Numerical and experimental study on failure behavior of steel-aluminium mechanical clinched joints under multiple test conditions

In this work, the numerical and experimental study was performed to explore the mechanical properties and failure behavior of steel-aluminium mechanical clinched joints under multiple test conditions. The stress distribution of the clinched joints and the failure mode were analyzed using finite element analysis software ABAQUS. The Gurson-Tvergaard-Needleman (GTN) model was used to simulate damage and failure of the joints. The experimental tests were conducted for the verification. It was found that the clinched joints under shear condition had a peak force of 4354N, which was much higher than that of the peel (624N) and cross tensile (1046N) conditions, while the peak load displacement and failure displacement have the opposite law. The failure mode of shear condition was neck fracture, while that of tensile and peel conditions were both pulling out failure. The finite element simulation results were in good agreement with the experimental ones and the failure mode was consistent. The Gurson-tvergaard-Needleman (GTN) model can accurately predict the mechanical properties and failure mode of clinched joints. Keywords: Steel-aluminium mechanical clinching, Mechanical properties, Damage model, Finite element simulatio

Radioiodine refractoriness score: A multivariable prediction model for postoperative radioiodine‐refractory differentiated thyroid carcinomas

Abstract Objective The purpose of the present study was to evaluate the clinical features of patients with radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC) and establish an effective risk score for postoperative radioiodine refractoriness. Subjects and methods Data were retrospectively collected from 5163 patients admitted to our center after thyroid surgery. Radioiodine refractoriness was defined according to criteria used in the 2015 American Thyroid Association guidelines. The scoring system was established by independent risk factors identified by univariate and multivariate analyses. The optimal index points for predicting the prevalence of radioiodine refractoriness and the model discriminatory power were assessed by receiver operating characteristic (ROC) curves. Results One hundred and twelve (2.2%) patients developed RAIR DTC. Smoking, tumor type (follicular thyroid cancer), extrathyroid extension, lymph node metastasis number (≥4), lymph node metastasis rate (≥53%), and pN stage (N1) were highly positively correlated with the prevalence of RAIR DTC. The cutoff value of seven points was found to be the best for predicting the prevalence of RAIR DTC, and the scoring system presented better discrimination than other single independent predictors. Conclusions Based on our multivariable prediction model, patients with ≥7 index points may need to undergo more active surveillance or aggressive treatment due to the high risk of RAIR DTC

Identification of Circulating Exosomal microRNAs Associated with Radioiodine Refractory in Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) has a favorable prognosis, but a fraction of cases show progressive behaviors, becoming radioiodine refractory (RAIR) PTC. To explore circulating exosomal microRNAs (miRNAs) associated with RAIR PTC, the miRNA profiles in exosomes from parental and induced RAIR cell lines were firstly identified with a next-generation sequencing technique. The Na+/I− symporter (NIS) related miRNAs were then validated by quantitative real-time PCR (qRT-PCR) in plasma of PTC patients with non-131I-avid metastases and those with 131I-avid metastases. The regulation of exosomal miRNAs on NIS were also verified. We identified that miR-1296-5p, upregulation in exosomes from RAIR cell lines, and the plasma of patients with RAIR PTC achieved the largest areas under the curve (AUC) of 0.911 and that it is an independent risk factor for RAIR PTC. In addition, miR-1296-5p was abundantly detected in the tissue of RAIR PTC and can directly target downstream gene of NIS. Taken together, our findings suggested that circulating exosomal miRNAs, particularly miR-1296-5p, may be involved in the pathogenesis of RAIR PTC by directly targeting NIS

miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis

Abstract Background Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease characterized by lymphocyte infiltration that destroys thyrocyte cells. The aim of the present study was to elucidate the role and mechanisms of tissue small extracellular vesicle (sEV) microRNAs (miRNAs) in the pathogenesis of HT. Methods Differentially expressed tissue sEV miRNAs were identified between HT tissue and normal tissue by RNA sequencing in the testing set (n = 20). Subsequently, using quantitative real-time polymerase chain reaction (qRT‒PCR) assays and logistic regression analysis in the validation set (n = 60), the most relevant tissue sEV miRNAs to HT were verified. The parental and recipient cells of that tissue sEV miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of sEV miRNAs that contribute to the development of HT. Results We identified that miR-142-3p encapsulated in T lymphocyte-derived tissue sEVs can induce Treg function defect and thyrocyte destruction through an intact response loop. Inactivation of miR-142-3p can effectively protect non-obese diabetic (NOD).H-2h4 mice from HT development display reduced lymphocyte infiltration, lower antibody titers, and higher Treg cells. Looking at the mechanisms underlying sEV action on thyrocyte destruction, we found that the strong deleterious effect mediated by tissue sEV miR-142-3p is due to its ability to block the activation of the ERK1/2 signaling pathway by downregulating RAC1. Conclusions Our findings highlight the fact that tissue sEV-mediated miR-142-3p transfer can serve as a communication mode between T lymphocytes and thyrocyte cells in HT, favoring the progression of HT