Purpose: The purpose of this study is to examine the effectiveness of introducing both rituximab (RTX) and ¹³¹I for active Graves' ophthalmopathy (GO) with hyperthyroidism. Methods: In total, 217 patients suffering from active GO with hyperthyroidism were included in this research. All subjects were randomly assigned to 3 groups. Patients in group A solely received ¹³¹I treatment; group B1 underwent a methylprednisolone treatment in combination with ¹³¹I treatment; and group B2 received an RTX in combination with ¹³¹I treatment. Hyperthyroidism treatment outcomes, orbital volumetry, ophthalmic assessments, serum cytokine levels, and adverse effects were measured after treatment. Results: The orbital volumetry principle was significantly different from 24 weeks after the start of treatment among all 3 groups, and improvements in most ophthalmic parameters were regarded significantly different among 3 groups (all p < 0.05). The expression levels of miR-146a and most serum cytokines were regarded significantly different from 24 weeks after the start of treatment among 3 groups (all p < 0.05). Conclusions: In comparison with other therapies, RTX treatment in combination with ¹³¹I treatment is considered to be more effective for hyperthyroidism with active GO.

Many biomedically critical proteins are underrepresented in proteomics and biochemical studies because of the difficulty of their production in Escherichia coli. These proteins might possess posttranslational modifications vital to their functions, tend to misfold and be partitioned into bacterial inclusion bodies, or act only in a stoichiometric dimeric complex. Successful production of these proteins requires efficient interaction between these proteins and a specific "facilitator," such as a protein-modifying enzyme, a molecular chaperone, or a natural physical partner within the dimeric complex. Here we report the design and application of a protein interaction moduleassisted function X (PIMAX) system that effectively overcomes these hurdles. By fusing two proteins of interest to a pair of well-studied protein-protein interaction modules, we were able to potentiate the association of these two proteins, resulting in successful production of an enzymatically active cyclin-dependent kinase complex and hyperphosphorylated tau protein, which is intimately linked to Alzheimer disease. Furthermore, using tau isoforms quantitatively phosphorylated by GSK-3␤ and CDK5 kinases via PIMAX, we demonstrated the hyperphosphorylation-stimulated tau oligomerization in vitro, paving the way for new Alzheimer disease drug discoveries. Vectors for PIMAX can be easily modified to meet the needs of different applications. This approach thus provides a convenient and modular suite with broad implications for proteomics and biomedical research. Molecular & Cellular Proteomics

In teleoperation, the operator is often required to command the motion of the remote robot and monitor its behavior. However, such an interaction demands a heavy workload from a human operator when facing with complex tasks and dynamic environments. In this article, we propose a shared control method to assist the operator in the manipulation tasks to reduce the workload and improve the efficiency. We adopt a task-parameterized hidden semi-Markov model to learn a manipulation skill from several human demonstrations. We utilize the learned model to predict the manipulation target given the current observed robotic motion trajectory and subsequently estimate the desired robotic motion given the current input of the operator. The estimated robotic motion is then utilized to correct the input of the operator to provide manipulation assistance. In addition, a set of virtual reality devices are used to capture the operator's motion and display the vision feedback from the remote site. We evaluate our approach through two manipulation tasks with a dual-arm robot. The experimental results show the effectiveness of the proposed method.

No abstract

The multi-target kinase inhibitor sorafenib has been approved for the treatment of patients with advanced differentiated thyroid cancer. However, different sensitivities to sorafenib have been observed, and few patients have benefited from sorafenib treatment in the long term. In the event of acquired resistance to sorafenib it is not beneficial to continue treatment in most patients. Autophagy can be induced in a variety of cancer treatments and plays an important role in cancer treatment. The role of autophagy in sorafenib treatment of thyroid cancer has not been fully demonstrated. The present study investigated whether autophagy is activated by sorafenib during the treatment of thyroid cancer, examined the underlying mechanisms, and explored potential strategies to enhance the therapeutic sensitivity of sorafenib. Chloroquine (CQ) is an autophagy inhibitor that has been reported to increase sensitivity to various cancer treatments. Thyroid cancer xenograft model mice were treated with sorafenib, CQ, or a combination of sorafenib and CQ. We observed that CQ or sorafenib treatment suppressed tumor growth, while mice treated with the combination of sorafenib and CQ displayed significantly reduced tumor growth compared with those treated with sorafenib or CQ alone. Western blotting results indicated that sorafenib concurrently inhibited the activities of the MAPK and AKT/mTOR pathways in thyroid cancer. Autophagy was activated by sorafenib in thyroid cancer, both in vitro and in vivo, which was at least in part due to suppression of the AKT/mTOR pathway. Combination treatment including CQ could inhibit the autophagic flux induced by sorafenib. Silencing the key autophagy gene ATG5 using small interfering RNA also increased the anticancer effect of sorafenib. In summary, the present study revealed that inhibition of autophagy enhances the anticancer effect of sorafenib, and the combination of CQ with sorafenib treatment represents a potential therapeutic strategy for treating advanced differentiated thyroid cancer.

The evidence of this study suggests that a combinatorial approach that inhibits both the MAPK and PI3K/AKT/mTOR pathways exerts a greater antitumor effect than sorafenib alone in thyroid cancer cell lines.

Abstract. The sharply increasing incidence of thyroid cancer has attracted considerable attention over the last few years. The combination of surgery, radioiodine ablation and thyroid-stimulating hormone suppression is usually efficient for the majority of thyroid tumors. However, advanced thyroid cancer that is recurrent, metastatic and 131 I-refractory, or medullary thyroid cancer, pose a therapeutic challenge. Autophagy is a process that metabolizes damaged cytoplasmic organelles and long-lived proteins in order to recycle cellular materials and maintain homeostasis. It has been confirmed that autophagy plays a dual role during cancer development, progression and treatment, mainly depending on the type and stage of the tumor. Autophagy modulation has become a potential therapeutic target for diverse diseases. The mechanism of thyroid tumorigenesis and cancer progression was largely demonstrated to be correlated with the dysregulation of the Ras/Raf/mitogenactivated protein kinase kinase̸extracellular signal-regulated kinase and the phosphoinositide 3-kinase̸Akt̸mammalian target of rapamycin pathways, as well as with abnormal epigenetic modifications. Those mechanisms are associated with autophagy regulation and may be beneficial for the treatment of advanced thyroid cancer. However, the number of available studies on the role of autophagy in thyroid cancer development, progression and treatment outcome, is currently limited. The aim of this review was to elaborate on the relevant knowledge and future prospectives of autophagy in the treatment of thyroid cancer.

The expression levels of microRNA (miR)-221-3p and miR-222-3p in thyroid cancer have been found to be upregulated compared with those in normal tissues. The present study aimed to determine the effects and potential underlying mechanisms of miR-221-3p and miR-222-3p on the regulation of radioactive iodine ( 131 I) uptake and radiosensitivity of thyroid cancer cells. The potential regulatory target genes of miR-221-3p and miR-222-3p were predicted by bioinformatics analysis, and reverse transcription-quantitative polymerase chain reaction was used to verify miR-221-3p, miR-222-3p and target gene expression levels in thyroid cancer tissues and cell lines. Overexpression of miR-221-3p or miR-222-3p in cell models was performed using lentivirus infection. Knockdown of miR-221-3p and miR-222-3p in cells was achieved using oligonucleotide inhibitor transfection.Western blotting was used to analyze the expression levels of target proteins. In addition, the effects of miR-221-3p and miR-222-3p on the radiosensitivity of thyroid cancer cells were verified using a colony formation assay. The results of the present study revealed that the expression levels of miR-221-3p and miR-222-3p were significantly upregulated, while the expression levels of suppressor of cytokine signaling 3 (SOCS3) were downregulated in thyroid cancer tissues. Furthermore, miR-221-3p and miR-222-3p overexpression downregulated the expression levels of SOCS3, E-cadherin and solute carrier family 5 member 5 (NIS), and upregulated the expression levels of phosphorylated STAT3 and vimentin. Following the overexpression of miR-221-3p or miR-222-3p in the FTC133 and TPC1 cell lines, their radiosensitivity was suppressed. In conclusion, the findings of the present study suggested that miR-221-3p and miR-222-3p may downregulate the expression levels of NIS and promote radioresistance. The potential mechanism was hypothesized to be associated with the miR-221-3p and miR-222-3p targeting of the SOCS3 gene, which may subsequently activate the STAT3 signaling pathway.