Recent reports showed that haematological and neurological expressed 1-like (HN1L) gene participated in tumorigenesis and tumour invasion. However, the expression and role of HN1L in breast cancer remain to be investigated. Here, bioinformatics, western blot and immunohistochemistry were used to detect the expression of HN1L in breast cancer. Wound healing, transwell assay, immunofluorescence assay and mass spectrum were used to explore the role and mechanism of HN1L on the migration and invasion of breast cancer, which was confirmed in vivo using a nude mice model. Results showed that HN1L was significantly over-expressed in breast cancer tissues, which was positively correlated with M metastasis of breast cancer patients. Silencing HN1L significantly inhibited the invasion and metastasis of breast cancer cells in vitro and lung metastasis in nude mice metastasis model of breast cancer. Mechanistically, HN1L interacted with HSPA9 and affected the expression of HMGB1, playing a key role in promoting the invasion and metastasis of breast cancer cell. These results suggested that HN1L was an appealing drug target for breast cancer. 相似文献
With a pace of about twice the observed rate of global warming, the temperature on the Qinghai‐Tibetan Plateau (Earth's ‘third pole’) has increased by 0.2 °C per decade over the past 50 years, which results in significant permafrost thawing and glacier retreat. Our review suggested that warming enhanced net primary production and soil respiration, decreased methane (CH4) emissions from wetlands and increased CH4 consumption of meadows, but might increase CH4 emissions from lakes. Warming‐induced permafrost thawing and glaciers melting would also result in substantial emission of old carbon dioxide (CO2) and CH4. Nitrous oxide (N2O) emission was not stimulated by warming itself, but might be slightly enhanced by wetting. However, there are many uncertainties in such biogeochemical cycles under climate change. Human activities (e.g. grazing, land cover changes) further modified the biogeochemical cycles and amplified such uncertainties on the plateau. If the projected warming and wetting continues, the future biogeochemical cycles will be more complicated. So facing research in this field is an ongoing challenge of integrating field observations with process‐based ecosystem models to predict the impacts of future climate change and human activities at various temporal and spatial scales. To reduce the uncertainties and to improve the precision of the predictions of the impacts of climate change and human activities on biogeochemical cycles, efforts should focus on conducting more field observation studies, integrating data within improved models, and developing new knowledge about coupling among carbon, nitrogen, and phosphorus biogeochemical cycles as well as about the role of microbes in these cycles. 相似文献
Based on the N-terminal sequencing of poly (vinyl alcohol) dehydrogenase (PVADH), a 1,644-bp gene encoding a truncated PVADH (tPVADH) was amplified using the synthetic gene (GenBank accession No. JQ235753) as a template, and was further transformed into Pichia pastoris GS115 with the vector pPIC9K. The maximal tPVADH activity reached 546 U/mL in shake flask. The influence of methanol concentration and induction temperature on tPVADH production was further investigated in 3-L bioreactor. When the methanol concentration and induction temperature were controlled at 15 g/L and 22 °C, respectively, the maximal tPVADH activity reached 8,464 U/mL, which was nearly 10 times that of mature PVADH expressed under the same condition and was the highest level ever reported. The reason responsible for the significant improvement of tPVADH production at low induction temperature was explored in terms of cell viability, extracellular proteases activity, and alcohol oxidase activity. 相似文献
Silica nanoparticles are increasingly used in the biomedical fields due to their excellent solubility, high stability and favorable biocompatibility. However, despite being considered of low genotoxicity, their bio-related adverse effects have attracted particular concern from both the scientific field and the public. In this study, human cervical adenocarcinoma cells (HeLa line) were exposed to 0.01 or 1.0 mg/mL of hydrophilic silica nanoparticles. The 1H NMR spectroscopy coupled with multivariate statistical analysis were used to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media. At the early stage of silica nanoparticles-exposure, no obvious dose–effect of HeLa cell metabolome was observed, which implied that cellular stress-response regulated the metabolic variations of HeLa cell. Silica nanoparticles induced the increases of lipids including triglyceride, LDL, VLDL and lactate/alanine ratio and the decreases of alanine, ATP, choline, creatine, glycine, glycerol, isoleucine, leucine, phenylalanine, tyrosine, and valine, which involved in membrane modification, catabolism of carbohydrate and protein, and stress-response. Subsequently, a complicated synergistic effect of stress-response and toxicological-effect dominated the biochemical process and metabolic response, which was demonstrated in the reverse changes of some metabolites including acetate, ADP, ATP, choline, creatine, glutamine, glycine, lysine, methionine, phenylalanine and valine between 6 and 48 h post-treatment of silica nanoparticles. The toxicological-effects induced by high-dosage silica nanoparticles could be derived from the elevated levels of ATP and ADP, the utilization of glucose and amino acids and the production of metabolic end-products such as glutamate, glycine, lysine, methionine, phenylalanine, and valine. The results indicated that it is important and necessary to pursue further the physiological responses of silica nanoparticles in animal models and human before their practical use. NMR-based metabolomic analysis helps to understand the biological mechanisms of silica nanoparticles and their metabolic fate, and further, it offers an ideal platform for establishing the bio-safety of existing and new nanomaterials. 相似文献
The effects of exercise are not limited to muscle, and its ability to mitigate some chronic diseases is under study. A more complete understanding of how exercise impacts non‐muscle tissues might facilitate design of clinical trials and exercise mimetics. Here, we focused on lactate's ability to mediate changes in liver and brain bioenergetic‐associated parameters. In one group of experiments, C57BL/6 mice underwent 7 weeks of treadmill exercise sessions at intensities intended to exceed the lactate threshold. Over time, the mice dramatically increased their lactate threshold. To ensure that plasma lactate accumulated during the final week, the mice were run to exhaustion. In the liver, mRNA levels of gluconeogenesis‐promoting genes increased. While peroxisome proliferator‐activated receptor‐gamma co‐activator 1 alpha (PGC‐1α) expression increased, there was a decrease in PGC‐1β expression, and overall gene expression changes favored respiratory chain down‐regulation. In the brain, PGC‐1α and PGC‐1β were unchanged, but PGC‐1‐related co‐activator expression and mitochondrial DNA copy number increased. Brain tumor necrosis factor alpha expression fell, whereas vascular endothelial growth factor A expression rose. In another group of experiments, exogenously administered lactate was found to reproduce some but not all of these observed liver and brain changes. Our data suggest that lactate, an exercise byproduct, could mediate some of the effects exercise has on the liver and the brain, and that lactate itself can act as a partial exercise mimetic.
Increasing concerns over limited petroleum resources and associated environmental problems are motivating the development of efficient cell factories to produce chemicals, fuels, and materials from renewable resources in an environmentally sustainable economical manner. Bacillus spp., the best characterized Gram-positive bacteria, possesses unique advantages as a host for producing microbial enzymes and industrially important biochemicals. With appropriate modifications to heterologous protein expression and metabolic engineering, Bacillus species are favorable industrial candidates for efficiently converting renewable resources to microbial enzymes, fine chemicals, bulk chemicals, and fuels. Here, we summarize the recent advances in developing Bacillus spp. as a cell factory. We review the available genetic tools, engineering strategies, genome sequence, genome-scale structure models, proteome, and secretion pathways, and we list successful examples of enzymes and industrially important biochemicals produced by Bacillus spp. Furthermore, we highlight the limitations and challenges in developing Bacillus spp. as a robust and efficient production host, and we discuss in the context of systems and synthetic biology the emerging opportunities and future research prospects in developing Bacillus spp. as a microbial cell factory. 相似文献
Bark beetles are among the most destructive of pine forest pests and they form close symbiotic relationships with ophiostomatoid fungi. Although some fungi are considered to be mutualistic symbionts of bark beetles with respect to the supply of nutrients, detrimental effects of fungal symbionts on larval growth have also been frequently reported. The mechanisms of such antagonistic effects are hypothesized to be a decrease in nutritional resources caused by competition for saccharides by the fungi. Here, we provide experimental evidence that three beetle-associated fungi modify the nutritional content of an artificial phloem diet, leading to a detrimental effect on the growth of Dendroctonus valens larvae. When larvae were fed a diet of pine phloem in agar medium colonized with any of these fungi, feeding activity was not affected but weight significantly decreased. Additional analysis showed that fungi depleted the fructose and glucose concentrations in the phloem media. Furthermore, these detrimental effects were neutralized by supplementing the media with fructose or glucose, suggesting that fungi may affect larval growth by modifying diet saccharide contents. These data indicate that fungus-induced nutritional changes in bark beetle diet can affect larval growth, and that the mechanism involves fungus-induced saccharide depletion from the larval diet. 相似文献