A sufficient and necessary condition of existence of blow-up radial solutions for a k-Hessian equation with a nonlinear operator

In this paper, we establish the results of nonexistence and existence of blow-up radial solutions for a k-Hessian equation with a nonlinear operator. Under some suitable growth conditions for nonlinearity, the result of nonexistence of blow-up solutions is established, a sufficient and necessary condition on existence of blow-up solutions is given, and some further results are obtained.&nbsp

Solvability and asymptotic properties for an elliptic geophysical fluid flows model in a planar exterior domain

In this paper, we study the solvability and asymptotic properties of a recently derived gyre model of nonlinear elliptic Schrödinger equation arising from the geophysical fluid flows. The existence theorems and the asymptotic properties for radial positive solutions are established due to space theory and analytical techniques, some special cases and specific examples are also given to describe the applicability of model in gyres of geophysical fluid flows

Existence and asymptotic analysis of positive solutions for a singular fractional differential equation with nonlocal boundary conditions

In this paper, we focus on the existence and asymptotic analysis of positive solutions for a class of singular fractional differential equations subject to nonlocal boundary conditions. By constructing suitable upper and lower solutions and employing Schauder’s fixed point theorem, the conditions for the existence of positive solutions are established and the asymptotic analysis for the obtained solution is carried out. In our work, the nonlinear function involved in the equation not only contains fractional derivatives of unknown functions but also has a stronger singularity at some points of the time and space variables

Activated NK cells kill hepatic stellate cells via p38/PI3K signaling in a TRAIL-involved degranulation manner

NK cells are important in regulating hepatic fibrosis via their cytotoxic killing of hepatic stellate cells (HSCs). NK cells are activated by both cytokines such as IL-12 and IL-18, and innate immune stimuli such as ligation of TLRs. The secretion of IL-18 depends upon activation of the inflammasome, whereas TLRs are stimulated by microbial products. In the case of NK cells, IL-18 acts synergistically with stimulation of TLR3 to cause cell activation and cytotoxic function. In the present study, we activated NK cells to kill HSCs via IL-18 and TLR3 ligand stimulation, and dissected the signaling pathways or molecules critical for such activation or killing. We find that such activation depends on signaling via the p38/PI3K/AKT pathway, and that the activatedNK cells mediate HSC death in a TRAIL-involved mechanism. As liver fibrosis is a major global health problem with no good solution, these results emphasize that the p38/PI3K/AKT pathway in NK cells may be a novel drug target to promote fibrosis regression

Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection

Background and aims HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. Methods Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting. Culture and coculture of monocytes and NK cells were used to determine NK cell activation, using intracellular cytokines staining. Results In chronic HBV infection, monocytes express higher levels of PD-L1, HLA-E, interleukin (IL)-10 and TGF-β, and NK cells express higher levels of PD-1, CD94 and IL-10, compared with healthy individuals. HBV employs hepatitis B surface antigen (HBsAg) to induce suppressive monocytes with HLA-E, PD-L1, IL-10 and TGF-β expression via the MyD88/NFκ B signalling pathway. HBV-treated monocytes induce NK cells to produce IL-10, via PD-L1 and HLA-E signals. Such NK cells inhibit autologous T cell activation. Conclusions Our findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition

Hepatitis B virus–induced imbalance of inflammatory and antiviral signaling by differential phosphorylation of STAT1 in human monocytes

It is not clear how hepatitis B virus (HBV) modulates host immunity during chronic infection. In addition to the key mediators of inflammatory response in viral infection, monocytes also express a high-level IFN-stimulated gene, CH25H, upon response to IFN-a exerting an antiviral effect. In this study, the mechanism by which HBV manipulates IFN signaling in human monocytes was investigated. We observed that monocytes from chronic hepatitis B patients express lower levels of IFN signaling/stimulated genes and higher levels of inflammatory cytokines compared with healthy donors. HBV induces monocyte production of inflammatory cytokines via TLR2/MyD88/NF-kB signaling and STAT1-Ser727 phosphorylation and inhibits IFN-a–induced stat1, stat2, and ch25h expression through the inhibition of STAT1-Tyr701 phosphorylation and in an IL-10–dependent, partially autocrine manner. Further, we found that enhancement of STAT1 activity with a small molecule (2-NP) rescued HBV-mediated inhibition of IFN signaling and counteracted the induction of inflammatory cytokines. In conclusion, HBV contributes to the monocyte inflammatory response but inhibits their IFN-a/b responsiveness to impair antiviral innate immunity. These effects are mediated via differential phosphorylation of Tyr701 and Ser727 of STAT1

HER2-Displaying M13 Bacteriophages induce Therapeutic Immunity against Breast Cancer

The advent of trastuzumab has significantly improved the prognosis of HER2-positive (HER2+) breast cancer patients; nevertheless, drug resistance limits its clinical benefit. Anti-HER2 active immunotherapy represents an attractive alternative strategy, but effective immunization needs to overcome the patient's immune tolerance against the self-HER2. Phage display technology, taking advantage of phage intrinsic immunogenicity, permits one to generate effective cancer vaccines able to break immune tolerance to self-antigens. In this study, we demonstrate that both preventive and therapeutic vaccination with M13 bacteriophages, displaying the extracellular (EC) and transmembrane (TM) domains of human HER2 or its Δ16HER2 splice variant on their surface (ECTM and Δ16ECTM phages), delayed mammary tumor onset and reduced tumor growth rate and multiplicity in ∆16HER2 transgenic mice, which are tolerant to human ∆16HER2. This antitumor protection correlated with anti-HER2 antibody production. The molecular mechanisms underlying the anticancer effect of vaccine-elicited anti-HER2 antibodies were analyzed in vitro against BT-474 human breast cancer cells, sensitive or resistant to trastuzumab. Immunoglobulins (IgG) purified from immune sera reduced cell viability mainly by impairing ERK phosphorylation and reactivating retinoblastoma protein function in both trastuzumab-sensitive and -resistant BT-474 cells. In conclusion, we demonstrated that phage-based HER2 vaccines impair mammary cancer onset and progression, opening new perspectives for HER2+ breast cancer treatment

Existence of positive solutions for a singular nonlinear fractional differential equation with integral boundary conditions involving fractional derivatives

In this article, by using the spectral analysis of the relevant linear operator and Gelfand’s formula, some properties of the first eigenvalue of a fractional differential equation are obtained. Based on these properties and through the fixed point index theory, the singular nonlinear fractional differential equations with Riemann–Stieltjes integral boundary conditions involving fractional derivatives are considered under some appropriate conditions, and the nonlinearity is allowed to be singular in regard to not only time variable but also space variable and it includes fractional derivatives. The existence of positive solutions for boundary conditions involving fractional derivatives is established. Finally, an example is given to demonstrate the validity of our main results

Existence and uniqueness of solutions for systems of fractional differential equations with Riemann–Stieltjes integral boundary condition

In this article, we first establish an existence and uniqueness result for a class of systems of nonlinear operator equations under more general conditions by means of the cone theory and monotone iterative technique. Furthermore, the iterative sequence of the solution and the error estimation of the system are given. Then we use this new result to study the existence and uniqueness of the solution for boundary value problems of systems of fractional differential equations with a Riemann–Stieltjes integral boundary condition in real Banach spaces. The results obtained in this paper are more general than many previous results and complement them