Search

Gastric cancer is one of the most lethal human malignancies in the world. Although great efforts are put in developing novel therapeutic targets, the effective targeting drugs are still limited. Recent studies reveal the abnormality of Hippo/YAP axis play critical role in the oncogenic process of gastric cancer. It is of great importance to demonstrate the regulation of Hippo signaling activity and YAP protein turnover in gastric cancer. Besides, the phosphorylation cascade on YAP function, which has been thoroughly investigated, the ubiquitination of YAP is also important in Hippo signaling status. Here, We utilized the DUB (Deubiquitinase) siRNA library to identify critical DUB for Hippo signaling. We discovered OTUB1 as a critical factor to facilitate gastric cancer cell stemness and progression, which deubiquitinated and stabilized YAP protein. The clinical data analysis implicated OTUB1 was higher expressed in gastric cancer, which correlated with YAP activity and poor survival. OUTB1 interacted with YAP protein via its OTU domain (Ovarian tumor domain) and deubiquitinated YAP at several lysine sites (K90, K280, K343, K494 and K497), which subsequently inhibited YAP degradation. Our study revealed a novel deubiquitinase of Hippo/YAP axis and one possible therapeutic target for YAP-driven gastric cancer.

Background Ubiquitous mitochondrial creatine kinase (uMtCK) transfers high-energy phosphates from mitochondrially generated ATP to creatine to generate phosphocreatine. uMtCK overexpression has been reported in several malignant tumors, however, the clinical significance and impact of uMtCK in gastric cancer (GC) has not been comprehensively studied. Methods We first examined uMtCK expression in GC by quantitative real-time PCR and western blot assays. Then the clinicopathological significance of aberrant uMtCK expression was determined by immunohistochemical staining in a GC tissue microarray. Kaplan–Meier analysis was used for survival analysis. The biological functions of uMtCK in GC cells were explored by wound-healing, transwell assays and glucose metabolism assays in vitro as well as a liver metastasis model by spleen injection in nude mice in vivo. Results We verified that the expression of uMtCK was substantially elevated in GC tissues, significantly associating with a poorer prognosis in GC patients, especially for those with advanced stage. In univariate and multivariate analyses, uMtCK expression emerged as an independent prognostic factor for both disease-free survival and overall survival. Functionally, we demonstrated that uMtCK promoted glycolysis in GC cells and facilitated their migration, invasion and liver metastasis in vitro and in vivo. Mechanistically, uMtCK enhanced GC progression in a HK2-dependent glycolysis via acting the JNK-MAPK/JUN signaling pathway. Conclusions uMtCK could serve as a novel independent prognostic biomarker as well as potential therapeutic target for GC patients, particularly for GC patients with an advanced UICC stage and tumor recurrence.

Background The Hippo pathway functions as a tumor-suppressor pathway in human cancers, while the dys-function of Hippo pathway is frequently observed in malignancies. Although the YAP/TAZ activity is tightly controlled by the phosphorylation cascade of MST-LATS-YAP/TAZ axis, it is still unclear why YAP/TAZ protein is activated in human cancers, even Hippo pathway is still active. Besides phosphorylation, recent studies implicate that several post-translational modifications also play critical roles in modulating TAZ function, including ubiquitination. Methods We work on the ER alpha positive breast cancer cell lines and performed western blots, real-time PCR, immuno-precipitation assay, in vitro ubiquitin assay and xenograft mice studies Results Here, by a DUB (Deubiquitinases) siRNA screening library, we discovered DUB1 as a critical modulator to facilitate gastric cancer stemness and progression, which deubiquitinated and activated TAZ protein. We also identified DUB1 was elevated in gastric cancer, which correlated with TAZ activation and poor survival. DUB1 associated with TAZ protein and deubiquitinated TAZ at several lysine sites, which subsequently stabilized and facilitated TAZ function. Conclusions Our study revealed a novel deubiquitinase of Hippo/TAZ axis and one possible therapeutic target for Hippo-driven gastric cancer.

The pandemic influenza A (H1N1) virus spread globally and posed one of the most serious global public health challenges. The traditional Chinese medicine is served as a complementary treatment strategy with vaccine immunization. Here, we demonstrated that the mixed polysaccharides (MPs) derived from shiitake mushroom, poriacocos, ginger, and tyangerine peel prevent the H1N1 virus infections in mice. MP pretreatment attenuated H1N1 virus-induced weight loss, clinical symptoms, and death. The lymphocytes detection results showed that the CD3+, CD19+, and CD25+ cell proportions were upregulated in thymus under MP pretreatment. Besides, MP pretreatment reduced the inflammatory cell infiltration and increased the cell proportions of CD19+, CD25+, and CD278+ in lung. However, MP treatment have no effective therapeutic effect after H1N1 virus challenge. The current study suggested that pretreatment with MPs could attenuate H1N1 virus-induced lung injury and upregulate humoral and cellular immune responses in nonimmunized mice.

Japanese eel (Anguilla japonica) is an important food source in East Asia whose population has dramatically declined since the 1970s. Despite past analysis with DNA sequencing, microsatellite and isozyme methods, management decisions remain hampered by contradictory findings. For example, it remains unresolved whether Japanese eels are a single panmictic population or whether they harbor significant substructure. Accurate assessment of population genetic substructure, both spatial and temporal, is essential for determining the relevant number of distinct management units appropriate for this species. In the present study, we assayed genetic variation genome-wide using Restriction Site Associated DNA Sequencing (RAD-seq) technology to analyze the population genetic structure of Japanese eels. For analysis of temporal isolation, five “cohort” samples were collected yearly from 2005 to 2009 in the Yangtze River Estuary. For analysis of spatial structure, five “arrival wave” samples were collected in China in 2009, and two arrival wave samples were collected in Japan in 2001. In each cohort of each arrival wave, five individuals were collected for a total of 55 eels sampled. In total, 214,210 loci were identified from these individuals, 106,652 of which satisfied quality checks and were retained for further analysis. There was relatively little population differentiation between arrival waves and cohorts collected either at different locations during the same year (Fst = 0.077) or at the same location collected over subsequent years (Fst = 0.082), and locations displayed no consistent isolation-by-distance.

Background Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. Objectives The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. Methods The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC0–24h/MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid Emax (Hill) equation. The dose was calculated based on the AUC0–24h/MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. Results The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 μg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 μg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC0–24h/MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. Conclusions A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. Suis infections.

Breast cancer is the leading cause of females characterized by high invasive potential. It is necessary to explore the underlying mechanism of breast cancer metastases and to find specific therapeutic targets. PKM2 is considered a new biomarker of cancer with upregulated expression in tumor tissue. PKM2 participates in the cancer-specific Warburg effect to regulate fast glucose intake consumption. Besides, PKM2 also contributes to cancer progression, especially tumor metastasis. In this study, we showed that PKM2 is upregulated in breast cancer tissues and the upregulating of PKM2 in breast cancer correlates with poor prognosis. PKM2 can regulate tumor progression by promoting tumor cell viability and mobility. Furthermore, overexpression of PKM2 can promote EMT to encourage tumor metastasis. These findings indicate PKM2 is a potentially useful diagnostic biomarker and therapeutic target in breast cancer.

Numerous studies have verified that electroacupuncture (EA) can relieve neuropathic pain through a variety of mechanisms. Synaptotagmin 1 (Syt-1), a synaptic vesicle protein for regulating exocytosis of neurotransmitters, was found to be affected by EA stimulation. However, the roles of Syt-1 in neuropathic pain and EA-induced analgesic effect remain unclear. Here, the effect of Syt-1 on nociception was assessed through an antibody blockade, siRNA silencing, and lentivirus-mediated overexpression of spinal Syt-1 in rats with spared nerve injury (SNI). EA was used for stimulating bilateral &ldquo, Sanjinjiao&rdquo, and &ldquo, Zusanli&rdquo, acupoints of the SNI rats to evaluate its effect on nociceptive thresholds and spinal Syt-1 expression. The mechanically and thermally nociceptive behaviors were assessed with paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different temperatures, respectively, at day 0, 7, 8, 14, and 20. Syt-1 mRNA and protein levels were determined with qRT-PCR and Western blot, respectively, and its distribution was observed with the immunohistochemistry method. The results demonstrated Syt-1 antibody blockade and siRNA silencing increased ipsilateral PWTs and PWLs of SNI rats, while Syt-1 overexpression decreased ipsilateral PWTs and PWLs of rats. EA significantly attenuated nociceptive behaviors and down-regulated spinal Syt-1 protein levels (especially in laminae I-II), which were reversed by Syt-1 overexpression. Our findings firstly indicate that Syt-1 is involved in the development of neuropathic pain and that EA attenuates neuropathic pain, probably through suppressing Syt-1 protein expression in the spinal cord.

The Bohai Bay Basin straddled the Eocene boundary between arid and wet climates in eastern China. The basin was simultaneously affected by both arid and wet climates, and contemporaneous sediments developed under both extremely arid and extremely wet conditions. Data from every well drilled in the oil fields in the Bohai Bay Basin have been used to study the lower fourth member and the upper third member of the Shahejie Formation. The spatial distribution of climate indicators in the lower fourth member of the Shahejie Formation shows that the climate boundary extended from the northern Jizhong Depression to the Bozhong Depression. The portion of the basin to the north of this boundary mostly developed coalbeds, dark mudstone, and oil shale (indicative of a warm and wet climate), whereas the portion of the basin to the south of this boundary mostly developed gypsum, rock salt, and magenta dolomitic mudstone (indicative of a hot and arid climate). During the formation of the upper third member of the Shahejie Formation, the climate boundary shifted southward to the region between the southern part of the Jizhong Depression and the Jiyang Depression. The wet climate zone in the north expanded southward, and the arid climate zone in the south shrank. This shift is evident in the vertical lithologic characteristics of the members that formed before and after this shift in the climate boundary. The lithologic succession in the central part of the basin exhibits significant changes, whereas the lithologic successions in the southern and northern parts of the basin remain homogeneous and stable through time. Therefore, between the formation of the third and fourth members of the Eocene Shahejie Formation, the Bohai Bay Basin experienced a significant climate change. This change directly affected the pattern of the Eocene climate zones in eastern China and is indicative of changes in the paleoclimate zones near the Tropic of Cancer.

In order to promote the development of China's heavy industry economy and improve industrial production efficiency, a bearing fault detection method based on ARM is proposed. Firstly, the component standard deviation of the original features of motor bearings is obtained by combining with the ARM bearing fault detection algorithm, and the fault parameters are compared according to the classification standard deviation, so that the gears can be eliminated effectively. In order to ensure the accuracy and efficiency of motor bearing fault detection, the bearing fault detection process is optimized based on ARM bearing fault detection algorithm. Finally, the experiment proves that the fault detection method based on ARM is feasible, and the precision of motor bearing fault detection method is obviously improved compared with the traditional method.

Nowadays accurate and efficient traffic flow prediction is strongly needed by individual travelers and public transport management. Traffic flow prediction, especially long-term prediction, plays an important role in the application of intelligent transportation systems (ITS). In this paper, we propose a personalized design model (ResDeconvNN) based on Convolutional Neural Network (CNN) for long-term traffic flow prediction of elevated highways in Shanghai. The next whole day flow information can be predicted using the previous day flows. Taking the correlation of traffic parameters into account, we analogy flow, speed and occupancy (FSO) to the 3 channels of RGB as the 3 inputs of model. So the raw data collected from loop detectors are transformed into a spatial-temporal matrix which has 3 channels. Our model consists of two modules: Residual net and deconvolutional neural network. First, we take advantage of the residual net in deep network to extract the features of traffic. Then, we develop a deconvolutional network module and apply it to decode the flow of the next day from the comprehensive spatial and temporal traffic features. Experimental results indicate that the proposed model is robust and can achieve a better prediction accuracy compared with the other existing popular approaches.

Traffic three elements consisting of flow, speed and occupancy are very important parameters representing the traffic information. Prediction of them is a fundamental problem of Intelligent Transportation Systems (ITS). Convolutional Neural Network (CNN) has been proved to be an effective deep learning method for extracting hierarchical features from data with local correlations such as image, video. In this paper, in consideration of the spatiotemporal correlations of traffic data, we propose a CNN-based method to forecast flow, speed and occupancy simultaneously by converting raw flow, speed and occupancy (FSO) data to FSO color images. We evaluate the performance of this method and compare it with other prevailing methods for traffic prediction. Experimental results show that our method has superior performance.

Hydrological dynamics of sedimentary basins are essential for understanding regional climatic pattern in the geological past. In previous qualitative studies lithologically depending on the occurrence of featured sedimentary rocks, the Eocene climate of China had been subdivided into three latitudinal zones, with one subtropical high-controlled arid zone throughout middle China, and two humid zones respectively in the north and south. However, recent advances on mammalian fauna distribution, plant fossil-based quantitative paleoclimatic reconstruction, and modeling experiment jointly suggest that the relatively humid monsoonal climate might have prevailed over the territory. Here we examine and compare sedimentary sequences of 10 Eocene sections across eastern China, and hence the lake level fluctuations, to discuss the nature of climate type. Our results show that, instead of the categorically zonal pattern, the hydroclimate dynamics is intensified landward. This is demonstrated by the fact that, in contrast to the wide developed coal layers around the periphery, evaporites are growingly occurred endocentrically to the central part of middle China. However, although we have had assumed that all evaporites are indicator of extreme aridity, the highly oscillated climate in the central part of middle China was humid in the majority of the Eocene, distinct from permanent arid as seen in deserts or steppe along modern horse latitude. From the upcountry distribution pattern of the Eocene hydrological dynamics, it appears that the relatively dry climate in central China was caused by the impact of continentality or rain shadow effect under monsoonal, or monsoon-like climate.

A novel alternating copolymer of sulfonated poly(ether ether ketone-alt-benzimidazole)s (SPEEK-alt-BI) was synthesized by polycondensation in our previous report. In this article, we examined the properties of SPEEK-alt-BI membranes, such as thermal and mechanical stability, hydrolysis, and swelling properties in water, and proton conductivities at various temperatures and humidity. The experimental results showed that SPEEK-alt-BI membranes exhibited promising oxidative and hydrolysis stabilities. Although the base moieties in SPEEK-alt-BI main chain would capture proton and form reversible salt hindering the proton transfer capability, the conductivity of membrane 60SPEEK-alt-BI-H [Sulfonation degree (S.D.), 60% in form of proton] could achieve 22.61 mS/cm at 80°C and 100% humidity. Meanwhile, the conductivity of membrane could reach 40.12 mS/cm with phosphorus acid doping. The methanol permeation coefficient of 60SPEEK-alt-BI membrane is 2.3 × 10−8 cm2/s at 20°C, which is magnitude lower than that of Nafion®117, 1.11 × 10−6 cm2/s. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Quantitative reconstructions of atmospheric CO2 by using terrestrial and marine records are critical for understanding the so-called “greenhouse” conditions in the Cretaceous, but data from terrestrial plants for several stages of this period remain quite limited. Using the stomatal index (SI) technique, here we estimate the Santonian (Late Cretaceous) CO2 contents based on a sequence of fossil cuticles of Ginkgo adiantoides (Ung.) Heer from three beds of the Yong’ancun Formation in Jiayin, Heilongjiang Province, northeastern China. By the regress function, SIs of Ginkgo fossils reveal a pronounced CO2 reduction from the early to late Santonian (∼661 and ∼565 ppm, respectively). The relatively high CO2 levels provide additional evidence for paleoclimatic warmth in this interval. Moreover, available paleobotanical data illustrate a decline trend of CO2 contents throughout the Late Cretaceous, punctuated by several fluctuations in particular episodes with different magnitudes. The CO2 contents shifted notably in the late Cenomanian, Turonian, early Santonian, late Campanian, and probably latest Maastrichtian. Furthermore, a comprehensive study based on CO2 data shows that the global mean land surface temperature (GMLST) fluctuated several times accordingly. The change ratios of GMLST (ΔT) increased from ∼3°C in late Cenomanian to ∼4.7°C in mid Turonian, and then dramatically reduced to ∼2.2°C in mid Coniacian. From the Santonian onward, it appears that the temperature gradually decreased with a few minor fluctuations.

Thermodynamic analysis of the correlation of H2S and COS has been carried out at the temperature range of 400–650 °C at which high temperature desulfurization of coal gas is usually performed. The correlation of the two sulfur species is mainly through the reaction H2S+CO→COS+H2. Simulated coal gas with the following composition CO 32.69%, H2 39.58%, CO2 18.27%, N2 8.92% and H2S 0.47% was used in this study, and the equilibrium concentrations of the two species at different temperatures were calculated. The results of Fe-based sorbents during sulfidation were compared with calculations. It is concluded that the above reaction may reach equilibrium concentration in the presence of the Fe-based sorbents, which means the Fe-based sorbents may effectively catalyze the reaction between H2S and CO. Because of the correlation of the two sulfur species, both can be effectively removed at high temperatures simultaneously, offering high temperature desulfurization some advantages over low temperature desulfurization processes.

This paper studies the influence of the addition of Mo on the sulfidation performance of Fe-based sorbent supported on fly ash for hot coal gas desulfurization. Sorbent samples were prepared using physical mixing method with different Mo oxide content. The sulfidation experiments were carried out in the temperature range of 400–600 °C. Gas compositions were analyzed using a GC. The structure and morphology of sorbent samples before and after sulfidation were examined by using SEM, XRD and compressive strength was also measured. The experimental results show that the fly ash supporter has some capability for sulfur removal from the hot coal gas. The addition of Mo may effectively improve the desulfurization efficiency and increase the compressive strength of iron-based sorbents.

This paper deals with the simultaneous removal of H 2 S and COS in the temperature range of 400–650 °C at 1 bar by using iron-based sorbents. The iron-based sorbents were prepared using iron oxide and cerium oxide with coal fine ash as the support. Simulated coal gas was used in the sulfidation experiments and 5% O 2 in N 2 gas was used for regeneration of sorbents. Both sulfidation and regeneration experiments have been carried out using a fixed-bed quartz reactor. The product gases were analyzed using a GC equipped with a TCD and a FPD. The results demonstrated that both H 2 S and COS can be effectively reduced using the iron-based sorbents supported on fine coal ash. XRD analysis shows that Fe 1− x S phase has formed during sulfidation indicating a high sulfur capacity of the sorbent. The mechanism of the removal of COS simultaneously with H 2 S is also discussed.

A novel alternating copolymer of sulfonated poly(ether ether ketone-benzimidazole)s (SPEEK-BI) was synthesized by polycondensation of aromatic bisphenol containing benzimidazole and a mixture of sulfonated and non-sulfonated difluorobenzophenones. By varying the amount of two difluorobenzophenones, the ratio of sulfonic acid unit to imidazole base was controlled straightforwardly. The polymer structure was characterized by 1 H NMR and IR spectroscopy. Two different methods of ion exchange capacity measurement supported a strong inter- and intra-molecular interaction between acid and base units, which resulted in an improved mechanical strength as well as avoiding phase separation. Tough membranes with good mechanical stability in hot water (80 C) and alcohol were obtained by solution casting, which is potential for applications in polymer electrolyte membrane fuel cells and membranes for separation of liquids or gases.

Mastitis is defined as the inflammation of the mammary gland. LPS, which is widely used to induce mastitis models for the study of this disease, triggers similar inflammation as Escherichia coli. Sophocarpine, isolated from Sophora alopecuroides L., exhibits multiple biological properties. The aim of the present study was to determine the anti-inflammatory effect and mechanism of action of sophocarpine on mastitis within an LPS-induced mouse model. ELISA and western blotting were performed to detect protein levels. The qPCR was performed to detect mRNA levels. The ELISA and qRT-PCR results showed that sophocarpine inhibited the expression of TNF-α, IL-1β and IL-6 in a dose-dependent manner. However, sophocarpine suppressed TLR4 expression. Further study showed that sophocarpine could suppress the phosphorylation of IκBα, p65 and p38. These results confirm that sophocarpine played an anti-inflammatory role in LPS-induced mastitis by regulating TLR4 and the NF-κB and MAPK signaling pathways in mammary gland tissues. Therefore, sophocarpine may be a potential therapeutic drug for the treatment of mastitis.

To analyze the internal atmosphere of tableware disinfection cabinet, determine the composition and sources of odor gas.Analyze the internal atmosphere of tableware disinfection cabinet by solid phase microextraction (SPME) with gas chromatography-mass spectrometry (GC-MS), and study the relationship between organic gas and auxiliary materials by simulating sterilization conditions.The organic gas had been detected in tableware disinfection cabinet both before and after use of it. The paint film and the sealing strip produced 56 and 76 kinds of organic gaseous substances after one cycle of sterilizer work respectively. Both UV irradiation and heating processes made the sealing strip produce 56 kinds of organic gaseous substances.UV irradiation and heating will induce auxiliary mainly came from the auxiliary material.

This study analyze the formation process and the requirement of various usage of road space after the introduction of the regulation on road space usage through the case studies of two types of road at Xi'an city. As the results, the following are made clear.1) the various form of activities appear on the street as a public space, based on people's various and indispensable activity needs. 2) These various form of activities on street space have been connived though it is illegal as for juridical because the system of self-management in the district exists.