The membrane-bound molecules programmed death 1 (PD-1) and its ligand PD-L1 (PD-1/PD-L1) belong to the immune checkpoint pathway. PD-1 pathway downregulates effector T cells in immune response, thereby causing immune suppression. Recent studies have revealed that membrane-bound PD-1 and PD-L1 also have soluble forms. These soluble forms increase the complexity and diversity of the composition and function of the PD-1/PD-L1 signaling pathway. However, the exact roles of these molecules remain unknown. The objective of this systematic review was to elucidate the biological significance of soluble PD-1/PD-L1 in human cancers and evaluate whether they are potential diagnostic, therapeutic, or prognostic biomarkers. We expect to provide new clues for future research on soluble PD-1/PD-L1 pathway in human malignant tumors.

During the process of aging, especially for postmenopausal females, the cell lineage commitment of mesenchymal stem cells (MSCs) shift to adipocyte in bone marrow, resulting in osteoporosis. However, the cell-intrinsic mechanism of this cell lineage commitment switch is poorly understood. As the post-transcription regulation by microRNAs (miRNAs) has a critical role in MSCs differentiation and bone homeostasis, we performed comprehensive miRNAs profiling and found miR-705 and miR-3077-5p were significantly enhanced in MSCs from osteoporosis bone marrow. Both miR-705 and miR-3077-5p acted as inhibitors of MSCs osteoblast differentiation and promoters of adipocyte differentiation, by targeting on the 3′untranslated region (3′UTR) of HOXA10 and RUNX2 mRNA separately. Combined inhibition of miR-705 and miR-3077-5p rescued the cell lineage commitment disorder of MSCs through restoring HOXA10 and RUNX2 protein level. Furthermore, we found excessive TNFα and reactive oxygen species caused by estrogen deficiency led to the upregulation of both miRNAs through NF-κB pathway. In conclusion, our findings showed that redundant miR-705 and miR-3077-5p synergistically mediated the shift of MSCs cell lineage commitment to adipocyte in osteoporosis bone marrow, providing new insight into the etiology of osteoporosis at the post-transcriptional level. Moreover, the rescue of MSCs lineage commitment disorder by regulating miRNAs expression suggested a novel potential therapeutic target for osteoporosis as well as stem cell-mediated regenerative medicine.

To better understand the elevational pattern of phylogenetic structure shown by alpine taxa and the underlying causes, we analyzed the phylogenetic structure of each elevational belt of alpine plants in the Hengduan Mountains Region, measured by net related index (NRI) and net nearest taxon index (NTI). We found both the indices of phylogenetic diversity indicated that alpine plants tended to show phylogenetic overdispersion at low elevational belts, implying that the distribution of alpine plants in these belts was mainly determined by interspecific competition. Alpine plants at higher elevational belts tended to phylogenetic clustering indicated by NRI, and NTI revealed phylogenetic clustering at the belts between 4300 m and 5500 m, which presumably suggested environment filtering and rapid speciation. Above 5500 m, NTI indicated that the phylogenetic structure became random again, perhaps due to the low intensity of filtering and the large distances between plants at the top of the scree slopes. We concluded that phylogenetic structure was, indeed, influenced by the environmental filter, interspecies interaction, rapid speciation during the uplift of the Qinghai-Tibet Plateau, and distance between plants.