A new class of pluripotent stem cell cytotoxic small molecules

10.1371/journal.pone.0085039PLoS ONE93-POLN

Circadian clock and vascular disease.

Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of cardiovascular events such as acute myocardial infarction. Circadian rhythm strongly influences human biology and pathology. The identification and characterization of mammalian clock genes revealed that they are expressed almost everywhere throughout the body in a circadian manner. In contrast to the central clock in the suprachiasmatic nucleus (SCN), the clock in each tissue or cell is designated as a peripheral clock. It is now accepted that peripheral clocks have their own roles specific to each peripheral organ by regulating the expression of clock-controlled genes (CCGs), although the oscillation mechanisms of the peripheral clock are similar to that of the SCN. However, little was known about how the peripheral clock in the vasculature contributes to the process of cardiovascular disorders. The biological clock allows each organ or cell to anticipate and prepare for changes in external stimuli. Recent evidence obtained using genetically engineered mice with disrupted circadian rhythm showed a novel function of the internal clock in the pathogenesis of endothelial dysfunction, hypertension and hemostasis. Loss of synchronization between the central and peripheral clock also contributes to the pathogenesis of cardiovascular diseases, as restoration of clock homeostasis could prevent disease progression. Identification of CCGs in each organ, as well as discovery of tools to manipulate the phase of each biological clock, will be of great help in establishing a novel chronotherapeutic approach to the prevention and treatment of cardiovascular disorders

Mapping Chinese diplomacy: relational contradictions and spatial tensions

This paper maps out contemporary discourses of Chinese diplomacy that have proliferated under the aegis of ‘major country diplomacy with Chinese characteristics’. We examine how these narratives are underpinned by webs of relationality that see China promoting equal and win–win partnerships with other state actors, yet are also defined by hierarchical premises for such diplomatic engagements. These relational contradictions are most clearly manifested when we interrogate the spatial dynamics of China’s diplomatic endeavours through the Belt and Road Initiative (BRI). By scrutinising the geopolitical imaginations, sites and scales associated with the BRI, we turn attention to three spatial tensions that are closely bounded up with the relational contradictions of Chinese diplomacy: ‘win–win’ diplomacy promoting a ‘harmonious world’ versus territorially based diplomacy; periphery diplomacy versus the global ambitions of BRI; and the centralisation versus decentralisation dimensions of Chinese diplomacy. This allows us to make sense of the multiplicity of descriptors that have been affixed to Chinese diplomacy, in order to underscore the ‘work’ they perform to bequeath (at times, divergent and contested) meanings to China’s new foreign policy approach. Hence, a relational and spatial understanding of Chinese diplomacy, we argue, can reveal a more nuanced picture of the promises, potential and disjunctures of China’s rapidly expanding geopolitical and diplomatic actions on the international stage