood cell counts. RESULTS: EOCOPD patients had distinct characteristics compared to N-EOCOPD patients. Increased neutrophil % and decreased lymphocyte % were associated with reduced pulmonary function, worse quality of life and more exacerbations, but they did not show statistical significance after adjusting by age, sex, BMI, smoking status, FEV1% and patient's medication. Subgroup analysis revealed a 1.372-fold increase in the OR of AE for every 1 unit increase in NLR in EOCOPD patients (p < .05). In N-EOCOPD patients, every 1% increase in blood eosinophil decreased the risk of exacerbation by 59.6%. CONCLUSIONS: Our study indicates that distinct white blood cell profiles in COPD patients, with or without eosinophilic inflammation, can help assess the risk of AE in clinical settings.

A mobile-based airway clearance care system using deep learning-based vision technology to support personalized home-based pulmonary rehabilitation for COAD patients: Development and usability testing.

Background: Excessive mucus secretion is a serious issue for patients with chronic obstructive airway disease (COAD), which can be effectively managed through postural drainage and percussion (PD + P) during pulmonary rehabilitation (PR). Home-based (H)-PR can be as effective as center-based PR but lacks professional supervision and timely feedback, leading to low motivation and adherence. Telehealth home-based pulmonary (TH-PR) has emerged to assist H-PR, but video conferencing and telephone calls remain the main approaches for COAD patients. Therefore, research on effectively assisting patients in performing PD + P during TH-PR is limited. Objective: This study developed a mobile-based airway clearance care for chronic obstructive airway disease (COAD-MoAcCare) system to support personalized TH-PR for COAD patients and evaluated its usability through expert validation. Methods: The COAD-MoAcCare system uses a mobile device through deep learning-based vision technology to monitor, guide, and evaluate COAD patients' PD + P operations in real time during TH-PR programs. Medical personnel can manage and monitor their personalized PD + P and operational statuses through the system to improve TH-PR performance. Respiratory therapists from different hospitals evaluated the system usability using system questionnaires based on the technology acceptance model, system usability scale (SUS), and task load index (NASA-TLX). Results: Eleven participant therapists were highly satisfied with the COAD-MoAcCare system, rating it between 4.1 and 4.6 out of 5.0 on all scales. The system demonstrated good usability (SUS score of 74.1 out of 100) and a lower task load (NASA-TLX score of 30.0 out of 100). The overall accuracy of PD + P operations reached a high level of 97.5% by comparing evaluation results of the system by experts. Conclusions: The COAD-MoAcCare system is the first mobile-based method to assist COAD patients in conducting PD + P in TH-PR. It was proven to be usable by respiratory therapists, so it is expected to benefit medical personnel and COAD patients. It will be further evaluated through clinical trials.

Phase-transited lysozyme nanofilm with co-immobilized copper ion and heparin as cardiovascular stent multifunctional coating.

Cardiovascular metal stents have shown potential in the treatment of coronary artery disease using percutaneous coronary intervention. However, thrombosis, endothelialization, and new atherosclerosis after stent implantation remain unsolved problems. Herein, a multifunctional coating material based on phase-transited lysozyme was developed to promote stent endothelialization and simultaneously reduce thrombus events by embedding moieties of heparin and co-immobilized copper ions for in-situ catalyzing nitric oxide (NO) generation. The lysozyme-based biomimetic coating is compatible with blood and enables facile loading and sustainable release of copper ions to produce NO with donors via catalytic reaction. The novel coating strategy displayed several bio-effects of anti-thrombosis; it synergistically promoted endothelial cell growth and inhibited smooth muscle cell growth. Thus, this systemic in vitro study will provide a foundation for developing multifunctional cardiovascular stents in clinical settings.

Stomatin-like protein-2 contributes the migration and invasion of breast cancer cells via regulating ERK/FOXO3a signaling pathway.

Breast cancer (BC) is the most common tumor in women, and its incidence is increasing, ranking first among female malignant tumors. It is urgently needed to find new and reliable biomarkers of BC and to understand the cellular changes that cause metastasis. Stomatin-like protein-2 (SLP-2) is a member of the stomatin protein superfamily. Studies have shown that SLP-2 was highly expressed in some tumors and played an important role in tumor genesis and development. SLP-2 regulated the extracellular signal-regulated kinase (ERK) pathway, and activation of ERK phosphorylated FOXO3a, which was involved in BC progression. However, its possible role in the progression of BC remains unclear. In this study, we found the high expression of SLP-2 in BC tissues and cells. SLP-2 promoted the viability of BC cells. In addition, we found that SLP-2 stimulated the motility of BC cells in vitro. Mechanically, our results revealed that SLP-2 could mediate FOXO3a expression and ERK signaling pathway, thereby contributing to the viability and motility of BC cells. Therefore, SLP-2 has the potential to serve as a promising target for BC treatment.

Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma.

We performed whole exome sequencing (WES) and microarray analysis to detect somatic variants and copy number alterations (CNAs) for underlying mechanisms in a case series of hepatocellular carcinoma (HCC) with paired DNA samples from tumor and adjacent nontumor tissues. Clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status and their associations with tumor mutation burden (TMB) and CNA burden (CNAB) were evaluated. WES from 36 cases detected variants in the TP53, AXIN1, CTNNB1, and SMARCA4 genes, amplifications of the AKT3, MYC, and TERT genes, and deletions of the CDH1, TP53, IRF2, RB1, RPL5, and PTEN genes. These genetic defects affecting the p53/cell cycle control, PI3K/Ras, and ß-catenin pathways were observed in approximately 80% of cases. A germline variant in the ALDH2 gene was detected in 52% of the cases. Significantly higher CNAB in patients with poor prognosis by E-S grade III, BCLC stage C, and recurrence than patients with good prognosis by grade III, stage A, grade III and nonrecurrence was noted. Further analysis on a large case series to correlate genomic profiling with clinicopathologic classifications could provide evidence for diagnostic interpretation, prognostic prediction, and target intervention on involved genes and pathways.

Lactate Efflux Inhibition by Syrosingopine/LOD Co-Loaded Nanozyme for Synergetic Self-Replenishing Catalytic Cancer Therapy and Immune Microenvironment Remodeling.

An effective systemic mechanism regulates tumor development and progression; thus, a rational design in a one-stone-two-birds strategy is meant for cancer treatment. Herein, a hollow Fe3 O4 catalytic nanozyme carrier co-loading lactate oxidase (LOD) and a clinically-used hypotensor syrosingopine (Syr) are developed and delivered for synergetic cancer treatment by augmented self-replenishing nanocatalytic reaction, integrated starvation therapy, and reactivating anti-tumor immune microenvironment. The synergetic bio-effects of this nanoplatform stemmed from the effective inhibition of lactate efflux through blocking the monocarboxylate transporters MCT1/MCT4 functions by the loaded Syr as a trigger. Sustainable production of hydrogen peroxide by catalyzation of the increasingly residual intracellular lactic acid by the co-delivered LOD and intracellular acidification enabled the augmented self-replenishing nanocatalytic reaction. Large amounts of produced reactive oxygen species (ROS) damaged mitochondria to inhibit oxidative phosphorylation as the substituted energy supply upon the hampered glycolysis pathway of tumor cells. Meanwhile, remodeling anti-tumor immune microenvironment is implemented by pH gradient reversal, promoting the release of proinflammatory cytokines, restored effector T and NK cells, increased M1-polarize tumor-associated macrophages, and restriction of regulatory T cells. Thus, the biocompatible nanozyme platform achieved the synergy of chemodynamic/immuno/starvation therapies. This proof-of-concept study represents a promising candidate nanoplatform for synergetic cancer treatment.

Separation and structural elucidation of a novel vardenafil analogue as an adulterant in a natural health care dietary supplement.

A novel vardenafil analogue was identified in dietary supplement as an adulterant in herbal formulations. The structure of this analogue was elucidated using HRMS, NMR after extraction from the pulverized powder. It was named morphardenafil as a morpholine ring has replaced the N-ethyl piperazine ring in vardenafil. A tablet of this dietary supplement contained about 50 mg of unspecified morphardenafil, which is 2.5 - 20-times the prescriptive dosage of Levetra, the commercial formulation of the vardenafil monohydrochloride salt in the market and probably places unwary consumers at risk for potentially serious adverse effects or drug-drug interaction (DDI).

Impact of lifetime air pollution exposure patterns on the risk of chronic disease.

Long-term exposure to air pollution can lead to cardiovascular disease, metabolic syndrome, and chronic respiratory disease. However, from a lifetime perspective, the critical period of air pollution exposure in terms of health risk is unknown. This study aimed to evaluate the impact of air pollution exposure at different life stages. The study participants were recruited from community centers in Northern Taiwan between October 2018 and April 2021. Their annual averages for fine particulate matter (PM2.5) exposure were derived from a national visibility database. Lifetime PM2.5 exposures were determined using residential address information and were separated into three stages (<20, 20-40, and >40 years). We employed exponentially weighted moving averages, applying different weights to the aforementioned life stages to simulate various weighting distribution patterns. Regression models were implemented to examine associations between weighting distributions and disease risk. We applied a random forest model to compare the relative importance of the three exposure life stages. We also compared model performance by evaluating the accuracy and F1 scores (the harmonic mean of precision and recall) of late-stage (>40 years) and lifetime exposure models. Models with 89% weighting on late-stage exposure showed significant associations between PM2.5 exposure and metabolic syndrome, hypertension, diabetes, and cardiovascular disease, but not gout or osteoarthritis. Lifetime exposure models showed higher precision, accuracy, and F1 scores for metabolic syndrome, hypertension, diabetes, and cardiovascular disease, whereas late-stage models showed lower performance metrics for these outcomes. We conclude that exposure to high-level PM2.5 after 40 years of age may increase the risk of metabolic syndrome, hypertension, diabetes, and cardiovascular disease. However, models considering lifetime exposure showed higher precision, accuracy, and F1 scores and lower equal error rates than models incorporating only late-stage exposures. Future studies regarding long-term air pollution modelling are required considering lifelong exposure pattern. .1.

Targeting Lung-Gut Axis for Regulating Pollution Particle-Mediated Inflammation and Metabolic Disorders.

Cigarette smoking (CS) or ambient particulate matter (PM) exposure is a risk factor for metabolic disorders, such as insulin resistance (IR), increased plasma triglycerides, hyperglycemia, and diabetes mellitus (DM); it can also cause gut microbiota dysbiosis. In smokers with metabolic disorders, CS cessation decreases the risks of serious pulmonary events, inflammation, and metabolic disorder. This review included recent studies examining the mechanisms underlying the effects of CS and PM on gut microbiota dysbiosis and metabolic disorder development; one of the potential mechanisms is the disruption of the lung-gut axis, leading to gut microbiota dysbiosis, intestinal dysfunction, systemic inflammation, and metabolic disease. Short-chain fatty acids (SCFAs) are the primary metabolites of gut bacteria, which are derived from the fermentation of dietary fibers. They activate G-protein-coupled receptor (GPCR) signaling, suppress histone deacetylase (HDAC) activity, and inhibit inflammation, facilitating the maintenance of gut health and biofunction. The aforementioned gut microbiota dysbiosis reduces SCFA levels. Treatment targeting SCFA/GPCR signaling may alleviate air pollution-associated inflammation and metabolic disorders, which involve lung-gut axis disruption.

Metabolomic analysis of circulating tumor cells derived liver metastasis of colorectal cancer.

Metabolic reprogramming is one of the essential features of tumor that may dramatically contribute to metastasis and collapse. The metabolic profiling is investigated on the patient derived tissue and cancer cell line derived mouse metastasis xenograft. As well-recognized "seeds" for remote metastasis of tumor, role of circulating tumor cells (CTCs) in the study of metabolic reprogramming feature of tumor is yet to be elucidated. More specifically, whether there is difference of metabolic features of liver metastasis in colorectal cancer (CRC) derived from either CTCs or cancer cell line is still unknown. In this study, comprehensive untargeted metabolomics was performed using high performance liquid chromatography-mass spectrometry (HPLC-MS) in liver metastasis tissues from CT26 cells and CTCs derived mouse models. We identified 288 differential metabolites associated with the pathways such as one carbon pool by folate, folate biosynthesis and histidine metabolism through bioinformation analysis. Multiple gene expression was upregulated in the CTCs derived liver metastasis, specifically some specific enzymes. These results indicated that the metabolite phenotype and corresponding gene expression in the CTCs derived liver metastasis tissues was different from the parental CT26 cells, displaying a specific up-regulation of mRNAs involved in the above metabolism-related pathways. The metabolic profile of CTCs was characterized on the liver metastatic process in colorectal cancer. The invasion ability and chemo drug tolerance of the CTCs derived tumor and metastasis was found to be overwhelming higher than cell line derived counterpart. Identification of the differential metabolites will lead to a better understanding of the hallmarks of the cancer progression and metastasis, which may suggest potential attractive target for treating metastatic CRC.

Associations between risk of Alzheimer's disease and obstructive sleep apnea, intermittent hypoxia, and arousal responses: A pilot study.

Objectives: Obstructive sleep apnea (OSA) may increase the risk of Alzheimer's disease (AD). However, potential associations among sleep-disordered breathing, hypoxia, and OSA-induced arousal responses should be investigated. This study determined differences in sleep parameters and investigated the relationship between such parameters and the risk of AD. Methods: Patients with suspected OSA were recruited and underwent in-lab polysomnography (PSG). Subsequently, blood samples were collected from participants. Patients' plasma levels of total tau (T-Tau) and amyloid beta-peptide 42 (Aß42) were measured using an ultrasensitive immunomagnetic reduction assay. Next, the participants were categorized into low- and high-risk groups on the basis of the computed product (Aß42 × T-Tau, the cutoff for AD risk). PSG parameters were analyzed and compared. Results: We included 36 patients in this study, of whom 18 and 18 were assigned to the low- and high-risk groups, respectively. The average apnea-hypopnea index (AHI), apnea, hypopnea index [during rapid eye movement (REM) and non-REM (NREM) sleep], and oxygen desaturation index (≥3%, ODI-3%) values of the high-risk group were significantly higher than those of the low-risk group. Similarly, the mean arousal index and respiratory arousal index (R-ArI) of the high-risk group were significantly higher than those of the low-risk group. Sleep-disordered breathing indices, oxygen desaturation, and arousal responses were significantly associated with an increased risk of AD. Positive associations were observed among the AHI, ODI-3%, R-ArI, and computed product. Conclusions: Recurrent sleep-disordered breathing, intermittent hypoxia, and arousal responses, including those occurring during the NREM stage, were associated with AD risk. However, a longitudinal study should be conducted to investigate the causal relationships among these factors.

Corrigendum: Heparin binding epidermal growth factor-like growth factor is a prognostic marker correlated with levels of macrophages infiltrated in lung adenocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.963896.].

Heparin binding epidermal growth factor-like growth factor is a prognostic marker correlated with levels of macrophages infiltrated in lung adenocarcinoma.

Background: The interactions between tumor cells and the host immune system play a crucial role in lung cancer progression and resistance to treatment. The alterations of EGFR signaling have the potential to produce an ineffective tumor-associated immune microenvironment by upregulating a series of immune suppressors, including inhibitory immune checkpoints, immunosuppressive cells, and cytokines. Elevated Heparin-binding EGF-like growth factor (HB-EGF) expression, one EGFR ligand correlated with higher histology grading, worse patient prognosis, and lower overall survival rate, acts as a chemotactic factor. However, the role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in the accumulation of immune cells in the tumor microenvironment remains unclear. Methods: The clinical association of HB-EGF expression in lung cancer was examined using the Gene Expression Omnibus (GEO) repository. HB-EGF expression in different cell types was determined using single-cell RNA sequencing (scRNA-seq) dataset. The correlation between HB-EGF expression and cancer-immune infiltrated cells was investigated by performing TIMER and ClueGo pathways analysis from TCGA database. The chemotaxis of HB-EGF and macrophage infiltration was investigated using migration and immunohistochemical staining. Results: The high HB-EGF expression was significantly correlated with poor overall survival in patients with lung adenocarcinoma (LUAD) but not lung squamous cell carcinoma (LUSC). Moreover, HB-EGF expression was correlated with the infiltration of monocytes, macrophages, neutrophils, and dendritic cells in LUAD but not in LUSC. Analysis of scRNA-seq data revealed high HB-EGF expression in lung cancer cells and myeloid cells. Results from the pathway analysis and cell-based experiment indicated that elevated HB-EGF expression was associated with the presence of macrophage and lung cancer cell migration. HB-EGF was highly expressed in tumors and correlated with M2 macrophage infiltration in LUAD. Conclusions: HB-EGF is a potential prognostic marker and therapeutic target for lung cancer progression, particularly in LUAD.

Glioblastoma stem cell-specific histamine secretion drives pro-angiogenic tumor microenvironment remodeling.

The communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of glioblastoma multiforme (GBM). However, the mechanisms by which GSCs proactively drive interactions with microenvironment is not well understood. In this study, we interrogated metabolites that are preferentially secreted from GSCs and found that GSCs produce and secrete histamine to shape a pro-angiogenic tumor microenvironment. This histamine-producing ability is attributed to H3K4me3 modification-activated histidine decarboxylase (HDC) transcription via MYC. Notably, HDC is highly expressed in GBM, which is associated with poor survival of these patients. GSC-secreted histamine activates endothelial cells by triggering a histamine H1 receptor (H1R)-Ca2+-NF-κB axis, thereby promoting angiogenesis and GBM progression. Importantly, pharmacological blockage of H1R using antihistamines impedes the growth of GBM xenografts in mice. Our findings establish that GSC-specific metabolite secretion remodels the tumor microenvironment and highlight histamine targeting as a potential strategy for GBM therapy.

Circulating tumor cell isolation for cancer diagnosis and prognosis.

Circulating tumor cells (CTCs) are tumor cells that shed from the primary tumor and intravasate into the peripheral blood circulation system responsible for metastasis. Sensitive detection of CTCs from clinical samples can serve as an effective tool in cancer diagnosis and prognosis through liquid biopsy. Current CTC detection technologies mainly reply on the biomarker-mediated platforms including magnetic beads, microfluidic chips or size-sensitive microfiltration which can compromise detection sensitivity due to tumor heterogeneity. A more sensitive, biomarker independent CTCs isolation technique has been recently developed with the surface-charged superparamagnetic nanoprobe capable of different EMT subpopulation CTC capture from 1 mL clinical blood. In this review, this new strategy is compared with the conventional techniques on biomarker specificity, impact of protein corona, effect of glycolysis on cell surface charge, and accurate CTC identification. Correlations between CTC enumeration and molecular profiling in clinical blood and cancer prognosis are provided for clinical cancer management.

Climate-mediated air pollution associated with COPD severity.

Air pollution has been reported to be associated with chronic obstructive pulmonary disease (COPD). Our study aim was to examine the mediating effects of air pollution on climate-associated health outcomes of COPD patients. A cross-sectional study of 117 COPD patients was conducted in a hospital in Taiwan. We measured the lung function, 6-min walking distance, oxygen desaturation, white blood cell count, and percent emphysema (low attenuation area, LAA) and linked these to 0-1-, 0-3-, and 0-5-year lags of individual-level exposure to relative humidity (RH), temperature, and air pollution. Linear regression models were conducted to examine associations of temperature, RH, and air pollution with severity of health outcomes. A mediation analysis was conducted to examine the mediating effects of air pollution on the associations of RH and temperature with health outcomes. We observed that a 1 % increase in the RH was associated with increases in forced expiratory volume in 1 s (FEV1), eosinophils, and lymphocytes, and a decrease in the total-lobe LAA. A 1 °C increase in temperature was associated with decreases in oxygen desaturation, and right-, left-, and upper-lobe LAA values. Also, a 1 µg/m3 increase in PM2.5 was associated with a decrease in the FEV1 and an increase in oxygen desaturation. A 1 µg/m3 increases in PM10 and PM2.5 was associated with increases in the total-, right-, left, upper-, and lower-lobe (PM2.5 only) LAA. A one part per billion increase in NO2 was associated with a decrease in the FEV1 and an increase in the upper-lobe LAA. Next, we found that NO2 fully mediated the association between RH and FEV1. We found PM2.5 fully mediated associations of temperature with oxygen saturation and total-, right-, left-, and upper-lobe LAA. In conclusion, climate-mediated air pollution increased the risk of decreasing FEV1 and oxygen saturation and increasing emphysema severity among COPD patients. Climate change-related air pollution is an important public health issue, especially with regards to respiratory disease.

Path-Dependent Anisotropic Colloidal Assembly of Magnetic Nanocomposite-Protein Complexes.

Anisotropic self-assembly of nanoparticles (NPs) stems from the fine-tuning of their surface functionality and NP interaction. Strategies involving ligand interaction, protein interaction, and external stimulus have been developed. However, robust construction of monodispersed magnetic NPs to tens of microns of anisotropically aligned colloidal assembly triggered by adsorbed protein intermolecular interaction is yet to be elucidated. Here, we present the NP-protein interaction, magnetic force, and protein corona intermolecular interaction serially but independently induced path-dependent self-assembly of 100 nm Fe3O4@SiO2 nanocomposites. Dynamic formation of the micron-sized anisotropic magnetic assembly was reproducibly realized in a continuous medium in a controllable manner. Formation of the primary globular clusters upon the unique NP-protein complexes with the help of ions acts as the prerequisite for the anisotropic colloidal assembly, followed by the magnetic force-driven pre-organization and protein intermolecular electrostatic interaction-mediated elongation. The protein concentration rather than the protein original structure plays a more pivotal role in the NP-protein interaction and subsequent colloidal assembly process. Two typical serum proteins fibrinogen and bovine serum albumin enable formation of the anisotropic colloidal assembly but with a different subtle morphology. Furthermore, the obtained micron-sized magnetic colloidal assembly can be dissociated rapidly by adding a negative electrolyte in the medium due to the interference in the NP-protein interaction. However, the self-assembly process can be recycled based on the dissociated colloidal assembly.

lnc-IL7R Expression Reflects Physiological Pulmonary Function and Its Aberration Is a Putative Indicator of COPD.

Despite rapidly evolving pathobiological mechanistic demystification, coupled with advances in diagnostic and therapeutic modalities, chronic obstructive pulmonary disease (COPD) remains a major healthcare and clinical challenge, globally. Further compounded by the dearth of available curative anti-COPD therapy, it is posited that this challenge may not be dissociated from the current lack of actionable COPD pathognomonic molecular biomarkers. There is accruing evidence of the involvement of protracted 'smoldering' inflammation, repeated lung injury, and accelerated lung aging in enhanced predisposition to or progression of COPD. The relatively novel uncharacterized human long noncoding RNA lnc-IL7R (otherwise called LOC100506406) is increasingly designated a negative modulator of inflammation and regulator of cellular stress responses; however, its role in pulmonary physiology and COPD pathogenesis remains largely unclear and underexplored. Our previous work suggested that upregulated lnc-IL7R expression attenuates inflammation following the activation of the toll-like receptor (TLR)-dependent innate immune system, and that the upregulated lnc-IL7R is anti-correlated with concomitant high PM2.5, PM10, and SO2 levels, which is pathognomonic for exacerbated/aggravated COPD in Taiwan. In the present study, our quantitative analysis of lnc-IL7R expression in our COPD cohort (n = 125) showed that the lnc-IL7R level was significantly correlated with physiological pulmonary function and exhibited COPD-based stratification implications (area under the curve, AUC = 0.86, p < 0.001). We found that the lnc-IL7R level correctly identified patients with COPD (sensitivity = 0.83, specificity = 0.83), precisely discriminated those without emphysematous phenotype (sensitivity = 0.48, specificity = 0.89), and its differential expression reflected disease course based on its correlation with the COPD GOLD stage (r = −0.59, p < 0.001), %LAA-950insp (r = −0.30, p = 0.002), total LAA (r = −0.35, p < 0.001), FEV1(%) (r = 0.52, p < 0.001), FVC (%) (r = 0.45, p < 0.001), and post-bronchodilator FEV1/FVC (r = 0.41, p < 0.001). Consistent with other data, our bioinformatics-aided dose−response plot showed that the probability of COPD decreased as lnc-IL7R expression increased, thus, corroborating our posited anti-COPD therapeutic potential of lnc-IL7R. In conclusion, reduced lnc-IL7R expression not only is associated with inflammation in the airway epithelial cells but is indicative of impaired pulmonary function, pathognomonic of COPD, and predictive of an exacerbated/ aggravated COPD phenotype. These data provide new mechanistic insights into the ailing lung and COPD progression, as well as suggest a novel actionable molecular factor that may be exploited as an efficacious therapeutic strategy in patients with COPD.