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Altered glutamine metabolism is an important aspect of cancer metabolic reprogramming. The GLS isoform GAC (glutaminase C), the rate-limiting enzyme in glutaminolysis, plays a vital role in cancer initiation and progression. Our previous studies demonstrated that phosphorylation of GAC was essential for its high enzymatic activity. However, the molecular mechanisms for GAC in maintaining its high enzymatic activity and protein stability still need to be further clarified. FAIM/FAIM1 (Fas apoptotic inhibitory molecule) is known as an important anti-apoptotic protein, but little is known about its function in tumorigenesis. Here, we found that knocking down FAIM induced macroautophagy/autophagy through suppressing the activation of the MTOR pathway in lung adenocarcinoma. Further studies demonstrated that FAIM could promote the tetramer formation of GAC through increasing PRKCE/PKCε-mediated phosphorylation. What's more, FAIM also stabilized GAC through sequestering GAC from degradation by protease ClpXP. These effects increased the production of α-ketoglutarate, leading to the activation of MTOR. Besides, FAIM also promoted the association of ULK1 and MTOR and this further suppressed autophagy induction. These findings discovered new functions of FAIM and elucidated an important molecular mechanism for GAC in maintaining its high enzymatic activity and protein stability.

Objective To explore the improvements in sleep duration, drowsiness and daytime fatigue in patients with sleep-wake disturbance after ischemic stroke treated by needling at Baihui (百会GV20) and Sishencōng (四神聪EX-HN1). Methods A total of 81 patients with post-stroke sleep-wake disturbance were randomly divided into 2 groups, i.e. a control group (39 cases) and a treatment group (42 cases). In the control group, the basic treatment for ischemic stroke was administered. In the treatment group, on the base of the treatment as the control group, acupuncture was applied to GV20 and EX-HN1. The treatment was given once a day, 30 min each time, totally for 4 weeks. The daytime sleep duration, sleep need, Epworth Sleepiness Score (ESS) and Fatigue Severity Scale (FSS) score were observed in the patients of two groups before and after treatment. The therapeutic effects were observed. Results After treatment, the daytime sleep duration and sleep need were all reduced to different extents in the patients of two groups. The daytime sleep duration and sleep need in the treatment group were lower than those in the control group (all P Conclusion Acupuncture at GV20 and EX-HN1 effectively reduces daytime sleep duration, relieves drowsiness and daytime fatigue and improves daytime function of the patients with post-stroke sleep-wake disturbance.

The depth of surface/subsurface damage layer is the key index of surface quality of sapphire. In this paper, that depth model of the surface/subsurface damage lay characterized by the crack length was established according to the mechanical theory of indentation fracture. The cutting relation between abrasive and workpiece and the difference of the depth of subsurface damage crack are analyzed. It is preliminarily estimated that the length of sub-surface damage crack of free abrasive sapphire is about 2.46 times that of fixed abrasive when considering only the contact hardness of abrasive grain under static load. Diamond abrasives with size of W20 were adopted to carry out experiments in free and fixed lapping methods. The results show that the surface/subsurface damage depth is 9.87μm and 3.63μm respectively. It is easier to obtain good sub-surface quality by using the fixed abrasive method than free abrasive at the same particle size.

Background Toward identifying new strategies to target gastric cancer stem-like cells (CSCs), we evaluated the function of the tumour suppressor CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) in gastric CSC maintenance. Methods We examined the expression of CDK5RAP3 and CD44 in gastric cancer patients. The function and mechanisms of CDK5RAP3 were checked in human and mouse gastric cancer cell lines and in mouse xenograft. Results We show that CDK5RAP3 is weakly expressed in gastric CSCs and is negatively correlated with the gastric CSC marker CD44. CDK5RAP3 overexpression decreased expression of CSC markers, spheroid formation, invasion and migration, and reversed chemoresistance in gastric CSCs in vitro and vivo. CDK5RAP3 expression was found to be regulated by extracellular-related kinase (ERK) signalling. ERK inhibitors decreased spheroid formation, migration and invasion, and the expression of epithelial-to-mesenchymal transition (EMT)-related proteins in both GA cells and organoids derived from a genetically engineered mouse model of GA. Finally, CDK5RAP3 expression was associated with reduced lymph-node metastasis and better prognosis, even in the presence of high expression of the EMT transcription factor Snail, among patients with CD44-positive GA. Conclusions Our results demonstrate that CDK5RAP3 is suppressed by ERK signalling and negatively regulates the self-renewal and EMT of gastric CSCs.

Inhibiting cancer metabolism via glutaminase (GAC) is a promising strategy to disrupt tumor progression. However, mechanism regarding GAC acetylation remains mostly unknown. In this study, we demonstrate that lysine acetylation is a vital post-translational modification that inhibits GAC activity in non-small cell lung cancer (NSCLC). We identify that Lys311 is the key acetylation site on GAC, which is deacetylated by HDAC4, a class II deacetylase. Lys311 acetylation stimulates the interaction between GAC and TRIM21, an E3 ubiquitin ligase of the tripartite motif (TRIM) family, therefore promoting GAC K63-linked ubiquitination and inhibiting GAC activity. Furthermore, GAC

Objective To observe the effects of fuzhengbutu (strengthening antipathogenic qi and tonifying the earth) acupuncture–moxibustion therapy on walking function in the patients with post-stroke hemiplegia. Methods A total of 57 patients with hemiplegia after ischemic stroke treated in our hospital from January 2018 through to October 2018 were collected as the study objects. According to random number table, they were divided into a treatment group (29 cases) and a control group (28 cases). In the treatment group, the fuzhengbutu acupuncture–moxibustion therapy combined with rehabilitation treatment was adopted. In the control group, the rehabilitation treatment was given. The persistent walking time and pause time in PIERENSTEP gait measurable training and test system as well as the score of Berg balance scale (BBS) were compared between the two groups. Results In the treatment group, the persistent walking time after treatment(1.47 ± 0.28) s was shorter obviously versus before treatment (2.12 ± 0.38) s, indicating the significant difference (P 0.05). In the control group, the persistent walking time after treatment (1.88 ± 0.22) s was shorter obviously versus before treatment (2.18 ± 0.30) s, indicating the significant difference (P 0.05). Before treatment, the differences were not significant in the persistent walking time and pause duration in the patients of either group (P > 0.05). After treatment, the persistent walking time in the treatment group was shorter obviously than the control group (P 0.05). Before treatment, there was no difference in BBS score between the two groups (P > 0.05). In the treatment group, BBS score (42.79 ± 2.78) after treatment was higher than (35.86 ± 2.64) before treatment, indicating the significant difference (P Conclusion Based on rehabilitation treatment, Fuzhengbutu acupuncture–moxibustion therapy effectively improves the walking function of the patients with hemiplegia after ischemic stroke.

Bladder cancer is a common malignant urinary tumor, and patients with bladder cancer have poor prognosis. Abnormal lipid metabolism in peroxisomes is involved in tumor progression. Hydroxysteroid dehydrogenase-like 2 (HSDL2) localized in peroxisomes regulates fatty acid synthesis. In the present study, we reported that HSDL2 was upregulated in two human bladder cancer cell lines 5637 and T24 compared to normal human urothelial cells. Furthermore, lentiviral-mediated HSDL2 knockdown inhibited the proliferation and colony formation while promoted the apoptosis of human bladder cancer T24 cells in vitro. In nude mice HSDL2 knockdown inhibited the growth of T24 derived xenografts in vivo. In conclusion, our results suggest that HSDL2 plays an oncogenic role in bladder cancer and might serve as a potential target for bladder cancer therapy.

Grainyhead-like 1 (GRHL1) is a transcription factor involved in embryonic development. However, little is known about the biological functions of GRHL1 in cancer. In this study, we found that GRHL1 was upregulated in non-small cell lung cancer (NSCLC) and correlated with poor survival of patients. GRHL1 overexpression promoted the proliferation of NSCLC cells and knocking down GRHL1 inhibited the proliferation. RNA sequencing showed that a series of cell cycle-related genes were altered when knocking down GRHL1. We further demonstrated that GRHL1 could regulate the expression of cell cycle-related genes by binding to the promoter regions and increasing the transcription of the target genes. Besides, we also found that EGF stimulation could activate GRHL1 and promoted its nuclear translocation. We identified the key phosphorylation site at Ser76 on GRHL1 that is regulated by the EGFR-ERK axis. Taken together, these findings elucidate a new function of GRHL1 on regulating the cell cycle progression and point out the potential role of GRHL1 as a drug target in NSCLC.

Objective: To investigate the effect of fluvastatin (Flu) combined with corbrin capsule (CC) on the pulmonary function (PF) in patients with chronic obstructive pulmonary disease (COPD). Methods: Totally, 156 patients with COPD treated in our hospital were assigned: 86 patients in the research group (RG), who were treated with Flu plus CC, and 70 patients in the control group (CG), who were treated with CC plus conventional drugs. The changes in inflammatory factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and procalcitonin (PCT), of the two groups before and after treatment were compared. The complications, psychological status, quality of life (QOL) and recurrence rate of the two groups were analyzed. Results: The total effective rate in the RG was dramatically higher than that in the CG (P

CXXC5 is a member of the CXXC‐type zinc‐finger protein family. Proteins in this family play a pivotal role in epigenetic regulation by binding to unmethylated CpG islands in gene promoters through their characteristic CXXC domain. CXXC5 is a short protein (322 amino acids in length) that does not have any catalytic domain, but is able to bind to DNA and act as a transcription factor and epigenetic factor through protein‐protein interactions. Intriguingly, increasing evidence indicates that expression of the CXXC5 gene is controlled by multiple signaling pathways and a variety of transcription factors, positioning CXXC5 as an important signal integrator. In addition, CXXC5 is capable of regulating various signal transduction processes, including the TGF‐β, Wnt and ATM‐p53 pathways, thereby acting as a novel and crucial signaling coordinator. CXXC5 plays an important role in embryonic development and adult tissue homeostasis by regulating cell proliferation, differentiation and apoptosis. In keeping with these functions, aberrant expression or altered activity of CXXC5 has been shown to be involved in several human diseases including tumourigenesis. This review summarizes the current understanding of CXXC5 as a transcription factor and signaling regulator and coordinator.

Macroautophagy/autophagy is a multistep cellular process that sequesters cytoplasmic components for lysosomal degradation. BECN1/Beclin1 is a central protein that assembles cofactors for the formation of a BECN1-PIK3C3-PIK3R4 complex to trigger the autophagy protein cascade. Discovering the regulators of BECN1 is important for understanding the mechanism of autophagy induction. Here, we demonstrate that TRIM59, a tripartite motif protein, plays an important role in autophagy regulation in non-small cell lung cancer (NSCLC). On the one hand, TRIM59 regulates the transcription of BECN1 through negatively modulating the NFKB pathway. On the other hand, TRIM59 regulates TRAF6 induced K63-linked ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3 complex. We further demonstrate that TRIM59 can mediate K48-linked ubiquitination of TRAF6 and promote the proteasomal degradation of TRAF6. Taken together, our findings reveal novel dual roles for TRIM59 in autophagy regulation by affecting both the transcription and the ubiquitination of BECN1. Abbreviations: ACTB: actin beta; BECN1: beclin 1; CHX: cycloheximide; CQ: chloroquine; GFP: green fluorescent protein; HA: haemagglutinin tag; His: polyhistidine tag; LC3B: microtubule associated protein 1 light chain 3 beta; NFKB: nuclear factor kappa B; NFKBIA: NFKB inhibitor alpha; NSCLC: non-small cell lung cancer; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; RELA: RELA proto-oncogene, NF-kB subunit; SQSTM1: sequestosome 1; tGFP: Turbo green fluorescent protein; TRAF6: TNF receptor associated factor 6; TRIM59: tripartite motif containing 59; B: ubiquitin

Glutamine metabolism plays an important role in cancer development and progression. Glutaminase C (GAC), the first enzyme in glutaminolysis, has emerged as an important target for cancer therapy and many studies have focused on the mechanism of enhanced GAC expression in cancer cells. However, little is known about the post-translational modification of GAC. Here, we report that phosphorylation is a crucial post-translational modification of GAC, which is responsible for the higher glutaminase activity in lung tumor tissues and cancer cells. We identify the key Ser314 phosphorylation site on GAC that is regulated by the NF-κB-PKCε axis. Blocking Ser314 phosphorylation by the S314A mutation in lung cancer cells inhibits the glutaminase activity, triggers genetic reprogramming, and alleviates tumor malignancy. Furthermore, we find that a high level of GAC phosphorylation correlates with poor survival rate of lung cancer patients. These findings highlight a previously unappreciated mechanism for activation of GAC by phosphorylation and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation.

The choice of abrasive particle size is crucial to improve the lapping efficiency and surface quality in lapping of sapphire wafer by fixed abrasive (FA) pad. A model for the penetration depth of a single abrasive is developed with fixed abrasive pad. A serious of lapping tests were carried out using FA pads embedded with different size of diamond particles to verify the validity of the developed model. Results show that the penetration depth of abrasive is related not only to the particle size, but to the hardness ratio of the work-piece to the pad as well. The material removal rate of sapphire is proportional to the square of abrasive particle size, while the average surface roughness is proportional to the abrasive particle size.

Fatty acid binding protein 4 (FABP4) is a member of the fatty acid binding protein family which involved in a variety of biological cellular processes, including tumorigenesis. However, the role of this key adipokine in cervical cancer is still unclear. In this study, we explored the function of FABP4 in cervical cancer and the underlying molecular mechanisms. FABP4 was specifically elevated in tissue samples from patients with cervical squamous cell carcinoma (CSCC) but not with cervical adenocarcinoma, and the level of FABP4 was correlated with E-cadherin and Vimentin expression. In vitro, exogenous FABP4 promoted the migration and invasion of CSCC cells in a dose-dependent manner, and reorganized the actin cytoskeletons in F-Actin staining and TGF-β induced EMT assays. Importantly, the AKT/GSK3β/Snail pathway appears to be involved in FABP4-induced EMT in CSCC cells. In conclusion, our research demonstrated elevated FABP4 promoted EMT via the activation of AKT/GSK3β/Snail pathway in CSCC.

COMMD protein family is an evolutionarily conserved gene family implicated in a number of critical processes including inflammation, copper homeostasis, sodium balance, endosomal sorting and cancer. In an effort to profile the expression pattern of COMMD family in several non-small cell lung cancer (NSCLC) cell lines, we found that compared with that in human bronchial epithelial (HBE) cells, the mRNA expression levels of five COMMD genes including COMMD3, COMMD4, COMMD5, COMMD6 and COMMD8 were significantly down-regulated, whereas COMMD9 was up-regulated in NSCLC cell lines. Here we reported that the expression of COMMD9 protein was significantly increased in various NSCLC cell lines and tissue samples. SiRNA-induced knocking down of COMMD9 inhibited proliferation and migration, arrested cell cycle at G1/S transition and induced autophagy in NSCLC cells. Mechanistically, COMMD9 interacted with the TFDP1 through COMM domain, and DNA-binding domain of TFDP1 was required for this interaction. Moreover, decreased expression COMMD9 attenuated TFDP1/E2F1 activation accompanied with enhanced p53 signaling pathway. Taken together, these findings demonstrate that COMMD9 participates in TFDP1/E2F1 activation and plays a critical role in non-small cell lung cancer.

The gene trim7 encodes at least four isoforms Glycogenin-interacting protein 1 (GNIP1), GNIP2, GNIP3 and Tripartite motif containing 7 (TRIM7). GNIP1, the longest isoform, has been reported acting as an oncogene. However, it is very interesting that TRIM7, the shortest isoform, only 15 amino acids different from GNIP1 in C-terminal, acts in a completely different way from that of GNIP1 in our present study. TRIM7 expression was decreased in tumor compared with adjacent normal tissues, and the level of TRIM7 was negatively correlated with clinical stage of 94 patients with lung cancer. In vitro, TRIM7 dramatically inhibited the proliferation and migration of tumor cells, and promoted cell apoptosis. Further study showed that TRIM7 interacted with p65 via its C-terminal which is different from GNIP1. The interaction between TRIM7 and p65 promoted the ubiquitination of p65 and finally accelerated the degradation of p65 via 26S proteasome. In vivo, the tumor volume and weight were decreased by TRIM7 stable expression. Meanwhile, Ki67 was down-regulated, thyroid transcription factor 1 (TTF-1) and Caspase 3 were up-regulated in TRIM7 overexpression group in xenograft model. It is very impressive that TRIM7t (a truncated TRIM7 without C-terminal sequence that different with GNIP1) had little effect on the tumor growth in vivo. These findings highlight a curious mechanism for negative regulation of NF-kappa B signaling pathway by TRIM7 and demonstrate that TRIM7 would be a potential therapeutic target for lung cancer.

The anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase, is responsible for the transition from metaphase to anaphase and the exit from mitosis. The anaphase promoting complex subunit 10 (APC10), a subunit of the APC/C, executes a vital function in substrate recognition. However, no research has reported the connection between APC10 and cancer until now. In this study, we uncovered a novel, unprecedented role of APC10 in tumor progression, which is independent of APC/C. First, aberrant increase of APC10 expression was validated in non-small cell lung cancer (NSCLC) cells and tissues, and the absence of APC10 repressed cell proliferation and migration. Of great interest, we found that APC10 inhibition induced cell cycle arrest at the G0/G1 phase and reduced the expression of the APC/C substrate, Cyclin B1; this finding is different from the conventional concept of the accumulation of Cyclin B1 and cell cycle arrest in metaphase. Further, APC10 was found to interact with glutaminase C (GAC), and the inhibition of APC10 weakened glutamine metabolism and induced excessive autophagy. Taken together, these findings identify a novel function of APC10 in the regulation of NSCLC tumorigenesis and point to the possibility of APC10 as a new target for cancer therapy.

Breast cancer is the most common malignant tumor among women in China, which seriously threatens women's physical and mental health. Tumorigenesis is closely related to the dysregulation of cell cycle. The cell cycle progression includes interphase and mitotic phase (M phase). Cyclin B1 is a key protein in regulating M phase, which is essential for the whole cell cycle progression. CyclinB1 can be degraded through ubiquitination mediated by the anaphase promoting complex/cyclosome (APC/C). However, the mechanism of how CyclinB1 is deubiquitinated in breast cancer still remains unclear. In this study, we discovered that CyclinB1 interacted with ubiquitin-specific peptidase 14 (USP14). Based on the deubiquitinating function of USP14, we detected the effect of USP14 on the ubiquitination of CyclinB1. Inhibiting the activity of USP14 or USP14 knockdown significantly increased the ubiquitination of CyclinB1. In accordance with this, knocking down USP14 arrested cell cycle at G2/M phase. Knocking down USP14 with siRNAs significantly inhibited the proliferation and migration of breast cancer cells. In conclusion, our study demonstrated that USP14 regulated the cell cycle of breast cancer cells by regulating the ubiquitination of CyclinB1, which will provide a solid theoretical basis for the development of anti-cancer drugs targeting USP14.

The Ag/TiO2 and Ag2O/TiO2 films were deposited by magnetron sputtering on the polyester fabrics. The Kelvin probe system was simply developed and used to investigate the photoelectric properties of Ag/TiO2 and Ag2O/TiO2 junctions. The measured work functions of the deposited Ag, Ag2O and TiO2 are 4.65 e V , 5.53 e V and 5.03 e V , respectively. Ag2O/TiO2 junction has a 0.12 e V larger E F difference than Ag/TiO2 junction, indicating that Ag2O/TiO2 junction has a higher ability of charge separation than Ag/TiO2 junction. The photocatalytic activities of samples towards RB solution under 365 nm UV light were investigated. The results show that the Ag/TiO2 and Ag2O/TiO2 coated polyester fabrics have a far better photocatalytic performance than TiO2 coated polyester fabrics. And the photocatalytic activity of Ag2O/TiO2 coated sample is prominently higher than that of Ag/TiO2 coated sample, which is attributed to the larger E F difference and the wider space charge region of Ag2O/TiO2 junction compared with that of Ag/TiO2 junction.

The production cost of the sapphire substrate was restricted by the efficiency of processing and the surface quality. A proposed level orthogonal experiment was conducted to reveal the effect of workbench speed, lapping pressure, the Concentration of triethanolamine and abrasive pad types on the material removal rate and surface roughness and morphology of sapphire substrate when lapped with a diamond fixed-abrasive pad. The results showed that the average material removal rate of sapphire is about 24μm/min, and the surface roughness Ra achieves 0.36μm when the 200/230 mesh diamond fixed-abrasive pad was used. The material removal rate and the surface roughness as the optimization goal, the optimal lapping parameters were as follows: the lapping pad with raised, lapping pressure 0.075MPa, workbench speed 120rpm and the Concentration of triethanolamine 1%. Under these optimal machining parameters, the material removal rate reached 42μm /min and the surface roughness Ra reached 0.37μm.

This paper presents a system of tensile test based on multi-agent virtual instrument to reduce difficulty and improve intelligence of virtual instrument development. Each software unit of the virtual instrument was designed independent agent. The multi-agent system was generated by the interaction between the agents, and applied successfully to low-carbon steel tensile test experiments. The experimental results show that the response speed and sensitivity of virtual instrument have been improved. Other the development of virtual instrument becomes more simplified, and enhance the ability of the system reconfigurable and intelligent level.

The reconstruction of defect profiles based on ultrasonic guided waves means the acquisition of defect profiles and parameters from ultrasonic guided wave signals. To achieve multi-resolution approximation, this paper proposed a reconstruction approach based on Radial Wavelet Basis Function Neural Network (RWBFNN), which combines wavelet analysis and neural network. Gaussian radial basis functions and Mexican hat wavelet frames are used as scaling functions and wavelet functions respectively. The training and testing samples contain simulation data and experimental data. The input data sets are defect echo signals, and the output data sets are 2-D profile parameters. To reduce the training time and simplify the profile reconstruction procedure without losing accuracy, Extreme Learning Machine (ELM) is adopted simultaneously. The results indicate that significant advantages can be obtained over other defect profile reconstruction schemes, and the accuracy of the predicted defect profile can be controlled by the resolution of the network with the lower computational complexity.

In this paper, the transient spin grating method was used to measure the attenuation rate of the diffraction signals of the intrinsic spin gratings of the intrinsic GaAs/AlGaAs quantum wells in different periods at room temperature, and the electron spin diffusion coefficient Ds = 121±6cm2/s was obtained. The electron spin diffusion coefficients of GaAs/AlGaAs quantum well were in good agreement with that of p-type GaAs/AlGaAs quantum well, indicating that the doping type for GaAs/AlGaAs quantum well has no significant effect on the diffusion rate of spin-polarized electrons. In this paper, the widely used formula of transient spin grating diffraction signal attenuation rate was used to fit the diffraction experimental results of the transient spin grating in the intrinsic GaAs/AlGaAs quantum well. The measured electron spin relaxation time was much shorter than that measured by the saturation absorption method. The reason for the deviation in the measured spin relaxation time was analyzed. The dynamic law of transient spin grating modulation attenuation over time was derived. The decay rate formula was modified, and the modified formula was used to fit the experimental data in the transient spin grating diffraction to obtain the spin relaxation time τs = 123 ps. The result was consistent with the measured electron spin relaxation time by the saturation absorption method.

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib has been approved based on the clinical benefit in non-small cell lung cancer (NSCLC) patients over the past decade. Unfortunately, cancer cells become resistant to this agent via various mechanisms, and this limits the improvement in patient outcomes. Thus, it is urgent to develop novel agents to overcome erlotinib resistance. Here, we propose a novel strategy to overcome acquired erlotinib resistance in NSCLC by inhibiting glutaminase activity. Compound 968, an inhibitor of the glutaminase C (GAC), when combined with erlotinib potently inhibited the cell proliferation of erlotinib-resistant NSCLC cells HCC827ER and NCI-H1975. The combination of compound 968 and erlotinib not only decreased GAC and EGFR protein expression but also inhibited GAC activity in HCC827ER cells. The growth of erlotinib-resistant cells was glutamine-dependent as proved by GAC gene knocked down and rescue experiment. More importantly, compound 968 combined with erlotinib down-regulated the glutamine and glycolysis metabolism in erlotinib-resistant cells. Taken together, our study provides a valuable approach to overcome acquired erlotinib resistance by blocking glutamine metabolism and suggests that combination of EGFR-TKI and GAC inhibitor maybe a potential treatment strategy for acquired erlotinib-resistant NSCLC.

Solved the problem of high efficient and stable feeding in the structure design of the armature guide ring automatic assembly equipment of the automobile windscreen wiper motor, and the design of feeding mechanism of armature guide ring automatic assembly equipment is designed by using the principle of conflict resolution in TRIZ innovative design theory. By analyzing the relationship between the function design requirements of the feeding mechanism and the 39 engineering parameters in the TRIZ, the contradiction matrix of the feeding mechanism is established, and the principle of the conflict resolution is analyzed and the corresponding principle solutions are found. The design scheme is evaluated according to the traditional design experience. The design scheme of the feeding mechanism of the armature guide ring automatic assembly equipment is determined.

Cdc42 is a Ras-related small GTP-binding protein. A previous study has shown that Cdc42 binding to the γ subunit of the coatomer protein complex (γCOP) is essential for Cdc42-regulated cellular transformation, but the molecular mechanism involved is not well understood. Here, we demonstrate that constitutively-active Cdc42 binding to γCOP induced the accumulation of epithelial growth factor receptor (EGFR) in the cells, sustained EGF-stimulated extracellular signal-regulated kinase (ERK), JUN amino-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) signaling and promoted cell division. Moreover, constitutive Cdc42 activity facilitated the nuclear translocation of EGFR, and this indicates a novel mechanism through which Cdc42 might promote cellular transformation.

The processing technology of sapphire with a high material removal rate a good surface quality is critical for its applications. The experiment of sapphire lapping and polishing was carried out by using three different fixed abrasive pad (FAP). Their material removal rate (MRR) and surface roughness (Ra) were measured and analyzed. Results indicate that a MRR of 5.6μm/min reaches in rough lapping and a MRR of 0.4μm/min in fine lapping. The average surface roughness Ra of rough lapping and fine lapping is 142nm and 1.2nm respectively. The processing efficiency of sapphire wafer is effectively improved and a good surface quality is obtained when FAP adopted.

Glioblastoma is one of the most aggressive brain tumors with high morbidity and mortality. Hypoxia is often the common characteristic of tumor microenvironment, and hypoxia-inducible factor-1α (HIF-1α) is an essential factor regulating the migratory activity of cancer cells including glioblastoma. Recently, mitochondrial dynamics was found to be involved in the aggression of cancer cells. However, whether dynamin-related protein 1 (Drp1) contributes to the migration of human glioblastoma cells under hypoxia remains unknown. In the present study, hypoxia was found to upregulate the transcription and expression of Drp1, and stimulated mitochondrial fission in glioblastoma U251 cells. Inhibition of HIF-1α with echinomycin blocked hypoxia‑induced expression of Drp1. Notably, Drp1 inhibitor Mdivi-1 efficiently attenuated hypoxia-induced mitochondrial fission and migration of U251 cells. In addition, three U251 stable cell lines expressing GFP, GFP-Drp1 and dominant negative GFP-Drp1‑K38A were established to examine the direct role of Drp1 in hypoxia-induced migration. MTT assay showed that there was no significant difference in proliferation of three cell lines. Compared with the GFP cell line, exogenously expressed GFP-Drp1-K38A inhibited hypoxia-induced migration of U251 cells, while stable expression of GFP-Drp1 enhanced the migration of U251 cells under hypoxia. Therefore, this study indicates the involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells, and suggests Drp1 to be a potential therapeutic target to suppress the aggression of glioblastoma in the future.

We herein simulate the scheduling process of automatic guided vehicle (AGV for short) with Plant Simulation, and try to obtain an optimal configuration for meeting practical engineering requirement in one assembly plant. We defined the predetermined loading station, unloading station and walking path simulation, and obtain a specific simulation time. Then, we build AGV simulation model, import data, define procedures and run the simulation process. By running the model repeatedly, we obtained the cost time and utilization rate of AGVs in each group in the process, and compared the simulation time to obtain the appropriate number of AGVs. The machine utilization results verified our simulated AGV configuration.

Aims at the performance of the oil distribution plate parts with laser direct rapid forming, and referring to the role of ultrasonic vibration in areas such as casting, welding, sintering etc. , and utilizing the neural networks and the genetic algorithm to optimize the process parameters, the article does the basic research of laser direct rapid forming distribution plate parts based on the ultrasonic vibration. The results indicates that this study can greatly enhance the wear resistance, the corrosion resistance and the fatigue properties etc. of the laser sintering distribution plate parts, having a good guidance to the practical production.

According to the insufficient ability of the existing ultrasonic guided wave detection technique, proposed a method for small defects in pipes based on time reversal (TR) ultrasonic guided wave. The L(0,2) mode guided waves was encouraged in the simulation research experiment. Results show that the guided wave detection signal has linear superposition properties, realized the detection energy focus on the location of the defects, and improved the ability of detection for small defects. The experiment lay a foundation for the miniaturization of the detection equipment.

This paper does a comprehensive research on job safety analysis framework, characteristics and issues involved in Great Wall Drilling Company Mud logging operation; through research on Mud logging operation safety situation and all kinds of accidents, detailed discussions have been made on the all kind of feature including identify the job hazards and assess the risk personnel ; through JSA(job safety analysis) cases verifying the applicability and effectiveness of JSA method in Great Wall Drilling Company Mud logging operation proposed in this paper, we can see that the JSA method can be used to evaluate program.

Four-wheel drive omni-directional mobile robots (FDOMRs) usually carry limited energy and have to accomplish their tasks before deadlines. Energy saving can be achieved in several ways, and one of that is determining a velocity trajectory. To find the minimum energy trajectory, a practical cost function is chosen as the total energy drawn from the batteries. However, the cost function is a free final time optimal control problem, which is usually complex and has no explicit solution. A normalized time variable is used to transform the original problem into a fixed final time optimal control problem, which is solved by using uniform control vector parameterization. Various simulations are performed and the consumed energy is compared to the normal control method that without minimum energy consumption control. Simulation results show that the energy saving is much more compared to the traditional control, the operational time of the FDOMR with given batteries is lengthened and the efficiency of battery is improved.

Fuzzy robust design will be applied to optimal design of cycloid pin wheel reducer, and it is established that fuzzy robust optimal design mathematical model of cycloid pin wheel reducer in order to achieve the goal of the small size and high efficiency. Genetic algorithms correlation functions in MATLAB is used to solve the model, and optimal methods and calculation examples is given.

The fuzzy theory and robust design is applied to the optimization design of the loader transmission, and put forward the fuzzy optimization design method of loader Transmission based on the robust idea. It is established the fuzzy robust optimization design model of loader transmission which has the goal of small size and high efficiency, and finally shows the optimal method and calculation example.