Protein kinases mediate increment of the phosphorylation of cyclic AMP -responsive element binding protein in spinal cord of rats following capsaicin injection

BACKGROUND: Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB) is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK 1/2), PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection. RESULTS: We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively) significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group. CONCLUSION: These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli

Transient mTOR Inhibition Facilitates Continuous Growth of Liver Tumors by Modulating the Maintenance of CD133+ Cell Populations

The mammalian target of the rapamycin (mTOR) pathway, which drives cell proliferation, is frequently hyperactivated in a variety of malignancies. Therefore, the inhibition of the mTOR pathway has been considered as an appropriate approach for cancer therapy. In this study, we examined the roles of mTOR in the maintenance and differentiation of cancer stem-like cells (CSCs), the conversion of conventional cancer cells to CSCs and continuous tumor growth in vivo. In H-Ras-transformed mouse liver tumor cells, we found that pharmacological inhibition of mTOR with rapamycin greatly increased not only the CD133+ populations both in vitro and in vivo but also the expression of stem cell-like genes. Enhancing mTOR activity by over-expressing Rheb significantly decreased CD133 expression, whereas knockdown of the mTOR yielded an opposite effect. In addition, mTOR inhibition severely blocked the differentiation of CD133+ to CD133- liver tumor cells. Strikingly, single-cell culture experiments revealed that CD133- liver tumor cells were capable of converting to CD133+ cells and the inhibition of mTOR signaling substantially promoted this conversion. In serial implantation of tumor xenografts in nude BALB/c mice, the residual tumor cells that were exposed to rapamycin in vivo displayed higher CD133 expression and had increased secondary tumorigenicity compared with the control group. Moreover, rapamycin treatment also enhanced the level of stem cell-associated genes and CD133 expression in certain human liver tumor cell lines, such as Huh7, PLC/PRC/7 and Hep3B. The mTOR pathway is significantly involved in the generation and the differentiation of tumorigenic liver CSCs. These results may be valuable for the design of more rational strategies to control clinical malignant HCC using mTOR inhibitors

High endemicity of alveolar echinococcosis in Yili Prefecture, Xinjiang Autonomous Region, the People’s Republic of China: infection status in different ethnic communities and in small mammals

Alveolar echinococcosis (AE) is a neglected zoonosis caused by the larval stage of the fox/dog tapeworm Echinococcus multilocularis. In this study, we collected data on 286 AE cases reported from Yili Prefecture, Xinjiang Autonomous Region, the People’s Republic of China from 1989 to 2015 with an annual incidence (AI) of 0.41/100,000. Among the patients, 73.08% were diagnosed in the last 11 years. The incidence (0.51–1.22 cases/100,000 residents) was higher in the high-altitude mountainous areas than those in low level areas (0.19–0.29/100,000 residents). In term of ethnic group, the AI of AE in Mongolian (2.06/100,000 residents) and Kazak (0.93/100,000) groups had higher incidence than the other ethnic groups, indicating sheep-farming activity is a risk for infection given that sheep farming is mainly practiced by these two groups in the prefecture. A total of 1411 small mammals were captured with 9.14% infected with E. multilocularis metacestodes. Microtus obscurus was the dominant species captured in the mountainous pasture areas with 15.01% infection rate, whereas Mus musculus and Apodemus sylvaticus were the dominant small mammals in the low altitude areas. Only 0.40% of A. sylvaticus were infected with E. multilocularis. These findings show that Yili Prefecture is a highly endemic area for AE and that the high-altitude pasture areas favorable for M. obscurus may play an important role in its transmission in this region

Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Endoglin (CD105) has been considered a prognostic marker for hepatocellular carcinoma (HCC), and widely used as an appropriate targeting for antiangenesis therapy in some cancers. Our aim was to evaluate the distribution and expression of CD105 in the liver of patients with HCC, and to discuss whether CD105 may be used as an appropriate targeting for antiangenesis therapy in HCC.</p> <p>Methods</p> <p>Three parts of liver tissues from each of 64 patients with HCC were collected: tumor tissues (TT), adjacent non-tumor (AT) liver tissues within 2 cm, and tumor free tissues (TF) 5 cm far from the tumor edge. Liver samples from 8 patients without liver diseases served as healthy controls (HC). The distribution and expression of CD105 in tissues were evaluated by immunohistochemistry, Western blotting analysis, and real-time PCR. HIF-1alpha and VEGF₁₆₅protein levels in tissues were analyzed by Immunohistochemistry and Western blotting analysis or ELISA.</p> <p>Results</p> <p>CD105 was positively stained mostly in a subset of microvessels 'endothelial sprouts' in TT of all patients while CD105 showed diffuse positive staining, predominantly on hepatic sinus endothelial cells in the surrounding of draining veins in TF and AT. The mean score of MVD-CD105 (mean ± SD/0.74 mm²) was 19.00 ± 9.08 in HC, 153.12 ± 53.26 in TF, 191.12 ± 59.17 in AT, and 85.43 ± 44.71 in TT, respectively. Using a paired <it>t </it>test, the expression of CD105 in AT and TF was higher than in TT at protein (MVD, <it>p </it>= 0.012 and <it>p </it>= 0.007, respectively) and mRNA levels (<it>p </it>< 0.001 and <it>p </it>= 0.009, respectively). Moreover, distribution and expression of CD105 protein were consistent with those of HIF-1alpha and VEGF₁₆₅protein in liver of patients with HCC. The level of <it>CD105 </it>mRNA correlated with VEGF₁₆₅level in TF (r = 0.790, <it>p </it>= 0.002), AT (r = 0.723, <it>p </it>< 0.001), and TT (r = 0.473, <it>p </it>= 0.048), respectively.</p> <p>Conclusion</p> <p>It is demonstrated that CD105 was not only present in neovessels in tumor tissues, but also more abundant in hepatic sinus endothelium in non-tumor tissues with cirrhosis. Therefore, CD105 may not be an appropriate targeting for antiangenesis therapy in HCC, especially with cirrhosis.</p

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Deep-Learning-Based Defect Evaluation of Mono-Like Cast Silicon Wafers

Solar cells based on mono-like cast silicon (MLC-Si) have been attracting increasing attention in the photovoltaic (PV) market due to their high energy conversion efficiency and low cost. As in the production of monocrystalline silicon (MC-Si) and polycrystalline silicon (PC-Si) cells, various defects will inevitably occur during the production process of MLC-Si cells. Although computer vision technology has been employed for defect detection in the production processes, it is still difficult to achieve high accuracy in detecting defects in PV cells using traditional machine vision methods due to defect similarity and complex background. To address this challenge, a deep-learning-based quality assessment algorithm of MLC-Si wafers is proposed. Focusing on the dislocation defects, four different deep learning models are used to conduct migration learning and selected different optimizers (ADAM and SGDM) are used to optimize the network models, achieving good results in evaluating and comparing the quality of ML-Si wafers. On this basis, an improved network model MVGG-19 based on the VGG-19 is designed to improve the prediction accuracy further. The experimental results show that the prediction error of the improved network model is reduced by 63% (compared with VGG-19) and the reasoning speed reaches 10.22 FPS, indicating good detection performance

Panax ginseng abuse exhibits a pro-inflammatory effect by activating the NF-κB pathway

P. ginseng (Panax ginseng C. A. Meyer) is a well-known traditional medicine that has been used for thousands of years to treat diseases. However, “ginseng abuse syndrome” (GAS) often occurs due to an inappropriate use such as high-dose or long-term usage of ginseng; information about what causes GAS and how GAS occurs is still lacking. In this study, the critical components that potentially caused GAS were screened through a step-by-step separation strategy, the pro-inflammatory effects of different extracts on messenger RNA (mRNA) or protein expression levels were evaluated in RAW 264.7 macrophages through quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. It was found that high-molecular water-soluble substances (HWSS) significantly increased the expression of cytokines (cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin 6 (IL-6)) and cyclooxygenase 2 (COX-2) protein; gel filtration chromatography fraction 1 (GFC-F1) further purified from HWSS showed prominent pro-inflammatory effects by increasing the transcription of cytokines (COX-2, iNOS, tumor necrosis factor alpha (TNF-α), and interleukin 1β (IL-1β)) as well as the expression of COX-2 and iNOS protein. Moreover, GFC-F1 activated nuclear factor-kappa B (NF-кB) (p65 and inhibitor of nuclear factor-kappa B alpha (IκB-α)) and the p38/MAPK (mitogen-activated protein kinase) signaling pathways. On the other hand, the inhibitor of the NF-κB pathway (pyrrolidine dithiocarbamate (PDTC)) reduced GFC-F1-induced nitric oxide (NO) production, while the inhibitors of the MAPK pathways did not. Taken together, GFC-F1 is the potential composition that caused GAS through the production of inflammatory cytokines by activating the NF-кB pathway