The localization of prenylated Ras at the plasma membrane promotes activation of Ras by receptor tyrosine kinases and stimulates oncogenic signaling by mutant Ras. The Nogo-B receptor (NgBR) is a ...transmembrane receptor that contains a conserved hydrophobic pocket. Here, we demonstrate that the NgBR promotes the membrane accumulation of Ras by directly binding prenylated Ras at the plasma membrane. We show that NgBR knockdown diminishes the membrane localization of Ras in multiple cell types. NgBR overexpression in NIH-3T3 fibroblasts increases membrane-associated Ras, induces the transformed phenotype in vitro, and promotes the formation of fibrosarcoma in nude mice. NgBR knockdown in human breast cancer cells reduces Ras membrane localization, inhibits epidermal growth factor (EGF)-stimulated Ras signaling and diminishes tumorigenesis of xenografts in nude mice. Our data demonstrate that NgBR is a unique receptor that promotes accumulation of prenylated Ras at the plasma membrane and promotes EGF pathways.
Abstract
The Associated Proton beam Experiment Platform (APEP) beamline is the first proton irradiation facility to use naturally-stripped protons which come from H-beams interacting with the ...residual gas in the linac beampipe at CSNS. The stripped beam current, which is in the order of 0.1% of the original H-beam and approximately 10 μA, should be measured precisely to provide the proton number for irradiation experiments. Therefore, a low-intensity beam current measurement system was developed with considerations to eliminate the external interferences. An anti-interference design is adopted in this system with an elaboration of probes, cables and electronic low-noise technology to minimize the impact of environmental noise and interferences. This improves the signal-to-noise ratio and enables a more precise measurement of the microampere level pulsed beam current. The system was installed and tested during the summer maintenance in 2021 and 2022. It shows a good agreement with the measurement of the Faraday cup.
Abstract
Cloud-network integration(CNI) is an inevitable choice to enhance the supply capacity of industrial Internet. In traditional industrial control systems, there are problems such as ...insufficient depth of perception, insufficient connectivity and insufficient analytical predictability. Firstly, an industrial CNI control architecture is proposed in this paper. Then a software-defined PLC integrated development & runtime environment based on the cloud framework is developed and deployed on a private cloud platform. An efficient 5G private network is created to facilitate wireless omnidirectional connectivity of cloud PLC. The problems of complex industrial field circuits and difficult to unify protocols are solved through 5G intelligent terminal devices. Finally, the cloud control architecture and software platform are successfully applied to the remote centralized control of the tundish preparation system in a steel enterprise’s two steelmaking plants. The results shows that the innovative system architecture meet the requirements for high-performance access, transmission, computing and storage in industrial plants, which achieves the cloud control of entire process industrial automation production.
The analysis of the failure processes and mechanisms of rockfalls that are associated with underground mining activities is presented. The study area is located in Kaiyang Phosphorite Mine in ...Southwest China, where the geological condition is dominated by anti-dip slopes with layers inclined backward into the natural slope with decreasing strength in the rock mass from the upper (dolomite-rich) to the lower (shale-rich) strata. The analysis is based on field investigation and laboratory experimental study using a gravitational simulation device. The results support the proposed failure mechanism by demonstrating the process of failure from the deformation of the roof and floor in the stopes, to the development of surface cracks near the top of slopes, and eventually to the formation of rockfalls as the surface cracks propagate along pre-existing joints. The rockfalls are classified into one of three failure modes: crack–toppling, crack–sliding, and crack–slumping, in which the failures are governed by the corresponding characteristics of the rock mass structure. The study of the failure process and their spatial and temporal correlation with the underground workings reveals warning signs or indicators of impending slope instability. Improved understanding of the failure process and indicators can aid in early identification and timely warning of geohazards in phosphorite mines.
•Failure processes and modes of rockfall induced by underground mining are proposed.•Failure processes are found to be highly dependent on the joint structures.•Spatial and temporal relations between rockfalls, mining and rainfall are revealed.•We found a high compatibility of the results from the field and laboratory studies.•The formation of tension cracks is found in common and can be used as indicators.
n--Type semi--conductive nanometer material MgFe2O4 was synthesized by solid--state reaction of inorganic reagents MgSO4, Fe(NO3)3*9H2O, and NaOH. The process was a convenient, environment friendly, ...inexpensive and efficient preparation method for MgFe2O4 nanomaterial. X--ray diffraction (XRD) was used to confirm the material structure and transmission electron microscopy (TEM), high--resolution transmission electron microscopy (HRTEM) to depict the crystallite microstructure. Conductance responses of the nanocrystalline MgFe2O4 thick film were measured by exposing the film to reducing gases like methane (CH4), hydrogen sulfide (H2S), liquefied petroleum gas (LPG) and ethanol gas (C2H5OH). It was found that the sensor exhibited various sensing responses to these gases at different operating temperature. Furthermore, the sensor exhibited a fast response and a good recovery. Successive on and off responses could be repeated without observing major changes in the response signal.
Chemically protected sodium butyrate (CSB) is a new kind of sodium butyrate. Our previous study found that 1,000 mg/kg of CSB had the potential capacity of improving growth performance and promoting ...early development of small intestine in broilers. This study aimed to investigate the effect of long-term antibiotics or CSB supplementation for intestinal microflora dynamical regulation in broilers. One hundred ninety-two 1-day-old Arbor Acres male broilers were randomly allocated into 3 dietary treatment (8 replicates per treatment) and fed with a basal diet (CON), a diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg) (ANT), or a diet supplemented with 1,000 mg/kg of CSB, respectively. Results showed that dietary supplementation of CSB or ANT treatment elevated the weight gain and feed conversion ratio (FCR; P < 0.05), as compared with control (CON) group. Additionally, CON, CSB, or ANT administration dynamically altered the gut microbiota composition as time goes on. The increased presence of potential pathogens, such as Romboutsia and Shuttleworthia, and decreased beneficial bacteria such as Alistipes, Akkermansia, and Bacteroides were verified in new gut homeostasis reshaped by long-term antibiotics treatment, which has adverse effects on intestinal development and health of broilers. Conversely, CSB supplementation could dynamically enhance the relative abundance of Bacteroides, and decrease Romboutsia and Shuttleworthia in new microflora, which has positive effects on intestinal bacteria of broilers compared with CON group. Meanwhile, CSB supplementation was significantly increased the concentration of propionic acid and total short chain fatty acids (total SCFA; P < 0.05) in comparison with CON and ANT groups. Moreover, CSB treatment significantly increased anti-inflammatory and antioxidative capacities (P < 0.05) of broilers compared with ANT group. Taken together, we revealed characteristic structural changes of gut microbiota throughout long-term CSB or ANT supplementation in broilers, which provided a basic data for evaluating the mechanism of action affecting intestinal health by CSB or ANT administration and CSB as an alternative to antibiotics in the broilers industry.
Sorption thermal energy storage is considered as a promising method to reduce energy consumption of building heating. MgCl2⋅6H2O could be a good candidate due to its high energy storage density. This ...paper first summarizes phase equilibrium lines of four MgCl2 hydration/dehydration processes to evaluate reaction enthalpy and entropy variation. Thermal diffusivities and specific heat of MgCl2, MgCl2·6H2O and MgCl2-ENG composite are determined which are compared with common counterparts of MgSO4·7H2O and MgSO4-ENG. Then the performance of open sorption thermal energy storage system is assessed in terms of various sorbents. Results show that the obtained thermal conductivities of MgCl2·6H2O range from 0.15 W m−1 K−1 to 0.96 W m−1 K−1 at the temperature range of 15–70 °C while thermal conductivities of MgSO4·7H2O range between 0.29 W m−1 K−1 and 0.68 W m−1 K−1 at 20–45 °C. At 20 °C testing temperature, thermal conductivities of composite MgCl2 are improved which range between 0.97 W m−1 K−1 and 2.92 W m−1 K−1 under the condition of 500–900 kg m−3 density and 67–80% mass ratio of salt. Besides, MgCl2 composite is preferable for open sorption thermal energy storage which could achieve stable heat output for more than 4 h under the conditions of 15.4 °C inlet temperature, 40% relative humidity and 0.26 m s−1 air velocity.
•Light flash method proves to be suitable to measure thermal diffusivity of hydrates.•Thermal conductivity of MgCl2·6H2O is between 0.15 W m−1 K−1 and 0.96 W m−1 K−1.•Thermal conductivity of composite MgCl2 ranges from 0.97 W m−1 K−1 to 2.92 W m−1 K−1.•MgCl2-ENG composite is a desirable candidate for open sorption thermal energy storage.
Results from studies using molecular and genetic methods in humans and rodents suggest that brain-derived neurotrophic factor (BDNF) is involved in the behavioral effects of abused drugs, making ...understanding of its genomic structure and regulation of substantial interest. Recently, we have reported that the human BDNF gene contains seven upstream exons that can each be spliced independently to the major BDNF coding exon to form diverse bipartite BDNF transcripts. We also identified a novel “BDNFOS” gene that is transcribed to produce alternatively spliced natural antisense transcripts (NATs); its fifth exon overlaps with the protein coding exon VIII of human BDNF. To better understand BDNF's genomic structure and differential regulation, we now describe the rodent BDNF gene and transcripts. This gene includes six bipartite transcripts that are generated by six independently transcribed exons, each of which is spliced to a major coding exon and a tripartite transcript that is composed of two upstream exons and one coding exon. In addition, we found no evidence for antisense, opposite strand BDNFOS gene transcripts in mice or rats. The BDNF rodent splice variants display specific patterns of differential expression in different brain regions and peripheral tissues. Acute cocaine administration increased striatal expression of a specific BDNF4 splice variant by up to 5-fold. Interestingly, however, neither experimenter- nor self-administered chronic cocaine administration enhanced striatal BDNF expression. These data suggest a role of specific BDNF promoter regions and regulatory sequences in stimulant-induced alterations in BDNF expression, and in the alterations that changed BDNF expression is likely to confer in the brain.
Sequence variability in two mitochondrial DNA (mtDNA) regions, namely cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 4 (nad4), and internal transcribed spacer (ITS) of rDNA ...among and within three cestodes, Spirometra erinaceieuropaei, Taenia multiceps and Taenia hydatigena, from different geographical origins in China was examined. A portion of the cox1 (pcox1), nad4 genes (pnad4) and the ITS (ITS1+5.8S rDNA+ITS2) were amplified separately from individual cestodes by polymerase chain reaction (PCR). Representative amplicons were subjected to sequencing in order to estimate sequence variability. While the intra-specific sequence variations within each of the tapeworm species were 0-0.7% for pcox1, 0-1.7% for pnad4 and 0.1-3.6% for ITS, the inter-specific sequence differences were significantly higher, being 12.1-17.6%, 18.7-26.2% and 31-75.5% for pcox1, pnad4 and ITS, respectively. Phylogenetic analyses based on the pcox1 sequence data revealed that T. multiceps and T. hydatigena were more closely related to the other members of the Taenia genus, and S. erinaceieuropaei was more closely related to the other members of the Spirometra genus. These findings demonstrated clearly the usefulness of mtDNA and rDNA sequences for population genetic studies of these cestodes of socio-economic importance.
To evaluate the efficacy and safety of different medical treatment in advanced or unresectable angiosarcoma.
This study was a single-center retrospective clinical study. Fifty-five advanced or ...unresectable angiosarcoma patients treated in Sun-Yat Sen University Cancer Center from January 2005 to August 2020 were enrolled. There were 34 patients who received first-line doxorubicin-based chemotherapy (doxorubicin group), 12 patients received first-line doxorubicin or liposome doxorubicin plus paclitaxel or albumin bound paclitaxel chemotherapy (combination therapy group), and 4 patients received first-line paclitaxel-based treatment (paclitaxel group). There were 6 patients who received anti-angiogenesis targeted therapy, another 2 patients received anti-PD-1 antibody plus anti-angiogenesis targeted therapy. Targeted therapy and immunotherapy plus targeted therapy included 5 cases of first-line therapy and 3 cases of second-line therapy. The therapeutic effect was evaluated by RECIST 1.1 standard. The adverse reactions were evaluated by CTCAE4.0 standard. Kaplan-Meier survival analysis was evaluated with Log rank test. Cox proportional hazard model was used to analyze the influencing factors.
There were 18 patients achieved partial response (PR) in 34 patients in the doxorubicin group, median progression-free survival (mPFS) was 4.5 months, and median overall survival (mOS) was 15 months. Four patients achieved PR in 12 patients in the combination therapy group, mPFS and mOS were 4 months and 19 months. Two patients achieved PR in 4 patients in the paclitaxel group, mPFS and mOS were 3 months and 9 months. However, only 1 in 6 patients achieved PR for anti-angiogenesis targeted therapy, mPFS and mOS were 3 months and 16 months. Two patients who received anti-PD-1 immunotherapy combined with anti-angiogenesis targeted therapy acquired PR for 17 months and more than 16 months. Median PFS (7.5 months) were longer in those with primary liver, lung and spleen angiosarcoma than in those with other primary site (3.0 months,
=0.028). The mOS (20 months) was longer in females than that in males (12 months,
=0.045). Primary tumor site, sex, age and treatment were not independent prognostic factors for angiosarcoma patients (
>0.05). Grade 3-4 cardiac toxicity was found in 2 patients in the combination therapy group.
Doxorubicin-based and paclitaxel-based chemotherapy are the most important treatment for advanced angiosarcoma. Potential efficacy for targeted therapy combined with anti-PD-1 immunotherapy are showed in some patients with long duration of response and moderate adverse event.
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