A multidimensional model incorporating radiomics score and liquid biopsy for the prediction of malignant and benign pulmonary nodules.

Background: As the lesions in pulmonary nodules (PNs) are small and the clinical manifestations lack specificity, the etiology of PNs is complex, predisposing them to misdiagnoses missed diagnoses. Thus, the diagnosis and treatment of PNs remains challenging and an important clinical problem. Methods: This study prospectively enrolled 156 patients with computed tomography (CT)-diagnosed PNs who underwent circulating genetically abnormal cell (CAC) testing between January 2020 and December 2021. We collected data on clinical features closely related to the nature of PNs, such as age, smoking history, and type of nodule. All internal regions of interest (ROIs) of PNs in this study were segmented. Radiomic feature extraction was performed on the ROIs, and a radiomics model was constructed using least absolute shrinkage and selection operator (LASSO) regression to obtain a radiomics score (Rad-score). A comprehensive model combining clinical features, Rad-score, and liquid biopsy was constructed using logistic regression analysis. The diagnostic performance of the model was evaluated using receiver operating characteristic (ROC) curves. Results: In this study, 5 radiomics features were screened for model construction. The area under the ROC curve (AUC) of the radiomics model was 0.844 [95% confidence interval (CI): 0.766-0.915] in the training set. The Rad-score, clinical features, and CAC were further combined to construct a multidimensional analysis model. The AUC of the synthesized model was 0.943 (95% CI: 0.881-0.978) in the training set. Conclusions: A multidimensional model is an effective tool for the noninvasive diagnosis of malignant PNs. The validation and combination of multiple diagnostic methods is a productive avenue of research trend for the identification of malignant PNs.

A Red-Emitting COF Ionic Exchanged With Green-Emitting Tb(III) Complex Anion: Synthesis, Characterization, Ratiometric Emission Sensing, and Removal of Picric Acid.

Picric acid (PA) is an important chemical product which has been widely used in dye manufacturing, antiseptics, and pharmaceuticals. Owing to PA's extreme electron-deficient structure, its natural degradation is hard, leading to accumulation in the environment and finally threatening the ecosystem and human health. In this case, PA detection and removal becomes more and more important, concerning environmental protection and human health. In this study, an ionic covalent organic framework (I-COF) was synthesized and modified with a luminescent Tb(III) emitter (Tb(DPA)3 3-, DPA = pyridine-2,6-dicarboxylic acid), via ionic exchange. The resulting composite material (Tb-COF) was fully characterized by geometric analysis, IR, XRD, porosity analysis, SEM/TEM, and elemental analysis. It was found that Tb(DPA)3 3- was loaded into the hexagonal cage in an I-COF host with an ionic exchange ratio of 41%. The as-synthesized Tb-COF showed weak Tb(III) emission and strong red COF emission, after adding PA, Tb(III) emission was increased whereas COF emission weakened greatly, showing sensing behavior. Linear working curves were observed with good selectivity. The sensing mechanism was revealed as follows. PA molecules replaced the [Tb(PDA)3]3- component trapped in Tb-COF, releasing free luminescent [Tb(PDA)3]3-. After incorporating PA in the hexagonal cage, the COF emission was quenched. This sensing mechanism ensured a good selectivity over competing species, including cations, anions, and nitrocompounds. The adsorption and removal performance of I-COF for PA were investigated as well.

A Series of Photosensitizes for Fe3+ in Aqueous Solution and Cells With Colorimetric and Fluorescent Channels: Synthesis and Performance.

Ferrum (Fe) is a widely existing metal element and nearly the most important trace element in living species, including human beings. The design of chemosensors for Fe ions faces issues related to the d-d transition of Fe(II) and Fe(III) ions, which makes them efficient electron trappers and energy quenchers. Most fluorescent dyes cannot afford such d-d quenching, showing emission turn off effect towards both Fe(II) and Fe(III) ions with poor selectivity. As a consequence, the development for Fe with emission turn on effect and good selectivity shall be continued and updated. In this work, three rhodamine-derived chemosensors modified by different lengths of alkyl chains having electron-donating N and O atoms were synthesized and explored for the selective optical sensing of Fe(III). These chemosensors showed colorimetric and fluorescent emission turn on sensing for Fe(III), showing two sensing channels. These chemosensors showed good selectivity, which was assigned to the sieving effect of alkyl chains with electron-donating N and O atoms. The N atom was found to be more effective in associating with Fe(III), compared to the O atom. Their fluorescent cell imaging experiment was carried out to confirm the possibility of being used for cell imaging.

Hypoxia Upregulates NOTCH3 Signaling Pathway to Promote Endothelial-Mesenchymal Transition in Pulmonary Artery Endothelial Cells.

BACKGROUND: To investigate the effect of hypoxia on pulmonary artery endothelial cells and the role of NOTCH3 in endothelial-mesenchymal transition (EnMT) and to provide a research model for pulmonary disease and explain the pathogenesis of the pulmonary disease. METHODS: Pulmonary artery endothelial cells were divided into two groups and cultured in normoxic and hypoxic environments, respectively. QPCR, western blot, and immunofluorescence were used to detect endothelial cell-specific marker protein and mRNA expression in each group, and the ability of endothelial cells migration was evaluated by scratch and transwell experiment. RESULTS: The pulmonary artery endothelial cells in the normoxic group presented a typical pebble-like arrangement, and the endothelial cells in hypoxic culture showed a long spindle appearance. Hypoxia induced high expression of NOTCH3, Jagged-1, Hes1, c-Src, and CSL. Immunofluorescence showed that endothelial cells in hypoxic culture began to express the α-SMA, and the expression of vWF increased with hypoxia. Cell viability, scratch, and transwell results showed that endothelial cells in the hypoxic group were more capable of viability and migration than those in the normoxic group. The induction of EnMT by hypoxia can be inhibited by using notch3-specific inhibitor DAPT and Jagged-1. This study also found that miR-7-5p can regulate endothelial NOTCH3, indicating that miRNA is also involved in the process of endothelial-mesenchymal transformation. CONCLUSION: Hypoxia promotes the transformation of endothelial cells into mesenchymal cells by opening the NOTCH3 pathway, which lays the foundation for disease progression or clinical prognosis, and is of great significance in the treatment of diseases.

CHOP overexpression sensitizes human non-small cell lung cancer cells to cisplatin treatment by Bcl-2/JNK pathway.

C/EBP homologous protein (CHOP), a 29 kDa cellular protein, plays a role in regulating tumor proliferation, differentiation, metabolism, cell death, and in tumor resistance to chemotherapy. Non-small cell lung cancer (NSCLC) is a tumor of the respiratory system and drug resistance is prevalent among NSCLC clinical cell cultures. Herein, our study elucidated the effect of CHOP on NSCLC cells with cisplatin resistance and its mechanism. In a NSCLC cell line with cisplatin-resistance, CHOP expression was decreased, compared with A549 cells. Overexpression of CHOP decreased the cell viability and enhanced cell apoptosis in the cells treated with cisplatin. Expression of CHOP also inhibited the cell proliferation and metastasis. CHOP increased the therapeutic effect of cisplatin on NSCLC cells through the Bcl-2/JNK pathway. In summary, CHOP regulated cisplatin resistance in cells of NSCLC by promoting the expression of apoptotic proteins and inhibiting the Bcl-2/JNK signaling pathway, indicating the antitumor effects of CHOP.

The methylation profiles of PRDM promoters in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the leading malignant tumors worldwide. Aberrant gene promoter methylation contributes to NSCLC, and PRDM is a tumor suppressor gene family that possesses histone methyltransferase activity. This study aimed to investigate whether aberrant methylation of PRDM promoter is involved in NSCLC. MATERIALS AND METHODS: Primary tumor tissues, adjacent nontumorous tissues, and distant lung tissues were collected from 75 NSCLC patients including 52 lung squamous cell carcinoma (LSCC) patients and 23 lung adenocarcinoma patients. The expression of PRDMs was detected by polymerase chain reaction (PCR), Western blot, and immunohistochemical analysis. The methylation of PRDM promoters was detected by methylation-specific PCR. The correlation of methylation and expression of PRDMs with clinicopathological characteristics of patients were analyzed. RESULTS: mRNA expression of PRDM2, PRDM5, and PRDM16 was low or absent in tumor tissues compared to distant lung tissues. The methylation frequencies of PRDM2, PRDM5, and PRDM16 in tumor tissues were significantly higher than those in distal lung tissues. In LSCC patients, methylation of PRDM2 and PRDM16 was correlated with smoking status and methylation of PRDM5 was correlated with tumor differentiation. CONCLUSION: The expression of PRDM2, PRDM5, and PRDM16 is low or absent in NSCLC, and this is mainly due to gene promoter methylation. Smoking may be an important cause of PRDM2 and PRDM16 methylation in NSCLC.

Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract.

BACKGROUND/AIMS: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism. METHODS: Primary AECII were isolated from rat lung tissues and exposed to CSE. Apoptosis was detected by flow cytometry. Protein expression was detected by Western blot analysis. RESULTS: Primary rat AECII maintained morphological and physiological characteristic after 3 passages. CSE increased the expression of ER specific pro-apoptosis factors CHOP and caspase 12, and the phosphorylation of JNK in AECII. CSE activated ER stress signaling and increased the phosphorylation of PERK, eIF2α and IRE1. Furthermore, CSE induced the expression of Hrd1, a key factor of ER-associated degradation, in AECII. Knockdown of Hrd1 led to more than 2 fold increase of apoptosis, while overexpression of Hrd1 attenuated CSE induced apoptosis of AECII. CONCLUSIONS: Our results suggest that ER stress induces HRD1 to protect alveolar type II epithelial cells from apoptosis induced by CSE.

Bevacizumab induces A549 cell apoptosis through the mechanism of endoplasmic reticulum stress in vitro.

AIMS: To observe the effect of bevacizumab on human A549 cells and explore its mechanism. METHODS: After different concentrations (0 µM, 1 µM, 5 µM, 25 µM) of bevacizumab treating in A549 cells, CCK8 assay detect the impact of bevacizumab on A549 cell proliferation and flow cytometry determine the effect of bevacizumab on human A549 cells apoptosis. Real-time PCR and Western blotting detect the changing expression of the target gene (CHOP, caspase-4, IRE1, XBP-1) on mRNA and Protein level. RESULTS: Treatment with bevacizumab for 24-hr have induced cell death in a does-dependent manner dramatically (P<0.05). In terms of the mRNA level, expression of XBP-1 has increased obviously in each group (1 µM, 5 µM, 25 µM) (P<0.01); the expression of CHOP (25 µM) and caspase-4 (5 µM) have increased slightly (P<0.05). In terms of the protein level, the expression of CHOP has increased obviously in each group (1 µM, 5 µM, 25 µM) when compared with the control group (0 µM) (P<0.05). As for caspase-4 (5 µM, 25 µM), the expression have increased slightly when compared with the control group (0 µM) (P<0.05). CONCLUSION: Bevacizumab can induce A549 cell apoptosis through the mechanism of endoplasmic reticulum stress.