The role of CBL-CIPK signaling in plant responses to biotic and abiotic stresses.

Plants have a variety of regulatory mechanisms to perceive, transduce, and respond to biotic and abiotic stress. One such mechanism is the calcium-sensing CBL-CIPK system responsible for the sensing of specific stressors, such as drought or pathogens. CBLs perceive and bind Calcium (Ca2+) in response to stress and then interact with CIPKs to form an activated complex. This leads to the phosphorylation of downstream targets, including transporters and ion channels, and modulates transcription factor levels and the consequent levels of stress-associated genes. This review describes the mechanisms underlying the response of the CBL-CIPK pathway to biotic and abiotic stresses, including regulating ion transport channels, coordinating plant hormone signal transduction, and pathways related to ROS signaling. Investigation of the function of the CBL-CIPK pathway is important for understanding plant stress tolerance and provides a promising avenue for molecular breeding.

Realizing Synthetic Dimensions and Artificial Magnetic Flux in a Trapped-Ion Quantum Simulator.

Synthetic dimension is a potent tool in quantum simulation of topological phases of matter. Here we propose and demonstrate a scheme to simulate an anisotropic Harper-Hofstadter model with controllable magnetic flux on a two-leg ladder using the spin and motional states of a single trapped ion. We verify the successful simulation of this model by comparing the measured dynamics with theoretical predictions under various coupling strength and magnetic flux, and we observe the chiral motion of wave packets on the ladder as evidence of the topological chiral edge modes. We develop a quench path to adiabatically prepare the ground states for varying magnetic flux and coupling strength, and we measure the chiral current on the ladder for the prepared ground states, which allows us to probe the quantum phase transition between the Meissner phase and the vortex phase. Our work demonstrates the trapped ion as a powerful quantum simulation platform for topological quantum matter.

[Best evidence summary for awake prone positioning in treating hypoxemic due to COVID-19 infection].

Objective: To retrieve, evaluate, and summarize the best evidence for the treatment of hypoxemia in patients with COVID-19 infection using the awake prone positioning, with the aim of guiding healthcare professionals in the standardized implementation of this therapy. Methods: A systematic search was conducted in databases including UpToDate, BMJ Best Practice, JBI Evidence-Based Healthcare Center, American Association of Critical-Care Nurses, Intensive Care Society, European Respiratory Society, World Health Organization website, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang. The retrieved literature was subjected to quality assessment and evidence extraction. Results: A total of ten publications were included, consisting of one thematic evidence summary, one guideline, two systematic reviews, three randomized controlled trials, and three expert consensus statements. This summary synthesizes thirty key pieces of evidence in five categories: organizational management and training, risk assessment, preparatory operations, implementation key points, and risk control. Conclusions: Awake prone positioning is beneficial for improving hypoxemia in patients with COVID-19 and is easy to implement. Medical institutions should develop nursing management systems, operational standards, and best practices for awake prone positioning based on evidence-based evidence in order to improve the quality of care management for such patients.

Dual kinase inhibitor for EGFR mutants and ErbB2 limit breast cancer.

Mutations in the epidermal growth factor receptor (EGFR) have been found in more than 10% of non-small cell lung cancer (NSCLC) patients in North America. The vast majority of these differences are L858R point mutations in Exon 21. Currently, monoclonal antibodies directed against the extracellular domain of EGFR or small molecule/tyrosine kinase inhibitors (TKI) are the stalwarts of NSCLC therapy. Resistance, however, gradually develops because of the T790 mutation towards first and second generation TKIs. The third generation TKI AZD9291 (Osimertinib) has a high affinity for both activating and the acquired resistant mutation (T790 M) in EGFR, with a low affinity towards wild-type EGFR. Recent research, however, suggests that the EGFR (C797S) mutation in the tyrosine kinase domain is a likely cause of resistance to AZD9291. Another significant transformation mechanism associated with this resistance is erbB2 amplification. Our laboratory has developed a small kinase inhibitor, ER121 (MW: ∼500), that inhibits the erbB2/HER2 tyrosine kinases in addition to the EGFR C797S mutations. We have identified a TKI, ER121 targeting the mutant EGFR(T790 M). Using in vitro and in vivo models, examined the efficacy of ER121 on mutant EGFR cell lines. This has enabled us to establish that ER121 is well tolerated when administered orally and produces significant inhibitory activity against human cancers generated by mutant EGFR and amplified ErbB2.

Asperosaponin VI Protects Against Bone Loss Due to Hindlimb Unloading in Skeletally Growing Mice Through Regulating Microbial Dysbiosis Altering the 5-HT Pathway.

Osteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI (AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6 J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200 mg/kg/day). AVI was administrated orally for 4 weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as Clostridium and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss.

Experimental Realization of the Rabi-Hubbard Model with Trapped Ions.

Quantum simulation provides important tools in studying strongly correlated many-body systems with controllable parameters. As a hybrid of two fundamental models in quantum optics and in condensed matter physics, the Rabi-Hubbard model demonstrates rich physics through the competition between local spin-boson interactions and long-range boson hopping. Here, we report an experimental realization of the Rabi-Hubbard model using up to 16 trapped ions and present a controlled study of its equilibrium properties and quantum dynamics. We observe the ground-state quantum phase transition by slowly quenching the coupling strength, and measure the quantum dynamical evolution in various parameter regimes. With the magnetization and the spin-spin correlation as probes, we verify the prediction of the model Hamiltonian by comparing theoretical results in small system sizes with experimental observations. For larger-size systems of 16 ions and 16 phonon modes, the effective Hilbert space dimension exceeds 2^{57}, whose dynamics is intractable for classical supercomputers.

Observation of Non-Markovian Spin Dynamics in a Jaynes-Cummings-Hubbard Model Using a Trapped-Ion Quantum Simulator.

The Jaynes-Cummings-Hubbard (JCH) model is a fundamental many-body model for light-matter interaction. As a leading platform for quantum simulation, the trapped ion system has realized the JCH model for two to three ions. Here, we report the quantum simulation of the JCH model using up to 32 ions. We verify the simulation results even for large ion numbers by engineering low excitations and thus low effective dimensions; then we extend to 32 excitations for an effective dimension of 2^{77}, which is difficult for classical computers. By regarding the phonon modes as baths, we explore Markovian or non-Markovian spin dynamics in different parameter regimes of the JCH model, similar to quantum emitters in a structured photonic environment. We further examine the dependence of the non-Markovian dynamics on the effective Hilbert space dimension. Our Letter demonstrates the trapped ion system as a powerful quantum simulator for many-body physics and open quantum systems.

Quantum Simulation of the Two-Dimensional Weyl Equation in a Magnetic Field.

Quantum simulation of 1D relativistic quantum mechanics has been achieved in well-controlled systems like trapped ions, but properties like spin dynamics and response to external magnetic fields that appear only in higher dimensions remain unexplored. Here we simulate the dynamics of a 2D Weyl particle. We show the linear dispersion relation of the free particle and the discrete Landau levels in a magnetic field, and we explicitly measure the spatial and spin dynamics from which the conservation of helicity and properties of antiparticles can be verified. Our work extends the application of an ion trap quantum simulator in particle physics with the additional spatial and spin degrees of freedom.

Experimental Realization of Multi-ion Sympathetic Cooling on a Trapped Ion Crystal.

Trapped ions are one of the leading platforms in quantum information science. For quantum computing with large circuit depth and quantum simulation with long evolution time, it is of crucial importance to cool large ion crystals at runtime without affecting the internal states of the computational qubits, thus the necessity of sympathetic cooling. Here, we report multi-ion sympathetic cooling on a long ion chain using a narrow cooling beam focused on two adjacent ions, and optimize the choice of the cooling ions according to the collective oscillation modes of the chain. We show that, by cooling a small fraction of ions, cooling effects close to the global Doppler cooling limit can be achieved. This experiment therefore demonstrates an important enabling step for quantum information processing with large ion crystals.

Protective effect of sonic hedgehog signaling pathway activation on acute myocardial infarction.

To study changes in the sonic hedgehog (Shh) signaling pathway in acute myocardial infarction (AMI) and the protective effect of changes in Shh signaling pathway activity on AMI, specific pathogen-free (SPF) C57BL/6 mice were treated with left anterior descending (LAD) ligation to establish an AMI model. The samples were collected on the 1st, 3rd, 14th, and 21st days after AMI induction. After the operations, the mice were administered the Shh signaling pathway receptor agonist SAG1.3 (5 mg/kg/d) and antagonist SANT-1 (3.3 mg/kg/d) by intraperitoneal injection. The myocardial ischemia model was established by oxygen glucose deprivation (OGD) in vitro. The AMI mouse model and the in vitro OGD-induced myocardial ischemia model were established. The Smo agonist SAG1.3 was used to activate the Shh signaling pathway, thereby reducing the expression of Bcl-2 and Bax. The number of apoptotic cells was reduced. Administration of the antagonist SANT-1 inhibited Shh signaling pathway activity by increasing the expression of Bcl-2 and Bax, and the number of apoptotic cells increased. In conclusion, activation of the Shh signaling pathway improved cardiac functions and myocardial remodeling and reduced the apoptosis of myocardial cells.

Chemoembolisation with polyvinyl alcohol for advanced hepatocellular carcinoma with portal vein tumour thrombosis and arterioportal shunts: efficacy and prognostic factors.

AIM: To evaluate the efficacy and to identify prognostic factors of polyvinyl alcohol (PVA) chemoembolisation for treating advanced hepatocellular carcinoma (HCC) with portal vein (PV) tumour thrombosis (PVTT) and arterioportal shunts. MATERIALS AND METHODS: The clinical data of 145 advanced HCC patients with PVTT and arterioportal shunts were collected. The patients were divided into two groups: group A, with main PV invasion, (n=56) and group B, with PV branch invasion, (n=89). Based on arterioportal shunt types, different particle sizes of PVA were used for chemoembolisation. The overall survival (OS), time to progression (TTP), and postoperative complications were analysed retrospectively. RESULTS: The median OS of all patients was 10.1 months. The median OS of group A and group B was 8.2 and 12.5 months, respectively (χ2=6.03, p=0.01). The overall 6-, 12-, and 18-month survival rates of groups A and B were 63.8%, 24.9%, and 6.3%, and 78.1%, 55.2%, and 23.7%, respectively. After embolisation, there were two cases of acute liver failure and three cases of upper gastrointestinal bleeding. Cox multivariate survival analysis revealed that main PVTT (HR [hazard ratio]=1.75, p=0.01), Child-Pugh B class (HR=1.99, p=0.003) and tumour burden ≥50% (HR=3.25, p<0.001) were independent risk factors. A dose of oxaliplatin >100 mg (HR=0.48, p<0.001) was an independent protection factor. CONCLUSION: Treatment of advanced HCC with PVTT and arterioportal shunts by PVA chemoembolisation is safe and effective. The patients achieved a better prognosis with the dose of oxaliplatin >100 mg, while main PVTT, Child-Pugh B class, and tumour burden ≥50% were poor prognostic indicators.

The association between the UBQLN1 polymorphism and Alzheimer's disease risk: A systematic review.

Recently, some studies suggested that UBQLN1 variant was associated with AD risk. However, the results were inconsistent. This meta-analysis aimed to determine the association between UBQLN1 variant and AD risk. We searched the electronic databases PubMed, Embase, and CNKI databases. Random-effects model was used. All statistical tests were performed using the STATA 11.0 software (StataCorp, College Station, TX, USA). UBQLN1 variant was not associated with the risk of AD (OR=1.05; 95%CI, 0.92-1.19; I2=35%). The corresponding pooled ORs were not materially altered in sensitivity analysis. The Galbraith plot was used to find the source of the heterogeneity and no study was the outlier. The shape of the funnel plot showed symmetry. Egger's test found no evidence of publication bias (P=0.8). These results suggest that the UBQ-8i polymorphism was not associated with AD risk.

A set of novel microsatellite markers developed for an economically important tree, Dracontomelon duperreanum, in China.

Dracontomelon duperreanum, the most representative species of the family Anacardiaceae, is an important multipurpose tree in China and Vietnam. However, no genetic diversity studies have been reported on this species. In this study, we identified 11 microsatellite markers for D. duperreanum by using the restriction-site-associated DNA sequencing (RAD-seq) method and examined their polymorphisms in 22 samples obtained from the South China Botanical Garden, South China. We could detect only two or three alleles for each microsatellite marker. The mean observed and expected heterozygosities were 0.41 and 0.39, respectively, which were lower than those reported for the species with similar life history forms. These relatively low genetic diversities in this common plant species are unexpected and might have resulted from its extensive cultivation. To our knowledge, this is the first report of microsatellite markers in the genus Dracontomelon. These microsatellite markers will be valuable for studying the genetic diversities and structures in D. duperreanum and other Dracontomelon species.

Enantioselective apoptosis and oxidative damage induced by individual isomers of profenofos in primary hippocampal neurons.

The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L-1. The cell viability and lactate dehydrogenase (LDH) efflux indicated that (-)-PFF exposure was associated with more toxic effects than (+)-PFF above the concentration of 5 mg L-1 (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L-1 (-)-PFF, (+)-PFF and rac-PFF for 24 h reached 23.4%, 9.2% and 14.2% (P < 0.01), respectively. Hippocampal neurons incubated with (-)-PFF, (+)-PFF and rac-PFF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) and a dose-dependent inhibition of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, implying that the defense system of the tests induces oxidative damage. A statistically significant difference was observed between the two enantiomers at 5 mg L-1 and above. Moreover, the results showed that (-)-PFF exposure caused a significant loss in mitochondrial transmembrane potential (MMP), an upregulation of Ca2+ and Bax protein expression, a downregulation of Bcl-2 protein expression, and the activation of caspase-3 and caspase-9 in a dose-dependent manner; (+)-PFF and rac-PFF exhibited these effects to a lesser degree. All results suggest that PFF induced apoptosis in rat hippocampal neurons via the mitochondria-mediated pathway, and oxidative stress is one of the factors of PFF-induced apoptosis. In addition, (-)-PFF appears to play an important role in oxidative stress and apoptosis, indicating that enantioselectivity should be considered when assessing ecotoxicological effects and health risks of chiral pesticides.

[Retrospectively analysis on 95 postpartum hemorrhage women treated with obstetrics and gynecology in intensive care unit].

Objective: To review the clinical aspects and pathogenesis of postpartum hemorrhage (PPH) and investigate the optimal protocols for intervention. Methods: From February 2009 to December 2015, data of normal labour and casearean birth women admitted to intensive care unit (ICU) in our hospital because of hematobilia were selected. 95 patients were divided into three groups (e. g ≥500-1 000 ml, ≥1 000-1 500 ml, ≥1 500-2 500 ml and ≥2 500 ml group) according to the bleeding volume. A retrospective analysis was performed to study the pathogenesis of PPH, organ function, surgical intervention and clinical prognosis on hemorrhage. Results: The data comprised 20 504 women over the 6-year period. 95 (0.463%) of which resulted in PPH and were admitted to ICU. 9 of these patients with PPH unsurvived. The value of creatinine and urea nitrogen, the score of APACHE Ⅱ and the possibility of multiple organ dysfunction syndromethe (MODS) increased with the amount of bleeding (P<0.05). For patients with PPH caused by injury of birth canal and/or placenta factors, there was significant difference among three groups on amount of bleeding (P<0.05). For patients with surgical intervention such as vaginal packing, interventional treatment and exploratory laparotomy conducted in 6 hours, the volume of transfusion was(759±114) ml. The volume of transfusion was (2 000±829) ml and (4 999±1 699) ml in 6 to 12 hours intervention group and in greater than 12 hours intervention group, respectively. The volume of transfusion significant increased over intervention time. There was a statistically significant difference in all groups (P<0.05). Conclusions: Classified treatment should be conducted according the classification on the amount of bleeding. Patients with severe PPH and/or tendency of organ failure should be admitted to ICU. Measures for maintenance of the function of organs are necessary, while appropriate surgical intervention is also needed based on the cooperation between ICU and obstetrical department, and the cure rate could be improved.

A large family of antivirulence regulators modulates the effects of transcriptional activators in Gram-negative pathogenic bacteria.

We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44-100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family.

[Clinical effect of polyvinyl alcohol particles combined with chemoembolization in treatment of hepatocellular carcinoma complicated by hepatic arteriovenous shunt and related and prognostic factors].

Objective: To investigate the clinical effect of polyvinyl alcohol (PVA) particles combined with chemoembolization using chemotherapeutic agents or chemotherapeutic agents lipiodol emulsion (CALE) in the treatment of hepatocellular carcinoma (HCC) complicated by hepatic arteriovenous shunt (HAVS) and related prognostic factors. Methods: A retrospective analysis was performed for the clinical data of 133 patients with HCC complicated by HAVS. HAVS was classified into slow-flow HAVS, intermediate-flow HAVS, and high-flow HAVS, which were treated with 300-500µm, 500-710µm, and 710-1000µm PVA particles, respectively. The patients with slow-flow and intermediate-flow HAVS underwent embolization with PVA combined with chemotherapeutic agents followed by CALE, while those with high-flow HAVS underwent the treatment with PVA combined with chemotherapeutic agents alone. The survival time, progression-free survival time, and postoperative complications were followed up and analyzed. The Kaplan-Meier method was used to calculate cumulative survival rate and the Cox proportional hazards model was used to determine prognostic factors. Results: The median overall survival (OS) of 133 patients was 9.1 months, and the 6-, 12-, and 24-month survival rates were 73.7%, 36.2%, and 10.2%, respectively. The median OS of slow-flow group (36 patients), intermediate-flow group (58 patients), and high-flow group (39 patients) were 7.3, 9.1, and 10.8 months, respectively. And the 6- and 12-month survival rates were 69.2%/19.0%, 72.4%/39.2%, and 77.8%/42.7%, respectively. There was no significant difference in survival time between the patients with different types of HAVS (χ2= 2.865,P= 0.239). The incidence rates of postoperative gastroesophageal variceal bleeding and acute liver failure were 1.1% and 0.4%, respectively. The results of Cox regression analysis showed that preoperative alpha-fetoprotein level≥400 ng/ml (HR= 2.105,P= 0.006) was an independent risk factor, while multiple embolizations (HR= 0.482,P= 0.011), tumor remission (HR= 0.431,P= 0.041), and multimodality therapy (HR= 0.416,P= 0.004) were independent protective factors. Conclusion: PVA particles combined with chemotherapeutic agents or CALE is safe and effective in the treatment of HCC complicated by HAVS. Patients with multiple embolizations, tumor remission, and multimodality therapy tend to have good prognosis, while those with a high level of alpha-fetoprotein before embolization often have poor prognosis.

Testing the mutant selection window hypothesis in vitro and in vivo with Staphylococcus aureus exposed to fosfomycin.

The purpose of this study was to test the mutant selection window (MSW) hypothesis in vitro and in vivo with Staphylococcus aureus exposed to fosfomycin. With the in vitro time-kill studies, S. aureus ATCC 29213 [with a minimal concentration that inhibits colony formation by 99% (MIC99) of 2.2 µg/mL and a mutant prevention concentration (MPC) of 57.6 µg/mL] lost fosfomycin susceptibility at antibiotic concentrations (2×, 4×, and 8× MIC) that are between the lower and upper boundaries of the MSW. In the tissue-cage model, S. aureus was exposed to fosfomycin pharmacokinetics at concentrations below the MIC99, between the MIC99 and the MPC, and above the MPC, respectively. Changes in susceptibility and counts of total and resistant viable bacteria were monitored in tissue-cage fluid obtained daily. However, the selection of resistant mutants was not observed during antibacterial treatment and 48 h after the termination of fosfomycin treatment, regardless of the fosfomycin dosage. Besides, we found no differences between the in vitro-isolated mutant and its sensitive parental strain, which indicates the absence of fitness cost of fosfomycin resistance in S. aureus ATCC 29213. These findings demonstrate that agar plate determinations do not fit the MSW for fosfomycin treatment of rabbits infected with S. aureus ATCC 29213; therefore, the existence of the window must be demonstrated not only in vitro but also in vivo. Further research is needed on the exact mechanism of resistance.

Identification of lung cancer oncogenes based on the mRNA expression and single nucleotide polymorphism profile data.

This study aimed to identify the oncogenes associated with lung cancer based on the mRNA and single nucleotide polymorphism (SNP) profile data. The mRNA expression profile data of GSE43458 (80 cancer and 30 normal samples) and SNP profile data of GSE33355 (61 pairs of lung cancer samples and control samples) were downloaded from Gene Expression Omnibus database. Common genes between the mRNA profile and SNP profile were identified as the lung cancer oncogenes. Risk subpathways of the selected oncogenes with the SNP locus were analyzed using the iSubpathwayMiner package in R. Moreover, protein-protein interaction (PPI) network of the oncogenes was constructed using the HPRD database and then visualized using the Cytoscape. Totally, 3004 DEGs (1105 up-regulated and 1899 down-regulated) and 125 significant SNPs closely related to 174 genes in the lung cancer samples were identified. Also, 39 common genes, like PFKP (phosphofructokinase, platelet) and DGKH-rs11616202 (diacylglycerol kinase, eta) that enriched in sub-pathways such as galactose metabolism, fructose and mannose metabolism, and pentose phosphate pathway, were identified as the lung cancer oncogenes. Besides, PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1), RORA (RAR-related orphan receptor A), MAGI3 (membrane associated guanylate kinase, WW and PDZ domain containing 3), PTPRM (protein tyrosine phosphatase, receptor type, M), and BMP6 (bone morphogenetic protein 6) were the hub genes in PPI network. Our study suggested that PFKP and DGKH that enriched in galactose metabolism, fructose and mannose metabolism pathway, as well as PIK3R1, RORA, and MAGI3, may be the lung cancer oncogenes.