The ability to respond to differential levels of oxygen is important to all respiring cells. The response to oxygen deficiency, or hypoxia, takes many forms and ranges from systemic adaptations to those that are cell autonomous. Perhaps the most ancient of the cell-autonomous adaptations to hypoxia is a metabolic one: the Pasteur effect, which includes decreased oxidative phosphorylation and an increase in anaerobic fermentation. Because anaerobic fermentation produces far less ATP than oxidative phosphorylation per molecule of glucose, increased activity of the glycolytic pathway is necessary to maintain free ATP levels in the hypoxic cell. Here, we present genetic and biochemical evidence that, in mammalian cells, this metabolic switch is regulated by the transcription factor HIF-1. As a result, cells lacking HIF-1␣ exhibit decreased growth rates during hypoxia, as well as decreased levels of lactic acid production and decreased acidosis. We show that this decrease in glycolytic capacity results in dramatically lowered free ATP levels in HIF-1␣-deficient hypoxic cells. Thus, HIF-1 activation is an essential control element of the metabolic state during hypoxia; this requirement has important implications for the regulation of cell growth during development, angiogenesis, and vascular injury.Decreased environmental oxygen forces cells and tissues to adapt in multiple ways. In response to hypoxia, a significant number of changes in gene expression occur, resulting in elevated transcription of angiogenic factors, hematopoietic factors, and some metabolic enzymes (21). The switch between the two forms of respiration utilized by animal cells, aerobic versus anaerobic, was first noted by Pasteur in the late 19th century (12,22). As the oxygen level decreases, the generation of ATP shifts from the oxidative phosphorylation pathway in the mitochondria to the oxygen-independent pathway of glycolysis in the cytoplasm. Although glycolysis is less efficient than oxidative phosphorylation in the generation of ATP, in the presence of sufficient glucose glycolysis can sustain ATP production due to increases in the activity of the glycolytic enzymes (12,22). Perhaps nowhere has this forced adaptation been the focus of so much study as in transformed cells; this is because in solid tumors it is clear that a large percentage of the cell population is at least transiently hypoxic (1).Earlier in the 20th century, Otto Warburg demonstrated that tumors differed from normal tissues in their utilization of the glycolytic pathway (26). For a given amount of glucose, tumor fragments ex vivo produced far more lactate than sections of nontransformed tissues under normoxic conditions. In vivo the situation is likely to be more complex. Within individual tumors, there are some areas that may respond to hypoxia by exhibiting the normal physiological switch to glycolysis similar to that employed by all nontransformed cells in response to lowered oxygen levels. Concurrently, many other areas of transformed cells in solid tumors may adapt to h...

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In the era of knowledge networking, the structure and production mode of knowledge are constantly changing. This article creatively introduces the knowledge mapping method in design research, and based on the perspective of the National Natural Science Foundation of China (NSFC) to compile literature, uses word frequency analysis, co-word analysis, and citation analysis to construct knowledge graphs of design science. This study graphically shows the distribution and flow law of knowledge within design discipline and probes into the research frontier and evolution trend of Chinese design science.

SSTR expression of the pancreas is significantly reduced in ANP. Correction of the abnormal metabolism of eicosanoids and improvement in pancreatic microcirculation may be the major mechanism of somatostatin analogs in the treatment of ANP and inhibition of pancreatic enzymes via their receptors plays a minor role.

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OBJECTIVE:  To investigate the effects of different doses of angiotensin II (AngII) on the proliferation of hepatic stellate cells (HSC) and collagen synthesis in rats. METHODS:  Pronase E and collagen I were used to isolate the HSC, and 3H‐TdR,3H‐Leu and 3H‐pro incorporation methods were used to evaluate the effects of the different doses of AngII on HSC DNA, protein and proline synthesis. RESULTS:  It was found that 10‐9−10−6 mol/L AngII could increase the 3H‐TdR incorporation rate of the HSC (P < 0.05), but only 10−6 mol/L and 10−7 mol/L AngII could significantly increase the 3H‐Leu incorporation rate of the HSC (P < 0.01); 10−9−10−6 mol/L AngII caused a significant increment of the 3H‐pro incorporation rate of the HSC in a dose‐dependent manner. CONCLUSIONS:  The appropriate dose of AngII may promote HSC proliferation and collagen synthesis.

Studies reported the effects of different types and different levels of abstraction of analogical stimuli on designers. However, specific, single visual analogical stimuli on the effects of designers have not been reported. We define this type of stimuli as specific analogical stimuli. We used the extended linkography method to analyze the facilitating and limiting effects of specific analogical stimuli and free association analogical stimuli (nonspecific analogical stimuli) on the students' creativity at different design levels. The results showed that: (1) Advanced students focused on exploring the depth of the design problem while beginning students tended to explore the breadth of the design problem. (2) Nonspecific analogical stimuli enhanced the creativity of beginning students. However, its impact on advanced students is less pronounced. (3) The specific analogical stimuli attract the students into design fixation. Furthermore, it has a more pronounced effect on advanced students. These results illustrate the differences in the effects of specific analogy stimuli on the students at different design levels. It clarifies the use of analogical stimuli in design and the teaching of analogical design methods in design education.