Search

Climate change has an immense impact on the environment, ecology, agriculture, and economy. As the most influential climate prediction platform in the world, the Intergovernmental Panel on Climate Change provides important data on predicted future climate change trends. Based on 10 models under the RCP8.5 and RCP4.5 emission scenarios, in this study, we obtained 0.5 × 0.5° data through down-scaling data processing and predicted future rainfall and temperature changes in the Beijing–Tianjin–Hebei region of China. Combined with historical observed data of 198 meteorological stations in the region, the relationships between the predicted values of the model and the measured values were analyzed using the Taylor diagram method. The results show that (1) the future precipitation capacity assessed by the global climate system is generally higher than observed data; (2) for assessment of future temperatures, RCP8.5 shows a larger increase than RCP4.5; (3) for the Beijing–Tianjin–Hebei region, our results show that the Atmospheric Chemistry Coupled Version of Model for Interdisciplinary Research on Climate-Earth System (MIROC-ESM-CHEM) model is more consistent with the evaluation of future precipitation capacity, the Hadley Centre Global Environment Model, version 2-Earth System(HadGEM2-ES) model is more consistent with the future RCP4.5 scenario temperature evaluation, and the MIROC-ESM-CHEM model is more consistent with the future RCP8.5 scenario temperature evaluation. HIGHLIGHTS The future changes and related uncertainties of rainfall and temperature in the Beijing–Tianjin–Hebei region on an annual average scale was analyzed.; Combined with observed historical data the relationships between the model's predicted values and the measured values were analyzed.; A more suitable climate model in Beijing-Tianjin-Hebei region was selected after comparison.;

Physical exercise is essential for the amelioration of insulin resistance (IR). The mechanisms in charge of improved IR, regulated by exercise, are insufficiently studied. Previous research revealed that Sirtuin 6 (SIRT6)--mediated insulin signaling acts a crucial element in hepatic IR. The objective of our research was to determine the effects of exercise on SIRT6-mediated insulin signaling in liver of IR rats. Forty male Sprague Dawley rats were randomly assigned to four groups (n = 10 rats each): control rats fed with standard chow (Lean group); sedentary rats fed with a high-fat diet (HFD-SED); rats fed with HFD and submitted to 8 week chronic swimming exercise training (HFD-CE); and rats fed HFD and submitted to one acute swimming exercise training (HFD-AE). HFD feeding lead to increased body weight, accumulation of hepatic triglyceride and serum free fatty acids, and enhanced gluconeogenesis. Besides, HFD feeding decreased body insulin sensitivity. Hepatic USP10 and SIRT6 protein levels decreased under obese status. Both chronic and acute exercise intervention alleviated physiological and metabolic status, increased hepatic USP10 and SIRT6 levels, improved insulin signaling transduction, and inhibited gluconeogenesis. These results showed that exercise intervention regulated SIRT6-mediated insulin signaling, which contributes to our understanding of the molecular mechanisms behind IR, in that a regular exercise can mitigate the effects of IR. Key words: exercise, insulin resistance, SIRT6, insulin signaling transduction, gluconeogenesis. L'exercice physique est essentiel pour permettre d'attenuer la resistance a l'insuline. Les modes d'action en jeu dans l'attenuation de la resistance a l'insuline par un exercice physique regule ont ete trop peu etudies. Des recherches anterieures ont revele que la voie de signalisation de l'insuline mediee par SIRT6 est une caracteristique cruciale de l'ischemie-reperfusion (IR) hepatique. Notre recherche portait sur les effets de l'exercice physique sur la voie de signalisation de l'insuline mediee par SIRT6 dans le foie de rat soumis a une IR. Nous avons reparti aleatoirement 40 rats Sprague Dawley males dans quatre groupes (n = 10 rats chacun) : rats temoins avec administration d'une moulee standard (groupe maigre); rats sedentaires avec administration d'un regime alimentaire a haute teneur en matieres grasses (RHMG-SED); rats avec administration d'un RHMG et d'un entrainement physique a long terme (nage sur 8 semaines--RHMG-ELT) et avec exercice physique a court terme (nage ponctuelle--RHMD-ECT). L'administration d'un RHMG menait a une augmentation de la masse corporelle, a l'accumulation de triglycerides dans le foie et d'acides gras libres dans le serum, ainsi qu'a une augmentation de la gluconeogenese. Par ailleurs, l'administration du RHMG entrainait une diminution de la sensibilite de l'organisme a l'insuline. Les taux hepatiques d'USP10 et de SIRT6 en proteines diminuaient a l'etat obese. Tant a long terme qu'a court terme, l'administration de l'exercice physique permettait d'ameliorer l'etat physiologique et metabolique, d'augmenter les taux hepatiques d'USP10 et de SIRT6, d'ameliorer la transduction dans les voies de signalisation de l'insuline, ainsi que d'inhiber la gluconeogenese. Ces consequences revelaient que l'administration d'un exercice physique entraine une regulation de la voie de signalisation de l'insuline mediee par SIRT6, ce qui permet d'obtenir des progres notables dans l'accomplissement des modes d'action moleculaires latents, ce qui liait l'administration d'un exercice physique a l'attenuation des effets de l'IR. Mots-cles : exercice physique, resistance a l'insuline, SIRT6, transduction dans les voies de signalisation de l'insuline, gluconeogenese., Introduction Insulin primarily controls blood glucose via promoting glucose ingestion in insulin-sensitive tissue containing skeletal muscle, adipose tissues, and liver. It also suppresses glucose production in related tissues and organ. [...]

At present, there are no official approved drugs for improving muscle endurance. Our previous research found acute phase protein orosomucoid (ORM) is an endogenous anti‐fatigue protein, and macrolides antibiotics erythromycin can elevate ORM level to increase muscle bioenergetics and endurance parameters. Here, we further designed, synthesized and screened a new erythromycin derivative named HMS‐01, which lost its antibacterial activity in vitro and in vivo. Data showed that HMS‐01 could time‐ and dose‐dependently prolong mice forced‐swimming time and running time, and improve fatigue index in isolated soleus muscle. Moreover, HMS‐01 treatment could increase the glycogen content, mitochondria number and function in liver and skeletal muscle, as well as ORM level in these tissues and sera. In Orm‐deficient mice, the anti‐fatigue and glycogen‐elevation activity of HMS‐01 disappeared. Therefore, HMS‐01 might act as a promising small molecule drug targeting ORM to enhance muscle endurance. [ABSTRACT FROM AUTHOR]

When simulating groundwater flow in unconfined and convertible aquifers using a groundwater model with the block‐centered finite‐difference approach, such as MODFLOW, it frequently encounters drying and rewetting of cells. Although many drying and rewetting simulation methods have been proposed in the past, balancing simulation accuracy and convergence capability all at once is difficult. MODFLOW‐2005, which has second‐order accuracy, employs a trial‐and‐error method, but it suffers from computational instability when large quantities of grid cells are dried. MODFLOW‐NWT adopts the upstream‐weighting approach and Newton iteration method to ensure the stability of the drying and rewetting simulations. However, the upstream‐weighting approach has only first‐order accuracy, and the Newton iteration method is complex to implement because it necessitates the establishment of an additional Jacobian matrix. The methods employed by MODFLOW‐NWT are also available in MODFLOW 6, therefore it inherits both the strengths and weaknesses of MODFLOW‐NWT. In this study, a new method, Picard iteration‐based always active cell (PAAC), is proposed. Similar to MODFLOW‐NWT, the PAAC method also uses dry cells as active cells. The PAAC method, however, does not use the upstream‐weighting approach and has second‐order accuracy. Moreover, it ensures good convergence stability even under the Picard iteration method. In addition to discussing the algorithm, five cases were used to comprehensively compare the simulation effects of the PAAC method with MODFLOW‐2005 and MODFLOW‐NWT, including an analytical solution, repeated drying‐rewetting of multi‐layer grids, pumping well problem, perched aquifer problem and a nearly dry single‐layer grid, which verified the practicability of the PACC method. Key Points: A new physically‐based method to simulating the drying‐rewetting problems of groundwater model, Picard iteration‐based always active cellThe new method performed robust convergence even with the Picard iteration method and a general PCG solverThe new method achieved second‐order accuracy [ABSTRACT FROM AUTHOR]

As a widely considerable target in chemical biology and pharmacological research, rat sarcoma (RAS) gene mutations play a critical driving factor in several fatal cancers. Despite the great progress of RAS subtype‐specific inhibitors, rapid acquired drug resistance could limit their further clinical applications. Proteolysis targeting chimera (PROTAC) has emerged as a powerful tool to handle "undruggable" targets and exhibited significant therapeutic benefit for the combat of drug resistance. Owing to unique molecular mechanism and binding kinetics, PROTAC is expected to become a feasible strategy to break the bottleneck of classical RAS inhibitors. This review aims to discuss the current advances of RAS inhibitors and especially focus on PROTAC strategy targeting RAS mutations and their downstream effectors for relevant cancer treatment. [ABSTRACT FROM AUTHOR]

The transformation process of soil water plays an important role in the hydrological cycle, and is a link to other water processes. Study on the regularity of soil water transformation under agricultural plantation is favorable to understanding the influence of human activities on soil water conversion. Typical crop was selected in Beijing-Tianjin-Hebei(BTH) region and the study on regularity of field-scale soil water transformation was carried out by means of crop-soil water field experimental observation combined with model simulation. In the field experiment, testing and observation of irrigated and rainfed maize were simultaneously carried out in the adjacent fields respectively to form a comparative experimental study. The experimental observation data were used to establish the soil water model, which is calibrated in many aspects, such as field water content change during the maize growth period, the soil profile water content distribution at different moments, maize leaf area index and plant height. The results show that this model has an efficient simulation effect. Quantitative study on field evapotranspiration regularity, field soil water flux under irrigated and rainfed modes, impact mechanism of soil water deep seepage during maize growth period was achieved through the simulation of soil water process, and related reference conclusions were also proposed for water resources management and conservation in BTH.