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Introduction: High-altitude pulmonary edema (HAPE) is a severe and potentially fatal condition with limited treatment options. Although ceramide kinase (CERK)-derived ceramide-1-phosphate (C1P) has been demonstrated to offer protection against various pulmonary diseases, its effects on HAPE remain unclear. Objectives: Our study aimed to investigate the potential role of CERK-derived C1P in the development of HAPE and to reveal the molecular mechanisms underlying its protective effects. We hypothesized that CERK-derived C1P could protect against HAPE by stabilizing circadian rhythms and maintaining mitochondrial dynamics. Methods: To test our hypothesis, we used CERK-knockout mice and established HAPE mouse models using a FLYDWC50-1C hypobaric hypoxic cabin. We utilized a range of methods, including lipidomics, transcriptomics, immunofluorescence, Western blotting, and transmission electron microscopy, to identify the mechanisms of regulation. Results: Our findings demonstrated that CERK-derived C1P played a protective role against HAPE. Inhibition of CERK exacerbated HAPE induced by the hypobaric hypoxic environment. Specifically, we identified a novel mechanism in which CERK inhibition induced aryl hydrocarbon receptor nuclear translocator-like (ARNTL) autophagic degradation, inducing the circadian rhythm and triggering mitochondrial damage by controlling the expression of proteins required for mitochondrial fission and fusion. The decreased ARNTL caused by CERK inhibition impaired mitochondrial dynamics, induced oxidative stress damage, and resulted in defects in mitophagy, particularly under hypoxia. Exogenous C1P prevented ARNTL degradation, alleviated mitochondrial damage, neutralized oxidative stress induced by CERK inhibition, and ultimately relieved HAPE. Conclusions: This study provides evidence for the protective effect of C1P against HAPE, specifically, through stabilizing circadian rhythms and maintaining mitochondrial dynamics. Exogenous C1P therapy may be a promising strategy for treating HAPE. Our findings also highlight the importance of the circadian rhythm and mitochondrial dynamics in the pathogenesis of HAPE, suggesting that targeting these pathways may be a potential therapeutic approach for this condition.

Backgrounds: High-altitude pulmonary edema (HAPE) is a life-threatening disease without effective drugs. Caffeine is a small molecule compound with antioxidant biological activity used to treat respiratory distress syndrome. However, it is unclear whether caffeine plays a role in alleviating HAPE.Methods: We combined a series of biological experiments and label-free quantitative proteomics analysis to detect the effect of caffeine on treating HAPE and explore its mechanism in vivo and in vitro.Results: Dry and wet weight ratio and HE staining of pulmonary tissues showed that the HAPE model was constructed successfully, and caffeine relieved pulmonary edema. The proteomic results of mice lungs indicated that regulating mitochondria might be the mechanism by which caffeine reduced HAPE. We found that caffeine blocked the reduction of ATP production and oxygen consumption rate, decreased ROS accumulation, and stabilized mitochondrial membrane potential to protect AT1 cells from oxidative stress damage under hypoxia. Caffeine promoted the PINK1/parkin-dependent mitophagy and enhanced mitochondrial fission to maintain the mitochondria quality control process.Conclusion: Low-dose of caffeine alleviated HAPE by promoting PINK1/parkin-dependent mitophagy and mitochondrial fission to control the mitochondria quality. Therefore, caffeine could be a potential treatment for HAPE.

ABSTRACT The intestinal microbiota is significantly affected by the external environment, but our understanding of the effects of extreme environments such as plateaus is far from adequate. In this study, we systematically analyzed the variation in the intestinal microbiota and 76 blood clinical indexes among 393 healthy adults with different plateau living durations (Han individuals with no plateau living, with plateau living for 4 to 6 days, with plateau living for >3 months, and who returned to the plain for 3 months, as well as plateau-living Tibetans). The results showed that the high-altitude environment rapidly (4 days) and continually (more than 3 months) shaped both the intestinal microbiota and clinical indexes of the Han population. With prolongation of plateau living, the general characteristics of the intestinal microbiota and clinical indexes of the Han population were increasingly similar to those of the Tibetan population. The intestinal microbiota of the Han population that returned to the plain area for 3 months still resembled that of the plateau-living Han population rather than that of the Han population on the plain. Moreover, clinical indexes such as blood glucose were significantly lower in the plateau groups than in the nonplateau groups, while the opposite result was obtained for testosterone. Interestingly, there were Tibetan-specific correlations between glucose levels and Succinivibrio and Sarcina abundance in the intestine. The results of this study suggest that a hypoxic environment could rapidly and lastingly affect both the human intestinal microbiota and blood clinical indexes, providing new insights for the study of plateau adaptability. IMPORTANCE The data presented in the present study demonstrate that the hypoxic plateau environment has a profound impact on the gut microbiota and blood clinical indexes in Han and Tibetan individuals. The plateau-changed signatures of the gut microbiota and blood clinical indexes were not restored to the nonplateau status in the Han cohorts, even when the individuals returned to the plain from the plateau for several months. Our study will improve the understanding of the great impact of hypoxic environments on the gut microbiota and blood clinical indexes as well as the adaptation mechanism and intervention targets for plateau adaptation.

Accurate estimation of high-resolution satellite precipitation products like Global Precipitation Measurement (GPM) and Tropical Rainfall Measuring Mission (TRMM) is critical for hydrological and meteorological research, providing a benchmark for the continued development and future improvement of these products. This study aims to comprehensively evaluate the Integrated Multi-Satellite Retrievals for GPM (IMERG) and TRMM 3B42V7 products at multiple temporal scales from 1 January 2015 to 31 December 2017 over the Huang-Huai-Hai Plain in China, using daily precipitation data from 59 meteorological stations. Three commonly used statistical metrics (CC, RB, and RMSE) are adopted to quantitatively verify the accuracy of two satellite precipitation products. The assessment also takes into account the precipitation detection capability (POD, FAR, CSI, and ACC) and frequency of different precipitation intensities. The results show that the IMERG and 3B42V7 present strong correlation with meteorological stations observations at annual and monthly scales (CC > 0.90), whereas moderate at the daily scale (CC = 0.76 and 0.69 for IMERG and 3B42V7, respectively). The spatial variability of the annual and seasonal precipitation is well captured by these two satellite products. And spatial patterns of precipitation gradually decrease from south to north over the Huang-Huai-Hai Plain. Both IMERG and 3B42V7 products overestimate precipitation compared with the station observations, of which 3B42V7 has a lower degree of overestimation. Relative to the IMERG, annual precipitation estimates from 3B42V7 show lower RMSE (118.96 mm and 142.67 mm, respectively), but opposite at the daily, monthly, and seasonal scales. IMERG has a better precipitation detection capability than 3B42V7 (POD = 0.83 and 0.67, respectively), especially when detecting trace and solid precipitation. The two precipitation products tend to overestimate moderate (2–10 mm/d) and heavy (10–50 mm/d) precipitation events, but underestimate violent (>50 mm/d) precipitation events. The IMERG is not found capable to detecting precipitation events of different frequencies more precisely. In general, the accuracy of IMERG is better than 3B42V7 product in the Huang-Huai-Hai Plain. The IMERG satellite precipitation product with higher temporal and spatial resolutions can be regarded a reliable data sources in studying hydrological and climatic research.

The combination of strain sensors and wearable devices is an important topic in the field of human–machine interface. We describe a stretchable, flexible, ultrasensitive, simple and low-cost strain sensor based on the PDMS/MWCNTs/PDMS sandwich structure. The sensitive film was prepared by the layer-by-layer self-assembly method. The sensor exhibited the stable mechanical properties in the high measurement range (0.1%–75%) with the gauge factor more than 100. We demonstrate a proof of concept to detect the full-scale change of the human motions, including large movements of human limbs and subtle deformations on human skin. Moreover, the sensor was attached to the throat and face to monitor the human expression during speaking, crying, smiling and swallowing. Due to its excellent characteristics, it could open up a new way for the development of the next generation of high-tech applications, like intelligent devices, wearable electronics and human–machine interface systems. [ABSTRACT FROM AUTHOR]