Although sphingosine 1-phosphate (Sph-1-P) is reportedly involved in diverse cellular processes and the physiological roles of this bioactive sphingolipid have been strongly suggested, few studies have revealed the presence of Sph-1-P in human samples, including body fluids and cells, under physiological conditions. In this study, we identified Sph-1-P as a normal constituent of human plasma and serum. The Sph-1-P levels in plasma and serum were 191+/-79 and 484+/-82 pmol/ml (mean+/-SD, n=8), respectively. Furthermore, when Sph-1-P was measured in paired plasma and serum samples obtained from 6 healthy adults, the serum Sph-1-P/plasma Sph-1-P ratio was found to be 2.65+/-1.26 (mean+/-SD). It is most likely that the source of discharged Sph-1-P during blood clotting is platelets, because platelets abundantly store Sph-1-P compared with other blood cells, and release part of their stored Sph-1-P extracellularly upon stimulation. We also studied Sph-1-P-related metabolism in plasma. [3H]Sph was stable and not metabolized at all in plasma, but was rapidly incorporated into platelets and metabolized mainly to Sph-1-P in platelet-rich plasma. [3H]Sph-1-P was found to be unchanged in plasma, revealing that plasma does not contain the enzymes needed for Sph-1-P degradation. In summary, platelets can convert Sph into Sph-1-P, and are storage sites for the latter in the blood. In view of the diverse biological effects of Sph-1-P, the release of Sph-1-P from activated platelets may be involved in a variety of physiological and pathophysiological processes, including thrombosis, hemostasis, atherosclerosis and wound healing.

PurposeAlthough the mental health status of doctoral students deserves attention, few scholars have paid attention to factors related to their mental health problems. We aimed to investigate the prevalence of depression and anxiety in doctoral students and examine possible associated factors. We further aimed to assess whether mentoring relationships mediate the association between research self-efficacy and depression/anxiety.MethodsA cross-sectional study was conducted among 325 doctoral students in a medical university. The Patient Health Questionnaire 9 and Generalized Anxiety Disorder 7 scale were used to assess depression and anxiety. The Research Self-Efficacy Scale was used to measure perceived ability to fulfill various research-related activities. The Advisory Working Alliance Inventory-student version was used to assess mentoring relationships. Linear hierarchical regression analyses were performed to determine if any factors were significantly associated with depression and anxiety. Asymptotic and resampling methods were used to examine whether mentoring played a mediating role.ResultsApproximately 23.7% of participants showed signs of depression, and 20.0% showed signs of anxiety. Grade in school was associated with the degree of depression. The frequency of meeting with a mentor, difficulty in doctoral article publication, and difficulty in balancing work–family–doctoral program was associated with both the level of depression and anxiety. Moreover, research self-efficacy and mentoring relationships had negative relationships with levels of depression and anxiety. We also found that mentoring relationships mediated the correlation between research self-efficacy and depression/anxiety.ConclusionThe findings suggest that educational experts should pay close attention to the mental health of doctoral students. Active strategies and interventions that promote research self-efficacy and mentoring relationships might be beneficial in preventing or reducing depression and anxiety.

A multiscale architecture with interlaced submicrometer ridges and nanoprotrusions is built on a polydimethylsiloxane (PDMS) surface by a combination of self‐assembly, soft lithography, and physical treatment (see picture). The multiscale structure reduces activated‐platelet adhesion under flow conditions, which is significant for the development of blood‐contacting materials.

Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) is a routine method for gene expression analysis, and reliable results depend on proper normalization by stable reference genes. Caloric restriction (CR) is a robust lifestyle intervention to slow aging and delay onset of age-associated diseases via inducing global changes in gene expression. Reliable normalization of RT-qPCR data becomes crucial in CR studies. In this study, the expression stability of 12 candidate reference genes were evaluated in inguinal white adipose tissue (iWAT), skeletal muscle (Sk.M) and liver of CR mice by using three algorithms, geNorm, NormFinder, and Bestkeeper. Our results showed β2m, Ppia and Hmbs as the most stable genes in iWAT, Sk.M and liver, respectively. Moreover, two reference genes were sufficient to normalize RT-qPCR data in each tissue and the suitable pair of reference genes was β2m-Hprt in iWAT, Ppia-Gusb in Sk.M and Hmbs-β2m in liver. By contrast, the least stable gene in iWAT or Sk.M was Gapdh, and in liver was Pgk1. Furthermore, the expression of Leptin and Ppar-γ were profiled in these tissues to validate the selected reference genes. Our data provided a basis for gene expression analysis in future CR studies.