Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver

Objective:Therapy for hepatocellular carcinoma(HCC)is a major challenge,and targeted therapies provide only a modest benefit in terms of overall survival.Treatment with antibodies to programmed cell death protein 1(PD-1)/PD-L1 can restore the functions of tumor-infiltrating T cells in HCC and has shown clinical efficacy in 20%of patients with advanced HCC.Novel approaches are urgently needed to treat HCC and to augment the efficacy of immunotherapy.Methods:Tumor-bearing mice were treated with Agrocybe aegerita galectin(AAGL)alone or in combination with anti-PD-1,and the tumor sizes and lifespans of mice were determined.Transcriptome analysis,cytokine analysis,flow cytometry analysis of the number and proportion of immune cell subsets in the liver and spleen,and molecular and cellular analyses of tumors were used to define the underlying mechanisms.Results:AAGL significantly inhibited the growth of liver tumors in a dose-dependent manner.Furthermore,AAGL increased the expression of multiple cytokines and chemokines in tumor-bearing mouse livers;this effect was associated with the activation and migration of T cells and macrophages,in agreement with the in vitro results.Importantly,the aggregation of T cells and macrophages induced by AAGL in tumor-bearing mouse livers clearly enhanced the response to PD-1 blockade immunotherapy.Conclusions:The results showed that AAGL induced the activation and migration of lymphocytes to the liver,and that the combination of AAGL and anti-PD-1 may be a promising strategy for HCC treatment.

Research on the Forming Mechanism of Micro/Nano Features during the Cast Molding Process

Cast molding process has provided a reliable, simple and cost-effective way to fabricate micro structures since decades ago. In order to obtain structures with fine, dense and deep nano-size features by cast molding, it is necessary to study the forming mechanism in the process. In this paper, based on major steps of cast molding, filling models of liquid are established and solved; and the forming mechanism of liquid is revealed. Moreover, the scale effect between the liquid and the cavity on the filling velocity of liquid is studied.It is also interesting to find out that the wettability of liquid on the cavity may be changed from wetting to dewetting depends on the pressure difference. Finally, we experimentally verify some of our modeling results on the flowing and filling state of the liquid during the cast molding process.

A Note on Double Minimality

It is known that a minimal prime system is either a subshift or with a connected phase space(Keynes and Newton TransAmMath Soc 217:237-255,1976).We show that a double minimal system is a subshift;this implies immediately that no non-periodic map has 4-fold topological minimal self-joinings.We also prove that a POD system is either uniformly rigid or is a subshift.

Chaos in the sense of Li-Yorke and the order of the inverse limit space

Let l=[0,1] and ω0 be the first limit ordinal number. Assume that f:l→l is continuous, piece-wise monotone and the set of periods of f is {2i: i∈{0}∪N}. It is known that the order of （l, f） is ω0 or ω0 + 1. It is shown that the order of the inverse limit space （l, f） is ω0 （resp. ω0 + 1） if and only if f is not （resp. is） chaotic in the sense of Li-Yorke.

Regionally proximal relation of order d along arithmetic progressions and nilsystems

The regionally proximal relation of order d along arithmetic progressions,namely AP[d]for d 2 N,is introduced and investigated.It turns out that if(X;T)is a topological dynamical system with AP[d]=Δ,then each ergodic measure of(X;T)is isomorphic to a d-step pro-nilsystem,and thus(X;T)has zero entropy.Moreover,it is shown that if(X;T)is a strictly ergodic distal system with the property that the maximal topological and measurable d-step pro-nilsystems are isomorphic,then AP[d]=RP[d]for each d 2 N.It follows that for a minimal 1-pro-nilsystem,AP[d]=RP[d]for each d 2 N.An example which is a strictly ergodic distal system with discrete spectrum whose maximal equicontinuous factor is not isomorphic to the Kronecker factor is constructed.

Strictly Ergodic Models Under Face and Parallelepiped Group Actions

The Jewett-Krieger theorem states that each ergodic system has a strictlyergodic topological model.In this article,we show that for an ergodic system onemay require more properties on its strictly ergodic model.For example,the orbitclosure of points in diagonal under face transforms may be also strictly ergodic.Asan application,we show the pointwise convergence of ergodic averages along cubes,which was firstly proved by Assani(J Anal Math 110:241-269,2010).

Topology and topological sequence entropy

Let X be a compact metric space and T:X-→X be continuous.Let h*(T)be the supremum of topological sequence entropies of T over all the subsequences of Z+and S(X)be the set of the values h*(T)for all the continuous maps T on X.It is known that{0}■S(X)■{0,log 2,log 3,...}∪{∞}.Only three possibilities for S(X)have been observed so far,namely S(X)={0},S(X)={0,log 2,∞}and S(X)={0,log 2,log 3,...}∪{∞}.In this paper we completely solve the problem of finding all possibilities for S(X)by showing that in fact for every set{0}?A?{0,log 2,log 3,...}∪{∞}there exists a one-dimensional continuum XAwith S(XA)=A.In the construction of XAwe use Cook continua.This is apparently the first application of these very rigid continua in dynamics.We further show that the same result is true if one considers only homeomorphisms rather than continuous maps.The problem for group actions is also addressed.For some class of group actions(by homeomorphisms)we provide an analogous result,but in full generality this problem remains open.