Genomic Sequencing and Analysis of Enzootic Nasal Tumor Virus Type 2 Provides Evidence for Recombination within the Prevalent Chinese Strains.

In recent years, the clinical cases of ENTV-2 infection have increased and become prevalent in several provinces of China. In this study, we reported the occurrence of ENTV-2 in one goat farm in Chongqing, southwest China. The complete genome of an emerged ENTV-2 isolate (designated as CQ2) was sequenced with 7468 bp in length. Phylogenetic analysis revealed that ENTV-2 consisted of two main lineages. Lineage 1 was composed of Chinese strains and could be subdivided into five sublineages. CQ2 and the other six recent isolates from China were clustered in sublineage 1.5; however, CQ2 was significantly different from the other six isolates. Furthermore, recombination analysis suggested that CQ2 might be a recombinant variant derived from sublineage 1.5 and sublineage 1.2 strains, with the recombination region in areas of pro and pol genes. In conclusion, we sequenced and analyzed the complete genome of a potential ENTV-2 recombinant, which may contribute to our understanding of the genetic variation and evolution of ENTV-2 in China.

The road to evolution of ProTx2: how to be a subtype-specific inhibition of human Nav1.7.

The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development.

Nickel-Catalyzed Enantioselective Synthesis of Dienyl Sulfoxide.

Sulfoxides are widely used in the pharmaceutical industry and as ligands in asymmetric catalysis. However, the efficient asymmetric synthesis of this structural motif remains limited. In this study, we disclosed a Ni-catalyzed enantioconvergent reaction that utilizes both racemic allenyl carbonates and ß-sulfinyl esters. Our method employs cheap and more sustainable Ni(II) as a precatalyst and successfully overcomes the challenging poisoning effect and instability of sulfenate generated in situ. This enables the synthesis of a series of dienyl sulfoxides with enantioselectivity of up to 98 % ee. The product exhibits tremendous potential in various applications, including diastereoselective Diels-Alder reactions, coordination with transition metals, and incorporation into medicinal compounds, among others. Using a combination of experimental and computational methods, we have uncovered an interesting associated outersphere mechanism that contrasts with conventional mechanisms commonly observed in asymmetric transition metal catalysis.

[Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache].

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

Comparing fixed-array and functionally-defined channel of interest approaches to infant functional near-infrared spectroscopy data.

Functional near-infrared spectroscopy (fNIRS) is increasingly used to study brain function in infants, but the development and standardization of analysis techniques for use with infant fNIRS data have not paced other technical advances. Here we quantify and compare the effects of different methods of analysis of infant fNIRS data on two independent fNIRS datasets involving 6-9-month-old infants and a third simulated infant fNIRS dataset. With each, we contrast results from a traditional, fixed-array analysis with several functional channel of interest (fCOI) analysis approaches. In addition, we tested the effects of varying the number and anatomical location of potential data channels to be included in the fCOI definition. Over three studies we find that fCOI approaches are more sensitive than fixed-array analyses, especially when channels of interests were defined within-subjects. Applying anatomical restriction and/or including multiple channels in the fCOI definition does not decrease and in some cases increases sensitivity of fCOI methods. Based on these results, we recommend that researchers consider employing fCOI approaches to the analysis of infant fNIRS data and provide some guidelines for choosing between particular fCOI approaches and settings for the study of infant brain function and development.

Naringin Promotes Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells via Wnt/ß-Catenin.

Purpose: This investigation intended to unravel the effect and mechanism of naringin on the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs). Methods: hDPSCs were induced to differentiate, and the degree of cell differentiation was observed by alizarin red staining, Oil Red O staining, and Alcian blue staining. hDPSCs were treated with 0, 20, 40, and 80 µmol/L naringin for 48 h, respectively. The proliferation rate and chemotaxis of the cells were measured by MTT and transwell assay, alkaline phosphatase (ALP) activity and osteogenic differentiation degree by ALP staining and alizarin red staining, and gene expression of osteogenic markers by qRT-PCR. Additionally, western blot was performed to test the levels of Wnt/ß-catenin signaling-related proteins in hDPSCs. Results: The isolated hDPSCs with spindle-shaped morphology had good differentiation capability. Further experiments confirmed naringin-caused increases in the proliferation rate and migration ability of hDPSCs. In addition, compared with the control group, naringin-treated cells had strong ALP activity and ossification levels and higher expression of Runx2, OPN, DSPP, and DMP1. The western blot results showed that naringin significantly activated Wnt/ß-catenin signaling in hDPSCs. Conclusion: Taken together, naringin enhances the proliferation, migration, and osteogenesis of hDPSCs through stimulating Wnt/ß-catenin signaling pathway.

[Study of molecular mechanism for a blood sample with A3 phenotype].

OBJECTIVE To explore the molecular mechanism for a blood sample with mixed-field hemagglutination upon determination of ABO blood group. METHODS Serological techniques were employed to identify the erythrocyte phenotype. The A and B antigens were detected by flow cytometry. The preliminary genotype of ABO gene was assayed with sequence-specific primer-polymerase chain reaction (PCR-SSP). Exons 6 and 7 of the ABO gene were amplified with PCR and analyzed by direct sequencing. Haplotypes of the ABO gene were analyzed by cloning sequencing as well. RESULTS The serological reaction pattern has supported an O phenotype when all the tubes were centrifuged for the first time. However, a mixed-field hemagglutination of red blood cells (RBCs) with anti-A antibodies was present after the tube was centrifuged five times later. A antigens were detected on the surface of partial red blood cells of the sample by flow cytometry. PCR- SSP results have shown that the preliminary ABO genotype was A/O. Analysis of the fragments of exons 6 and 7 of the ABO gene has indicated that heterozygosis lied as follows: 261G/A, 425T/T, 467C/T, 646A/T, 681A/G, 745C/T, 771C/T, 829A/G, conjecturing the genotype to be A307/O02, which was confirmed by haplotype sequence analysis. Compared with A101 allele, A307 allele has two missense mutations, 467C> T and 745C> T, which have resulted in substitutions Pro156Leu and Arg249Trp in the A glycosyltransferase polypeptide chain. CONCLUSION A variant allele (A307) has been identified for the first time in mainland China, which is responsible for the formation of A3 phenotype.

Facile surface immobilization of ATRP initiators on colloidal polymers for grafting brushes and application to colloidal crystals.

Bromo-initiators for atom transfer radical polymerization (ATRP) were successfully immobilized on the surfaces of cross-linked poly(methyl methacrylate) (PMMA) spheres by soap-free emulsion polymerization using CBr(4) as the chain transfer agent. Subsequent surface-initiated ATRP (SI-ATRP) afforded a layer of PMMA brushes covalently attached to the sphere surfaces. Colloidal crystal films of these monodisperse spheres were then studied to identify the relationship between variation in particle diameter and the optical properties. The particle diameters were controlled by varying the feed monomer proportions in soap-free emulsion polymerization and the thickness of the grafted brush layer. It was found that the particle diameter could successfully be controlled to obtain crystal films that produce a variety of brilliant colors in the visible region. The results of this study can provide useful information for facile preparation of surface-immobilized ATRP initiators on colloidal polymers and can be employed for grafting polymer brushes.