Upregulation Of Microglial Zeb1 Ameliorates Brain Damage After Acute Ischemic Stroke

Microglia are a key immune-competent cell type that respond to environmental and physiological changes during ischemic stroke. However, the molecular mechanisms controlling post-ischemic microglia activity are unclear. Understanding these mechanisms may ultimately reduce disease burden and allow the manipulation of microglia responses to shape the outcomes of stroke. Here, we report that, after experimentally induced stroke, ZEB1 is highly expressed in ipsilateral cerebral hemisphere, where it is upregulated mainly in microglia. Using a conditional transgenic mouse, we found that ZEB1 upregulation in microglia regulates immune responses in the CNS and alleviates brain injury after ischemic stroke. Our data indicate that ZEB1 overexpression mediates microglia responses and, in turn, inhibits the production of astrocytic CXCL1 through the TGF-β1-dependent pathway. Reduced CXCL1 leads to a decline in neutrophil infiltration into the brain, thereby reducing CNS inflammation. Our results demonstrate the importance of ZEB1 in microglia-orchestrated neuroinflammation and suggest a potential means for reducing stroke-induced neurological injury. Li et al. show that ZEB1 overexpression mediates microglia responses and, in turn, inhibits production of astrocytic CXCL1 through the TGF-β1-dependent pathway. Reduced CXCL1 leads to the decline of neutrophil infiltration into the brain. This demonstrates the importance of ZEB1 in microglia-orchestrated neuroinflammation and suggests a potential means for reducing stroke-induced neurological injury

RETRACTED: A study on expression level and nutritional status of IGFBP-2 after left neck anastomosis combined with placement of feeding nutritional applicators carrying ^(125)I particles in the treatment of esophageal cancer

BackgroundTo explore the changes and significance of the expression level and nutritional status of human insulin-like growth factor binding protein-2 (IGFBP2) after the treatment of esophageal cancer with left neck anastomosis combined with placement of feeding nutritional applicators carrying ^(125)I particles.MethodsA total of 110 patients with esophageal cancer (observation group: left neck anastomosis combined with placement of feeding nutritional applicators carrying ^(125)I particles) and 100 healthy people (control group) were enrolled at the same period. Then enzyme-linked immunosorbent assay (ELISA) was carried out to detect level of IGFBP-2. Lymphocyte count and serum albumin were measured by immune analyzer and automatic protein analyzer to evaluate nutritional status. Logistic regression analysis was used to analyze the relationship between serum IGFBP-2, nutritional status and prognosis of esophageal cancer after combined treatment.ResultsThe albumin, lymphocyte absolute value and PNI detection value of the control group were lower than those of the observation group 1 month after treatment, and the difference was statistically significant compared with the control group. The detection value of IGFBP-2 in early patients before and after treatment was lower than that in middle and late patients, and the detection values of albumin, lymphocyte absolute value and PNI were higher than those in middle and late patients, the differences were statistically significant. Serum IGFBP-2 level was negatively correlated with PNI, and albumin and lymphocyte absolute value were positively correlated with PNI. The detection value of IGFBP-2 in patients with good prognosis was significantly lower than that in patients with poor prognosis, and the detection values of albumin, lymphocyte absolute value and PNI were significantly higher than those in patients with poor prognosis. The AUC (0.887,95% CI: 0.799-0.975) of IGFBP-2, albumin, lymphocyte absolute value and PNI in predicting poor prognosis of esophageal cancer was the largest, and the sensitivity and specificity were 94.12% and 92.47%, respectively.ConclusionsLeft neck anastomosis combined with ^(125)I particle application nutritional tube is helpful for the decrease of serum IGFBP-2 and the increase of various nutritional status indicators, which is beneficial for the improvement of the patient’s condition

Long-term vegetation changes in the four mega-sandy lands in Inner Mongolia, China.

Desertification in China has become one of the most serious ecological and social problems. The four mega-sandy lands (Hulunbeir, Horqin, Otindag, and Mu Us) in Inner Mongolia are reported to be the most widespread and seriously desertified areas in China. To explore changes of vegetation activity and the possible driving forces in the four mega-sandy lands over the last three decades. We investigated spatiotemporal variations in the growing-season (May-September) normalized difference vegetation index (NDVI) and their relationships with climate factors and human activities during 1982-2011, using two NDVI datasets from Global Inventory Modelling and Mapping Studies (GIMMS) and Moderate Resolution Imaging Spectroradiometer (MODIS). We found a significant overall NDVI increase in Mu Us, but no such trends in the other three. A significant increase was in south and northeast Mu Us and southeast Horqin, and a decrease in south Hulunbeir, northwest Horqin, and central Otindag. NDVI trends were positively correlated with precipitation and uncorrelated with temperature and wind speed in all sandy lands except Mu Us. NDVI trends showed a large spatial heterogeneity in the four sandy lands. Precipitation was a major determiner for the interannual variations and spatial patterns of NDVI at regional scale, whereas human activities were the cause of NDVI variations at local scale. The consistent interannual variations between two NDVI datasets of GIMMS and MODIS for all four sandy lands suggested that GIMMS NDVI was appropriate for investigating long-term vegetation changes in sandy lands.National Natural Science Foundation of China [31330012, 31021001]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA05050300]SCI(E)[email protected]

Long-term vegetation changes in the four mega-sandy lands in Inner Mongolia, China

Desertification in China has become one of the most serious ecological and social problems. The four mega-sandy lands (Hulunbeir, Horqin, Otindag, and Mu Us) in Inner Mongolia are reported to be the most widespread and seriously desertified areas in China. To explore changes of vegetation activity and the possible driving forces in the four mega-sandy lands over the last three decades. We investigated spatiotemporal variations in the growing-season (May-September) normalized difference vegetation index (NDVI) and their relationships with climate factors and human activities during 1982-2011, using two NDVI datasets from Global Inventory Modelling and Mapping Studies (GIMMS) and Moderate Resolution Imaging Spectroradiometer (MODIS). We found a significant overall NDVI increase in Mu Us, but no such trends in the other three. A significant increase was in south and northeast Mu Us and southeast Horqin, and a decrease in south Hulunbeir, northwest Horqin, and central Otindag. NDVI trends were positively correlated with precipitation and uncorrelated with temperature and wind speed in all sandy lands except Mu Us. NDVI trends showed a large spatial heterogeneity in the four sandy lands. Precipitation was a major determiner for the interannual variations and spatial patterns of NDVI at regional scale, whereas human activities were the cause of NDVI variations at local scale. The consistent interannual variations between two NDVI datasets of GIMMS and MODIS for all four sandy lands suggested that GIMMS NDVI was appropriate for investigating long-term vegetation changes in sandy lands

Secure and distributed data discovery and dissemination in wireless sensor networks

A data discovery and dissemination protocol for wireless sensor networks (WSNs) is responsible for updating configuration parameters of, and distributing management commands to, the sensor nodes. All existing data discovery and dissemination protocols suffer from two drawbacks. First, they are based on the centralized approach; only the base station can distribute data items. Such an approach is not suitable for emergent multi-owner-multi-user WSNs. Second, those protocols were not designed with security in mind and hence adversaries can easily launch attacks to harm the network. This paper proposes the first secure and distributed data discovery and dissemination protocol named DiDrip. It allows the network owners to authorize multiple network users with different privileges to simultaneously and directly disseminate data items to the sensor nodes. Moreover, as demonstrated by our theoretical analysis, it addresses a number of possible security vulnerabilities that we have identified. Extensive security analysis show DiDrip is provably secure. We also implement DiDrip in an experimental network of resource-limited sensor nodes to show its high efficiency in practice. 2014 IEEE.Scopus2-s2.0-8492513637

Long-term vegetation changes in the four mega-sandy lands in Inner Mongolia, China

Desertification in China has become one of the most serious ecological and social problems. The four mega-sandy lands (Hulunbeir, Horqin, Otindag, and Mu Us) in Inner Mongolia are reported to be the most widespread and seriously desertified areas in China. To explore changes of vegetation activity and the possible driving forces in the four mega-sandy lands over the last three decades. We investigated spatiotemporal variations in the growing-season (May-September) normalized difference vegetation index (NDVI) and their relationships with climate factors and human activities during 1982-2011, using two NDVI datasets from Global Inventory Modelling and Mapping Studies (GIMMS) and Moderate Resolution Imaging Spectroradiometer (MODIS). We found a significant overall NDVI increase in Mu Us, but no such trends in the other three. A significant increase was in south and northeast Mu Us and southeast Horqin, and a decrease in south Hulunbeir, northwest Horqin, and central Otindag. NDVI trends were positively correlated with precipitation and uncorrelated with temperature and wind speed in all sandy lands except Mu Us. NDVI trends showed a large spatial heterogeneity in the four sandy lands. Precipitation was a major determiner for the interannual variations and spatial patterns of NDVI at regional scale, whereas human activities were the cause of NDVI variations at local scale. The consistent interannual variations between two NDVI datasets of GIMMS and MODIS for all four sandy lands suggested that GIMMS NDVI was appropriate for investigating long-term vegetation changes in sandy lands

Development of Novel Ecto-Nucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) Inhibitors for Tumor Immunotherapy

The cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes–TANK-binding kinase 1–interferon regulating factor 3 (cGAS-STING-TBK1-IRF3) axis is now acknowledged as the major signaling pathway in innate immune responses. However, 2′,3′-cGAMP as a STING stimulator is easily recognized and degraded by ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which reduces the effect of tumor immunotherapy and promotes metastatic progression. In this investigation, the structure-based virtual screening strategy was adopted to discover eight candidate compounds containing zinc-binding quinazolin-4(3H)-one scaffold as ENPP1 inhibitors. Subsequently, these novel inhibitors targeting ENPP1 were synthesized and characterized by NMR and high-resolution mass spectra (HRMS). In bioassays, 7-fluoro-2-(((5-methoxy-1H-imidazo[4,5-b]pyridin-2-yl)thio)methyl)quina-zolin-4(3H)-one(compound 4e) showed excellent activity against the ENPP1 at the molecular and cellular levels, with IC50 values of 0.188 μM and 0.732 μM, respectively. Additionally, compound 4e had superior selectivity towards metastatic breast cancer cells (4T1) than towards normal cells (LO2 and 293T) in comparison with cisplatin, indicating that compound 4e can potentially be used in metastatic breast cancer therapy. On the other hand, compound 4e upgraded the expression levels of IFN-β in vivo by preventing the ENPP1 from hydrolyzing the cGAMP to stimulate a more potent innate immune response. Therefore, this compound might be applied to boost antitumor immunity for cancer immunotherapy. Overall, our work provides a strategy for the development of a promising drug candidate targeting ENPP1 for tumor immunotherapy

Satellite-indicated long-term vegetation changes and their drivers on the Mongolian Plateau

The Mongolian Plateau, comprising the nation of Mongolia and the Inner Mongolia Autonomous Region of China, has been influenced by significant climatic changes and intensive human activities. Previous satellite-based analyses have suggested an increasing tendency in the vegetation cover over recent decades. However, several ground-based observations have indicated a decline in vegetation production. This study aimed to explore long-term changes in vegetation greenness and land surface phenology in relation to changes in temperature and precipitation on the Plateau between 1982 and 2011 using the normalized difference vegetation index (NDVI). Across the Plateau, a significantly positive trend in the growing season (May-September) NDVI was observed from 1982 to 1998, but since that time, the NDVI has not shown a persistent increase, thus causing an insignificant trend over the entire study period. For the steppe vegetation (a major vegetation type on the Plateau), the NDVI increased significantly in spring but decreased in summer. Precipitation was the dominant factor related to changes in steppe vegetation. Warming in spring contributed to earlier vegetation green-up only in meadow steppe vegetation, implying that water deficiency in typical and desert steppe vegetation may eliminate the effect of warming. Our results also suggest a combined effect of climatic and non-climatic factors and highlight the need to examine the role of regional human activities in the control of vegetation dynamics.National Natural Science Foundation of China [31330012, 31321061]; National Basic Research Program of China on Global Change [2010CB950600]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA05050300]SCI(E)[email protected]