Male sexual arousal (SA) has been known as a multidimensional experience involving closely interrelated and coordinated neurobehavioral components that rely on widespread brain regions. Recent functional neuroimaging studies have shown relation between abnormal/altered dynamics in these circuits and male sexual dysfunction. However, alterations in the topological1 organization of structural brain networks in male sexual dysfunction are still unclear. Here, we used graph theory2 to investigate the topological properties of large-scale structural brain networks, which were constructed using inter-regional correlations of cortical (...) thickness between 78 cortical regions (subcortical regions were not included due to the used cortical surface model) in 40 patients with psychogenic erectile dysfunction (pED) and 39 normal controls. Compared with normal controls, pED patients exhibited a less optimal global topological organization with reduced global and increased local efficiencies. Our results suggest disrupted neural integration among distant brain regions in pED patients, consistent with previous reports of impaired white matter structure and abnormal functional integrity in pED. Additionally, disrupted global network topology in pED was observed to be primarily relevant to altered subnetwork and nodal properties within the networks mediating the cognitive, motivational and inhibitory processes of male SA, possibly indicating disrupted integration of these networks in the whole brain networks and might account for pED patients’ abnormal cognitive, motivational and inhibitory processes for male SA. In total, our findings provide evidence for disrupted integrity in large-scale brain networks underlying the neurobehavioral processes of male SA in pED and provide new insights into the understanding of the pathophysiological mechanisms of pED. (shrink)

Bromodomain‐containing 4 (BRD4), a member of Bromo and Extra‐Terminal (BET) family, recognizes acetylated histones and is of importance in transcription, replication, and DNA repair. It also binds non‐histone proteins, DNA and RNA, contributing to development, tissue growth, and various physiological processes. Additionally, BRD4 has been implicated in driving diverse diseases, ranging from cancer, viral infection, inflammation to neurological disorders. Inhibiting its functions with BET inhibitors (BETis) suppresses the progression of several types of cancer, creating an impetus for translating these chemicals (...) to the clinic. The diverse roles of BRD4 are largely dependent on its interaction partners in different contexts. In this review we discuss the molecular mechanisms of BRD4 with its interacting partners in physiology and pathology. Current development of BETis is also summarized. Further understanding the functions of BRD4 and its partners will facilitate resolving the liabilities of present BETis and accelerate their clinical translation. (shrink)

Plato's Theaetetus develops an inquiry concerning the definition of knowledge. Famously, after Socrates and Theaetetus have discussed the three candidates for the definition of knowledge, the end of the dialogue seems to leave us in a situation of aporia. The present article focuses on the last hypothesis raised in the dialogue and tries to determine whether this hypothesis can be seen, under appropriate qualification, as acceptable within a Platonic framework. This hypothesis is connected with a dream theory that unfolds two (...) crucial factors for understanding the definition of knowledge, i.e. elements and logos. So the aim of this paper is twofold: on the one hand, to make clear what elements properly are; on the other hand, to find an account of logos suitable to make it a necessary condition for the definition of knowledge. As will emerge from this paper, the first two candidates for the definition of knowledge are indeed not sufficient for gaining an adequate definition, but they nonetheless foreshadow the third hypothesis and are necessary conditions for understanding the third one. (shrink)