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This article evaluated the performance of 19 Coupled Model Intercomparison Project phase 6 (CMIP6) models in simulating the Arctic sea ice from the perspective of annual cycle, spatial pattern and temporal variation. Based on the evaluation, five models with better comprehensive performance capacity were optimized as the ensemble to project the response of the East Asian winter climate to the sea ice‐free Arctic occurring under the SSP2‐4.5 and SSP5‐8.5 scenarios, respectively. The ensemble projections indicate that the sea ice‐free Arctic is followed by a weakening of the East Asian winter monsoon, which is characterized with the shallower East Asian trough and weaker East Asian jet stream. Concurrently, the winter surface net radiation flux is projected to increase in the East Asian‐western North Pacific region. These changes favour large‐scale warming in the East Asian‐western North Pacific region. Moreover, the warming is more pronounced under the sea ice‐free Arctic of SSP2‐4.5 than under that of SSP5‐8.5. The winter precipitation tends to increase along the East Asian coast from South China to the Sea of Okhotsk. Such an increase is closely associated with the enhancement of low‐level moisture. Due to larger enhancement of moisture, there appears greater increase of precipitation in the monsoon region from South China to Japan under the sea ice‐free Arctic of SSP5‐8.5 compare to that under SSP2‐4.5. Substantial changes are also projected for the temperature and precipitation extremes, such as a general increase in warm days and warm nights and an overall intensification of extreme precipitation in the East Asian‐western North Pacific region. [ABSTRACT FROM AUTHOR]

Background and Purpose: Non‐alcoholic fatty liver disease (NAFLD) affects over 25% of the general population and lacks an effective treatment. Recent evidence implicates disrupted mitochondrial calcium homeostasis in the pathogenesis of hepatic steatosis. Experimental Approach: In this study, mitochondrial calcium uniporter (MCU) was inhibited through classical genetic approaches, viral vectors or small molecule inhibitors in vivo to study its role in hepatic steatosis induced by high‐fat diet (HFD). In vitro, MCU was overexpressed or inhibited to change mitochondrial calcium homeostasis, endoplasmic reticulum–mitochondrial linker was adopted to increase mitochondria‐associated membranes (MAMs) and MICU1‐EF hand mutant was used to decrease the sensitivity of mitochondrial calcium uptake 1 (MICU1) to calcium and block MCU channel. Key Results: Here, we found that inhibition of liver MCU by AAV virus and classical genetic approaches can prevent HFD‐induced liver steatosis. MCU regulates mitochondrial calcium homeostasis and affects lipid accumulation in liver cells. In addition, a HFD in mice enlarged the MAM. The high‐calcium environment produced by MAM invalidated the function of MICU1 and led to persistent open of MCU channels. Therefore, it caused mitochondrial calcium overload and liver fat deposition. Inhibition of MAM and MCU alleviated HFD‐induced hepatic steatosis. MCU inhibitors (Ru360 and mitoxantrone) can block MCU channels and reduce mitochondrial calcium levels. Intraperitoneal injection of MCU inhibitors (0.01‐μM·kg−1 bodyweight) can alleviate HFD‐induced hepatic steatosis. Conclusion and Implications: These findings provide molecular insights into the way HFD disrupts mitochondrial calcium homeostasis and identify MCU as a promising drug target for the treatment of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Ceiling culture is an inverted and closed cell culture system which represents a novel method for exploring adipocyte characteristics and function. Although the role of ceiling culture in mature adipocyte dedifferentiation has been extensively studied, its potential effects on preadipocyte differentiation remain unclear. In this study, we established a simplified dish ceiling culture method for 3T3-L1 preadipocytes and showed that our novel ceiling culture method could reproduce the function of the traditional flask ceiling culture. Then, we investigated the effects of ceiling culture on 3T3-L1 preadipocyte differentiation by Oil red O staining and RT-qPCR. The results showed that ceiling culture significantly impaired triglyceride accumulation and adipogenic marker genes expression in 3T3-L1 preadipocytes. These findings suggest that ceiling culture inhibited 3T3-L1 preadipocyte differentiation while inducing mature adipocytes dedifferentiation. Taken together, our data facilitate the understanding of the property of ceiling culture and promote the study of revealing the underlying mechanisms of mature adipocytes dedifferenatiation. [ABSTRACT FROM AUTHOR]