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Donggutuo (DGT) is one of the richest archaeological localities in the Nihewan Basin of North China, thereby providing key information about the technological behaviours of early hominins in eastern Asia. Although DGT has been subject of multiple excavations and technological studies over the past several decades, few detailed studies on the lithic assemblages have been published. Here we summarize and describe the DGT lithic assemblages, examining stone tool reduction methods and technological skills. DGT dates to ca. 1.1 Ma, close to the onset of the mid-Pleistocene climate transition (MPT), indicating that occupations at DGT coincided with increased environmental instability. During this time interval, the DGT knappers began to apply innovative flaking methods, using free hand hard hammer percussion (FHHP) to manufacture pre-determined core shapes, small flakes and finely retouched tools, while occasionally using the bipolar technique, in contrast to the earlier and nearby Nihewan site of Xiaochangliang (XCL). Evidence for some degree of planning and predetermination in lithic reduction at DGT parallels technological developments in African Oldowan sites, suggesting that innovations in early industries may be situational, sometimes corresponding with adaptations to changes in environments and local conditions. [ABSTRACT FROM AUTHOR]

Xiaochangliang (XCL), located in the Nihewan Basin of North China, is a key archaeological locality for understanding the behavioural evolution of early humans. XCL dates to ca. 1.36 Ma, making it one of the earliest sites in Northeast Asia. Although XCL represents the first excavation of an Early Pleistocene site in the Nihewan Basin, identified and excavated in the 1970’s, the lithic assemblages have never been published in full detail. Here we describe the lithic assemblages from XCL, providing information on stone tool reduction techniques and the influence of raw materials on artefact manufacture. The XCL hominins used both bipolar and freehand reduction techniques to manufacture small flakes, some of which show retouch. Bipolar reduction methods at XCL were used more frequently than previously recognized. Comparison of XCL with other Early Pleistocene sites in the Nihewan Basin indicates the variable use of bipolar and freehand reduction methods, thereby indicating a flexible approach in the utilization of raw materials. The stone tools from XCL and the Nihewan sites are classifiable as Mode I lithic assemblages, readily distinguished from bifacial industries manufactured by hominins in Eastern Asia by ca. 800 ka. [ABSTRACT FROM AUTHOR]

Testes-specific protease 50 (TSP50) is abnormally overexpressed in many kinds of cancers and promotes cell proliferation and migration. However, whether TSP50 can influence the tumor microenvironment, especially the function of immune cells in the microenvironment, remains largely unknown. We demonstrated that exposure to the conditioned medium from TSP50-overexpressing cells, or co-culture with TSP50-overexpressing cells, enhanced the cytokine production and phagocytic activities of macrophages, and induced M2b polarization. Further investigation showed that production of TNF-α and IL-1β was strongly induced by TSP50 in TSP50-overexpressing cells. TSP50-induced TNF-α and IL-1β were main factors that mediated the effects of TSP50-overexpressing cells on macrophages. The NF-κB pathway could be activated in macrophages upon the treatment of conditioned medium of TSP50-overexpressing cells and its activation is necessary for the observed effects on macrophages. Taken together, our results suggested that oncogenic TSP50 expressed in cells could activate surrounding macrophages and induce M2b polarization, partly through inducing TNF-α/ IL-1β secretion and subsequent NF-κB pathway activation. This implies a potential mechanism by which oncogene TSP50 regulates tumor microenvironment to support tumor development. [ABSTRACT FROM AUTHOR]

Inflammation and renal tubular injury are major features of acute kidney injury (AKI). Many cytokines and chemokines are released from injured tubular cells and acts as proinflammatory mediators. However, the role of IL-19 in the pathogenesis of AKI is not defined yet. In bilateral renal ischemia/reperfusion injury (IRI)-induced and HgCl2-induced AKI animal models, real-time quantitative (RTQ)-PCR showed that the kidneys, livers, and lungs of AKI mice expressed significantly higher IL-19 and its receptors than did sham control mice. Immunohistochemical staining showed that IL-19 and its receptors were strongly stained in the kidney, liver, and lung tissue of AKI mice. In vitro, IL-19 upregulated MCP-1, TGF-β1, and IL-19, and induced mitochondria-dependent apoptosis in murine renal tubular epithelial M-1 cells. IL-19 upregulated TNF-α and IL-10 in cultured HepG2 cells, and it increased IL-1β and TNF-α expression in cultured A549 cells. In vivo, after renal IRI or a nephrotoxic dose of HgCl2 treatment, IL-20R1-deficient mice (the deficiency blocks IL-19 signaling) showed lower levels of blood urea nitrogen (BUN) in serum and less tubular damage than did wild-type mice. Therefore, we conclude that IL-19 mediates kidney, liver, and lung tissue damage in murine AKI and that blocking IL-19 signaling may provide a potent therapeutic strategy for treating AKI. [ABSTRACT FROM AUTHOR]

The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacological role of β-nitrostyrene in esophageal cancer remain unclear. Here, a β-nitrostyrene derivative, CYT-Rx20, was synthesized and assessed for its anti-cancer activities and underlying mechanism in esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by promoting apoptosis through activation of caspase cascade and poly(ADP-ribose) polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell migration and invasion by regulating the expression of epithelial to mesenchymal transition (EMT) markers. CYT-Rx20 decreased cell viability and migration through suppression of the PI3K/AKT and STAT3 pathways. Of note, the cytotoxicity and anti-migratory effect of CYT-Rx20 were enhanced by co-treatment with SC79 (AKT activator) or colivelin (STAT3 activator), suggesting the dependency of esophageal cancer cells on AKT and STAT3 for survival and migration, an oncogene addiction phenomenon. In xenograft tumor-bearing mice, CYT-Rx20 significantly reduced tumor growth of the implanted esophageal cancer cells accompanied by decreased Ki-67, phospho-AKT, and phospho-STAT3 expression. In orthotopic esophageal cancer mouse model, decreased tumor growth and lung metastasis with reduced Ki-67 and phospho-STAT3 expression were observed in mice treated with CYT-Rx20. Together, our results suggest that CYT-Rx20 is a potential β-nitrostyrene-based anticancer compound against the tumor growth and metastasis of esophageal cancer., Competing Interests: The authors have declared that no competing interests exist.