Temperature dependence of stimulated Raman scattering from a VYO4 crystal.

The microstructural, electrical, and optical properties of crystals are critical to laser device performance, and the temperature-dependence effect of crystals has gained a great deal of attention in research. The linewidth, stimulated Raman scattering (SRS) shift, and intensity of the characteristic peak at 890 cm-1 of YVO4 crystal have been investigated between 148 and 448 K. As the crystal temperature increases, the bond length increases and the crystal force constant decreases, and the phonon softening process arises in the crystal at high temperature. The temperature effect on Raman shift and full width at half maximum is explained in detail in terms of the phonon anharmonic effect. The temperature dependence of SRS can be well demonstrated by an empirical equation. This work can provide new insights into the further understanding of lattice anharmonicity and contribute to the discovery of new optoelectronic materials.

Circ_0000808 promotes the development of non-small cell lung cancer by regulating glutamine metabolism via the miR-1827/SLC1A5 axis.

BACKGROUND: Circular RNA (circRNA) has been proved to be an important molecular target for cancer treatment. However, the function and molecular mechanism of circ_0000808 in non-small cell lung cancer (NSCLC) are still unclear. METHODS: Quantitative real-time PCR was used to detect the expression of circ_0000808, miR-1827, and solute carrier family 1 member 5 (SLC1A5). Cell proliferation, apoptosis, migration, and invasion were measured by cell counting kit 8 assay, colony formation assay, EdU staining, flow cytometry, wound healing assay, and transwell assay. The protein expression was measured by Western blot analysis. Dual-luciferase reporter assay and RIP assay were used to investigate the interactions between miR-1827 and circ_0000808 or SLC1A5. Cell glutamine metabolism was assessed by determining glutamine uptake, glutamate production, and α-ketoglutarate production. Xenograft mouse model was used to assess the in vivo effects of circ_0000808. RESULTS: Circ_0000808 expression was upregulated in NSCLC tissues and cancer cells, and its silencing inhibited NSCLC cell proliferation, migration, and invasion and led to apoptosis. Further results confirmed that circ_0000808 interacted with miR-1827 to positively regulate SLC1A5. The rescue experiments showed that miR-1827 inhibitor reversed the suppressive effect of circ_0000808 knockdown on the malignant behaviors of NSCLC cells. Also, SLC1A5 overexpression abolished the inhibition effect of miR-1827 on NSCLC cell progression. In addition, circ_0000808/miR-1827/SLC1A5 axis positively regulated the glutamine metabolism process in NSCLC cells. Moreover, circ_0000808 knockdown reduced the NSCLC tumor growth in vivo. CONCLUSION: In summary, our data showed that circ_0000808 enhanced the progression of NSCLC by promoting glutamine metabolism through the miR-1827/SLC1A5 axis.

EGFR Inhibitor CL-387785 Suppresses the Progression of Lung Adenocarcinoma.

OBJECTIVE: This study aimed to explore the influence of the irreversible EGFR inhibitor CL-387785 on invasion, metastasis, and radiation sensitization of non-small cell lung cancer cells. METHODS: The proliferation inhibitory rate at different time points was detected by MTT assay. The apoptosis of H1975 cells treated with CL-387785 was detected using flow cytometry. The invasion and migration of H1975 cells treated with CL-387785 were determined by Transwell assay and wound healing assay. The survival fraction (SF) of H1975 cells cultured with CL- 387785 under X-ray (0, 2, 4, 6, 8, and 10 Gy) was detected by cloning formation experiment, and the sensitization ratio (SER) was calculated by clicking the multi-target model to fit the cell survival curve. RESULTS: CL-387785 restrained H1975 cell proliferation in a concentration- and time-dependent manner. CL-387785 promoted H1975 cell apoptosis and reduced cell migration distance and the number of transmembrane cells. The SF treated by different concentrations of CL-387785 (10, 25, 50, and 100 nM) was all below 0 nM. The radiation SER of CL-387785 (10, 25, 50 and 100 nM) were 1.17, 1.39, 2.88, and 3.64, respectively. CONCLUSION: The invasion and metastasis of H1975 cells were restrained by irreversible EGFR inhibitor CL-387785. CL-387785 also exhibited the effect of radiotherapy sensitization.

LINC00599 influences smoke-related chronic obstructive pulmonary disease and regulates CSE-induced epithelial cell apoptosis and inflammation by targeting miR-212-5p/BASP1 axis.

LINC00599 has been reported to be upregulated in response to cigarette smoking. However, the effect and underlying mechanism of LINC00599 in chronic obstructive pulmonary disease (COPD) are still under exploration. In this study, LINC00599 was upregulated in the COPD patients and was of clinical value to distinguish COPD patients. COPD cell models were established using 16HBE cells under cigarette smoke extract (CSE) treatment. LINC00599 levels were elevated in a dose and time-dependent way in response to CSE stimulation. The effect of LINC00599 on CSE-induced 16HBE cells was explored. The results showed that LINC00599 deficiency reversed the CSE-induced inhibition on cell viability and proliferation, and rescued the CSE-induced enhancement on cell 16HBE cell apoptosis and inflammation response. Moreover, LINC00599 bound with miR-212-5p to upregulate the BASP1 (brain abundant membrane attached signal protein 1) expression. MiR-212-5p was expressed at a low level in the tissue samples of COPD patients, and its levels were upregulated in LINC00599 silenced cells. BASP1 was targeted by miR-212-5p and its upregulation was identified in the tissue samples of COPD patients and cell models. BASP1 levels were downregulated after miR-212-5p overexpression or LINC00599 silencing. Moreover, the rescue assays demonstrated that BASP1 overexpression reversed the effect of silenced LINC00599 on 16HBE cells after CSE treatment, which indicated that LINC00599 promoted the COPD development by regulating BASP1 expression. In conclusion, LINC00599 facilitated CSE-induced cell apoptosis and inflammation response, while inhibiting the cell viability and proliferation in COPD progression via modulating miR-212-5p/BASP1 axis.

Exploring the mechanism of miR320a in regulating PDL1 upon lung cancer pathogenesis.

The tumour suppressive role of miRNA320a is observed in many cancer types like in colon, lung, breast, and osteosarcoma but it is inversely reported in prostate cancer and in MPM cell lines. miRNA320a targets programmed death ligand 1 (PDL1) negatively in many cancer types and recently in Malignant pleural mesothelioma. In this background it is important to understand the regulatory mechanism of miRNA320a in determining PDL1 expression in different pathological stages of lung cancer. Histology was used to grade the initial and advanced stage of lung cancer following carcinogenic injection. Immunohistochemistry and Western blotting technique were used to analyse PDL1 protein expression. In-situ hybridization was used to determine miRNA320a signals. Initially, using the chemical carcinogen Diethylnitrosamine (25 µg/g), we successfully initiate initial and advanced stage of lung cancer following 6 months and 9 months of carcinogenic injection. The formation of initial and advanced stage of lung cancer is confirmed through histopathological changes which show neoplastic appearance in initial lung cancer and appearance of more mitotic cells along with tissue hardness in the advanced lung cancer stages. In miRNA320a blocked tissue the cancer condition becomes worse with decreased tissue elasticity along with more proliferative cells. Immunohistochemistry and Western blotting studies show that PDL1 is overexpressed in the advanced stages rather than in initial lung cancer because the expression of miRNA320a is overexpressed in initial stages but restricted in advanced stages of lung cancer. miRNA32a blocking studies confirm that miRNA320a expression act as a tumour suppressor that directly controls PDL1 expression that lack of miRNA320a enhances PDL1 expression as well as it triggers lung cancer advances. In summary, miRNA320a possess tumour suppressor function that limits PDL1 expression in initial lung cancer but its control over PDL1 suppression is lost once miRNA320a is downregulated in advanced stage of lung cancer.

Hypoxia-induced PVT1 promotes lung cancer chemoresistance to cisplatin by autophagy via PVT1/miR-140-3p/ATG5 axis.

Lung cancer is one of the most common and lethal malignant tumors and the cases increased rapidly. Elevated chemoresistance during chemotherapy resistance remains a challenge. Hypoxia is one of the components that lead to chemoresistance. PVT1 participates in various tumor drug resistance and is associated with hypoxia conditions. The present study aimed to analyze the regulatory relationship of hypoxia and PVT1 and the mechanism of PVT1 in the hypoxia-induced chemoresistance process of lung cancer. The expression of PVT1 in lung cancer and adjacent tissues, and cell lines were analyzed using the TCGA database and qPCR. The regulatory relationship between hypoxia and PVT1 was validated and analyzed with qPCR, luciferase reporter system, and CHIP-qPCR. The role of PVT1 in chemoresistance ability induced by hypoxia was analyzed with CCK-8 assay and flow cytometry. The roles of PVT1, hypoxia, and chemoresistance were also analyzed with LC3-GFP transfection, WB, and IHC. Finally, the results were further validated in xenograft models. PVT1 is highly expressed in lung cancer and cell lines, and the expression of PVT1 is regulated by HIF-1α, and the luciferase reporter assay and CHIP-qPCR analysis indicated that HIF-1α could bind to the promoter region of PVT1 and regulate PVT1 expression. PVT1 participated in hypoxia-induced chemoresistance and induced higher viability and lower apoptosis rate by the autophagy signaling pathway via PVT1/miR-140-3p/ATG5 axis. All the findings were validated in the xenograft models. In conclusion, these results suggest that the expression of PVT1 is regulated by HIF-1α and participates in hypoxia-induced chemoresistance.

The mechanism of radiotherapy for lung adenocarcinoma in promoting protein SIRT6-mediated deacetylation of RBBP8 to enhance the sensitivity of targeted therapy.

BACKGROUND: Lung cancer has the fastest increase in morbidity and mortality, and is one of the most threatening malignant tumors to human health and life. Both radiotherapy and targeted therapy are typical treatments after lung cancer surgery. Radiotherapy is a means of locally killing cancer lesions, and it plays an important role in the entire management of lung cancer. Gefitinib is one of the most commonly used targeted therapy drugs in the treatment of lung cancer. The purpose of this project is to explore the mechanism by which deacetylation of RBBP8 mediated by radiotherapy-promoting protein SIRT6 in lung adenocarcinoma enhances the sensitivity of targeted therapy. METHODS: In both the cell experiments and the animal experiments, the samples were divided into five groups: Model group, RT group, CT group, RT+CT group, and RT+CT+inhibitor group. The CCK8 method was used to detect the viability of each group of cells. The flow cytometry experiment was used to analyze the apoptotic characteristics of each group of cells. The scratch test was used to detect the migration ability of each group of cells. Transwell invasion test was used to determine the invasion ability of each group of cells. The lung tumor tissues of each group of mice were collected to analyze the tumor size, volume, and metastasis characteristics. The TUNEL experiment was used to detect the apoptosis characteristics of the cells in the lung cancer tissues of each group mice. Immunohistochemistry experiments were used to analyze the distribution and relative expression characteristics of protein SIRT6 in mouse lung cancer tissues. The colorimetric experiments were used to detect the activity of Caspase 3 and Caspase 8 in each group. Western blot method was used to detect the expression of SIRT6, RBBP8, and MYC in each group. RESULTS: In each experiment, the results of the experiment have mutually proven consistency, and there is no contradiction. In addition to the Model group, the other 4 groups used different treatment methods. The better the curative effect, the lower the cell viability of cancer cells and the higher the apoptotic ratio. This is reflected in the CCK8 test, flow cytometry analysis, cell scratch test, Transwell cell migration test, and TUNEL detection. At the same time, colorimetric detection and Western blot analysis also analyzed the levels of SIRT6, RBBP8 and other cancer-related proteins in each group at the molecular level, implying the importance of SIRT6 protein in the treatment process. CONCLUSION: Our project has proved that radiotherapy can promote the protein SIRT6 to deacetylate RBBP8 proteins, and ultimately enhance targeted therapy drug sensitivity.

The Cardiovascular and Cerebrovascular Health in North China From 2006 to 2011: Results From the KaiLuan Study.

Background: The American Heart Association (AHA) defined cardiovascular health in terms of four behaviors (smoking, diet, physical activity, body weight) and three factors (plasma glucose, cholesterol, blood pressure). By this definition, the prevalence of ideal cardiovascular health behaviors and factors is negatively correlated with all-cause mortality and risks of cardiovascular and cerebrovascular diseases and malignancy. We analyzed the trends in cardiovascular and cerebrovascular health behaviors and factors in the population of the KaiLuan study for 2006-2011, reported the results, and provided evidence for prevention. Methods and Results: We calculated the prevalence of cardiovascular and cerebrovascular health behaviors and factors from KaiLuan data for 2006-2007, 2008-2009, and 2010-2011. The prevalence of ideal cardiovascular and cerebrovascular health behaviors and factors is low in the KaiLuan population. Conclusions: The prevalence of ideal cardiovascular and cerebrovascular health behaviors and factors is low in the KaiLuan population. Clinical Trial Registration: http://www.chictr.org/cn/proj/show.aspx?proj=1441, unique identifier: ChiCTR-TNC-11001489.

Survival, Chemotherapy and Chemosensitivity Predicted by CTC Cultured In Vitro of SCLC Patients.

PURPOSE: The prognosis for small cell lung cancer (SCLC) patients receiving later-line treatment is very poor and there is still no standard treatments after the second-line setting. Analyzing the susceptibility of chemotherapeutic drugs with circulating tumor cells (CTCs) cultured in vitro may contribute to optimize the therapeutic regimen. However, so far CTCs have been barely used for studying their chemosensitivity due to the lack of technology to obtain wholly intact and viable CTCs. METHODS: Based on a retrospective study of the therapeutic response of 99 patients with unresectable SCLC, the CTC count in 14 SCLC patients was detected before and after chemotherapy to evaluate its role as a potential marker of response. Furthermore, the drug susceptibility of CTCs cultured in vitro obtained from ClearCell FX® System was tested and the therapy response was evaluated. RESULTS: All of the 99 patients received the first-line chemotherapy and the objective response rate (ORR) was 74.7%. A total of 36 patients received the second-line therapy and the average duration was 2.6 months, and only 11 cases out of them received the third-line therapy but no one responded. The change of CTC counts was identified to be correlated with therapy response. However all the five SCLC patients who were administered with the drugs according to the drug susceptibility test of CTCs for two cycles underwent progression of disease. CONCLUSION: The results showed that the responses of chemotherapy are very poor in later lines and the drug susceptibility test using CTCs primary cultured in vitro may not benefit the improvement of therapeutic regimen of SCLC patients.

Mechanism of intrinsic resistance of lung squamous cell carcinoma to epithelial growth factor receptor-tyrosine kinase inhibitors revealed by high-throughput RNA interference screening.

Although targeted therapy has achieved a great breakthrough in the treatment of lung adenocarcinoma, there are still no effective targeted drugs for lung squamous cell carcinoma (SqCC). In addition, as immunotherapy can only prolong the overall survival (OS) of lung SqCC by ≤5 months, chemotherapy and radiotherapy are still the main types of therapy for advanced SqCC. The expression level of epithelial growth factor receptor (EGFR) in patients with lung SqCC is higher compared with those with adenocarcinoma, but the former group is intrinsically resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Therefore, if the drug resistance in patients with lung SqCC could be reversed, the majority of patients may benefit from EGFR-TKIs. In the present study, the high-throughput RNA interference technology was used to screen the genes involved in the EGFR-TKI erlotinib resistance of lung SqCCs, and integrin-linked kinase (ILK) was identified to be the most effective. The role of ILK in erlotinib resistance was further studied in cell lines, and the expression of ILK was analyzed in patients with SqCC and adenocarcinoma. Finally, the mechanism of ILK in EGFR-TKIs resistance was analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) and ingenuity pathway analysis (IPA). The results demonstrated that the ILK gene knockdown could overcome erlotinib resistance by inhibiting cell proliferation, inducing apoptosis and blocking the cell cycle at the G2/M phase. The expression of ILK in patients with SqCC was significantly higher compared with those with adenocarcinoma with sensitizing EGFR mutations. In addition, the cell cycle pathway 'G2/M DNA damage and checkpoint regulation' was identified to be significantly inhibited by ILK knockdown in IPA, KEGG and GO analysis. The results of the present study may improve the understanding of EGFR-TKI resistance in lung SqCCs, thus promoting the development of potential targeted therapies for lung SqCCs.