Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease. IPF is characterized by excessive accumulation of the extracellular matrix (ECM) in the alveolar parenchyma and ...progressive lung scarring. The pathogenesis of IPF and whether the ECM involved in the process remain unknown.
To identify potential treatment target and ECM associated proteins that may be involved in the development of IPF, we employed isobaric tag for relative and absolute quantitation (iTRAQ) combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to examine protein expression in lung tissues from IPF patients.
A total of 662 proteins with altered expression (455 upregulated proteins and 207 downregulated proteins) were identified in lung tissue of IPF patients compared with control. KEGG pathway enrichment analysis showed that the altered proteins in lung tissue mainly belonged to the PI3K-Akt signaling, focal adhesion, ECM-receptor interaction, and carbon metabolism pathways. According to the bioinformatic definition of the matrisome, 229 matrisome proteins were identified in lung tissue. These proteins comprised the ECM of lung, of which 104 were core matrisome proteins, and 125 were matrisome-associated proteins. Of the 229 ECM quantified proteins, 56 significantly differentially expressed proteins (19 upregulated proteins and 37 downregulated proteins) were detected in IPF lung tissue samples. In addition to proteins with well-known functions such as COL1A1, SCGB1A1, TAGLN, PSEN2, TSPAN1, CTSB, AGR2, CSPG2, and SERPINB3, we identified several novel ECM proteins with unknown function deposited in IPF lung tissue including LGALS7, ASPN, HSP90AA1 and HSP90AB1. Some of these differentially expressed proteins were further verified using Western blot analysis and immunohistochemical staining.
This study provides a list of proteomes that were detected in IPF lung tissue by iTRAQ technology combined with LC-MS/MS. The findings of this study will contribute better understanding to the pathogenesis of IPF and facilitate the development of therapeutic targets.
In this Letter, we demonstrate that chemical oxidation polymerization of o-phenylenediamine (OPD) by potassium bichromate at room temperature results in the formation of submicrometer-scale ...poly(o-phenylenediamine) (POPD) colloids. Such colloids can absorb and quench dye-labeled single-stranded DNA (ssDNA) very effectively. In the presence of a target, a hybridization event occurs, which produces a double-stranded DNA (dsDNA) that detaches from the POPD surface, leading to recovery of dye fluorescence. With the use of an oligonucleotide (OND) sequence associated with human immunodeficiency virus (HIV) as a model system, we demonstrate the proof of concept that POPD colloid-quenched fluorescent OND can be used as a probe for fluorescence-enhanced nucleic acid detection with selectivity down to single-base mismatch.
Background and Aims
Primary liver cancer (PLC) is a common malignancy with poor survival and requires long-term follow-up. Hence, nomograms need to be established to predict overall survival (OS) and ...cancer-specific survival (CSS) from different databases for patients with PLC.
Methods
Data of PLC patients were downloaded from Surveillance, Epidemiology, and End Results (SEER) and the Cancer Genome Atlas (TCGA) databases. The Kaplan Meier method and log-rank test were used to compare differences in OS and CSS. Independent prognostic factors for patients with PLC were determined by univariate and multivariate Cox regression analyses. Two nomograms were developed based on the result of the multivariable analysis and evaluated by calibration curves and receiver operating characteristic curves.
Results
OS and CSS nomograms were based on age, race, TNM stage, primary diagnosis, and pathologic stage. The area under the curve (AUC) was 0.777, 0.769, and 0.772 for 1-, 3- and 5-year OS. The AUC was 0.739, 0.729 and 0.780 for 1-, 3- and 5-year CSS. The performance of the two new models was then evaluated using calibration curves.
Conclusions
We systematically reviewed the prognosis of PLC and developed two nomograms. Both nomograms facilitate clinical application and may benefit clinical decision-making.
Interstitial lung disease requires frequent re-examination, which directly causes excessive cumulative radiation exposure. To date, AI has not been applied to CT for enhancing clinical care; thus, we ...hypothesize AI may empower CT with intelligence to realize automatic and accurate pulmonary scanning, thus dramatically decrease medical radiation exposure without compromising patient care.
Facial boundary detection was realized by recognizing adjacent jaw position through training and testing a region proposal network (RPN) on 76,882 human faces using a preinstalled 2-dimensional camera; the lung-fields was then segmented by V-Net on another training set with 314 subjects and calculated the moving distance of the scanning couch based on a pre-generated calibration table. A multi-cohort study, including 1,186 patients was used for validation and radiation dose quantification under three clinical scenarios.
A U-HAPPY (United imaging Human Automatic Planbox for PulmonarY) scanning CT was designed. Error distance of RPN was 4·46±0·02 pixels with a success rate of 98·7% in training set and 2·23±0·10 pixels with 100% success rate in testing set. Average Dice's coefficient was 0·99 in training set and 0·96 in testing set. A calibration table with 1,344,000 matches was generated to support the linkage between camera and scanner. This real-time automation makes an accurate plan-box to cover exact location and area needed to scan, thus reducing amounts of radiation exposures significantly (all, P<0·001).
U-HAPPY CT designed for pulmonary imaging acquisition standardization is promising for reducing patient risk and optimizing public health expenditures.
The National Natural Science Foundation of China.
Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy is a ...novel treatment for PAP with hypercholesterolemia. However, this treatment has never been described in a patient without hypercholesterolemia. Here, we present a case of successful treatment with atorvastatin for a patient with possibly unclassified PAP without hypercholesterolemia who responded poorly to whole lung lavage therapy and inhaled granulocyte-macrophage colony-stimulating factor. After 18 months of atorvastatin treatment, the patient experienced improvements in dyspnea, radiographic abnormalities and pulmonary function. The present case study supports the feasibility of statin therapy for PAP regardless of the level of cholesterol.
A novel single-labeled fluorescent oligonucleotide (OND) probe for the detection of nanomolar silver(I) ion in aqueous solution is developed based on the inherent quenching ability of ...deoxyguanosines. The formation of a hairpin structure of the OND-Ag(+) complex brings deoxyguanosines close to a dye, leading to a decreased fluorescence intensity of the dye owning to photoinduced electron transfer from the dye to deoxyguanosines.
Background
Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop ...an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early.
Methods
This prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from 2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The prediction model’s performance was assessed in terms of discrimination, calibration, and clinical usefulness.
Results
This study included 127 patients, (72 men 56.7%; median age, 54 years interquartile range, 48-63 years, split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846–0.957), good calibration (Hosmer–Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P < 0.001).
Conclusions
We developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making.
To overcome the disadvantage of linear dissimilarity analysis (DISSIM) when monitoring nonlinear processes, a kernel dissimilarity analysis algorithm, termed KDISSIM here, is presented, which is the ...nonlinear version of DISSIM algorithm. A kernel dissimilarity index is introduced to quantitatively evaluate the differences between nonlinear data distribution structures, which can reflect the changes of nonlinear process correlations and operating conditions. In KDISSIM algorithm, the input space is first nonlinearly mapped into a high-dimensional feature space, where the initial nonlinear correlations are changed into linear ones. Then the process operating condition can be effectively tracked by investigating the linear data distributions in the feature space. The idea and effectiveness of the proposed algorithm are illustrated with respect to the simulated data collected from one typical nonlinear numerical process and the well-known Tennessee Eastman benchmark chemical process. Both the results show that the proposed method works well to capture the underlying nonlinear process correlations thus providing a feasible and promising solution for nonlinear process monitoring.
In this paper, we demonstrate for the first time that poly(m-phenylenediamine) (PMPD) nanospheres and nanorods can be selectively synthesized via chemical oxidation polymerization of ...m-phenylenediamine (MPD) monomers using ammonium persulfate (APS) as an oxidant at room temperature. It suggests that the pH value plays a critical role in controlling the the morphology of the nanostructures and fast polymerization rate favors the anisotropic growth of PMPD under homogeneous nucleation condition. We further demonstrate that such PMPD nanostructures can be used as an effective fluorescent sensing platform for multiplex nucleic acid detection. A detection limit as low as 50 pM and a high selectivity down to single-base mismatch could be achieved. The fluorescence quenching is attributed to photoinduced electron transfer from nitrogen atom in PMPD to excited fluorophore. Most importantly, the successful use of this sensing platform in human blood serum system is also demonstrated.
Some equipment have low efficiencies and safety when their surfaces are covered with ice, such as wind turbine and airplane, so de-bonding ice on such kind of equipment surface is necessary. In this ...article, the ultrasonic de-icing method based on icing aluminum plate is researched by finite element method. First, the natural frequency of icing aluminum plate changing with thickness of ice is simulated by modal analysis. Then, the distributions of shear stresses at the interface between aluminum plate and ice layer changing with excitation frequencies are simulated by harmonic analysis. Second, the shear stress and de-icing area influenced by the size of piezoelectric ceramic and excitation voltage are analyzed. The simulation results show that there is lowest natural frequency with optimum thickness of ice layer used to de-bond ice for ultrasonic de-icing system. The optimum distribution law of shear stress at the interface between ice layer and aluminum is decided. In this condition, the shear stress and de-icing area increase along with the excitation voltage. However, the de-icing area increases slowly. All the simulation results lay a theoretical foundation for future experiments and application of ultrasonic de-icing.
PDF
