Chemoselectivity of the CuAAC/Ring Cleavage/Cyclization Reaction between Enaminones and α-Acylketenimine.

Ketenimines represent an important class of reactive species, useful synthetic intermediates, and synthons. However, in general, ketenimines preferentially undergoes nucleophilic addition reactions with hydroxyl and amino groups, and carbon functional groups remain a less studied subset of such systems. Herein, we develop a straightforward syntheses of pyridin-4(1H)-imines that is achieved by cyclization of a reacting enaminone unit with α-acylketenimine which is generated from the reactions of sulfonyl azides and terminal ynones in situ (CuAAC/Ring cleavage reaction). The cascade process preferentially starts with the nucleophilic α-C of the enaminone unit instead of an amino group, attacking the electron-deficient central carbon of ketenimine, and the chemoselectivity unconventional products pyridin-4(1H)-imines were formed by intramolecular cyclization.

Synthesis of Pyridin-1(2H)-ylacrylates and the Effects of Different Functional Groups on Their Fluorescence.

While fluorescent organic materials have many potential as well as proven applications and so have attracted significant attention, pyridine-olefin conjugates remain a less studied subset of such systems. Herein, therefore, we report on the development of the straightforward syntheses of pyridin-1(2H)-ylacrylates and the outcomes of a study of the effects of substituents on their fluorescent properties. Such compounds were prepared using a simple, metal-free and three-component coupling reaction involving 2-aminopyridines, sulfonyl azides and propiolates. The fluorescent properties of the ensuing products are significantly affected by the positions of substituents on the cyclic framework, with those located in central positions having the greatest impact. Electron-withdrawing groups tend to induce blue shifts while electron-donating ones cause red shifts. This work highlights the capacity that the micro-modification of fluorescent materials provides for fine-tuning their properties such that they may be usefully applied to, for example, the study of luminescent materials.

Rasmussen's encephalitis is characterized by relatively lower production of IFN-ß and activated cytotoxic T cell upon herpes viruses infection.

BACKGROUND: The etiology of Rasmussen's encephalitis (RE), a rare chronic neurological disorder characterized by CD8+ T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is unclear. METHODS: HHVs infection and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+ T cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex flow cytometry. Cell apoptosis was visualized by TUNEL staining. Viral infection, immune response and the severity of unihemispheric atrophy were subjected to correlation analysis. RESULTS: Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+ T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon-ß level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE. CONCLUSIONS: Compared with TBI, both RE and TLE had prevalently HHV infection and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV infection, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future.

HCMV infection and IFITM3 rs12252 are associated with Rasmussen's encephalitis disease progression.

OBJECTIVE: Rasmussen's encephalitis (RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses such as human cytomegalovirus (HCMV) has been hypothesized to be a potential trigger for RE. Interferon-induced transmembrane protein-3 (IFITM3) single-nucleotide polymorphism (SNP) rs12252 is associated with the severity of viral infection disease. This study aimed to address the possibility that HCMV infection and IFITM3 rs12252 might be associated with RE disease progression. METHODS: The expression of HCMV and IFITM3 was detected with immunohistochemical staining, in situ hybridization and immunofluorescence double staining. The genotype of IFITM3 rs12252 was detected using the Sanger sequencing method. A genetic association analysis was carried out for this SNP and HCMV antigen expression. The relationship between this SNP and the clinical characteristics of these patients was further analyzed. In in vitro study, HCMV replication in SH-SY5Y cells with overexpressed IFITM3 variant was detected by immunofluorescence and real-time RT-PCR. RESULTS: Elevated expression of HCMV and IFITM3 was observed in the brain tissue of RE patients. Moreover, the IFITM3 polymorphism rs12252-C was found to associate with HCMV high detection and rapid disease progression in RE patients with the IFITM3 rs12252-CC genotype. In vitro study showed the overexpressed IFITM3 variant was associated with HCMV high infection level. CONCLUSION: These results suggest that the IFITM3 rs12252-C is associated with the disease progression of RE patients via facilitating persistent HCMV infection in brain tissue and provides new insight into understanding the pathogenesis of RE.

Extraction and antioxidant activity of flavonoids of Morus nigra.

Morus nigra has a long history of medicinal use in Chinese medicine, but the study on it is limited, the flavonoids are one of the main biological active substances. In this study, the Morus nigra flavonoids were extracted by ultrasonic and antioxidant activities both in vitro and in vivo were measured. The results showed that hydroxyl radicals clearance rate and superoxide radical anion clearance rate in vitro increased with the concentration of the total flavonoids in the range of 0-1.05 mg/mL and the maximum clearance rate was 80.33% and 87.69%, respectively. After mice were treated with flavonoids, the content of malonaldehyde (MDA) in serum and liver decreased; the activities of superoxide dismutase (SOD) in serum and liver, catalase (CAT) in liver and glutathione peroxidase (GSH-PX) in blood and liver increased; Langhans cells increased in spleen. These results revealed that the Morus nigra flavonoids possessed strong antioxidant activity.

Replication of british rheumatoid arthritis susceptibility Loci in two unrelated chinese population groups.

Previous genome-wide association study by WTCCC identified many susceptibility loci of common autoimmune diseases in British, including rheumatoid arthritis (RA). Because of the genetic heterogeneity of RA, it is necessary to replicate these susceptibility loci in other populations. Here, three SNPs with strong RA association signal in the British were analyzed in Han Chinese, and two SNPs (rs6457617 and rs11761231) were genotyped in the test cohort firstly. The rs6457617 was significantly associated with RA in the test cohort. The individuals bearing the homozygous genotype CC had 0.39-fold risk than these bearing the wild-type genotype TT (P = 0.004, OR 0.39, [95% CI 0.21-0.74]). And the protective effect of allele C was confirmed in another validation cohort with 1514 samples (P genotye CC/TT = 5.9 × 10(-10), OR 0.34, [95% CI 0.24-0.48]). The rs6457617 can be used as a tagSNP of HLA-DQA1∗03 which encoded MHC-II α chain. Since MHC restriction is important for primary T-cells in positive selection and negative selection stages, MHC protein polymorphisms may be implicated in shaping the T-cell repertoire, including the emergence of a T-cell clone involved in the inflammatory arthritis.