Recent advances and current issues in single-cell sequencing of tumors

AbstractIntratumoral heterogeneity is a recently recognized but important feature of cancer that underlies the various biocharacteristics of cancer tissues. The advent of next-generation sequencing technologies has facilitated large scale capture of genomic data, while the recent development of single-cell sequencing has allowed for more in-depth studies into the complex molecular mechanisms of intratumoral heterogeneity. In this review, the recent advances and current challenges in single-cell sequencing methodologies are discussed, highlighting the potential power of these data to provide insights into oncological processes, from tumorigenesis through progression to metastasis and therapy resistance

Information filtering based on transferring similarity

In this Brief Report, we propose a new index of user similarity, namely the transferring similarity, which involves all high-order similarities between users. Accordingly, we design a modified collaborative filtering algorithm, which provides remarkably higher accurate predictions than the standard collaborative filtering. More interestingly, we find that the algorithmic performance will approach its optimal value when the parameter, contained in the definition of transferring similarity, gets close to its critical value, before which the series expansion of transferring similarity is convergent and after which it is divergent. Our study is complementary to the one reported in [E. A. Leicht, P. Holme, and M. E. J. Newman, Phys. Rev. E {\bf 73} 026120 (2006)], and is relevant to the missing link prediction problem.Comment: 4 pages, 4 figure

Insufficient Radiofrequency Ablation Promotes Angiogenesis of Residual Hepatocellular Carcinoma Via HIF-1α/VEGFA

Background: The mechanism of rapid growth of the residual tumor after radiofrequency (RF) ablation is poorly understood. In this study, we investigated the effect of hyperthermia on HepG2 cells and generated a subline with enhanced viability and dys-regulated angiogenesis in vivo, which was used as a model to further determine the molecular mechanism of the rapid growth of residual HCC after RF ablation. Methodology/Principal Findings: Heat treatment was used to establish sublines of HepG2 cells. A subline (HepG2 k) with a relatively higher viability and significant heat tolerance was selected. The cellular protein levels of VEGFA, HIF-1α and p-Akt, VEGFA mRNA and secreted VEGFA were measured, and all of these were up-regulated in this subline compared to parental HepG2 cells. HIF-1α inhibitor YC-1 and VEGFA siRNA inhibited the high viability of the subline. The conditioned media from the subline exerted stronger pro-angiogenic effects. Bevacizumab, VEGFA siRNA and YC-1 inhibited proangiogenic effects of the conditioned media of HepG2 k cells and abolished the difference between parental HepG2 cells and HepG2 k cells. For in vivo studies, a nude mouse model was used, and the efficacy of bavacizumab was determined. HepG2 k tumor had stronger pro-angiogenic effects than parental HepG2 tumor. Bevacizumab could inhibit the tumor growth and angiogenesis, and also eliminate the difference in tumor growth and angiogenesis between parental HepG2 tumor and HepG2 k tumor in vivo. Conclusions/Significance: The angiogenesis induced by HIF1α/VEGFA produced by altered cells after hyperthermia treatment may play an important role in the rapid growth of residual HCC after RF ablation. Bevacizumab may be a good candidate drug for preventing and treating the process

Immune Responses Following Mouse Peripheral Nerve Xenotransplantation in Rats

Xenotransplantation offers a potentially unlimited source for tissues and organs for transplantation, but the strong xenoimmune responses pose a major obstacle to its application in the clinic. In this study, we investigate the rejection of mouse peripheral nerve xenografts in rats. Severe intragraft mononuclear cell infiltration, graft distension, and necrosis were detected in the recipients as early as 2 weeks after mouse nerve xenotransplantation. The number of axons in xenografts reduced progressively and became almost undetectable at week 8. However, mouse nerve xenotransplantation only led to a transient and moderate increase in the production of Th1 cytokines, including IL-2, IFN-γ, and TNF-α. The data implicate that cellular immune responses play a critical role in nerve xenograft rejection but that further identification of the major effector cells mediating the rejection is required for developing effective means to prevent peripheral nerve xenograft rejection

New Insights on AES-like SPN Ciphers

It has been proved in Eurocrypt 2016 that if the details of the S-boxes are not exploited, an impossible differential and a zero-correlation hull can extend over at most 4 rounds of the AES. This paper concentrates on distinguishing attacks on AES-like SPN ciphers by investigating the details of both the S-boxes and the MDS matrices and illustrates some new insights on the security of these schemes. Firstly, we construct several types of $5$-round zero-correlation linear hulls for AES-like ciphers that adopt identical S-boxes to construct the round function and that have two identical elements in a column of the inverse of their MDS matrices. We then use these linear hulls to construct 5-round integrals provided that the difference of two sub-key bytes is known. Furthermore, we prove that we can always distinguish 5 rounds of such ciphers from random permutations even when the difference of the sub-keys is unknown. Secondly, the constraints for the S-boxes and special property of the MDS matrices can be removed if the cipher is used as a building block of the Miyaguchi-Preneel hash function. As an example, we construct two types of 5-round distinguishers for the hash function Whirlpool. Finally, we show that, in the chosen-ciphertext mode, there exist some nontrivial distinguishers for 5-round AES. To the best of our knowledge, this is the longest distinguishing attack for the round-reduced AES in the secret-key setting. Since the 5-round distinguisher for the AES can only be constructed in the chosen-ciphertext mode, the security margin for the round-reduced AES under the chosen-plaintext attack may be different from that under the chosen-ciphertext attack