Cytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses ...against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.
The Tienshan Mountains, with its status as "water tower", is the main water source and ecological barrier in Central Asia. The rapid warming affected precipitation amounts and fraction as well as the ...original glacier/snowmelt water processes, thereby affecting the runoff and water storage. The ratio of snowfall to precipitation (S/P) experienced a downward trend, along with a shift from snow to rain. Spatially, the snow cover area in Middle Tienshan Mountains decreased significantly, while that in West Tienshan Mountains increased slightly. Approximately 97.52% of glaciers in the Tienshan Mountains showed a retreating trend, which was especially obvious in the North and East Tienshan Mountains. River runoff responds in a complex way to changes in climate and cryosphere. It appears that catchments with a higher fraction of glacierized area showed mainly increasing runoff trends, while river basins with less or no glacierization exhibited large variations in the observed runoff changes. The total water storage in the Tienshan Mountains also experienced a significant decreasing trend in Middle and East Tienshan Mountains, but a slight decreasing trend in West Tienshan Mountains, totally at an average rate of -3.72 mm/a. In future, water storage levels are expected to show deficits for the next half-century.
Snowfall is a critical part of the hydrological system in high‐altitude regions and strongly impacted by climate change. This study uses a threshold temperature method to estimate spatial and ...temporal variations of snowfall at 71 stations across the Tibetan Plateau from 1960 to 2014. Regional air temperature and precipitation have increased by 0.039°C/yr, and 1.43 mm/yr, respectively. While warming rates have been fairly uniform across the plateau, spatial variations in snowfall trends are large, with decreases in the eastern and northeastern areas but increases at higher elevations in the center and west. Region‐wide snowfall increased during 1961–1990 and 1971–2000 but decreased in 1981–2010 and 1991–2014. Wintertime snowfall has increased, but summer snowfall has decreased. These divergent trends can be explained because maximum snowfall is recorded at temperatures between 1 and 2°C. Above/below this threshold snowfall usually decreases/increases with increased warming. Although maximum snowfall temperature is a key factor to understand future snowfall changes, concurrent influences such as changing moisture sources and atmospheric circulation patterns require further research.
Key Points
We use a two‐threshold temperature method to model snowfall at 71 stations across the Tibetan Plateau
Region‐wide snowfall increased during 1961‐1990 and 1971‐2000 but decreased in the more recent period 1981‐2010
Seasonal/elevational contrasts in snow trends can be explained in part referring to mean temperature
Plain Language Summary
The Tibetan Plateau is warming as a result of climate change. This is decreasing the amount of snow and ice in general. However, the biggest snowfalls occur when the temperatures are near freezing because warmer air can hold more moisture. We examine the trends in snowfall amounts using 71 stations for the last 45‐‐50~years. Early in the period the snow tended to increase, but since 1981 there has been a rapid decline in snowfall over most of the plateau, especially in the east and at moderate elevations around 2000~m above sea‐level. Above 3000~m, however, most areas have shown an increase in snowfall. Even though the snowline is therefore moving up the mountain, at the highest elevations (where it is still cold and below freezing) there is still plenty of snowfall, at least over the recent past. This is because where it is very cold increasing temperatures can bring more snow. Where it is already around freezing increasing temperatures will mean snow will change to rain and there will be a rapid decrease. This also means that there is a difference between the seasons with winter showing more snowfall, in general, and summer and autumn much less.
The arid region of Northwest China, located in the central Asia, responds sensitively to global climate change. Based on the newest research results, this paper analyzes the impacts of climate change ...on hydrology and the water cycle in the arid region of Northwest China. The analysis results show that: (1) In the northwest arid region, temperature and precipitation experienced “sharply” increasing in the past 50 years. The precipitation trend changed in 1987, and since then has been in a state of high volatility, during the 21st century, the increasing rate of precipitation was diminished. Temperature experienced a “sharply” increase in 1997; however, this sharp increasing trend has turned to an apparent hiatus since the 21st century. The dramatic rise in winter temperatures in the northwest arid region is an important reason for the rise in the average annual temperature, and substantial increases in extreme winter minimum temperature play an important role in the rising average winter temperature; (2) There was a significant turning point in the change of pan evaporation in the northwest arid area in 1993, i.e., in which a significant decline reversed to a significant upward trend. In the 21st century, the negative effects of global warming and increasing levels of evaporation on the ecology of the northwest arid region have been highlighted; (3) Glacier change has a significant impact on hydrology in the northwest arid area, and glacier inflection points have appeared in some rivers. The melting water supply of the Tarim River Basin possesses a large portion of water supplies (about 50%). In the future, the amount of surface water will probably remain at a high state of fluctuation.
•The sharp increasing of temperature has turned to hiatus since the 21st century.•Precipitation sharply increased in 1987, since then has been in a high volatility.•Negative effects of global warming on the ecology have been highlighted.•The amount of surface water will probably remain at a high state of fluctuation.
In cancer, epithelial-mesenchymal transition (EMT) is associated with metastasis. Characterizing EMT phenotypes in circulating tumor cells (CTCs) has been challenging because epithelial marker-based ...methods have typically been used for the isolation and detection of CTCs from blood samples. The aim of this study was to use the optimized CanPatrol CTC enrichment technique to classify CTCs using EMT markers in different types of cancers. The first step of this technique was to isolate CTCs via a filter-based method; then, an RNA in situ hybridization (RNA-ISH) method based on the branched DNA signal amplification technology was used to classify the CTCs according to EMT markers. Our results indicated that the efficiency of tumor cell recovery with this technique was at least 80%. When compared with the non-optimized method, the new method was more sensitive and more CTCs were detected in the 5-ml blood samples. To further validate the new method, 164 blood samples from patients with liver, nasopharyngeal, breast, colon, gastric cancer, or non-small-cell lung cancer (NSCLC) were collected for CTC isolation and characterization. CTCs were detected in 107 (65%) of 164 blood samples, and three CTC subpopulations were identified using EMT markers, including epithelial CTCs, biophenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs. Compared with the earlier stages of cancer, mesenchymal CTCs were more commonly found in patients in the metastatic stages of the disease in different types of cancers. Circulating tumor microemboli (CTM) with a mesenchymal phenotype were also detected in the metastatic stages of cancer. Classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulation and provides useful evidence for determining an appropriate clinical approach. This method is suitable for a broad range of carcinomas.
With the rapid development of medical imaging technology and computer technology, the medical imaging artificial intelligence of computer-aided diagnosis based on machine learning has become an ...important part of modern medical diagnosis. With the application of medical image security technology, people realize that the difficulty of its development is the inherent defect of advanced image processing technology. This paper introduces the background of colorectal cancer diagnosis and monitoring, and then carries out academic research on the medical imaging artificial intelligence of colorectal cancer diagnosis and monitoring and machine learning, and finally summarizes it with the advanced computational intelligence system for the application of safe medical imaging.In the experimental part, this paper wants to carry out the staging preparation stage. It was concluded that the staging preparation stage of group Y was higher than that of group X and the difference was statistically significant. Then the overall accuracy rate of multimodal medical image fusion was 69.5% through pathological staging comparison. Finally, the diagnostic rate, the number of patients with effective treatment and satisfaction were analyzed. Finally, the average diagnostic rate of the new diagnosis method was 8.75% higher than that of the traditional diagnosis method. With the development of computer science and technology, the application field was expanding constantly. Computer aided diagnosis technology combining computer and medical images has become a research hotspot.
Metabolic associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis. We demonstrated that ...phosphoenolpyruvate carboxykinase 1 (PCK1) plays a central role in MAFLD progression. Male mice with liver Pck1 deficiency fed a normal diet displayed hepatic lipid disorder and liver injury, whereas fibrosis and inflammation were aggravated in mice fed a high-fat diet with drinking water containing fructose and glucose (HFCD-HF/G). Forced expression of hepatic PCK1 by adeno-associated virus ameliorated MAFLD in male mice. PCK1 deficiency stimulated lipogenic gene expression and lipid synthesis. Moreover, loss of hepatic PCK1 activated the RhoA/PI3K/AKT pathway by increasing intracellular GTP levels, increasing secretion of platelet-derived growth factor-AA (PDGF-AA), and promoting hepatic stellate cell activation. Treatment with RhoA and AKT inhibitors or gene silencing of RhoA or AKT1 alleviated MAFLD progression in vivo. Hepatic PCK1 deficiency may be important in hepatic steatosis and fibrosis development through paracrine secretion of PDGF-AA in male mice, highlighting a potential therapeutic strategy for MAFLD.
Abstract
Revealing changes in actual evapotranspiration is essential to understanding regional extreme hydrological events (e.g., droughts). This study utilized the Global Land Evaporation Amsterdam ...Model (GLEAM) to analyse the spatial and temporal characteristics of actual evapotranspiration over 40 years in the Southeast River basin of China. The relationship between changes in actual evapotranspiration and the drought index was quantified. The results indicated a significant increase in actual evapotranspiration in the Southeast River basin from 1981 to 2020 (2.51 mm/year,
p
< 0.01). The actual evapotranspiration components were dominated by vegetation transpiration (73.45%) and canopy interception (18.26%). The actual evapotranspiration was closely related to the normalised difference vegetation index (r = 0.78,
p
< 0.01), and vegetation changes could explain 10.66% of the increase of actual evapotranspiration in the Southeast River basin since 2000. Meanwhile, actual evapotranspiration and standardised precipitation evapotranspiration index (SPEI) showed a highly significant negative spatial correlation, with a Moran's I index of − 0.513. The rise in actual evapotranspiration is an important trigger factor for seasonal droughts in the region. Therefore, these results help deepen the understanding of hydro-climatic process changes in the southeastern coastal region of China.
The grid-based precipitation dataset is an important source for studying precipitation change in the high mountains of Asia due to where precipitation stations are sparse. It is essential to evaluate ...the accuracy of grid-based precipitation datasets in the high mountains of Asia before selecting an appropriate grid-based dataset. Therefore, this study comprehensively evaluated the precipitation errors of four commonly utilized precipitation datasets (multi-source weighted-ensemble precipitation (MSWEP), global precipitation climatology centre (GPCC), global precipitation measurement (GPM), and soil moisture to rain-advanced scatterometer (SM2RAIN-ASCAT)) in the high mountains of Asia from temporal and spatial perspectives. It then decomposed the precipitation errors to reveal their sources. The results showed that MSWEP, GPCC, GPM, and SM2RAIN-ASCAT overestimated precipitation amount and probability compared with station observations. Meanwhile, all precipitation data sets except MSWEP data underestimated precipitation in the dry season. In terms of the average values of the error metrics, GPCC performed the best. There was an evident annual periodicity in the error assessment metrics for the four precipitation data sets. Multiple linear regression analysis revealed that four precipitation-related factors (false alarm precipitation, missed amount of precipitation, precipitation detected presented, and precipitation detected event) explained the root mean square error values for four precipitation data sets, with precipitation detected presented having the largest weight. The root mean square error of each product exhibits periodic fluctuations with changes in precipitation quantity, attributed to the occurrences of precipitation detected presented and precipitation detected events. These findings provide useful reference information for correcting biases in precipitation data sets for high mountains of Asia.
SLC2A5 is a high-affinity fructose transporter, which is frequently upregulated in multiple human malignant tumours. However, the function and molecular mechanism of SLC2A5 in colorectal cancer (CRC) ...remain unknown.
We detected the expression levels of SLC2A5 in CRC tissues and CRC cell lines by western blotting, qRT-PCR and immunohistochemistry. CRC cell lines with stable overexpression or knockdown of SLC2A5 were constructed to evaluate the functional roles of SLC2A5 in vitro through conventional assays. An intrasplenic inoculation model was established in mice to investigate the effect of SLC2A5 in promoting metastasis in vivo. Methylation mass spectrometry sequencing, methylation specific PCR, bisulphite sequencing PCR, ChIP-qPCR and luciferase reporter assay were performed to investigate the molecular mechanism underlying transcriptional activation of SLC2A5.
We found that SLC2A5 was upregulated in colorectal tumour tissues. Functionally, a high level of SLC2A5 expression was associated with increased invasion and metastasis capacities of CRC cells both in vitro and in vivo. Mechanistically, we unveiled that S100P could integrate to a specific region of SLC2A5 promoter, thereby reducing its methylation levels and activating SLC2A5 transcription.
Our results reveal a novel mechanism that S100P mediates the promoter demethylation and transcription activation of SLC2A5, thereby promoting the metastasis of CRC.
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