Lifei Yuan

Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are important components of the tumor microenvironment, which have been reported to localize in colorectal carcinomas where they promote tumor progression. One of the crucial effects they exerted is immune-suppression, which was reported recently, however, the overall mechanism has not been fully addressed. In this study, it was shown that TAMs were enriched in colorectal cancer, and their infiltration was associated with VCAM-1 expression. Human colorectal cancer-derived CAFs can promote the adhesion of monocytes by up-regulating VCAM-1 expression in colorectal cancer cells. Furthermore, CAFs can attract monocytes by secreting IL-8 rather than SDF-1 and subsequently promote M2 polarization of macrophages, which synergize with CAFs in suppressing the functioning of natural killer (NK) cells. It was also found that CAFs promoted M2 macrophages recruitment in tumor tissue in vivo, and after VCAM-1 knocking-down in tumor cells or depletion of macrophages, the pro-tumor effect of CAFs was partly abolished, but no change was observed in NK cells infiltration. Collectively, the findings in this work show that TAMs and CAFs function synergistically in the tumor microenvironment and have the capacity to regulate NK cells in colorectal cancer and this presents a novel mechanism.

// Meng Zhang 1, * , Jing Wang 1, * , Lingwei Jia 2 , Jin Huang 1 , Cheng He 1 , Fuqing Hu 2 , Lifei Yuan 1 , Guihua Wang 2 , Mingxia Yu 1 and Zhuoya Li 1 1 Department of Immunology, Basic Medical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China 2 Molecular Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, P.R. China * These authors have contributed equally to this work Correspondence to: Zhuoya Li, email: zhuoyali@mails.tjmu.edu.cn Keywords: activation-induced cell death, transmembrane TNF-α, secretory TNF-α, reverse signaling, apoptosis Received: June 29, 2016     Accepted: June 20, 2017     Published: July 10, 2017 ABSTRACT Secretory tumor necrosis factor-alpha (sTNF-α) is known to mediate activation- induced cell death (AICD). However, the role of tmTNF-α in AICD is still obscure. Here, we demonstrated that tmTNF-α expression significantly increased accompanied with enhanced apoptosis during AICD in Jurkat and primary human T cells. Knockdown or enhancement of tmTNF-α expression in activated T cells suppressed or promoted AICD, respectively. Treatment of activated T cells with exogenous tmTNF-α significantly augmented AICD, indicating that tmTNF-α as an effector molecule mediates AICD. As tmTNF-α can function as a receptor, an anti-TNF-α polyclonal antibody was used to trigger reverse signaling of tmTNF-α. This antibody treatment upregulated the expression of Fas ligand, TNF-related apoptosis-inducing ligand and tmTNF-α to amplify AICD, and promoted activated T cells expressing death receptor 4, TNF receptor (TNFR) 1 and TNFR2 to enhance their sensitivity to AICD. Knockdown of TNFR1 or TNFR2 expression totally blocked tmTNF-α reverse signaling increased sensitivity to sTNF-α- or tmTNF-α-mediated AICD, respectively. Our results indicate that tmTNF-α functions as a death ligand in mediation of AICD and as a receptor in sensitization of activated T cells to AICD. Targeting tmTNF-α in activated T cells may be helpful in facilitating AICD for treatment of autoimmune diseases.

Hexaurea-based receptors enable highly efficient sulfate extraction (over 97%) via liquid–liquid extraction, and a controllable release of the bound sulfate is achieved by acidifying the solution, as demonstrated in the U-tube experiment.

As a result of years of monitoring the ecological resiliency of natural areas and cities, it has become clear that it is both important and often feasible to implement ecological and environmental restoration in conjunction with ongoing processes of landscape change development and urbanization. Ecological resiliency and spatiotemporal evolution studies can objectively reveal the resiliency of ecosystems to external disturbances. Ecological monitoring and assessment can also help planners understand regional ecological spatial differentiation patterns and provided data support for planning. In this paper we have analyzes quantitatively the interrelationships of ecological factors in Dianchi Lake Basin (DLB) over the past 30 years and explored the spatial and temporal dynamics of ecological resiliency. Based on remote sensing images and primary data in 1995, 2005, 2010, 2015, 2018, and 2022, we used the center of gravity migration and kernel density analysis to explore the spatial and temporal changes of ecological resiliency. We built the overall resiliency evaluation system using entropy weight in the TOPSIS model, and finally simulate the future changes based on CA-Markov (CA-MC) model. The results show that from 1995 to 2022, the ecological resiliency of land use and vegetation cover in DLB decreased substantially. An important finding was that the ecological resiliency of riparian buffer zone and landscape pattern were generally increasing. The distribution of barycenter movement and kernel density of different levels of ecological resiliency differed significantly and showed fluctuating changes. The extreme low resiliency and extremely resilient areas shift to the northeast, the mildly resilient areas shift to the northwest, and the highly resilient areas shift to the southeast. The overall resiliency level of DLB is predicted to slowly increase from 2022 to 2030 by deduction of the CA-MC model. Our analysis suggests that the study of the evolution of regional ecological resiliency can provide a timely understanding of regional ecological evolution patterns and propose ecological protection strategies.