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Biomedical subjects

Lei Jiao

Publications and source records attributed to Lei Jiao.

10 recordsLinked to original sources

Nitrene equivalent mediated metal-free ring expansions of alkylidenecyclopropanes and an alkylidenecyclobutane.

The ring expansion of small-ring compounds provides a powerful method for the construction of various cyclic compounds. Herein, nitrene equivalent mediated metal-free ring expansions of alkylidenecyclopropanes (ACPs) and an alkylidenecyclobutane (ACB) were described. In this synthesis, a series of aryl-substituted cyclobutylidene and cyclopentylidene hydrazine derivatives were obtained under mild conditions in moderate to good yields. [reaction: see text]

Journal Article↗

Adoptive transfer of CD8alpha+ dendritic cells (DC) isolated from mice infected with Chlamydia muridarum are more potent in inducing protective immunity than CD8alpha- DC.

Chlamydial infections are serious public health concerns worldwide. In this study, we examined the role of dendritic cell (DC) subsets in inducing protective immunity against chlamydial infection using an adoptive transfer approach. We found that CD11c+CD8alpha+ (double-positive, DP) DC, compared with CD11c+CD8alpha- (single-positive, SP) DC isolated from infected mice, are more potent inducers of protective immunity. Specifically, mice pretreated with DPDC from infected mice, upon infection with Chlamydia trachomatis mouse pneumonitis (MoPn), experienced significantly less severe body weight loss and in vivo chlamydial growth. Analysis of MoPn-driven cytokine production by immune cells revealed that mice that were treated with DPDC produced significantly higher levels of Th1 (TNF-alpha, IFN-gamma, and IL-12) but lower levels of Th2 (IL-4, IL-5, and IL-13)-related cytokines than the recipients of SPDC following infection challenge. Moreover, DPDC-treated mice displayed significantly higher levels of MoPn-specific IgG2a production and delayed-type hypersensitivity responses compared with SPDC-treated mice. Furthermore, DPDC isolated from infected mice produced higher amounts of IL-12 and IL-10 in vitro in comparison with SPDC. These data indicate that CD8alpha+ DC have a significantly higher capacity in inducing protective immunity compared with CD8alpha- DC, demonstrating the crucial role of DC1-like cells in eliciting protection against C. trachomatis infection.

Adoptive Transfer↗

Do reaction conditions affect the stereoselectivity in the Staudinger reaction?

The stereochemistry is one of the critical issues in the Staudinger reaction. We have proposed the origin of the stereoselectivity recently. The effects of solvents, additives, and pathways of ketene generation on the stereoselectivity were investigated by using a clean Staudinger reaction, which is a sensitive reaction system to the stereoselectivity. The results indicate that the additives, usually existed and generated in the Staudinger reaction, and the pathways of the ketene generation do not generally affect the stereoselectivity. The solvent affects the stereoselectivity. The polar solvent is favorable to the formation of trans-beta-lactams. The addition orders of the reagents affect the stereoselectivity in the Staudinger reaction between acyl chlorides and imines. The addition of a tertiary amine into a solution of the acyl chloride and the imine generally decreases the stereoselectivity, which is affected by the interval between additions of the acyl chloride and the tertiary amine, and the imine substituents. Our current results provide further understanding on the stereochemistry of the Staudinger reaction between acyl chlorides and imines and on the factors affecting the stereochemistry and also provide a method to prepare beta-lactams with the desired relative configuration via rationally tuning the stereoselectivity-controlling factors in the Staudinger reaction.

Amines↗

Origin of the relative stereoselectivity of the beta-lactam formation in the Staudinger reaction.

The relative (cis, trans) stereoselectivity of the beta-lactam formation is one of the critical issues in the Staudinger reaction. Although many attempts have been made to explain and to predict the stereochemical outcomes, the origin of the stereoselectivity remains obscure. We are proposing a model that explains the relative stereoselectivity based on a kinetic analysis of the cis/trans ratios of reaction products. The results were derived from detailed Hammett analyses. Cyclic imines were employed to investigate the electronic effect of the ketene substituents, and it was found that the stereoselectivity could not be simply attributed to the torquoelectronic model. Based on our results, the origin of the relative stereoselectivity can be described as follows: (1) the stereoselectivity is generated as a result of the competition between the direct ring closure and the isomerization of the imine moiety in the zwitterionic intermediate; (2) the ring closure step is most likely an intramolecular nucleophilic addition of the enolate to the imine moiety, which is obviously affected by the electronic effect of the ketene and imine substituents; (3) electron-donating ketene substituents and electron-withdrawing imine substituents accelerate the direct ring closure, leading to a preference for cis-beta-lactam formation, while electron-withdrawing ketene substituents and electron-donating imine substituents slow the direct ring closure, leading to a preference for trans-beta-lactam formation; and (4) the electronic effect of the substituents on the isomerization is a minor factor in influencing the stereoselectivity.

Ethylenes↗

Chlamydia infection induces ICOS ligand-expressing and IL-10-producing dendritic cells that can inhibit airway inflammation and mucus overproduction elicited by allergen challenge in BALB/c mice.

Our previous study has shown that the adoptive transfer of dendritic cells (DCs) freshly isolated from Chlamydia-infected mice (iIDCs), unlike those from control naive mice (iNDCs), can inhibit systemic and cutaneous eosinophilia induced by OVA exposure. In the present study, we examined the mechanism by which iIDC inhibits allergen-specific Th2 cell differentiation in vitro and in vivo. The study revealed that iIDCs exhibited higher surface expression of CD8alpha and the ICOS ligand (ICOS-L), as well as higher IL-10 and IL-12 production than iNDCs. In vitro DC:CD4(+) T cell coculture experiments showed that iIDCs could inhibit allergen-specific Th2 cell differentiation and that the inhibitory effect could be abolished by the blockage of IL-10 or IL-12 activity. More interestingly, the coblockade of IL-10 and the ICOS-L showed synergistic effect in enhancing allergen-driven Th2 cytokine production. Furthermore, adoptive transfer of iIDCs, but not iNDCs, to OVA sensitized mice significantly inhibited airway eosinophilia and mucus overproduction following intranasal challenge with OVA. Overall, the data demonstrate a critical role played by ICOS-L-expressing and IL-10-producing DCs from Chlamydia-infected mice in the infection-mediated inhibition of allergic responses.

Allergens↗

A versatile method for the synthesis of 3-alkoxycarbonyl beta-lactam derivatives.

[reaction: see text] Ketene-imine cycloaddition reactions (the Staudinger reaction) of ethoxycarbonyl(phenylthio)ketene with various imines and subsequent desulfurization reactions were employed to synthesize 3-ethoxycarbonyl beta-lactam derivatives. The results indicate that the current approach provides a convenient, mild, and versatile method for synthesizing a variety of 3-alkoxycarbonyl trans-beta-lactam derivatives with good to excellent yields and diastereoselectivities.

Alkylation↗

Microwave- and photoirradiation-induced staudinger reactions of cyclic imines and ketenes generated from alpha-diazoketones. A further investigation into the stereochemical process.

Reactions of ketenes generated from alpha-diazoketones with a series of acyclic and cyclic imines were investigated under both microwave and photoirradiation conditions. The results indicate that the zwitterionic azabutadiene-type intermediates yielded from imines and ketenes undergo a conrotatory ring closure exclusively to produce beta-lactams. It is notable that no Woodward-Hoffmann product was found under the ultraviolet irradiation. The photoirradiation-induced Staudinger reaction shows a different stereoselectivity from the electrocyclic reaction of substituted 1,3-butadiene.

Azo Compounds↗

Resistance to chlamydial lung infection is dependent on major histocompatibility complex as well as non-major histocompatibility complex determinants.

Our previous work has shown that C3H/HeN and C57BL/6 mice have differential susceptibility to Chlamydia trachomatis mouse pneumonitis (C. muridarum) lung infection. C3H/HeN (H-2(k)) mice were found to be highly susceptible to C. muridarum infection with higher mortality and more severe morbidity compared to C57BL/6 (H-2(b)) mice. To examine the role of major histocompatibility complex (MHC) genes on host resistance to chlamydial lung infection, we compared MHC congenic mice, B6.H2k [C57BL/6 background, C3H MHC (H-2(k))] and C3H.H2b [C3H/HeN background, C57BL/6 MHC (H-2(b))] and their corresponding wild type C57BL/6 mice and C3H/HeN mice, respectively, in susceptibility to C. muridarum infection. We found that B6.H2k, C3H.H2b and C3H/HeN mice are more susceptible to chlamydial lung infection compared to the wild type C57BL/6 mice by showing more serious body weight loss, higher in vivo chlamydial growth and more severe pathologic changes. Congenic B6.H2k mice showed significantly lower levels of IL-12 and IFN-gamma production compared to C57BL/6 as well as C3H/HeN and C3H.H2b mice. One the other hand, although congenic C3H.H2b mice displayed similar cytokine response to C57BL/6 mice, they were highly susceptible to C. muridarum infection. Overall, the results suggest that protection against chlamydial lung infection is both MHC and non-MHC gene dependent, and that the interaction between MHC and non-MHC elements may contribute to host resistance to chlamydial infection.

Animals↗

Dendritic cells from Chlamydia-infected mice show altered Toll-like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin.

Our previous study has shown that Chlamydia lung infection can inhibit local eosinophilic inflammation induced by allergen sensitization and challenge, which is correlated with altered cytokine production. In the present study, we examined the role played by dendritic cells (DC) in chlamydial infection-mediated modulation of allergic responses. The results showed that DC freshly isolated from Chlamydia-infected mice (iIDC), unlike those from naive control mice (iNDC), could efficiently modulate immune responses to ovalbumin in vitro and in vivo. Co-culture of freshly isolated DC with naive CD4 cells from T cell receptor transgenic mice (DO11.10) showed that iIDC directed Th1-dominant, while iNDC directed Th2-dominant, allergen-specific CD4 T cell responses. Moreover, adoptive transfer of iIDC, but not iNDC, could inhibit systemic and local eosinophilia induced by allergen exposure. The reduction of eosinophilia was associated with a decrease in IL-5 receptor expression on bone marrow cells and the production of IL-5 and IL-13 by T lymphocytes. Analysis of the DC showed that iIDC expressed significantly higher levels of mRNA for Toll-like receptor 9 and produced more IL-12 compared to iNDC. The data demonstrate a critical role played by DC in infection-mediated inhibition of allergic responses.

Animals↗

Novel boundary element method for resolving plate bending problems.

This paper discusses the application of the boundary contour method for resolving plate bending problems. The exploitation of the integrand divergence free property of the plate bending boundary integral equation based on the Kirchhoff hypothesis and a very useful application of Stokes' Theorem are presented to convert surface integrals on boundary elements to the computation of bending potential functions on the discretized boundary points, even for curved surface elements of arbitrary shape. Singularity and treatment of the discontinued corner point are not needed at all. The evaluation of the physics variant at internal points is also shown in this article. Numerical results are presented for some plate bending problems and compared against analytical and previous solutions.

Algorithms↗