Kynurenine (Kyn) pathway is a significant metabolic pathway of tryptophan (Trp). The metabolites of the Kyn pathway are closely correlated with numerous diseases. Two main enzymes, indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO or TDO2), regulate the first and rate-limiting step of the Kyn pathway. These enzymes are directly or indirectly involved in various diseases, including inflammatory diseases, cancer, diabetes, and mental disorders. Presently, an increasing number of potential mechanisms have been revealed. In the present review, we depict the structure of IDO and TDO and explicate their functions in various diseases to facilitate a better understanding of them and to indicate new therapeutic plans to target them. Moreover, we summarize the inhibitors of IDO/TDO that are currently under development and their efficacy in the treatment of cancer and other diseases.

Three grinding stones from Shizitan Locality 14 (ca. 23,000-19,500 calendar years before present) in the middle Yellow River region were subjected to usewear and residue analyses to investigate human adaptation during the last glacial maximum (LGM) period, when resources were generally scarce and plant foods may have become increasingly important in the human diet. The results show that these tools were used to process various plants, including Triticeae and Paniceae grasses, Vigna beans, Dioscorea opposita yam, and Trichosanthes kirilowii snakegourd roots. Tubers were important food resources for Paleolithic hunter-gatherers, and Paniceae grasses were exploited about 12,000 y before their domestication. The long tradition of intensive exploitation of certain types of flora helped Paleolithic people understand the properties of these plants, including their medicinal uses, and eventually led to the plants' domestication. This study sheds light on the deep history of the broad spectrum subsistence strategy characteristic of late Pleistocene north China before the origins of agriculture in this region.ancient starch | late Paleolithic China | plant processing | usewear analysis | stone tool function

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Silver nanoparticles (AgNPs) have attracted considerable attentions due to their unique properties and diverse applications. Although it has been reported that AgNPs have acute toxic effects on a variety of cultured mammalian cells and animal models, few studies have been conducted to evaluate the associated risk of AgNPs to human health at non-cytotoxic doses. In this paper, HepG2 cells were exposed to 10 nm and 100 nm AgNPs under non-cytotoxic conditions, and cell viability was assessed. At low doses, AgNPs displayed “hormesis” effects by accelerating cell proliferation. Further studies indicated that the activation states of MAPKs were differentially regulated in this process. Specifically, by increasing the expression of downstream genes, p38 MAPK played a central role in non-cytotoxic AgNP-induced hormesis. Moreover, the treatment of HepG2 cells with silver ions (Ag+) at the same dose levels induced distinct biological effects, suggesting that different intrinsic properties exist for AgNPs and Ag+.