Melanoma patients frequently have elevated serum levels of interleukin-6 (IL-6), which is correlated with a poor prognosis. IL-6 activates STAT3 phosphorylation, inducing the transcription of genes that regulate tumor cell proliferation and antiapoptosis. In addition, recent evidence suggests that IL-6 induces the epithelial-to-mesenchymal transition and enhances the invasiveness of tumor cells of epithelial origin. However, it is unknown whether IL-6 affects mesenchymal tumor cells. In this study, we examined the effects of IL-6 on melanoma cells and found that IL-6 can enhance their metastatic potential by regulating the expression of Twist and N-cadherin. First, we confirmed that human melanoma tissues express IL-6 (especially at the lesion site), the IL-6 receptor, N-cadherin, and nuclear Twist. Next, we found that IL-6 induces STAT3 phosphorylation in WM-266-4 human melanoma cells, resulting in transient upregulation of Twist, which is a key regulator of metastasis. Importantly, the expression of N-cadherin, a protein downstream of Twist, was also increased on the cell surface after treatment with IL-6. These cells showed enhanced invasiveness, assessed using an invasion assay, and formed more metastatic nodules in the lungs of NOD-SCID mice after an intravenous injection. Importantly, melanoma cells with knocked-down N-cadherin formed less lung nodules compared with control in the NOD-SCID mouse model. Our data suggest that increased serum IL-6 in cancer patients could increase the invasiveness of melanoma cells and accelerate metastasis. Blocking IL-6 in the melanoma microenvironment may therefore inhibit disease progression.

Score-based generative models are a novel class of generative models that have shown state-of-the-art sample quality in image synthesis, surpassing the performance of GANs in multiple tasks. Here we present ProteinSGM, a score-based generative model that produces realistic de novo proteins and can inpaint plausible backbones and functional sites into structures of predefined length. With unconditional generation, we show that score-based generative models can generate native-like protein structures, surpassing the performance of previously reported generative models. We apply conditional generation to de novo protein design by formulating it as an image inpainting problem, allowing precise and modular design of protein structure.

Score-based generative models are a novel class of generative models that have shown state-of-the-art sample quality in image synthesis, surpassing the performance of GANs in multiple tasks. Here we present ProteinSGM, a score-based generative model that produces realistic de novo proteins and can inpaint plausible backbones and functional sites into structures of predefined length. With unconditional generation, we show that score-based generative models can generate native-like protein structures, surpassing the performance of previously reported generative models. We apply conditional generation to de novo protein design by formulating it as an image inpainting problem, allowing precise and modular design of protein structure.

The worldwide transition from analog to digital broadcasting has now been completed, and the need to study next-generation standards for ultra-high-definition TV (UHDTV) broadcasting, as well as broadcasting and communication convergence systems is rapidly growing. In particular, high-resolution mobile broadcasting services are needed to satisfy recent consumer demands. Therefore, the development of highly efficient convergence broadcasting systems that provide fixed/mobile broadcasting through a single channel is needed. In this paper, a service scenario and the requirements for providing 4 K UHD and high-definition (HD) convergence broadcasting services through a terrestrial single channel are analyzed by employing the latest transmission and video codec technologies. Optimized transmission parameters for 6-and 8-MHz terrestrial bandwidths are drawn, and receiving performances are measured under additive white Gaussian noise (AWGN) and time-varying typical urban (TU)-6 channel to find the threshold of visibility (TOV). From the results, reliable receiving of HD layer data can be achieved at a 6-MHz bandwidth when the maximum receiver velocity is 140 km/h and no higher due to the limit of bandwidth. When the bandwidth is extended to 8 MHz, reliable receiving of both 4 K UHD and HD layer data can be achieved under a very fast fading multipath channel.

BackgroundMelanocytes are present in both basal epidermis and hair follicles. Melanocyte stem cells have been found in hair follicle bulge. During embryogenesis, the outer cells of the bulge differentiate into the sebaceous gland (SG) and proliferate.ObjectiveTo identify and determine the distribution and morphological characteristics of melanocytes in human SGs.MethodsA total of 171 biopsy specimens of face and scalp were studied. Of these specimens, 103 samples contained SGs. We conducted a retrospective review of slides stained with H&E, F-M, anti-S100, anti-c-kit, anti-HMB-45, anti-CD1a, anti-MITF, and anti-tyrosinase. The presence and distribution of melanocytes in human SGs was also evaluated by electron microscopy. In addition, melanocytes were isolated from SGs for primary culture.ResultsS-100-positive cells were observed mainly at the periphery of SGs in 34 of 54 specimens. We did not find F-M-positive and HMB-45-positive cells in SGs. CD1a-positve cells were identified in two specimens. We also found c-kit-, MITF-, and tyrosinase-positive cells in SGs. Electron micrograph showed the presence of melanocytes in the suprabasal portion of SGs. These melanocytes showed fewer melanin-containing granules than the melanocytes of basal epidermis. However, the individually distributed melanosomes in suprabasal melanocytes were larger than those in epidermal melanocytes. Primary culture of melanocytes derived from SGs showed morphologically homogeneous, slender cell bodies with few dendrites.ConclusionOur study confirms the presence of non-melanogenic melanocytes and Langerhans cells in human SGs. In addition, the characteristics of the melanocytes in SGs were found to be different from those of the epidermal melanocytes.