ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression

Background Cell metabolism plays a pivotal role in tumor progression,and targeting cancer metabolism might effectively kill cancer cells.We aimed to investigate the role of hexokinases in prostate cancer(PCa)and identify a crucial target for PCa treatment.Methods The Cancer Genome Atlas(TCGA)database,online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase(ADPGK)in PCa.The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo.Quantitative proteomics,metabolomics,and extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)tests were performed to evaluate the impact of ADPGK on PCa metabolism.The underlying mechanisms were explored through ADPGK overexpression and knockdown,co-immunoprecipitation(Co-IP),ECAR analysis and cell counting kit-8(CCK-8)assays.Results ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival(OS)in prostate adenocarcinoma(PRAD).Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs.non-PCa tissues.High ADPGK expression indicates worse survival outcomes,and ADPGK serves as an independent factor of biochemical recurrence.In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration,and ADPGK inhibition suppressed malignant phenotypes.Metabolomics,proteomics,and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa.Mechanistically,ADPGK binds aldolase C(ALDOC)to promote glycolysis via AMP-activated protein kinase(AMPK)phosphorylation.ALDOC was positively correlated with ADPGK,and high ALDOC expression was associated with worse survival outcomes in PCa.Conclusions In summary,ADPGK is a driving factor in PCa progression,and its high expression contributes to a poor prognosis in PCa patients.ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling,suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.

Evaluation of Tianji and ECMWF high-resolution precipitation forecasts for extreme rainfall event in Henan in July 2021

The extreme rainfall event of July 17 to 22, 2021 in Henan Province, China, led to severe urban waterlogging and flood disasters. This study investigated the performance of high-resolution weather forecasts in predicting this extreme event and the feasibility of weather forecast-based hydrological forecasts. To achieve this goal, high-resolution precipitation forecasts from the Tianji weather system and the forecast system of the European Centre for Medium-Range Weather Forecasts (ECMWF) were evaluated with the spatial verification metrics of structure, amplitude, and location. The results showed that Tianji weather forecasts accurately predicted the amplitude of 12-h accumulated precipitation with a lead time of 12 h. The location and structure of the rainfall areas in Tianji forecasts were closer to the observations than ECMWF forecasts. Tianji hourly precipitation forecasts were also more accurate than ECMWF hourly forecasts, especially at lead times shorter than 8 h. The precipitation forecasts were used as the inputs to a hydrological model to evaluate their hydrological applications. The results showed that the runoff forecasts driven by Tianji weather forecasts could effectively predict the extreme flood event. The runoff forecasts driven by Tianji forecasts were more accurate than those driven by ECMWF forecasts in terms of amplitude and location. This study demonstrates that high-resolution weather forecasts and corresponding hydrological forecasts can provide valuable information in advance for disaster warnings and leave time for people to act on the event. The results encourage further hydrological applications of high-resolution weather forecasts, such as Tianji weather forecasts, in the future.

Evolution of Polymer Melt Conformation and Entanglement under High-Rate Elongational Flow

Using molecular dynamics(MD)simulations,this study explores the fluid properties of three polymer melts with the same number of entanglements,Z,achieved by adjusting the entanglement length Ne,while investigating the evolution of polymer melt conformation and entanglement under high-rate elongational flow.The identification of a master curve indicates consistent normalized linear viscoelastic behavior.Surprising findings regarding the steady-state viscosity at various elongational rates(Wi_(R)>4.7)for polymer melts with the same Z have been uncovered,challenging existing tube models.Nevertheless,the study demonstrates the potential for normalizing the steady-state elongational viscosity at high rates(Wi_(R)>4.7)by scaling with the square of the chain contour length.Additionally,the observed independence of viscosity on the elongational rate at high rates suggests that higher rates lead to a more significant alignment of polymer chains,a decrease in entanglement,and a stretching in contour length of polymer chains.Molecular-level tracking of tagged chains further supports the assumption of no entanglement under rapid elongation,emphasizing the need for further research on disentanglement in polymer melts subjected to high-rate elongational flow.These results carry significant implications for understanding and predicting the behavior of polymer melts under high-rate elongational flow conditions.