Assessment of ecological environment in arid region based on the improved remote sensing ecological index: A case study of Wuchuan County, Inner Mongolia at the northern foot of Yin Mountains.

Real-time assessment of ecological environment quality in arid and semi-arid regions is crucial for the sustainable development of ecological environments in China. In this study, we constructed a topsoil remote sensing ecological index (TRSEI) by coupling five indicators, greenness, wetness, dryness, topsoil grain size, and heat, with the Google Earth Engine (GEE). With the index, we evaluated the ecological environment quality of Wuchuan County from 1990 to 2020, and examined the spatio-temporal variations of ecological environment quality and its driving factors by using univariate linear regression, multiple regression residual analysis, and Hurst index. Results showed that the first principal component of the TRSEI in the study area contributed over 70%, with a mean eigenvalue of 0.148, indicating the effective integration of various ecological indicators by TRSEI. The topsoil grain size index was essential for the assessment of ecological environment quality in arid and semi-arid regions. From 1990 to 2020, the fluctuation range of TRSEI in the study area was between 0.289 and 0.458, showing an overall slight deterioration trend. The ecological environment quality of cropland and de-farming region had improved, with the improved area accounting for 47.9% of the total area. The grassland, barren land, and construction land areas had deteriorated, with the deteriorated area accounting for 52.1% of the total area. In the future, 36.9% of the regions would experience continuous improvement in ecological environment quality, while 41.4% might continue to dete-riorate. Human activities were the primary driving factor for the changes in ecological environment quality in arid and semi-arid regions, accounting for 88.6% of the total area. Climate change also had a significant impact, accounting for 11.4% of the total area. The TRSEI could effectively assess the ecological environment quality of arid and semi-arid regions, providing a scientific basis for ecological conservation and construction in these areas.

Inhibition of USP10 induces myeloma cell apoptosis by promoting cyclin D3 degradation.

The cell cycle regulator cyclin D3 (CCND3) is highly expressed in multiple myeloma (MM) and it promotes MM cell proliferation. After a certain phase of cell cycle, CCND3 is rapidly degraded, which is essential for the strict control of MM cell cycle progress and proliferation. In the present study, we investigated the molecular mechanisms regulating CCND3 degradation in MM cells. By utilizing affinity purification-coupled tandem mass spectrometry, we identified the deubiquitinase USP10 interacting with CCND3 in human MM OPM2 and KMS11 cell lines. Furthermore, USP10 specifically prevented CCND3 from K48-linked polyubiquitination and proteasomal degradation, therefore enhancing its activity. We demonstrated that the N-terminal domain (aa. 1-205) of USP10 was dispensable for binding to and deubiquitinating CCND3. Although Thr283 was important for CCND3 activity, it was dispensable for CCND3 ubiquitination and stability modulated by USP10. By stabilizing CCND3, USP10 activated the CCND3/CDK4/6 signaling pathway, phosphorylated Rb, and upregulated CDK4, CDK6 and E2F-1 in OPM2 and KMS11 cells. Consistent with these findings, inhibition of USP10 by Spautin-1 resulted in accumulation of CCND3 with K48-linked polyubiquitination and degradation that synergized with Palbociclib, a CDK4/6 inhibitor, to induce MM cell apoptosis. In nude mice bearing myeloma xenografts with OPM2 and KMS11 cells, combined administration of Spautin-l and Palbociclib almost suppressed tumor growth within 30 days. This study thus identifies USP10 as the first deubiquitinase of CCND3 and also finds that targeting the USP10/CCND3/CDK4/6 axis may be a novel modality for the treatment of myeloma.

Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1.

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.