We report here on the isotopic analysis of the diet of one of the oldest modern humans found in Eurasia, the Tianyuan 1 early modern human dating to Ϸ40,000 calendar years ago from Tianyuan Cave (Tianyuandong) in the Zhoukoudian region of China. Carbon and nitrogen isotope analysis of the human and associated faunal remains indicate a diet high in animal protein, and the high nitrogen isotope values suggest the consumption of freshwater fish. To confirm this inference, we measured the sulfur isotope values of terrestrial and freshwater animals around the Zhoukoudian area and of the Tianyuan 1 human, which also support the interpretation of a substantial portion of the diet from freshwater fish. This analysis provides the direct evidence for the consumption of aquatic resources by early modern humans in China and has implications for early modern human subsistence and demography.archaeology ͉ Asia ͉ diet ͉ fish ͉ Late Pleistocene

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This study aimed to determine the anti-obesity effects and mechanisms of Cerasus humilis polyphenol (CHP) in C57BL/6 obese mice and 3T3-L1 cells. High-performance liquid chromatography−electrospray ionization-tandem mass spectrometry was used for the qualitative and quantitative identification of CHP components. The obese mice, induced by feeding high-fat diet (HFD), were treated with CHP (250 mg/kg/day) by gavage for 12 weeks. Orlistat was gavaged at 15.6 mg/kg bw/day, as a positive control group. The analysis revealed that the main components of CHP were procyanidin B2, cyanidin-3glucoside, and pelargonidin-3-glucoside. CHP dietary supplementation significantly reduced body weight and improved blood lipid measurements in HFD-fed mice (p < 0.01). Moreover, it inhibited mRNA expression of miR-122, Srebp-1c, and Cpt1a (p < 0.01) and reduced hepatic lipid deposition, as seen by hematoxylin and eosin staining. CHP downregulated the protein expression of PPARγ and C/EBPα in HFD-induced obese mice and inhibited adipocyte differentiation (p < 0.01). Compared with the HFD group, CHP supplementation had an obvious anti-inflammatory effect (decreased protein expression, such as TNF-α, IL-6, and MCP1), reducing leptin levels and TNF-α secretion in serum and cells (p < 0.01). CHP significantly inhibited the expression of miR-27a/b (53.3 and 29.9%, p < 0.01) in mice retroperitoneal white adipocytes, enhancing the expression of the target gene Prdm16 and significantly upregulating Sirt1 (105.5%, p < 0.01) compared with the HFD group. Moreover, CHP supplementation effectively improved oxidative stress (ROS, T-AOC, SOD, CAT, and GSH-Px) induced by HFD in obese mice (p < 0.01). Thus, CHP mitigates adipocyte differentiation, browning of white adipocytes, and reduction of inflammation and antioxidant activity to reduce obesity. Consequently, these results provide novel insights into the anti-obesity roles of CHP in HFD-induced obesity.

Diabetic retinopathy is a major complication in patients with diabetes. Herein, we investigate how hawthorn polyphenol extract (HPE) affects high glucose-induced oxidation, inflammation, and apoptosis in ARPE-19 cells. HPLC-MS/MS was used to determine HPE content and composition. Reactive oxygen species (ROS) production was assessed using fluorescence microscopy, while glucose-induced gene and protein expressions were analyzed using real-time PCR and western blotting in cells transfected with miR-34a mimics. We found that treating cells with 10 μg/ml of HPE, 30 μM procyanidin B2, chlorogenic acid, epicatechin, or resveratrol (positive control) significantly reduced ROS production and decreased apoptosis and inflammationrelated factors (p < .01). Moreover, the expression level of SIRT1 was increased, while that of acetylated NF-κB p65 and p53 proteins was decreased. These data suggest that HPE can inhibit oxidative damage, inflammation, and apoptosis through the AMPK/SIRT1/NF-κB pathway, and decrease miR-34a/SIRT1/p53 pathway activation in ARPE-19 cells, thereby demonstrating a potential use as a food additive to mitigate hyperglycemia-induced retinal damage. Practical applications Hawthorn polyphenol extract (HPE) significantly reduced ROS levels, apoptosis, and the expression of inflammation-related factors in ARPE-19 cells. HPE also inhibited the AMPK/SIRT1/NF-κB and miR-34a/SIRT1/p53 pathways, which are involved in hyperglycemia-induced inflammation and apoptosis of ARPE-19 cells by regulating acetylation. Thus, HPE, as a potential food additive, may mitigate hyperglycemiainduced retinal damage.

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