The timing of phenological events is highly sensitive to climate change, and may influence ecosystem structure and function. Although changes in flowering phenology among species under climate change have been reported widely, how species-specific shifts will affect phenological synchrony and community-level phenology patterns remains unclear. We conducted a manipulative experiment of warming and precipitation addition and reduction to explore how climate change affected flowering phenology at the species and community levels in an alpine meadow on the eastern Tibetan Plateau.We found that warming advanced the first and last flowering times differently and with no consistent shifts in flowering duration among species, resulting in the entire flowering period of species emerging earlier in the growing season.Early-flowering species were more sensitive to warming than mid-and late-flowering species, thereby reducing flowering synchrony among species and extending the community-level flowering season. However, precipitation and its interactions with warming had no significant effects on flowering phenology. Our results suggest that temperature regulates flowering phenology from the species to community levels in this alpine meadow community, yet how species shifted their flowering timing and duration in response to warming varied. This species-level divergence may reshape flowering phenology in this alpine plant community. Decreasing flowering synchrony among species and the extension of community-level flowering seasons under warming may alter future trophic interactions, with cascading consequences to community and ecosystem function.

MiR-873/CDK3 has been shown to play a critical role in ERα signaling and tamoxifen resistance. Thus, targeting this pathway may be a potential therapeutic approach for the treatment of ER positive breast cancer especially tamoxifen resistant subtype. Here we report that Norcantharidin (NCTD), currently used clinically as an ani-cancer drug in China, regulates miR-873/CDK3 axis in breast cancer cells. NCTD decreases the transcriptional activity of ERα but not ERβ through the modulation of miR-873/CDK3 axis. We also found that NCTD inhibits cell proliferation and tumor growth and miR-873/CDK3 axis mediates cell proliferation suppression of NCTD. More important, we found that NCTD sensitizes resistant cells to tamoxifen. NCTD inhibits tamoxifen induced the transcriptional activity as well ERα downstream gene expressions in tamoxifen resistant breast cancer cells. In addition, we found that NCTD restores tamoxifen induced recruitments of ERα co-repressors N-CoR and SMRT. Knockdown of miR-873 and overexpression of CDK3 diminish the effect of NCTD on tamoxifen resistance. Our data shows that NCTD regulates ERα signaling and tamoxifen resistance by targeting miR-873/CDK3 axis in breast cancer cells. This study may provide an alternative therapy strategy for tamoxifen resistant breast cancer.

With the development of nanotechnology, gold (Au) and graphene oxide (GO) nanoparticles have been widely used in various fields, resulting in an increased release of these particles into the environment. The released nanoparticles may eventually accumulate in sediment, causing possible ecotoxicological effects to benthic invertebrates. However, the impact of Au-NPs and GO-NPs on the cosmopolitan oligochaete, Tubifex tubifex, in sediment exposure is not known. Mortality, behavioral impact (GO-NP and Au-NP) and uptake (only Au-NP) of sediment-associated Au-NPs (4.9±0.14nm) and GO-NPs (116±0.05nm) to T. tubifex were assessed in a number of 5-day exposure experiments. The results showed that the applied Au-NP concentrations (10 and 60μg Au/g dry weight sediment) had no adverse effect on T. tubifex survival, while Au bioaccumulation increased with exposure concentration. In the case of GO-NPs, no mortality of T. tubifex was observed at a concentration range of 20 and 180μg GO/g dry weight sediment, whereas burrowing activity was significantly reduced at 20 and 180μg GO/g dry weight sediment. Our results suggest that Au-NPs at 60μg Au/g or GO-NPs at 20 and 180μg GO/g were detected by T. tubifex as toxicants during short-term exposures.

Transcriptional repressor zinc finger and BTB domain containing 1 (ZBTB1) is required for DNA repair. Since DNA repair defects often underlie genome instability and tumorigenesis, we determined to study the role of ZBTB1 in cancer. In this study, we found that ZBTB1 is downregulated in breast cancer and this downregulation is associated with poor outcome of breast cancer patients. ZBTB1 suppresses breast cancer cell proliferation and tumor growth. The majority of breast cancers are estrogen receptor (ER) positive and selective estrogen receptor modulators such as tamoxifen have been widely used in the treatment of these patients. Unfortunately, many patients develop resistance to endocrine therapy. Tamoxifen-resistant cancer cells often exhibit higher HER2 expression and an increase of glycolysis. Our data revealed that ZBTB1 play a critical role in tamoxifen resistance in vitro and in vivo. To see if ZBTB1 regulates HER2 expression, we tested the recruitments of ZBTB1 on HER2 regulatory sequences. We observed that over-expressed ZBTB1 occupies the estrogen receptor alpha (ERα) binding site of the HER2 intron in tamoxifen-resistant cells, suppressing tamoxifen-induced transcription. In an effort to identify potential microRNAs (miRNAs) regulating ZBTB1, we found that miR-23b-3p directly targets ZBTB1. MiR-23b-3p regulates HER2 expression and tamoxifen resistance via targeting ZBTB1. Finally, we found that miR-23b-3p/ZBTB1 regulates aerobic glycolysis in tamoxifen resistant cells. Together, our data demonstrate that ZBTB1 is a tumor suppressor in breast cancer cells and that targeting the miR-23b-3p/ZBTB1 may serve as a potential therapeutic approach for the treatment of tamoxifen resistant breast cancer.

Silver nanoparticles (AgNPs) are constituents of many consumer products, but the future of their production depends on ensuring safety. The stability of AgNPs in various physiological solutions and aging in storage may affect the accuracy of predicted nanoparticle toxicity. The goal of this study was to simulate the transformation of AgNPs in different media representatives to the life cycle in the environment and to identify their toxicity to Hepa1c1c7 cells in a long-term aging process. AgNPs coated with citrate, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and branched polyethyleneimine (BPEI) were studied. Our results show that the exposure media had a significant impact on the transformation of AgNPs. Citrate-coated AgNPs showed significant aggregation in phosphate-buffered saline. The aging of AgNPs in optimal storage showed that the charge-stabilized particles (citrate) were more unstable, with significant aggregation and shape changes, than sterically stabilized particles (PEG AgNPs, PVP AgNPs). The BPEI AgNPs showed the highest dissolution of AgNPs, which induced significantly increased toxicity to Hepa1c1c7 cells. Overall, our findings showed that storage and media of AgNPs influenced the transformation of AgNPs and that the resulting changes in the AgNPs’ physicochemical properties influenced their toxicity. Our study contributes to the understanding of AgNPs’ transformations under realistic exposure scenarios and increasing the predictability of risk assessments.

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Flowering and fruiting phenology of plants is sensitive to environmental cues, and changes in reproductive phenology of individual plant species under climate change have been widely reported. However, how species‐level phenological responses scale up to affect community‐level reproductive phenology patterns (synchrony and reproductive duration) are still unclear. An experiment on the effects of nitrogen (N) addition and precipitation changes on reproductive phenological traits of 52 species was conducted in an alpine meadow on the eastern Tibetan Plateau to determine the influence of the phenological response in different functional groups on community‐level reproductive phenology. N addition significantly delayed the onset date of reproductive phenology of sedges (early‐flowering species) and advanced the end date of reproduction of forbs (late‐flowering species). Meanwhile, N addition reduced the number of individuals involved in reproduction of sedges and forbs, but it increased that of grasses (late‐flowering species). Furthermore, N addition increased reproductive synchrony, delayed the onset and shortened the duration of reproductive phenology at the community level. However, precipitation changes and their interaction with N addition had no significant effect on reproductive phenology of the alpine plant community. Synthesis. These results suggested that differences in the direction and magnitude of response of different species to N enrichment lead to compression of reproductive duration at the community level, increasing the degree of overlap between reproductive events, which could change future species diversity, trophic interactions and productivity accumulation in alpine meadows on the Tibetan Plateau. Overall, knowledge of phenological responses from plant functional groups to the community level contributes to robust prediction and mechanistic understanding of community structure and function in response to future climate change.

The study presents an empirical efficiency analysis for China's iron and steel industry by applying data envelopment analysis. From a theoretical perspective, an improved method is proposed to allow decision makers to select the production function between linear and exponential forms under the assumption of variable returns-to-scale. From a practical perspective, the paper attempts to explore the production function form of 15 representative iron and steel companies in China. Furthermore, the cost efficiency is decomposed into technical efficiency and allocative efficiency in this context. Some suggestions are put forward to improve inefficient companies.