Free-electron lasing at 27 nanometres based on a laser wakefield accelerator.

X-ray free-electron lasers can generate intense and coherent radiation at wavelengths down to the sub-ångström region1-5, and have become indispensable tools for applications in structural biology and chemistry, among other disciplines6. Several X-ray free-electron laser facilities are in operation2-5; however, their requirement for large, high-cost, state-of-the-art radio-frequency accelerators has led to great interest in the development of compact and economical accelerators. Laser wakefield accelerators can sustain accelerating gradients more than three orders of magnitude higher than those of radio-frequency accelerators7-10, and are regarded as an attractive option for driving compact X-ray free-electron lasers11. However, the realization of such devices remains a challenge owing to the relatively poor quality of electron beams that are based on a laser wakefield accelerator. Here we present an experimental demonstration of undulator radiation amplification in the exponential-gain regime by using electron beams based on a laser wakefield accelerator. The amplified undulator radiation, which is typically centred at 27 nanometres and has a maximum photon number of around 1010 per shot, yields a maximum radiation energy of about 150 nanojoules. In the third of three undulators in the device, the maximum gain of the radiation power is approximately 100-fold, confirming a successful operation in the exponential-gain regime. Our results constitute a proof-of-principle demonstration of free-electron lasing using a laser wakefield accelerator, and pave the way towards the development of compact X-ray free-electron lasers based on this technology with broad applications.

Gram-Scale Synthesis of Loganetin from S-(+)-Carvone.

Loganetin is the aglycone moiety of loganin that has a 5,6-fused bicyclic framework and exhibits a wide range of interesting biological activities. A gram-scale synthesis of loganetin has been accomplished from the readily accessible S-(+)-carvone. The key reactions of the synthesis are a Favorskii rearrangement to introduce four stereocenters and a sulfuric acid-meditated deprotection/cyclization reaction to assemble the sensitive dihydropyran ring with complete stereoselectivity. This work also enables us to synthesize C1 methoxy loganetin and the enantiomer of loganetin successfully.

Coherent X-ray source generation with off-resonance laser modulation.

The generation of ultrashort coherent radiation in the extreme-ultraviolet (EUV) and soft X-ray regimes is of great significance in a broad range of research. In this paper, a promising scheme for generating coherent harmonic radiation using off-resonance seed laser modulation is discussed. The off-resonance seed laser, whose wavelength differs from the resonant wavelength of the undulator, is first used to modulate the angular distribution of the electron beam (e beam) in the undulator (modulator). After passing through a dispersion section, strong coherent micro-bunching is introduced into the e beam, which contains high-order harmonic components of the seed laser. Theoretical analysis and simulations indicate that this method can be used for the generation of coherent EUV and soft X-ray radiation at sub-gigawatt power in a meter-scale undulator (radiator).

Analysis of 50 cases of operated giant thoracic tumors.

PURPOSE: To study the experience of the surgical treatment of giant thoracic tumors and the ways to overcome intraoperative and postoperative difficulties. METHODS: A retrospective analysis of the data from 50 patients operated with giant thoracic tumors (26 men and 24 women; age range 0.5-77 years) was carried out. All patients were treated with different surgical resections. The resected tumors weighed between 628 and 2586 g (mean 1973) and the intraoperative blood loss was 400-1500 ml. RESULTS: The tumor was successfully resected in all patients. Forty-eight (96%) patients were treated and discharged after the operation. Two (4%) patients developed postoperative pulmonary edema; one of them died due to disseminated intravascular coagulation (DIC) and the other one was discharged after full recovery. During follow up, one patient died of an abdominal metastasis of malignant mesothelioma 1 year after operation, and another one with mature teratoma died 4 months after the operation but the cause of death was unknown. The success of surgical resection was not related to the pathological tumor type. The surgical treatment was determined by the invasion and distant metastasis of giant thoracic tumors and surrounding tissues. CONCLUSIONS: Patients with giant thoracic tumors often have severe symptoms that cannot be managed with conservative treatment. However, surgery can completely resolve the symptoms. In order to fully reveal the operative field, the incision has to be as close as possible to the tumor. Various surgical techniques, such as complete, segmented, or major portion incisions, can be used, and attention should be paid to avoid major intraoperative bleeding. Preventive measures against re-expansion pulmonary edema should be applied as soon as possible after the surgery.

Aquaporin 3 knockdown suppresses tumour growth and angiogenesis in experimental non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most common diseases encountered in medical oncology practice. The aim of the present study was to test the antitumour effects of short-hairpin RNA targeting aquaporin 3 (AQP3) in experimental NSCLC. Expression of AQP3 was suppressed in human A549 and H1299 NSCLC cell lines by short-hairpin RNA-mediated silencing. Therapeutic effects were assessed by examining tumorigenicity using a subcutaneous xenograft mouse model of NSCLC. Aquaporin 3 knockdown inhibited tumour growth and prolonged survival of mice with tumours. Aquaporin 3 knockdown suppressed tumour proliferation, marked by enhanced expression of p53, an increased ratio of cleaved caspase 3 to pro-caspase 3 and reduced expression of proliferating cell nuclear antigen and B-cell lymphoma-2 (bcl-2). Aquaporin 3 knockdown inhibited tumour angiogenesis, marked by decreased CD31 immunostaining and reduced expression of hypoxia-inducible factor-2α and vascular endothelial growth factor. Aquaporin 3 knockdown reduced cellular glycerol content and suppressed mitochondrial ATP formation. Aquaporin 3 knockdown in vitro significantly suppressed activities of matrix metalloproteinases MMP2 and MMP9, reduced AKT phosphorylation and decreased cell invasiveness of A549 and H1299 cells. In conclusion, AQP3 knockdown suppressed tumour growth and reduced angiogenesis in human NSCLS xenografts. Aquaporin 3 could thus be envisaged as a novel therapeutic target for NSCLC.

Andrographolide antagonizes cigarette smoke extract-induced inflammatory response and oxidative stress in human alveolar epithelial A549 cells through induction of microRNA-218.

Andrographolide is a major bioactive labdane diterpenoid isolated from Andrographis paniculata and has protective effects against cigarette smoke (CS)-induced lung injury. This study was done to determine whether such protective effects were mediated through modulation of microRNA (miR)-218 expression. Therefore, we exposed human alveolar epithelial A549 cells to cigarette smoke extract (CSE) with or without andrographolide pretreatment and measured the level of glutathione, nuclear factor-kappaB (NF-κB) activation, proinflammatory cytokine production, and miR-218 expression. We found that andrographolide pretreatment significantly restored the glutathione level in CSE-exposed A549 cells, coupled with reduced inhibitor κB (IκB)-α phosphorylation and p65 nuclear translocation and interleukin (IL)-8 and IL-6 secretion. The miR-218 expression was significantly upregulated by andrographolide pretreatment. To determine the biological role of miR-218, we overexpressed and downregulated its expression using miR-218 mimic and anti-miR-218 inhibitor, respectively. We observed that miR-218 overexpression led to a marked reduction in IκB-α phosphorylation, p65 nuclear accumulation, and NF-κB-dependent transcriptional activity in CSE-treated A549 cells. In contrast, miR-218 silencing enhanced IκB-α phosphorylation and p65 nuclear accumulation in cells with andrographolide pretreatment and reversed andrographolide-mediated reduction of IL-6 and IL-8 production. In addition, depletion of miR-218 significantly reversed the upregulation of glutathione levels in A549 cells by andrographolide. Taken together, our results demonstrate that andrographolide mitigates CSE-induced inflammatory response in A549 cells, largely through inhibition of NF-κB activation via upregulation of miR-218, and thus has preventive benefits in CS-induced inflammatory lung diseases.

Differential expression of ERCC-1 in the primary tumors and metastatic lymph nodes of patients with non-small cell lung cancer adenocarcinoma.

About 80 % of lung cancers are carcinomas that are classified histologically as non-small-cell lung carcinoma (NSCLC) and targeted chemotherapy of this cancer is currently based on sensitivity of the primary tumor to specific drugs. The purpose of this study was to compare the levels of four serum markers of cancer and the levels of six molecular markers which are possibly associated with drug selection in the primary tumors and metastatic lymph nodes of 39 consecutive NSCLC patients who were admitted to a single institution in China. Serum markers of cancer (neuron-specific enolase, carcinoembryonic antigen (CEA), cancer antigen 125, cytokeratin fragment 21-1) were measured by an automated electrochemiluminescence system and molecular markers (multidrug resistance protein 1, LDL receptor-related protein, ribonucleotide reductase M1, epidermal growth factor receptor, excision repair cross-complementing gene 1, and breast cancer 1) were measured by immunohistochemistry of the primary tumors and metastatic lymph nodes. The results indicate that the serum level of CEA was higher in NSCLC patients with adenocarcinoma relative to those with squamous cell carcinoma, but no significant differences in the other serum markers. Expression of excision repair cross-complementing gene 1 was significantly different in the primary tumors and metastatic sites of NSCLC patients with adenocarcinoma, but there were no other significant differences. This study provides an initial step toward the development of individualized chemotherapy of NSCLC based on measurement of molecular markers in the primary tumors and metastatic lymph nodes.

[Combined effects of interferon γ and γ ray irradiation on A549 cells in vitro].

OBJECTIVE: To define the role of interferon-γ on radiotherapy of lung cancer and explore a new way to clinical treatment. METHODS: A549 cells were exposed to γ ray with or without IFN-γ co-treatment. MTT assay was performed to evaluate cell viability. Western blot was used to observe the expression of P53 protein. RESULTS: The results showed that co-treatment of IFN-γ decreased the cell viability significantly compared with the γ ray irradiation group (71.4% ± 2.1% vs 44.1% ± 3.1%, n = 7, P < 0.01). In addition, the expression of P53 protein also increased significantly after co-treatment (P < 0.01); Furthermore, the cell cycle was changed obviously in co-treatment group compared with γ ray irradiation group, S phase increased (12.9% vs 20.9%, n = 5, P < 0.05) and also blocked the G2/M phase (28.8% vs 38.9%, n = 5, P < 0.05). CONCLUSIONS: The results suggested that γ ray irradiation combined with IFN-γ can increase the efficiency of radiotherapy on A549 cells and there is much broad prospect in the clinical treatment of lung cancer.

[Wedge resection and thermal cautery for malignant pleural effusion caused by lung cancer under vats].

OBJECTIVE: To discuss the treatment effect of wedge resection and thermal cautery of pleura for patients with malignant pleural effusion (MPE) caused by lung cancer under VATS. METHODS: 37 patients with MPE underwent wedge resection and thermal cautery of pleura under VATS, from June 2005 to December 2008. Postoperative tumor markers level was contrasted with the preoperative, and the control rate of pleural effusion and survival rate of the patients were compared with control group, including 25 patients undergoing intrapleural chemotherapeutics in the same period. RESULT: In the group, the control rate of pleural effusion was 100%, but 60% in control group (P = 0.005). The 1-year survival rate of the group and the control group was 78.38% and 60% respectively (P = 0.003). CEA and CA-125 were descended obviously in postoperative day 7 in the group(P = 0.002);in control group, there were no significant change of CEA and CA125 after treatment (P = 0.797). CONCLUSION: Wedge resection and thermal cautery of pleura under VATS can reduce tumor burden of patients with MPE to the maximum, and control MPE effectively and improve the quality of life for lung cancer patients with MPE.

[Diagnosis and surgical treatment of congenital bronchoesophageal fistula in adult].

OBJECTIVE: To explore the clinical characteristics, diagnosis and surgical treatment of adult congenital bronchoesophageal fistula. METHODS: Eleven cases of adult congenital bronchoesophageal fistula that were diagnosed and surgically treated between May 1990 and August 2010 had been reviewed. There were 7 male and 4 female patients, ranging in age from 28 to 66 years (mean 48.7 years). The chief clinical presentation included coughing and sputum in 10 cases, recurrent bouts of coughing after drinking liquid food in 6 cases, hemoptysis in 6 cases, low fever in 4 cases, chest pain in 3 cases. The duration of symptoms before diagnosis ranged from 5 to 36 years (mean 16.8 years). The diagnosis of bronchoesophageal fistula was confirmed most by esophagography. Associated diseased lung was resected in all patients (lobectomy in 10 cases and pneumonectomy in 1 case). The operation included right thoracotomy in 7 cases and left thoracotomy in 4 cases. The fistula was completely resected in 10 cases. The tract was simply divided and the end was sutured in 1 case. RESULTS: The postoperative course was uneventful in 10 patients who were discharged from hospital 10 to 18 d after operation. One patient suffered from esophageal fistula and received second operation. Regular follow-up was conducted on all 11 patients, proving that 3-year survival rate was 11/11 and 5-year survival rate was 9/11. CONCLUSION: Persistence of congenital bronchoesophageal fistula into adulthood is rare. The main symptom is nonspecific coughing and bouts of coughing after drinking liquid food. The most useful diagnostic method is the esophagography. Even though it is benign disease, life-threatening complications might occur and it must be treated surgically as soon as the diagnosis is established.

[The impact of antibiotic treatment in patients with influenza-like illness].

OBJECTIVE: To study the etiology of influenza-like illness (ILI) in Beijing, and to investigate the impact of antibiotic treatment on outcomes. METHODS: This was a prospective cohort study. Patients with diagnosis of influenza-like illness were prospectively enrolled for study of bacterial and viral pathogens. Demographic characteristics, underlying diseases, respiratory and extrapulmonary symptoms, laboratory tests were also collected for analysis of relationship between drug therapy and outcomes. RESULTS: A total of 476 cases were enrolled between Dec. 2006 and Apr. 2007, of whom 454 cases were used for analysis. Influenza virus was the most common pathogen( n = 197, 43.4%), with other pathogens rarely seen. The mean age of the patients was (33 +/- 13) years, and the ratio of male to female was 1.1:1. Twenty four patients (5.3% ) received influenza vaccine. The rate of antibiotic prescription after onset of illness was 63.4%, but none received antiviral drugs such as Oseltamivir and amantadine. Compared with influenza-negative patients, patients with influenza were older, had more underlying diseases and had greater severity of symptoms such as cough, sore throat, headache and myalgia (but with no statistical differences). The influenza syndrome (T > or = 39 degrees C plus cough, sore throat and headache or myalgia) was more common in the influenza group compared to the influenza-negative patients (P < 0.05). The ratio of antibiotic prescription was 67% in the influenza group, and the total white blood cell and platelet count, percentage of neutrophils were higher in antibiotic treatment patients compared with non-antibiotic treatment patients (P < 0.01). The cost in patients who received antibiotics was twice as much as non-antibiotic treatment patients (P < 0.05), but the defervescence time and respiratory symptom alleviation time did not differ. Cox regression analysis showed that the total white blood count and the differentials (OR value 1.049 and 1.014, respectively), but not antibiotic use were the independent risk factors for longer defervescence time. CONCLUSION: Influenza virus was the most common pathogen for adult patients with ILI in Beijing city during the winter and the spring seasons. Antibiotic treatment of adult patients with ILI did not improve illness resolution, while the cost was increased significantly.

[Clinicopathological features and prognosis of bronchial mucoepidermoid carcinoma: analysis of 21 cases].

OBJECTIVE: To investigate the clinicopathological features and prognosis of bronchial mucoepidermoid carcinoma. METHODS: Twenty-one with mucoepidermoid carcinoma, 16 males and 5 females, aged 40.8 (15 ~ 72) underwent surgical treatment, 13 cases undergoing lobectomy, 3 sleeve lobectomy, 4 pneumonectomy, and 1 case thoracic exploration, from February 1988 to June 2005. Bronchoscopy was done in all patients before operation. Follow-up was made for 68.3 months on average. RESULTS: Most patients presented the respiratory symptoms such as cough, dyspnea, hemoptysis, and obstructive pneumonia. Biopsy examination through bronchoscopy confirmed the diagnosis of bronchial mucoepidermoid carcinoma in 16 cases. Pathology showed 17 cases of low grade tumor and 4 cases of high grade tumor. Follow-up showed that 17 cases of low-grade group (stage T(1 - 3)N(0 - 1)M(0)) all survived, 8 of which had survived for more than 5 years, including one patient with hilar lymph node metastasis. However, none of the 4 cases with high-grade tumor survived for more than 1 year except one that survived for 13 months. CONCLUSION: Patients with low-grade mucoepidermoid carcinoma can be expected to be cured through curative resection, however, patients in high-grade group have poor prognosis because of metastasis. TNM staging, malignancy grade, and local lymph node metastasis play the key roles in prediction of prognosis.

[Enhanced-real time PCR: a highly sensitive method for SARS-coronavirus detection].

An enhanced real-time polymerase chain reaction (ERT-PCR) assay to detect the coronavirus associated with severe acute respiratory syndrome (SARS-Cov) has been designed for detection of SARS-Cov with high sensitivity and easy-to-interpret results, in which a target gene pre-amplification step preceded TaqMan real-time fluorescent PCR. The limit of detection of the ERT-PCR method was 10(-2) higher than the standard real-time PCR assay and 10(-7) higher than conventional PCR methods. The increased sensitivity of the assay would have major benefits in screening suspected SARS patients rapidly and efficiently and may help control the spread of SARS and other infectious diseases during future outbreak.

[Clinical diagnosis and surgical treatment of primary pulmonary lymphoma].

OBJECTIVE: To study the clinical characteristics, the principles of diagnosis and surgical treatment for primary pulmonary lymphoma. METHOD: Ten patients with primary pulmonary lymphoma were treated surgically and their clinical characteristics, the experiences of clinical diagnosis and surgical treatment were analyzed. The tumors located in left upper lobe in 2, left lower lobe in 1, right upper lobe in 3, right middle lobe in 3 and right lower lobe in 1. The main symptoms were cough and (or) hemoptysis. Imageological representations (X-ray and CT scanning of thorax) were similar to primary pulmonary carcinoma. Broncho-fibroscopic examination was performed on all cases with negative findings. Eight cases were mistakenly diagnosed as primary pulmonary carcinoma by imageological representations. Only 2 cases were diagnosed as primary pulmonary lymphoma by percutaneous needle biopsy and pathologic examination. All cases received pneumonectomy, ipsilateral hilar and mediastinal lymphadenectomy. All cases with non-Hodgkin's lymphoma received regular chemotherapy (MOPP and ABVD scheme for 1 case with Hodgkin's disease respectively, CHOP for 8 cases with non-Hodgkin's lymphoma), and 3 cases received radiotherapy postoperatively. RESULTS: Eight cases were non-Hodgkin's lymphoma (B-type) and 2 cases were Hodgkin's disease (mixed type) confirmed by pathological examination. Six cases with non-Hodgkin's lymphoma (3 cases for stage IE, 2 cases for stage II 1E, and 1 case for stage II 2E W) had been surviving for 18-42 months until the follow-up. Two cases with non-Hodgkin's lymphoma (stage II 2E, B-cell, low-grade) and 2 cases with Hodgkin's disease (stage IE and II 2E, mixed type) died in 24, 32, 8 and 17 months postoperatively respectively. CONCLUSIONS: Primary pulmonary lymphoma is a rare type of malignant lung neoplasm without special clinical features. The preoperative diagnosis is difficult. Treatment modalities include surgical treatment, radiotherapy and regular chemotherapy postoperatively.

[Value of carbon-11 choline positron emission tomography in patients with pulmonary abnormalities].

OBJECTIVE: To assess the value of carbon-11 choline (CH) positron emission tomography (PET) in patients with pulmonary nodules. METHODS: From September 2002 to December 2004, 39 patients with pulmonary nodules were imaged with CH-PET. CH-PET data was analyzed by visual method and semiquantitative method. When pulmonary nodules with abnormal CH uptake appeared in PET scans confirmed by visual method, their maximum and mean standard uptake value (SUVmax and SUVmean) were measured using semiquantitative method. Diagnoses were confirmed by surgery or biopsy and follow-up survey. RESULTS: Twenty-four cancerous and 3 inflammatory nodules and 1 bronchogenic cyst were detected by CH-PET and were diagnosed malignant with visual method. Three bronchial alveolar carcinoma, 2 metastatic tumor from kidney and colon, 3 fibrous nodules, 1 cryptococcosis, 1 hamartoma and 1 sclerosing hemangioma showed nothing abnormal in PET scans. For identification of pulmonary nodules with CH-PET, the sensitivity was 89% (24/29), the specificity was 60% (6/10), and the accuracy was 77% (30/39). There were differences in SUV between 8 squamous cell carcinomas and 9 adenocarcinomas (Z = -2.937, -2.887, P < 0.01). In diagnosing 70 resected enlarged lymph nodes beyond 1 cm in 17 lung cancer patients, CH-PET had the sensitivity of 86% (25/29), the specificity of 90% (37/41), and the accuracy of 89% (62/70). CH-PET confirmed 7 distant metastases in 25 lung cancer patients. In 5 cases suspected brain metastases CH-PET identified 2 cases positive correctly. CONCLUSIONS: CH-PET can confirm malignant pulmonary nodules, but still there were false positive and false negative cases. CH-PET can evaluate N stage effectively in patients with lung cancer. CH-PET can depict brain metastases accurately.

[Fluorine-18 fluorodeoxyglucose uptake in patients with benign pulmonary nodules].

OBJECTIVE: To assess the features of fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with benign pulmonary nodules. METHODS: From October 1998 to July 2004, 47 patients with benign pulmonary nodules were imaged with FDG-positron emission tomography (PET). Diagnoses were confirmed by surgery. FDG-PET data was analyzed by visual method and semi-quantitive method. When pulmonary nodules with abnormal FDG intake appeared in PET scans confirmed by visual method, their maximum and mean standard uptake value (SUVmax and SUVmean) and SUV of normal lung (SUVlung) were measured using semiquantitative method. RESULTS: Twenty-one cases showed nothing abnormal in PET scans, including 17 calcification and fibrosis, 2 hamartomas and 2 sclerosing hemangiomas. 26 pulmonary nodules were detected by FDG-PET (17 active tuberculous, 6 inflammatory pseudotumors, 3 cryptococcosis). FDG uptake of these 26 nodules was higher than that of normal lung (SUVmax, SUVmean and SUVlung were 3.04 +/- 1.65, 2.48 +/- 1.35 and 0.40 +/- 0.07, respectively, P < 0.001). Correlations were not found between FDG uptake and nodule size or SUV of normal lung or age or blood glucose level in these 26 patients (P > 0.05). SUV in 9 cases (9/26, 35%) were beyond 2.5. CONCLUSIONS: Some benign pulmonary nodules were FDG avid.

[Fluorine-18 fluorodeoxyglucose-positron emission tomography imaging of carcinoma of cardia or fundus of stomach].

OBJECTIVE: To investigate the value of fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) in carcinoma of cardia or fundus of stomach. METHODS: From April 1999 to April 2005, 57 patients with carcinoma of cardia or fundus of stomach were imaged with FDG-PET. FDG-PET imaging were analyzed by visual method combined with semiquantitative analysis. The results were compared with pathological findings and follow-up results. RESULTS: In 29 untreated patients, 25 T(2) to T(4) tumors were all FDG avid and 4 T(1) cases showed nothing abnormal at the primary site. In 24 patients performed curative operation 40 resected enlarged lymph nodes beyond 1 cm were diagnosed correctly by FDG-PET. FDG-PET revealed distant metastases in 5 patients and corrected them from curative surgery candidates to late stage. In 28 treated patients FDG-PET confirmed 22 cases with recurrence or metastasis. CONCLUSIONS: FDG-PET has limited value in confirming T stage in carcinoma of cardia or fundus of stomach. It showed potential in N and M staging and predicting treatment response.

[Development of New Molecular EZH2 on Lung Cancer Invasion and Metastasis].

Lung cancer is a serious threat to human health malignancies upward trend in morbidity and mortality. It is hot topic to investigate the molecular mechanisms of lung cancer development and explore the new therapeutic targets. The underlying mechanism of EZH2 on lung cancer development will demonstrate the new pathway of lung cancer development, invasion and metastasis. The exploration and application of new targeted molecular will improve the survival rate and living quality of lung cancer patients in future.

Inhibition of metabotropic glutamate receptor 1 suppresses tumor growth and angiogenesis in experimental non-small cell lung cancer.

Metabotropic glutamate receptor 1 (mGlu1 receptor) is expressed in many cancer cell types as compared to normal counterparts underscoring its potential role in tumor behavior. The aim of present study was to test the role of mGlu1 receptor in experimental non-small cell lung cancer (NSCLC). First, protein expression of mGlu1 receptor was higher in human NSCLC cell lines, including both adenocarcinoma and squamous carcinoma subtypes, when compared to normal bronchial epithelial cells. Inhibition of mGlu1 receptor by BAY36-7620 (an mGlu1 receptor-specific inhibitor) inhibited tumor growth and prolonged survival of mice with tumors of A549 or H1299. Treatment with BAY36-7620 suppressed AKT phosphorylation in A549 tumors and pre-treatment with BAY36-7620 blocked the L-quisqualate (a potent mGlu1 receptor agonist)-induced AKT phosphorylation in A549 cells. Treatment with BAY36-7620 reduced cellular proliferation of A549 cells. Treatment with BAY36-7620 enhanced cleaved PARP levels and reduced protein expression of bcl-2, HIF-1α, and VEGF. In contrast, treatment with L-quisqualate reduced cleaved PARP levels and enhanced protein expression of bcl-2, HIF-1α, VEGF, and IL-8, which was reversed by co-incubation with MK2206 (an AKT inhibitor). Pre-treatment with BAY36-7620 blocked the VEGF-induced AKT phosphorylation in HUVECs. Treatment of HUVECs with L-quisqualate resulted in enhancement of capillary tube formation, which was reversed by co-incubation with MK2206. Furthermore, mGlu1 receptor knockdown suppressed tumor growth and prolonged survival of mice with tumors of A549 or H1299. Collectively, inhibition of mGlu1 receptor suppressed tumor growth and angiogenesis in experimental NSCLC.

Ultrahigh brilliance quasi-monochromatic MeV γ-rays based on self-synchronized all-optical Compton scattering.

Inverse Compton scattering between ultra-relativistic electrons and an intense laser field has been proposed as a major route to generate compact high-brightness and high-energy γ-rays. Attributed to the inherent synchronization mechanism, an all-optical Compton scattering γ-ray source, using one laser to both accelerate electrons and scatter via the reflection of a plasma mirror, has been demonstrated in proof-of-principle experiments to produce a x-ray source near 100 keV. Here, by designing a cascaded laser wakefield accelerator to generate high-quality monoenergetic e-beams, which are bound to head-on collide with the intense driving laser pulse via the reflection of a 20-um-thick Ti foil, we produce tunable quasi-monochromatic MeV γ-rays (33% full-width at half-maximum) with a peak brilliance of ~3 × 10(22) photons s(-1) mm(-2) mrad(-2) 0.1% BW at 1 MeV. To the best of our knowledge, it is one order of magnitude higher than ever reported value of its kinds in MeV regime. This compact ultrahigh brilliance γ-ray source may provide applications in nuclear resonance fluorescence, x-ray radiology and ultrafast pump-probe nondestructive inspection.