MicroRNAs (miR), as important epigenetic control factors, reportedly regulate wound repair. However, our insufficient knowledge of clinically relevant miRs hinders their potential therapeutic use. For this, we performed paired small RNA and long RNA sequencing and integrative omics analysis in human tissue samples, including matched skin and acute wounds collected at each healing stage and chronic non-healing venous ulcers (VU). On the basis of the findings, we developed a compendium (https://www.xulandenlab.com/humanwounds-mirna-mrna), which will be an open, comprehensive resource to broadly aid wound healing research. With this first clinical, wound-centric resource of miRs and mRNAs, we identified 17 pathologically relevant miRs that exhibited abnormal VU expression and displayed their targets enriched explicitly in the VU gene signature. Intermeshing regulatory networks controlled by these miRs revealed their high cooperativity in contributing to chronic wound pathology characterized by persistent inflammation and proliferative phase initiation failure. Furthermore, we demonstrated that miR-34a, miR-424, and miR-516, upregulated in VU, cooperatively suppressed keratinocyte migration and growth while promoting inflammatory response. By combining miR expression patterns with their specific target gene expression context, we identified miRs highly relevant to VU pathology. Our study opens the possibility of developing innovative wound treatment that targets pathologically relevant cooperating miRs to attain higher therapeutic efficacy and specificity.

To decide whether a course of action is worth pursuing, individuals typically weigh its expected costs and benefits. Optimal decision-making relies upon accurate effort cost anticipation, which is generally assumed to be performed independently from goal valuation. In two experiments (n = 46), we challenged this independence principle of standard decision theory. We presented participants with a series of treadmill routes randomly associated to monetary rewards and collected both ‘accept’ versus ‘decline’ decisions and subjective estimates of energetic cost. Behavioural results show that higher monetary prospects led participants to provide higher cost estimates, although reward was independent from effort in our design. Among candidate cognitive explanations, they support a model in which prospective cost assessment is biased by the output of an automatic computation adjusting effort expenditure to goal value. This decision bias might lead people to abandon the pursuit of valuable goals that are in fact not so costly to achieve.