A Bayesian method with nonlinear noise model to calibrate constitutive parameters of soft tissue.

The measured mechanical responses of soft tissue exhibit large variability and errors, especially for the softest brain tissue, while calibrating its constitutive parameters in a deterministic way remains a common practice. Here we implement a Bayesian method considering the nonlinear noise model to calibrate constitutive parameters of brain tissue. A probability model is first developed based on the measured experimental data, likelihood function, and prior function, from which the posterior distributions of model parameters are formulated. The likelihood function considers the nonlinear behaviors of the constitutive response and noise distribution of the experimentally measured data. Meanwhile, the prior predictive distribution is computed to check the probability model preliminarily. Secondly, the Markov Chain Monte Carlo (MCMC) method is used to compute the posterior distributions of model parameters, enabling assessment of parameter uncertainty, correlation, and model calibration error. Finally, the posterior predictive distributions of the overall response, constitutive response, and noise response are computed to validate the probabilistic model, all of which are consistent with the corresponding data. Furthermore, the effect of the prior distribution, experimental data, and noise model on posterior distribution is studied. Our study provides a general approach to calibrating constitutive parameters of soft tissue despite errors and large variability in experimental data.

Study of non-uniform axial magnetic field induced deformation of a soft cylindrical magneto-active actuator.

Magneto-active polymers (MAPs) can undergo rapid and noticeable deformation through external wireless magnetic stimulation, offering a possibility to develop potential applications such as in actuators, flexible micro-grippers, soft robots, etc. In this paper, a theoretical model is presented to depict the relationship between nonlinear deformation and the external mechanical load applied on cylindrical samples in the presence of magnetic fields generated by an electromagnet. The geometrical and electromagnetic properties of the electromagnet are explicitly modeled in COMSOL Multiphysics based on the measured data. Furthermore, a finite element model is constructed to obtain detailed information (such as strain field), which cannot be obtained in experiments. The theoretical and simulation results fit quite well with the experimental results, showing the accuracy of the model construction. The proposed designing approach and model provide guidelines for researchers to enrich the applications of MAPs.

NF-κB and neutrophil extracellular traps cooperate to promote breast cancer progression and metastasis.

Aberrant NF-κB activation and neutrophil extracellular traps (NETs) are associated with breast cancer progression. How NF-κB and NETs modulate each other in breast cancer development remains unclear. Here, we found that NETs induced by phorbol 12-myristate 13-acetate promote breast cancer cell progression. In turn, cancer cells-derived factors, such as IL-8 and granulocyte colony-stimulating factor, stimulate neutrophils to form NETs. Mechanistically, NETs increased the interaction of NF-κB essential modifier (NEMO) with IκB kinase (IKK)α/ß and enhanced NF-κB activation. We then employed a cell-permeable peptide corresponding to the NEMO-binding domain (NBD) of IKKα/ß, termed NBD peptide, which disrupts NETs-mediated NEMO interaction with IKKα/ß and abolished NF-κB activation in vitro. NBD peptide also reduced IL-8 level and NETs formation, and suppressed primary tumor growth and/or lung metastasis in human breast cancer mouse xenograft models and mouse spontaneous breast cancer model. Blockade of NET formation using a peptidylarginine deiminase 4 (PAD4) pharmacologic inhibitor decreased NF-κB activation and tumor metastasis. Collectively, these data suggest that NF-κB associates with NETs to form a positive loop facilitating breast tumor progression and metastasis, and that selective inhibition of NF-κB and PAD4-dependent NETs provides an effective therapeutic approach for treating breast cancer.

The role of MYB proto-oncogene like 2 in tamoxifen resistance in breast cancer.

Despite the efficacy of tamoxifen in preventing disease relapse, a large portion of breast cancer patients show intrinsic or acquired resistance to tamoxifen, leading to treatment failure and unfavorable clinical outcome. MYB proto-oncogene like 2 (MYBL2) is a transcription factor implicated in the initiation and progression of various human cancers. However, its role in tamoxifen resistance in breast cancer remained largely unknown. In the present study, by analyzing public transcriptome dataset, we found that MYBL2 is overexpressed in breast cancer and is associated with the poor prognosis of breast cancer patients. By establishing tamoxifen-resistant breast cancer cell lines, we also provided evidence that MYBL2 overexpression contributes to tamoxifen resistance by up-regulating its downstream transcriptional effectors involved in cell proliferation (PLK1, PRC1), survival (BIRC5) and metastasis (HMMR). In contrast, inhibiting those genes via MYBL2 depletion suppresses cancer progression, restores tamoxifen and eventually reduces the risk of disease recurrence. All these findings revealed a critical role of MYBL2 in promoting tamoxifen resistance and exacerbating the progression of breast cancer, which may serve as a novel therapeutic target to overcome drug resistance and improve the prognosis of breast cancer patients.

Knockdown of LINC00662 represses AK4 and attenuates radioresistance of oral squamous cell carcinoma.

BACKGROUND: LncRNAs play crucial roles in the development of carcinomas. However, the investigation of LINC00662 in Oral squamous cell carcinoma (OSCC) is still elusive. METHODS: qRT-PCR assay tested the expression levels of LINC00662, hnRNPC and AK4. With exposure to irradiation, CCK-8, colony formation, flow cytometry and western blot experiments, respectively determined the function of LINC00662 in the radiosensitivity of OSCC cells. Then RIP and western blot assays affirmed the interaction between hnRNPC protein and LINC00662 or AK4. Finally, rescue assays validated the regulation mechanism of LINC00662 in the radioresistance of OSCC. RESULTS: In the present report, LINC00662 was overexpressed in OSCC and its silencing could alleviate radioresistance of OSCC. Furthermore, the interaction between hnRNPC protein and LINC00662 or AK4 was uncovered. Besides, LINC00662 regulated AK4 mRNA stability through binding to hnRNPC protein. To sum up, LINC00662 modulated the radiosensitivity of OSCC cells via hnRNPC-modulated AK4. CONCLUSION: The molecular mechanism of the LINC00662/hnRNPC/AK4 axis was elucidated in OSCC, which exhibited a promising therapeutic direction for patients with OSCC.

Knockdown of LINC00511 promotes radiosensitivity of thyroid carcinoma cells via suppressing JAK2/STAT3 signaling pathway.

Thyroid carcinoma is the most widespread malignancy in endocrine system with the increasing incidence. Despite of the advanced approaches to the management of thyroid carcinoma, the therapeutic effects remain unpleasant largely due to the radiosensitivity of thyroid carcinoma cells. LncRNAs play important part in the tumorigenesis and development, especially in the radiosensitivity of tumor cells. However, their roles in thyroid carcinoma still needed to be explored deeply. The purpose of our research is to inspect the possible biological role and regulation mechanism of LINC00511 desirable for therapies of thyroid carcinoma patients. In the present study, LINC00511 was significantly overexpressed in thyroid carcinoma and its silencing boosted radiosensitivity of thyroid carcinoma cells. Then we unveiled that LINC00511 regulated JAK2/STAT3 signaling pathway which was resistant to radiation treatment. Besides, TAF1 modulated JAK2 at transcriptional level. Moreover, LINC00511 bound to TAF1 and further promoted JAK2 expression. In conclusion, rescue experiments verified that the radiosensitivity of thyroid carcinoma cells was attributed to LINC00511/TAF1/JAK2/STAT3 axis. The current paper investigated the underlying mechanism of LINC00511 and set a new therapeutic direction for the therapy of thyroid carcinoma.