Cellular reprogramming can manipulate the identity of cells to generate the desired cell types1– 3. The use of cell intrinsic components, including oocyte cytoplasm and transcription factors, can enforce somatic cell reprogramming to pluripotent stem cells4– 7. By contrast, chemical stimulation by exposure to small molecules offers an alternative approach that can manipulate cell fate in a simple and highly controllable manner8– 10. However, human somatic cells are refractory to chemical stimulation owing to their stable epigenome2,11,12 and reduced plasticity13,14; it (...) is therefore challenging to induce human pluripotent stem cells by chemical reprogramming. Here we demonstrate, by creating an intermediate plastic state, the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells that exhibit key features of embryonic stem cells. The whole chemical reprogramming trajectory analysis delineated the induction of the intermediate plastic state at the early stage, during which chemical-induced dedifferentiation occurred, and this process was similar to the dedifferentiation process that occurs in axolotl limb regeneration. Moreover, we identified the JNK pathway as a major barrier to chemical reprogramming, the inhibition of which was indispensable for inducing cell plasticity and a regeneration-like program by suppressing pro-inflammatory pathways. Our chemical approach provides a platform for the generation and application of human pluripotent stem cells in biomedicine. This study lays foundations for developing regenerative therapeutic strategies that use well-defined chemicals to change cell fates in humans. (shrink)

With the e-commerce development and changing of hotels’ booking channels, the online word-of-mouth, as a new signal of quality, is becoming to attract more attention of consumers. Using the scenario experiment, this study explores the effect of online word-of-mouth on brand sensitivity of consumers during the decision making for hotel booking. The results show that if the information about hotels obtained is limited in the decision-making process, consumers would have a higher sensitivity to the hotel brand. Increasing information about the (...) online word-of-mouth can effectively reduce consumers’ brand sensitivity to hotels. Besides, the moderating effect of the hotel grade on the relationship between the online word-of-mouth and brand sensitivity is affected by the scale of the negative differences of word-of-mouth. (shrink)

內容簡介 本書旨在奉獻一部簡明的敵道學史讀本，對宋代以來道學在政治上、在文學裡、在群眾之中被誣、被毀、被害之事，不求窮盡，但求大端不遺，庶幾道學家之淒慘無助及儒士「雖千萬人吾往矣」之勇毅，讀者可以一目了然。筆者 本人同情道學理念，對敵道學大不以為然，時時有駁斥之心，但為了學術中立，不故意誘導讀者，本書在史實部分，只單方面呈現敵道學故事，盡可能讓道學一方以及筆者意見離場。.