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Background We have been investigating the molecular mechanisms of cisplatin-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC). Based on our previous findings, the present study investigates how the Mre11, Rad50, and NBS1 (MRN) DNA repair complex interacts at the molecular level with the programmed cell death ligand 1 (PD-L1) in cisplatin-induced chemoresistance. Methods Human HNSCC cell lines were used to determine the role played by PD-L1 in cisplatin resistance. Initial experiments investigated PD-L1 expression levels in cells exposed to cisplatin and whether PD-L1 interacts directly with the MRN complex. Finally, in vitro studies and in vivo experiments on BALB/c nu/nu mice were performed to determine whether interference of PD-L1 or NBS1 synthesis modulated cisplatin resistance. Results Exposure to cisplatin resulted in PD-L1 being upregulated in the chemoresistant but not the chemosensitive cell line. Subsequent co-immunoprecipitation studies demonstrated that PD-L1 associates with NBS1. In addition, we found that the knockdown of either PD-L1 or NBS1 re-sensitised the chemoresistant cell line to cisplatin. Finally, but perhaps most importantly, synergy was observed when both PD-L1 and NBS1 were knocked down making the formerly chemoresistant strain highly cisplatin sensitive. Conclusions PD-L1 plays a pivotal role in cisplatin resistance in chemoresistant human HNSCC cell lines.

The delivery of therapies to the cochlea is notoriously challenging. It is an organ protected by a number of barriers that need to be overcome in the drug delivery process. Additionally, there are multiple sites of possible damage within the cochlea. Despite the many potential sites of damage, acquired otologic insults preferentially damage a single location. While progress has been made in techniques for inner ear drug delivery, the current techniques remain non-specific and our ability to deliver therapies in a cell-specific manner are limited. Fortunately, there are proteins specific to various cell-types within the cochlea (e.g., hair cells, spiral ganglion cells, stria vascularis) that function as biomarkers of site-specific damage. These protein biomarkers have potential to serve as targets for cell-specific inner ear drug delivery. In this manuscript, we review the concept of biomarkers and targeted- inner ear drug delivery and the well-characterized protein biomarkers within each of the locations of interest within the cochlea. Our review will focus on targeted drug delivery in the setting of acquired otologic insults (e.g., ototoxicity, noise-induce hearing loss). The goal is not to discuss therapies to treat acquired otologic insults, rather, to establish potential concepts of how to deliver therapies in a targeted, cell-specific manner. Based on our review, it is clear that future of inner ear drug delivery is a discipline filled with potential that will require collaborative efforts among clinicians and scientists to optimize treatment of otologic insults.

Once the Internet of Things was proposed, it has received great attention from all walks of life and has become one of the top ten technologies that change the world. Therefore, more and more people are engaged in the research of the Internet of Things, after the unremitting efforts of all seniors. Now the Internet of Things has been applied to every aspect of our lives. However, in the application process of the Internet of Things, the protection of personal privacy will undoubtedly be involved. If this problem is not effectively resolved, it will become a major obstacle to the development of the Internet of Things. At present, the research of fully homomorphic technology has attracted great attention from the cryptography community. You can directly calculate the encrypted text encryption to obtain the output and decrypt the output. The result is the same as the output of the unencrypted plain text. This article first comprehensively describes the solution to the privacy protection problem in the existing Internet of Things, and then proposes to apply the fully homomorphic technology to the Internet of Things to make the services provided by the network more secure. Through the analysis of the basic composition and architecture of the existing Internet of Things system, a privacy protection interaction model for the Internet of Things is established, which uses a completely homomorphic technology. On this basis, the algorithm for implementing simple homomorphic encryption is improved, and general homomorphic encryption theory is proposed for some security issues. After using this method to encrypt privacy, the success rate of cracking dropped by 24%.

Hydroponic experiments were conducted to investigate the effects of different concentrations of sodium selenate (Na2SeO4) and sodium selenite (Na2SeO3) on durum wheat seed germination and seedling growth under salt stress. The treatments used were 0 and 50 mM NaCl solutions, each supplemented with Na2SeO4 or Na2SeO3 at 0, 0.1, 1, 2, 4, 8, or 10 μM. Salt alone significantly inhibited seed germination and reduced seedling growth. Addition of low concentrations (0.1–4 μM) of Na2SeO4 or Na2SeO3 mitigated the adverse effects of salt stress on seed germination, biomass accumulation, and other physiological attributes. Among them, 1 μM Na2SeO4 was most effective at restoring seed germination rate, germination energy, and germination index, significantly increasing these parameters by about 12.35, 24.17, and 11.42%, respectively, compared to salt-stress conditions. Adding low concentrations of Na2SeO4 or Na2SeO3 to the salt solution also had positive effects on chlorophyll fluorescence indices, decreased the concentrations of free proline and malondialdehyde, as well as electrolyte leakage, and increased catalase, superoxide dismutase, and peroxidase activities in roots and shoots. However, high concentrations (8–10 μM) of Na2SeO4 or Na2SeO3 disrupted seed germination and seedling growth, with damage caused by Na2SeO3 being more severe than that by Na2SeO4. It is thus clear that exogenous selenium can improve the adaptability of processing wheat to salt stress and maintain higher photosynthetic rate by decreasing the accumulation of reactive oxygen species and alleviating the degree of membrane lipid peroxidation. Na2SeO4 was more effective than Na2SeO3 at all given concentrations.

Social media can be a double-edged sword for society, either as a convenient channel exchanging ideas or as an unexpected conduit circulating fake news through a large population. While existing studies of fake news focus on theoretical modeling of propagation or identification methods based on machine learning, it is important to understand the realistic propagation mechanisms between theoretical models and black-box methods. Here we track large databases of fake news and real news in both, Weibo in China and Twitter in Japan from different cultures, which include their traces of re-postings. We find in both online social networks that fake news spreads distinctively from real news even at early stages of propagation, e.g. five hours after the first re-postings. Our finding demonstrates collective structural signals that help to understand the different propagation evolution of fake news and real news. Different from earlier studies, identifying the topological properties of the information propagation at early stages may offer novel features for early detection of fake news in social media.

Cisplatin-induced hearing loss is experienced by a high percentage of patients with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano-construct capable of sequestering extracellular cisplatin was developed to combat this problem. The nano-construct consisted of superparamagnetic iron oxide nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The glutathione-micelles were analyzed at the cellular level and in an organotypic study for safety evaluation. All utilized methods indicated that the micelles do not cause cellular toxicity or organ damage. The micelles’ ability to reduce cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin was pre-treated with the novel nano-construct before being added to growing cells. When compared to cells that were exposed to untreated cisplatin, cells in the pre-treated cisplatin group showed a significant increase in cell viability. This clearly demonstrates that the construct is able to protect the cells from cisplatin cytotoxicity and makes it highly likely that the novel nano-construct will be able to play a role in the protection of the inner ear from cisplatin-induced ototoxicity.

Background The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR. Methods A recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo. Results Rad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo. Conclusion Our findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2190-8) contains supplementary material, which is available to authorized users.

In weighted networks, redistribution of link weights can effectively change the properties of networks, even though the corresponding binary topology remains unchanged. In this paper, the effects of weight randomization on synchronization of coupled chaotic maps is investigated on regular weighted networks. The results reveal that synchronizability is enhanced by redistributing of link weights, i.e. coupled maps reach complete synchronization with lower cost. Furthermore, we show numerically that the heterogeneity of link weights could improve the complete synchronization on regular weighted networks.

Transplantation of cultured adult olfactory ensheathing cells has been shown to induce anatomical and functional repair of lesions of the adult rat spinal cord and spinal roots. Histological analysis of olfactory ensheathing cells, both in their normal location in the olfactory nerves and also after transplantation into spinal cord lesions, shows that they provide channels for the growth of regenerating nerve fibres. These channels have an outer, basal lamina-lined surface apposed by fibroblasts, and an inner, naked surface in contact with the nerve fibres. A crucial property of olfactory ensheathing cells, in which they differ from Schwann cells, is their superior ability to interact with astrocytes. When confronted with olfactory ensheathing cells the superficial astrocytic processes, which form the glial scar after lesions, change their configuration so that their outer pial surfaces are reflected in continuity with the outer surfaces of the olfactory ensheathing cells. The effect is to open a door into the central nervous system. We propose that this formation of a bridging pathway may be the crucial event by which transplanted olfactory ensheathing cells allow the innate growth capacity of severed adult axons to be translated into regeneration across a lesion so that functionally valuable connections can be established.