Bisphenol A drives di(2-ethylhexyl) phthalate promoting thyroid tumorigenesis via regulating HDAC6/PTEN and c-MYC signaling.

Bisphenol A (BPA) and di-(2-ethylhcxyl) phthalate (DEHP) are exist widespread in the environment and produce adverse effect to human as environmental disruptors (EDCs). Epidemiological studies have found that the exposure of DEHP and BPA could increase the susceptibility to thyroid diseases including thyroid cancer and benign thyroid nodules. Due to the existence of multiple pollutants in our daily life, the mixed toxic effects of exposure and their interrelationships may distinguish from the exposure to a single chemical, so it is of great significance to explore the mixed toxic effect of DEHP and BPA co-exposure. Thyroid, as one of the target organs of EDCs, is prone to tumor occurrence, however, whether the mixture of BPA and DEHP will affect the occurrence of thyroid cancer is still obscure. We aim to investigate the effect of single or combined exposure to BPA and DEHP on the occurrence of thyroid cancer. An animal model of exposure to BPA and DEHP was firstly established to evaluate their effect on DMD-induced thyroid cancer. Additionally, human thyroid cancer cells BCPAP and thyroid cells Nthy-ori3-1 were used to further clarify some possible mechanisms of BPA and MEHP, the main metabolite of DEHP. Consequently, we found that BPA alone could increase the incidence of thyroid tumors in female rats compared with DEHP, and DEHP enhanced the effect of BPA on cancer promotion. BPA alone and in combination with DEHP mainly induced the expression of HDAC6, inhibited tumor suppressor gene PTEN upregulated the expression of oncogene c-MYC, and eventually elevate the susceptibility to thyroid tumors. Mechanistically, BPA alone and in combination with MEHP could significantly induce the proliferation of BCPAP cells depending on HDAC6, which could modulate H3K9ac to inhibit PTEN, activate AKT signaling pathway, and simultaneously upregulate the expression of c-MYC. Interestingly, we found that BPA alone and in combination with MEHP could significantly induce the proliferation of Nthy-ori3-1 cells independent on HDAC6 via activating ERK signaling pathway. Taken together, these findings not only provide new evidence of the promoting effect of BPA and DEHP on thyroid cancer but also discusses some possible mechanisms underlying these effects.

BRCA2 3'-UTR Polymorphism rs15869 Alters Susceptibility to Papillary Thyroid Carcinoma via Binding hsa-mir-1178-3p.

OBJECTIVE: To investigate the associations of polymorphisms in the following DNA double-strand break repair (DSBR) genes with papillary thyroid carcinoma (PTC) risk (including RAD51 rs11852786, RAD51B rs963917, BRCA1 rs12516 and rs8176318, BRCA2 rs15869, XRCC4 rs2035990 and XRCC5 rs2440). MATERIALS AND METHODS: A matched case-control study was implemented to examine associations between PTC risk and the above polymorphisms. Subsequently, we evaluated the effects of the potential PTC susceptibility-related variant rs15869 on BRCA2 mRNA secondary structure and BRCA2 expression through bioinformatics analysis and experiment validation. Additionally, luciferase assay was used to identify whether rs15869 polymorphism can substantially affect the binding of hsa-miR-1178-3p to BRCA2 mRNA. Finally, Pearson correlation analysis was performed to determine the correlation between the expression of hsa-miR-1178-3p and BRCA2 mRNA and protein in thyroid tissues harboring rs15869 different genotypes. RESULTS: BRCA2 rs15869 CC genotype was associated with a higher risk of PTC than its AA genotype. Subsequently, stratified analyses came to the same conclusion in the female or age<50 population. Furthermore, we confirmed that the A-to-C substitution of rs15869 changed BRCA2 mRNA secondary structure and contributed to a decreased BRCA2 expression. Mechanistically, a significantly decreased luciferase activity verified a greater binding between hsa-miR-1178-3p and rs15869 C allele, but not the A allele, which was evidenced by the significant negative correlation between hsa-miR-1178-3p with BRCA2 mRNA and protein levels in thyroid tissues with AC and CC genotype but not AA genotype at rs15869. CONCLUSION: BRCA2 rs15869 is characterized as a potential biomarker associated with PTC risk, highlighting the contribution of the hsa-miR-1178-3p via functional exploration.

Bisphenol A at a human exposed level can promote epithelial-mesenchymal transition in papillary thyroid carcinoma harbouring BRAFV600E mutation.

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, alters the function of endocrine system and enhances the susceptibility to tumorigenesis in several hormone-dependent tumours as thyroid carcinoma. About 50% of papillary thyroid cancers (PTC), the most common type of thyroid malignancy, harbours the BRAFV600E mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAFV600E mutation on epithelial-mesenchymal transition (EMT) in PTC. Firstly, the level of BPA in plasma, the evaluation of BRAFV600E mutation and the level of EMT-related proteins in PTC samples were individually determined. Additionally, the migration, invasion, colony formation capacity and the expression of EMT-related proteins after exposure to BPA were precisely analysed in vitro thyroid cells genetically modified by the introduction of BRAFV600E mutation. Moreover, ERK-Cox2 signalling pathway was also introduced to explore the possible mechanism in PTC development. As expected, whether the clinical investigation or cultured thyroid cells demonstrated that BPA at a concentration compatible with human exposed levels (10-7  M) synergized with the BRAFV600E mutation promoted EMT via the activation of ERK-Cox2 signalling pathway. Our findings offer some evidence that BPA as an environmental risk factor can facilitate the progression of PTC harbouring BRAFV600E mutation.

Two-beam coherent combining based on Ti:sapphire chirped-pulse amplification at the repetition of 1 Hz.

In this Letter, we report the demonstration of the coherent beam combining (CBC) of two-beam femtosecond laser pulses based on chirped-pulse amplification (CPA). To the best of our knowledge, this is the first experimental realization of coherent combination pulses from Ti:sapphire CPA systems. In this experiment, the combined laser beams operate at a repetition rate of 1 Hz, and a reference laser is introduced to detect the phase error between the sub-beams. Finally, we realize a coherent combining efficiency of 90% which verified the feasibility for CPA CBC. Moreover, the influence of the amplification process on CBC is studied.

Coherent beam combination of multiple beams based on near-field angle modulation.

We proposed a new phase-locking technique for multibeam coherent beam combination. By near-field angle modulation and angular spectrum measurement, we obtained the relative phase between each pair of beams with one camera. This method is appropriate for multibeam schemes and possesses the advantages of high accuracy, resistance to energy fluctuation, and simplicity, as shown by the analysis in this study. In a proof-of-principle experiment, we realized the phase-locking of three beams, achieving a Strehl ratio of 89.5%. Our method may supply a scheme for multibeam coherent combining of ultra-intense bulk laser systems.

High-precision active synchronization control of high-power, tiled-aperture coherent beam combining.

We propose and demonstrate a high-precision active control technique for tiled-aperture coherent beam combining suitable for high-power laser pulses. The method is a hybrid structure based on the near-field interference fringe technique and single-crystal balanced optical cross-correlation, which enables the active loop to exhibit high accuracy, wide dynamic range, and good capacity for resisting energy disturbance. In the proof-of-principle experiment, we realized an adjustable beam combining bandwidth of approximately 100 Hz (limited by the speed of the piezoelectric transducer) and root-mean-square deviation of approximately λ/51 for two beam channels with a combining efficiency of 93%.