Immunoglobulin like transcript (ILT) 4, a negative regulator of immune response in allograft rejection, autoimmunity and infectious diseases, has recently been determined to serve important roles in tumor development. In the present study, the co expression of ILT4 and human leukocyte antigen G (HLA-G) in tissues of human primary colorectal cancer (CRC) was revealed, and its association with older age, advanced stage, regional lymph node involvement and poor overall survival time was identified. In CRC cell lines, ILT4 and HLA-G co expression and their autocrine regulation was demonstrated. ILT4 interference affected HLA-G expression and regulated the cell proliferation, invasion and migration of CRC. HLA-G fusion protein treatment also increased ILT4 expression in a dose dependent manner, thereby activating protein kinase B (AKT) and extracellular signal regulated kinase (ERK) signaling, and facilitating the proliferation, migration and invasion of CRC cells. Additionally, the AKT and ERK activation, and CRC cell malignant characteristics induced by HLA-G may be suppressed by blocking ILT4. The present results indicated that the interaction of ILT4 and its ligand HLA-G promotes CRC progression through AKT and ERK signal activation, providing a novel strategy of blocking ILT4/HLA-G for the treatment of CRC.

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The activation energies of the grain-boundary and different polarizations are researched to reveal the effect of the segregation structure on the performance.

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Mutations in Gap Junction Beta 2 (GJB2) have been reported to be a major cause of non-syndromic hearing loss in many populations worldwide. The spectrums and frequencies of GJB2 variants vary substantially among different ethnic groups, and the genotypes among these populations remain poorly understood. In the present study, we carried out a systematic and extended mutational screening of GJB2 gene in 1067 Han Chinese subjects with non-syndromic hearing loss, and the resultant GJB2 variants were evaluated by phylogenetic, structural and bioinformatic analysis. A total of 25 (23 known and 2 novel) GJB2 variants were identified, including 6 frameshift mutations, 1 nonsense mutation, 16 missense mutations and 2 silent mutations. In this cohort, c.235delC is the most frequently observed pathogenic mutation. The phylogenetic, structural and bioinformatic analysis showed that 2 novel variants c.127G>T (p.V43L), c.293G>C (p.R98P) and 2 known variants c. 107T>C (p.L36P) and c.187G>T (p.V63L) are localized at highly conserved amino acids. In addition, these 4 mutations are absent in 203 healthy individuals, therefore, they are probably the most likely candidate pathogenic mutations. In addition, 66 (24 novel and 42 known) genotypes were identified, including 6 homozygotes, 20 compound heterozygotes, 18 single heterozygotes, 21 genotypes harboring only polymorphism(s) and the wild type genotype. Among these, 153 (14.34%) subjects were homozygous for pathogenic mutations, 63 (5.91%) were compound heterozygotes, and 157 (14.71%) carried single heterozygous mutation. Furthermore, 65.28% (141/216) of these cases with two pathogenic mutations exhibited profound hearing loss. These data suggested that mutations in GJB2 gene are responsible for approximately 34.96% of non-syndromic hearing loss in Han Chinese population from Zhejiang Province in eastern China. In addition, our results also strongly supported the idea that other factors such as alterations in regulatory regions, additional genes, and environmental factors may contribute to the clinical manifestation of deafness.