The Comparison of Fama-French Five-Factor Model in Chinese A-share Stock Market and in Real Estate Sector

Purpose of the study This paper aims to test Fama-French five factors model in the Chinese A-share stock markets and in the real estate industry in order to better understand the Chinese markets and to provide the Chinese investors a reliable asset pricing model. Data and methodology The data is mainly extracted from Datastream. The tracking period is from July 1st 2002 to December 31st 2015 in total 162 months. There were more than 3000 listed companies in the Chinese A-share market and 138 listed companies in the real estate industry in this study. The methodology is mainly to apply Fama-French five factors model in the Chinese A-share stock markets and in the real estate industry along with other tests such as Durbin-Watson test and multicollinearity to evaluate the model performance. Findings The Fama-French five factors model performs well in the Chinese A-share market and the Chinese real estate industry with the data from July 2002 to December 2015. Value factor is not helpful on explaining the excess return of either A-share size-B/M portfolio or real estate industry size-B/M portfolio. The reason why value factor is insignificant in explaining A-share is the speculative environment in Chinese stock market. However, speculation is not the key which makes value factor insignificant in real estate market. Investment factor has limited explanatory power in the A-share size-B/M portfolio too. Surprisingly, five factors model performs better in the Chinese real estate industry than in the Chinese A-share market because five out of six factors are significant at 5 % level and the factors are less correlated

HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs.

Funder: the National Key R&D Program of China [2018YFA0107500], National Natural Science Foundation of China [81530043, 81930085 and 31771260], the Scientific Innovation Project of the Chinese Academy of Sciences [XDA16020403], the Social Development Project of Jiangsu Province [BE2016671], and the State Key Laboratory of Radiation Medicine and Protection, Soochow University [GZN1201804 and GZN1201903].Inflammatory factors such as IFNγ and TNFα could endow mesenchymal stem cells (MSCs) a potent immunomodulatory property, a process called licensing, but the mechanisms are not fully understood. We here found that glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to the active cortisol and thereby regulates tissue glucocorticoid (GC) levels, was greatly upregulated by IFNγ and TNFα in human umbilical cord-derived MSCs (UC-MSCs) in a synergistic manner. While IFNγ alone was not able to induce HSD11B1, it could increase the activity of NF-kB and thus augment the upregulation of HSD11B1 by TNFα. Interestingly, the upregulation of HSD11B1 by IFNγ and TNFα also required glucocorticoid receptor. Furthermore, HSD11B1 was shown to be required for the expression of TNF-stimulated gene 6 (TSG-6), an important anti-inflammatory effector molecule of MSCs. Therefore, the inflammatory factors IFNγ and TNFα can promote GC metabolism and thereby drive the expression of anti-inflammatory factor TSG-6 in human UC-MSCs, forming a potential negative feedback loop. These findings help to understand the relationship between inflammation and GC metabolism

Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes

Acentral tenet of nerve growth factor (NGF) action that is poorly understood is its ability to mediate cytoplasmic signaling, through its receptor TrkA, that is initiated at the nerve terminal and conveyed to the soma. We identified an NGF-induced protein that we termed Pincher (pinocytic chaperone) that mediates endocytosis and trafficking of NGF and its receptor TrkA. In PC12 cells, overexpression of Pincher dramatically stimulated NGF-induced endocytosis of TrkA, unexpectedly at sites of clathrin-independent macropinocytosis within cell surface ruffles. Subsequently, a system of Pincher-containing tubules mediated the delivery of NGF/TrkA-containing vesicles to cytoplasmic accumulations. These vesicles selectively and persistently mediated TrkA-erk5 mitogen-activated protein kinase signaling. A dominant inhibitory mutant form of Pincher inhibited the NGF-induced endocytosis of TrkA, and selectively blocked TrkA-mediated cytoplasmic signaling of erk5, but not erk1/2, kinases. Our results indicate that Pincher mediates pinocytic endocytosis of functionally specialized NGF/TrkA endosomes with persistent signaling potential

Inflammatory Cytokine-Induced Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 in Mesenchymal Stem Cells Are Critical for Immunosuppression

Cell-cell adhesion mediated by ICAM-1 and VCAM-1 is critical for T cell activation and leukocyte recruitment to the inflammation site and, therefore, plays an important role in evoking effective immune responses. However, we found that ICAM-1 and VCAM-1 were critical for mesenchymal stem cell (MSC)-mediated immunosuppression. When MSCs were cocultured with T cells in the presence of T cell Ag receptor activation, they significantly upregulated the adhesive capability of T cells due to the increased expression of ICAM-1 and VCAM-1. By comparing the immunosuppressive effect of MSCs toward various subtypes of T cells and the expression of these adhesion molecules, we found that the greater expression of ICAM-1 and VCAM-1 by MSCs, the greater the immunosuppressive capacity that they exhibited. Furthermore, ICAM-1 and VCAM-1 were found to be inducible by the concomitant presence of IFN-γ and inflammatory cytokines (TNF-α or IL-1). Finally, MSC-mediated immunosuppression was significantly reversed in vitro and in vivo when the adhesion molecules were genetically deleted or functionally blocked, which corroborated the importance of cell-cell contact in immunosuppression by MSCs. Taken together, these findings reveal a novel function of adhesion molecules in immunoregulation by MSCs and provide new insights for the clinical studies of antiadhesion therapies in various immune disorders. Copyright © 2010 by The American Association of Immunologists, Inc

Mesenchymal stromal cells pretreated with pro‐inflammatory cytokines promote skin wound healing through VEGFC ‐mediated angiogenesis

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COVID-19 infection: the perspectives on immune responses.

Funder: National Key R&D Program of China (2018YFA0107500), Suzhou 2020 Emergency Innovation Funding on COVID-19 Infection, the National Natural Science Foundation of China (81530043, 81861138015, 31771641 and 81571612)Funder: Italian Ministry of Healt

Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy.

Distinct metabolic programs, either energy-consuming anabolism or energy-generating catabolism, were required for different biological functions. Macrophages can adopt different immune phenotypes in response to various cues and exhibit anti- or pro-inflammatory properties relying on catabolic pathways associated with oxidative phosphorylation (OXPHOS) or glycolysis. Spermidine, a natural polyamine, has been reported to regulate inflammation through inducing anti-inflammatory (M2) macrophages. However, the underlying mechanisms remain elusive. We show here that the M2-polarization induced by spermidine is mediated by mitochondrial reactive oxygen species (mtROS). The levels of mitochondrial superoxide and H2O2 were markedly elevated by spermidine. Mechanistically, mtROS were found to activate AMP-activated protein kinase (AMPK), which in turn enhanced mitochondrial function. Furthermore, hypoxia-inducible factor-1α (Hif-1α) was upregulated by the AMPK activation and mtROS and was required for the expression of anti-inflammatory genes and induction of autophagy. Consistent with previous report that autophagy is required for the M2 polarization, we found that the M2 polarization induced by spermidine was also mediated by increased autophagy. The macrophages treated with spermidine in vitro were found to ameliorate Dextran Sulfate Sodium (DSS)-induced inflammatory bowel disease (IBD) in mice. Thus, spermidine can elicit an anti-inflammatory program driven by mtROS-dependent AMPK activation, Hif-1α stabilization and autophagy induction in macrophages. Our studies revealed a critical role of mtROS in shaping macrophages into M2-like phenotype and provided novel information for management of inflammatory disease by spermidine

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Health risk assessment of heavy metals in vegetables grown around battery production area

Battery production is one of the main sources of heavy metals that present great harm to human health even in low concentrations. Chromium (Cr), Cadmium (Cd) and Lead (Pb) were measured in edible portions of vegetables and soils around a battery production area in China, and the potential health risk of heavy metal contamination to the local population via vegetable consumption was evaluated. Their concentrations in edible portions of vegetables were 2.354 (0.078-14.878), 0.035 (0.003-0.230) and 0.039 (0.003-0.178) mg kg-1, respectively. Approximately 3 % of the Cd in the vegetable samples exceeded the maximum concentration allowable by national food safety criteria, although Pb content in all samples were within the criteria. Transfer factors (TF) from soils to vegetables were dependent on vegetable species. Leguminous vegetables were more likely to accumulate Cr, while leaf vegetables tended to show higher levels of concentration of Cd and Pb. Melon vegetables demonstrated a relatively low capacity for accumulating the heavy metals studied. TF were positively correlated with soil organic matter and negatively correlated with soil pH. The mean estimated daily intake of Cr, Cd and Pb via dietary consumption of vegetables was 0.011, 1.65 × 10-4 and 1.84 × 10-4 mg kg-1 of body weight per day, respectively, levels that were much lower than the reference doses recommended by USEPA (U.S. Environmental Protection Agency) and JECFA (Joint FAO/WHO Expert Committee on Food Additives), indicating that the potential health risk of Cr, Cd and Pb exposure via vegetable consumption to the local population around this battery production area could be negligible

Lessons learned from the blockade of immune checkpoints in cancer immunotherapy

Abstract The advent of immunotherapy, especially checkpoint inhibitor-based immunotherapy, has provided novel and powerful weapons against cancer. Because only a subset of cancer patients exhibit durable responses, further exploration of the mechanisms underlying the resistance to immunotherapy in the bulk of cancer patients is merited. Such efforts may help to identify which patients could benefit from immune checkpoint blockade. Given the existence of a great number of pathways by which cancer can escape immune surveillance, and the complexity of tumor-immune system interaction, development of various combination therapies, including those that combine with conventional therapies, would be necessary. In this review, we summarize the current understanding of the mechanisms by which resistance to checkpoint blockade immunotherapy occurs, and outline how actionable combination strategies may be derived to improve clinical outcomes for patients