Micro-Macro Modeling of Polymeric Fluids and Shear-Induced Microscopic Behaviors

This article delves into the micro-macro modeling of polymeric fluids, considering various microscopic potential energies, including the classical Hookean potential, as well as newly proposed modified Morse and Elastic-plastic potentials. These proposed potentials encompass microscopic-scale bond-breaking processes. The development of a thermodynamically consistent micro-macro model is revisited, employing the energy variational method. To validate the model's predictions, we conduct numerical simulations utilizing a deterministic particle-FEM method. Our numerical findings shed light on the distinct behaviors exhibited by polymer chains at the micro-scale in comparison to the macro-scale velocity and induced shear stresses of fluids under shear flow. Notably, we observe that polymer elongation, rotation, and bond breaking contribute to the zero polymer-induced stress in the micro-macro model when employing Morse and Elastic-plastic potentials. Furthermore, at high shear rates, polymer rotation is found to induce shear-thinning behavior in the model employing the classical Hookean potential

High-risk subtype: Clinical manifestations and molecular characteristics of submandibular gland adenoid cystic carcinoma

ObjectiveAdenoid cystic carcinoma of the head and neck mainly occurs in the major salivary glands, of which the parotid gland and submandibular gland are the most common. The purpose of this study was to clarify the site-specific differences in prognosis and molecular expression characteristics of the patients and to achieve stratified risk management of the clinical prognosis.MaterialsBy performing a single-centre retrospective analysis combined with analyses of the Surveillance, Epidemiology, and End Results (SEER) database, cBioPortal and GEO databases, the clinical prognostic characteristics and the differences in molecular expression patterns of ACC in the submandibular gland and parotid gland were analysed. Cox regression analysis, the chi-square test, Fisher’s test and the log-rank test were used to compare the significance of differences.ResultsCompared with patients with parotid gland ACC, the submandibular gland ACC is more likely to have metastases in the cervical lymph node (21.7% vs. 3.3%) and shows a higher rate of distant metastasis within 1 year after the primary site diagnosis (47.8% vs. 23.3%), a worse overall prognosis, more frequent mutations of MYB/MYBL1 (50% vs. 25%) and abnormal upregulation of the phosphatidylinositol-3 kinase (PI3K) pathway.ConclusionsSubmandibular gland ACC is associated with site-specific early cervical lymph node metastasis and hidden distant metastasis, along with rapid progression and a poor prognosis. A high MYB/MYBL1 mutation rate and abnormal upregulation of the PI3K pathway with MYB involvement were identified

The Systemic Immune Inflammatory Index Predicts No-Reflow Phenomenon after Primary Percutaneous Coronary Intervention in Older Patients with STEMI

Purpose: Coronary no-reflow phenomenon (NRP), a common adverse complication in patients with ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI), is associated with poor patient prognosis. In this study, the correlation between the systemic immune-inflammation index (SII) and NRP in older patients with STEMI was studied, to provide a basis for early identification of high-risk patients and improve their prognosis.Materials and methods: Between January 2017 and June 2020, 578 older patients with acute STEMI admitted to the Department of Cardiology of Hebei General Hospital for direct PCI treatment were selected for this retrospective study. Patients were divided into an NRP group and normal-flow group according to whether NRP occurred during the operation. Clinical data and the examination indexes of the two groups were collected. Logistic regression was used to analyze the independent predictors of NRP, and the receiver operating characteristic curve was used to further analyze the ability of SII to predict NRP in older patients with STEMI.Results: Multivariate logistic analysis indicated that hypertension (OR=2.048, 95% CI:1.252–3.352, P=0.004), lymphocyte count (OR=0.571, 95% CI:0.368–0.885, P=0.012), platelet count (OR=1.009, 95% CI:1.005–1.013, P<0.001), hemoglobin (OR=1.015, 95% CI:1.003–1.028, P=0.018), multivessel disease (OR=2.237, 95% CI:1.407–3.558, P=0.001), and SII≥1814 (OR=3.799, 95% CI:2.190–6.593, P<0.001) were independent predictors of NRP after primary PCI in older patients with STEMI. Receiver operating characteristic curve analysis demonstrated that SII had a high predictive value for NRP (AUC=0.738; 95% CI:0.686–0.790), with the best cut-off value of 1814, a sensitivity of 52.85% and a specificity of 85.71%.Conclusion: For older patients with STEMI undergoing primary PCI, SII is a valid predictor of NRP

Elevated Serum Growth Differentiation Factor 15 Levels in Hyperthyroid Patients

Background: Recent studies have shown that growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) superfamily, plays an important role in appetite, type 2 diabetes, and cardiovascular diseases. Since thyroid hormone has pleiotropic effects on whole-body energy metabolism, we aimed to explore the effect of thyroid hormone on circulating GDF15 levels in humans and GDF15 genes expression in C57BL/6 mice.Methods: A total of 134 hyperthyroid patients and 105 healthy subjects were recruited. Of them, 43 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism. Serum GDF15 levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. To determine the source for the increased circulating GDF15, C57BL/6 mice were treated with T3, and GDF15 gene expressions in the liver, skeletal muscle, brown adipose tissue (BAT), inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT) were analyzed by quantitative real-time polymerase chain reaction (PCR).Results: Serum GDF15 levels were significantly elevated in hyperthyroid patients as compared with healthy subjects (326.06 ± 124.13 vs. 169.24 ± 82.96 pg/mL; P &lt; 0.001). After thionamide treatment, GDF15 levels in hyperthyroid patients declined markedly from 293.27 ± 119.49 to 118.10 ± 71.83 pg/mL (P &lt; 0.001). After adjustment for potential confounders, serum GDF15 levels were independently associated with hyperthyroidism. T3 treatment increased GDF15 expression in the brown adipose tissue of C57BL/6 mice.Conclusions: Serum GDF15 levels were elevated in patients with hyperthyroidism and declined after thionamide treatment. Thyroid hormone treatment upregulated GDF15 expression in mice. Therefore, our results present the clinical relevance of GDF15 in humans under the condition of hyperthyroidism

Toll-like receptor 2 and Toll-like receptor 4 exhibit distinct regulation of cancer cell stemness mediated by cell death-induced high-mobility group box 1

Background: High-mobility group box 1 (HMGB1), a common extracellular damage associated molecular pattern molecule, is overexpressed in several solid tumors including pancreatic carcinoma. We previously observed that radiotherapy induced dying cells secrete HMGB1 and accelerate pancreatic carcinoma progression through an unclear mechanism.Methods: Using the Millicell system as an in vitro co-culture model, we performed quantitative reverse transcriptase-polymerase chain reaction, western blot and sphere forming ability analyses to access the effect of dying-cell-derived HMGB1 on CD133(+) cancer cell stemness in vitro and in vivo. Interactions between HMGB1 and Toll-like receptor 2(TLR2)/TLR4 were studied by co-immunoprecipitation. Western blot and short-hairpin RNA-based knockdown assays were conducted to detect HMGB1 and TLR2/TLR4 signaling activity.Findings: Radiation-associated, dying-cell-derived HMGB1 maintained stemness and contributed to CD133(+) cancer stemcell self-renewal in vitro and in vivo. In overexpressing and silencing experiments, we demonstrated that the process was activated by TLR2 receptor, whereas TLR4 antagonized HMGB1-TLR2 signaling. Wnt/beta-catenin signaling supported the HMGB1-TLR2 mediated stemness of CD133(+) cancer cells.Interpretation: Our results show how irradiation-induced cell death might enhance the stemness of resident cancer cells, and indicate HMGB1-TLR2 signaling as a potential therapeutic target for preventing pancreatic cancer recurrence. (c) 2018 Haitao Zhu. Published by Elsevier B.V

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications