The accurate estimation of stream water temperature is essential for understanding environmental controls on the structure and functioning of aquatic ecosystems. Few studies have coupled soil and stream water temperatures to capture the synergy of thermal balances between terrestrial and riverine systems. As a result, little is known about how multiple environmental stresses have affected water temperature, particularly for different orders of streams. Here we incorporated a new water transport scheme into the Dynamic Land Ecosystem Model (DLEM) to predict water temperature in 1st order and higher-order streams (>1st order). Driven by a 4-km geo-referenced dataset of multiple environmental factors, our new water temperature model was utilized to predict the spatiotemporal variations of water temperature in the U.S. Mid-Atlantic Region during 1900-2015. Results revealed that water temperature during 1970-2015 increased significantly (p < 0.05), and the rate of increase of the 1st order streams 0.32 degrees C.decade(-1) is higher than that of higher-order streams 0.28 degrees C . decade(-1). The buffering effect of groundwater on water temperature in 1st order streams diminished under the context of climate warming. Factorial analysis showed that climate change and variability explain most of the changes (similar to 80%) in stream water temperature since 1900. Land-use conversions (mostly from cropland to forest), CO2 fertilization, and land nitrogen management collectively explained a greater percent of change in water temperature in 1st order streams (24%) than higher-order streams (9%), implying that 1st order streams are particularly vulnerable to human activities.

Island ecosystem health is the integrative reflection of the states of different components on an island under multiple natural and anthropogenic influences. Evaluating island ecosystem health and identifying anthropogenic influences can provide important references for decision-makers in conserving the island ecosystem. In this study, island ecosystem health was evaluated by integrating three components (vegetation, soil, and landscape) using 12 factors sourced by field investigation and remote sensing. Baseline of the island ecosystem health was determined by ascertaining the natural area and context and eliminating the influences from natural factors. Then, the influences from each of the four typical types of island human activities, namely, building construction, traffic development, farming, and plantation, and the comprehensive influences from all of the four types on island ecosystem health were identified. Twenty-five islands in an important and typical archipelago in northern China were used as the study area. Results indicated that inhabited islands with small areas and uninhabited islands with large areas had good island ecosystem health, and the landscape component contributed most to the spatial variance. Traffic development, building construction, and farming generated negative influences and decreased the island ecosystem health by 28.56%, 23.38%, and 9.31%, respectively. By contrast, plantation increased the island ecosystem health by 17.14%. Overall, the four types of human activities increased the island ecosystem health by 2.74% and 5.91% for the inhabited and uninhabited islands, respectively. Scenario analyses revealed that the quality promotion of each human activity could improve the island ecosystem health more than the scale changes among different human activities. The results can help guide the spatial optimization of island human activities and the evaluation of island carrying capacity. (C) 2020 Elsevier Ltd. All rights reserved.

Adalimumab (ADA) is the only Food and Drug Administration-approved treatment for moderate-to-severe hidradenitis suppurativa, whereas etanercept and certolizumab-pegol have been shown to be ineffective, suggesting that the mechanism of action of ADA is distinct in hidradenitis suppurativa and may contribute to improved wound healing. Given that macrophages (M phi s) play pivotal roles throughout the wound healing process, an in vitro M phi differentiation assay was carried out to assess the impact of TNF-anti-TNF complexes on these cells. TNF-ADA complexes exhibited stronger inhibitory effects on inflammatory M phi differentiation. Moreover, RNA sequencing revealed several unique wound healing profiles for TNF-ADA-treated inflammatory M phi s, which were not observed for those treated with either TNF-etanercept or TNF-certolizumab-pegol complexes, including the inhibition of the matrix metalloproteinase (MMP) pathway. In addition, ADA administration was found to significantly reduce the levels of inflammatory MMP-1 and MMP-9 while promoting wound-healing MMP-13 and tissue inhibitor of metalloproteinases 2 levels in the circulation of the patients with hidradenitis suppurativa who responded to treatment. Our in vitro findings show that TNF-ADA-treated inflammatory M phi s exhibit a distinct profile resembling wound healing. Moreover, ADA not only differentially regulates MMP expression in patients with hidradenitis suppurativa responding to the therapy but also potentially induces a transition to a profile suggestive of wound healing.

It has been widely recognized that mechanical stretch can regulate the fate of stem cells (SCs). Previous research has shown that short-term mechanical stretch induces SC proliferation by activating the predominant transcription factor YAP, and YAP is a critical modulator in controlling epidermal proliferation. However, our study finds that after this phase, cell growth arrest appears, which is induced by long-term mechanical stretch. In the interfollicular epidermal SCs undergoing long-term mechanical stretch in vivo and in vitro, the level of H3K27me3 and its histone methyltransferase EZH2 are significantly elevated with suppressed expression of the target genes of YAP. EZH2 forms repressive H3K27me3 that suppresses gene transcription. Small-molecule inhibitor of EZH2 rescues significantly the cell growth arrest in interfollicular epidermal SCs induced by long-term mechanical stretch, thus promoting epidermal proliferation in vivo again. These findings reveal that there is an unexpected correlation between SC proliferation and the duration of mechanical stretch regulated by EZH2. This study of long-term mechanical stretch that induces cell growth arrest provides a strategy for clinical translation to promote skin regeneration.

Background & Aims: The nuclear factor of activated T-cells (NFAT) plays an important role in immune responses by regulating the expression of inflammatory genes. However, it is not known whether NFAT plays any role in the bile acid (BA)-induced hepatic inflammatory response. Thus, we aimed to examine the functional role of NFATc3 in cholestatic liver injury in mice and humans. Methods: Gene and protein expression and cellular localization were assessed in primary hepatocyte cultures (mouse and human) and cholestatic liver tissues (murine models and patients with primary biliary cholangitis [PBC] or primary sclerosing cholangitis [PSC]) by quantitative PCR, western blot and immunohistochemistry. Specific NFAT inhibitors were used in vivo and in vitro. Gene reporter assays and ChIP-PCR were used to determine promoter activity. Results: NFAT isoforms c1 and c3 were expressed in human and mouse hepatocytes. When treated with cholestatic levels of BAs, nuclear translocation of NFATc3 was increased in both human and mouse hepatocytes and was associated with elevated mRNA levels of IL-8, CXCL2, and CXCL10 in these cells. Blocking NFAT activation with pathway-specific inhibitors or knocking down Nfatc3 expression significantly decreased BA-driven induction of these cytokines in mouse hepatocytes. Nuclear expression of NFATc3/Nfatc3 protein was increased in cholestatic livers, both in mouse models (bile duct ligation or Abcb4(-/-)mice) and in patients with PBC and PSC in association with elevated tissue levels of Cxcl2 (mice) or IL-8 (humans). Gene reporter assays and ChIPPCR demonstrated that the NFAT response element in the IL-8 promoter played a key role in BA-induced human IL-8 expression. Finally, blocking NFAT activation in vivo in Abcb4(-/-)mice reduced cholestatic liver injury. Conclusions: NFAT plays an important role in BA-stimulated hepatic cytokine expression in cholestasis. Blocking hepatic NFAT activation may reduce cholestatic liver injury in humans. Lay summary: Bile acid induces liver injury by stimulating the expression of inflammatory genes in hepatocytes through activation of the transcription factor NFAT. Blocking this activation in vitro (in hepatocyte cultures) and in vivo (in cholestatic mice) decreased the expression of inflammatory genes and reduced liver injury. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The association of adiponectin with metabolism and cancer is well established. Since its discovery in 1990, adiponectin, as one of the adipose tissue-secreted adipokines, has been very widely studied in biomedical research. Low levels of circulatory adiponectin have been reported in obesity, inflammatory diseases and various types of cancers including colorectal cancer (CRC), which is highly linked with obesity and gut inflammation. However, the function and underlying mechanisms of adiponectin in CRC is not well understood. In addition, there are contradictory reports on the role of adiponectin in cancer. Therefore, further investigation is needed. In this review, we explore the information available on the relationship between adiponectin and CRC with respect to proliferation, cell survival, angiogenesis and inflammation. We also highlighted the knowledge gaps, filling in which could help us better understand the function and mechanisms of adiponectin in CRC.