Growing evidences suggest that the fibroblast growth factor/FGF receptor (FGF/FGFR) signaling has crucial roles in a multitude of processes during embryonic development and adult homeostasis by regulating cellular lineage commitment, differentiation, proliferation, and apoptosis of various types of cells. In this review, we provide a comprehensive overview of the current understanding of FGF signaling and its roles in organ development, injury repair, and the pathophysiology of spectrum of diseases, which is a consequence of FGF signaling dysregulation, including cancers and chronic kidney disease (CKD). In this context, the agonists and antagonists for FGF-FGFRs might have therapeutic benefits in multiple systems.

Synovitis, a common clinical symptom for osteoarthritis (OA) patients, is highly related to OA pathological progression and pain manifestation. The activated synovial macrophages have been demonstrated to play an important role in synovitis, but the mechanisms about macrophage activation are still not clear. In this study, we found that the exosome-like vesicles from osteoarthritic chondrocytes could be a new biological factor to stimulate inflammasome activation and increase mature IL-1β production in macrophages. The degraded cartilage explants produced more exosome-like vesicles than the nondegraded ones, while the exosome-like vesicles from chondrocytes could enter into joint synovium tissue and macrophages. Moreover, the exosome-like vesicles from osteoarthritic chondrocytes enhanced the production of mature IL-1β in macrophages. These vesicles could inhibit ATG4B expression via miR-449a-5p, leading to inhibition of autophagy in LPS-primed macrophages. The decreased autophagy promoted the production of mitoROS, which further enhanced the inflammasome activation and subsequent IL-1β processing. Ultimately, the increase of mature IL-1β may aggravate synovial inflammation and promote the progression of OA disease. Our study provides a new perspective to understand the activation of synovial macrophages and synovitis in OA patients, which may be beneficial for therapeutic intervention in synovitis-related OA patients.

Limitations of satellite radar altimetry for operational hydrology include its spatial and temporal sampling as well as measurement problems caused by local topography and heterogeneity of the reflecting surface. In this study, we develop an approach that eliminates most of these limitations to produce an approximately 3 day temporal resolution water level time series from the original typically (sub)monthly data sets for the Po River in detail, and for Congo, Mississippi, and Danube Rivers. We follow a geodetic approach by which, after estimating and removing intersatellite biases, all virtual stations of several satellite altimeters are connected hydraulically and statistically to produce water level time series at any location along the river. We test different data-selection strategies and validate our method against the extensive available in situ data over the Po River, resulting in an average correlation of 0.7, Root-Mean-Square Error of 0.8 m, bias of 20.4 m, and Nash-Sutcliffe Efficiency coefficient of 0.5. We validate the transferability of our method by applying it to the Congo, Mississippi, and Danube Rivers, which have very different geomorphological and climatic conditions. The methodology yields correlations above 0.75 and Nash-Sutcliffe coefficients of 0.84 (Congo), 0.34 (Mississippi), and 0.35 (Danube). Maillard et al., 2015]. Such studies were motivated to a large extent by the premise that satellite altimetry may fill the gap left by the decline of gauge stations database. Surprisingly, other hydrological data like discharge are available in the open domain globally to a larger extent than in situ water level data. Since it cannot realistically be expected that the distribution and availability of global in situ water level stations will be improved in the future, of course with regional exceptions, research on the use of geodetic satellite data needs to be expanded. It is expected that time series from individual altimetric missions over most rivers are of poor quality, due to the neighboring topography and the heterogeneity of the reflecting surface. Therefore, the time series from individual missions often carry uncertainties and contain data outages, which limit the operational use of altimetry for improving the global river water level databases. As a result, these limitations inhibit also the operational use of altimetric water level into hydrological and hydrodynamic models [Alsdorf et al., 2007].