[1] Glycerol dialkyl glycerol tetraether (GDGT) membrane lipids in surface sediments from 24 lakes in China and Nepal were analyzed. The result shows that branched GDGT lipids occur widely in the studied lake sediments. The different distribution of branched GDGTs between the Chinese soils from Weijers et al. (2007b) and the Chinese lake sediments indicates that the branched GDGTs in the lacustrine sediment are the mixture of allochthonous and autochthonous branched GDGTs. Our result supports the suggestion that temperature is the principal factor affecting the distribution of GDGTs. Seasonality, sources, and precipitation increase the uncertainty of the correlation between the methylation index of branched tetraethers (MBT)/cyclization ratio of branched tetraethers (CBT) proxy and the temperature. The correlations of the MBT/CBT index with mean annual air temperature (T) for the global lakes are T = 6.803 − 7.062 × CBT + 37.090 × MBT (n = 139, p < 0.0001, R 2 = 0.62, and RMSE = 5.24°C); for the global lakes with pH < 8.5, T = 3.949 − 5.593 × CBT + 38.213 × MBT (n = 100, p < 0.0001, R 2 = 0.73, and RMSE = 4.27°C). The significant correlation suggests that the MBT/CBT proxy might be used as a potential paleotemperature proxy in the limnic environment. The MBT/CBT proxy provides an independent way to evaluate and verify the sensitivities of the different proxies for paleotemperature reconstruction from lacustrine sediments.

Neural cells differentiated from pluripotent stem cells (PSCs), including both embryonic stem cells and induced pluripotent stem cells, provide a powerful tool for drug screening, disease modeling and regenerative medicine. High-purity oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) have been derived from PSCs recently due to the advancements in understanding the developmental signaling pathways. Extracellular matrices (ECM) have been shown to play important roles in regulating the survival, proliferation, and differentiation of neural cells. To improve the function and maturation of the derived neural cells from PSCs, understanding the effects of ECM over the course of neural differentiation of PSCs is critical. During neural differentiation of PSCs, the cells are sensitive to the properties of natural or synthetic ECMs, including biochemical composition, biomechanical properties, and structural/topographical features. This review summarizes recent advances in neural differentiation of human PSCs into OPCs and NPCs, focusing on the role of ECM in modulating the composition and function of the differentiated cells. Especially, the importance of using three-dimensional ECM scaffolds to simulate the in vivo microenvironment for neural differentiation of PSCs is highlighted. Future perspectives including the immediate applications of PSC-derived neural cells in drug screening and disease modeling are also discussed.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Pluripotent stem cells; Neural differentiation; Extracellular matrix; Three-dimensional; Drug screening Core tip: Neural cells derived from human pluripotent stem cells (hPSCs), including oligodendrocyte progenitor cells and neural progenitor cells, emerge as an unlimited and physiologically relevant cell source for drug screening, disease modeling, and regenerative medicine. Natural and synthetic extracellular matrices play an important role in regulating neural differentiation, cell migration, and the derived neural cell maturation. Recent advances in neural differentiation of hPSCs on extracellular matrices in 2-D and 3-D systems are reviewed in this paper. The immediate applications of the derived neural cells in drug screening and disease modeling are also discussed.

Human amniotic fluid-derived stem cells (hAFSCs) are a novel cell source for generating osteogenic cells to treat bone diseases. Effective induction of osteogenic differentiation from hAFSCs is critical to fulfil their therapeutic potential. In this study, naringin, the main active compound of Rhizoma drynariae (a Chinese herbal medicine), was used to stimulate the proliferation and osteogenic differentiation of hAFSCs. The results showed that naringin enhanced the proliferation and alkaline phosphatase activity (ALP) of hAFSCs in a dose-dependent manner in the range 1-100 µg/ml, while an inhibition effect was observed at 200 µg/ml. Consistently, the calcium content also increased with naringin concentration up to 100 µg/ml. The enhanced osteogenic differentiation of hAFSCs by naringin was further confirmed by the dose-dependent upregulation of marker genes, including osteopontin (OPN) and Collagen I from RT-PCR analysis. The increased osteoprotegerin (OPG) expression and minimal expression of receptor activator of nuclear factor-κB ligand (RANKL) suggested that naringin also inhibited osteoclastogenesis of hAFSCs. In addition, the gene expressions of bone morphogenetic protein 4 (BMP4), runt-related transcription factor 2 (RUNX2), β-catenin and Cyclin D1 also increased significantly, indicating that naringin promotes the osteogenesis of hAFSCs via the BMP and Wnt-β-catenin signalling pathways. These results suggested that naringin can be used to upregulate the osteogenic differentiation of hAFSCs, which could provide an attractive and promising treatment for bone disorders. Copyright © 2014 John Wiley & Sons, Ltd.

As a component of p53-dependent lncRNA (long non-coding RNA), PANDAR (the promoter of CDKN1A antisense DNA damage activated RNA) participates in the epigenetic regulation in human cancer. However, the involvement of PANDAR in cancer chemoresistance is unknown. In this study, we report that PANDAR serves as a negative regulator of cisplatin sensitivity in human ovarian cancer via PANDAR-SRFS2-p53 feedback regulation in nuclear. Our data showed that among the drugs commonly used in ovarian cancer therapy, cisplatin induces higher levels of PANDAR compared with doxorubicin and paclitaxel. We also proved that PANDAR exhibited higher expression in cisplatin-resistant ovarian cancer tissues and cells, compared with cisplatin-sensitive ones, and this expression pattern depends on wild-type p53 (wt-p53), not mutant-p53 (mt-p53). In vitro and in vivo, PANDAR overexpression improved cell survival rate and tumor growth in response to cisplatin, while depletion of PANDAR leads to a reduced tumor growth. Further investigation revealed that PANDAR-reduced cisplatin sensitivity was likely or partly due to the PANDAR-binding protein SFRS2 (arginine/serine-rich 2), a splicing factor with the ability to negative regulate p53 and its phosphorylation at Serine 15 (Ser15). This feedback regulation of PANDAR–SFRS2–p53 leads to a reduced transactivation of p53-related pro-apoptotic genes, such as PUMA (p53-upregulated modulator of apoptosis). In addition, in platinum-treated patients with relapsed ovarian cancer, resistant period was positively correlated with the expression of PANDAR and SFRS2, and inversely associated with expression of p53-Ser15 and PUMA in these clinical tissues. Last but not least, the role of PANDAR in chemoresistance was confirmed in patients with ovarian cancer. These findings reveal a novel regulatory maneuver of cancer cells in response to chemostress, and might shed light on overcoming cisplatin resistance in ovarian cancer.

These results support the association between PCOS and chronic inflammation.

Seasonal temperature variability over longer timescales could offer new insights into understanding different forcing factors and response processes in the climate system. Here we report an alkenone-based temperature reconstruction for growing season over the past 1600 years from the varved sediment in Lake Sihailongwan, northeastern China. The most notable cold spells occurred during the periods ad 480–860, ad 1260–1300, ad 1510–1570 and ad 1800–1900 with a temperature decrease of about 1°C compared with the 20th century. Based on the historical evidence such as ‘snow or frost in the summertime’ and ‘no ice during the wintertime’, we compile extreme cold summer events and warm winter events over the past 1600 years. The ‘Little Ice Age’ time period experienced more extreme cold summer/warm winter events, while the ‘Medieval Warm Period’ had milder winters. Comparatively, the natural proxy data show a general similar pattern with historical documents at decadal time scales, except for between ad 1620 and 1720. Our results show multidecadal to centennial variations in seasonal temperature, possibly caused by interactions of external natural forcing and atmosphere–ocean circulations.

The present study investigated the underlying role of growth arrest-specific transcript 5 (GAS5) in epithelial ovarian cancer (EOC), which is the main cause of death in women with malignant tumor of the genital system. In vivo GAS5 expression in 60 EOC specimens was evaluated by quantitative reverse transcription (qRT)-PCR, which was used to study the differences of GAS5 expression between EOC tissues and normal ovarian epithelium. In vitro GAS5 overexpression was applied to discover the biological functions in EOC cell lines. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide and colony formation assays were employed to investigate the effect on proliferation. The function of apoptosis was assessed by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and JC-1 probe staining, and migration and invasion were detected by Transwell assay. The data show that no significant differences of GAS5 expression were observed between normal ovarian epithelium and benign epithelial lesions; however, GAS5 expression was lower in EOC tissues compared with normal ovarian epithelial tissues (6.44-fold), which was closely related to lymph node metastasis (P=0.025) and tumor node metastasis stage (P=0.035). Moreover, exogenous GAS5-inhibited proliferation promoted apoptosis and decreased migration and invasion in ovarian cancer cells. Finally, through mitochondrial potential and western blot analyses, GAS5 could disrupt mitochondrial membrane potential and promote BAX, BAK, cleaved-caspase 3 and cleaved-caspase 9 expression. Taken together, the findings of the present study revealed that GAS5 is downregulated in EOC specimens, and GAS5 inhibits EOC cell proliferation, migration and invasion, and promotes cell apoptosis. GAS5 can serve as a novel therapeutic target in patients with EOC.

BackgroundThe aim of this study was to investigate the effects of sleep duration and bedtime on sperm health, and the possible mechanism involved.Material/MethodsWe randomly divided 981 healthy Chinese men into groups according to research-set bedtimes (A=8–10 PM, B=after 10 PM, and C=after midnight) and sleep durations: group 1=<6.0 h (short), group 2=7.0–8.0 h (average), and group 3=>9.0 h (long). Sperm morphology, count, survival, and motility were examined according to sleep patterns. Antisperm antibody (ASA) production in semen was determined.ResultsSperm counts and their survival rates were lower in the short sleepers as compared to others within each group (all P<0.01). The lower counts and survival rates were observed in different bedtimes, with significant differences found between measurements of C1 vs. A1 and C2 vs. A2 or B2 (all P<0.05 or 0.01). Semen motility was lower in the short sleepers as compared to the average and long sleepers (all P<0.01). There were differences in the bedtime-related results between measurements of C1 vs. A1 or B1 (P<0.05 or 0.01). Additionally, the population proportion for the ASA-positive participates and incidence of the ASA-expressed population obviously increased in the short sleepers as compared to others within each group (all P<0.05).ConclusionsShort and long sleep durations and late bedtime were associated with impaired sperm health in the study cohort, partly through increasing ASA production in the semen.