Molecular Conformer Search with Low-Energy Latent Space

Identifying low-energy conformers with quantum mechanical accuracy for molecules with many degrees of freedom is challenging. In this work, we use the molecular dihedral angles as features and explore the possibility of performing molecular conformer search in a latent space with a generative model named variational auto-encoder (VAE). We bias the VAE towards low-energy molecular configurations to generate more informative data. In this way, we can effectively build a reliable energy model for the low-energy potential energy surface. After the energy model has been built, we extract local-minimum conformations and refine them with structure optimization. We have tested and benchmarked our low-energy latent-space (LOLS) structure search method on organic molecules with 5-9 searching dimensions. Our results agree with previous studies

Long Non-Coding RNA-TMPO-AS1 as ceRNA Binding to let-7c-5p Upregulates STRIP2 Expression and Predicts Poor Prognosis in Lung Adenocarcinoma

Background: Striatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth. But the role of STRIP2 in lung adenocarcinoma (LUAD) has not been discovered clearly. Thus, the aim of our study is to explore the function and underlying mechanism of STRIP2 in LUAD. Methods: Expression of STRIP2 was determined using the Cancer Genome Atlas (TCGA), GTEx, Ualcan, and the Human Protein Altas databases. The Correlation of STRIP2 and survival was detected by PrognoScan and Kaplan–Meier plotter databases. Besides, the correlation between STRIP2 expression and tumor immune infiltration as well as immune checkpoints were analyzed by the ssGSEA method. The biological function of STRIP2 and its co-expression genes was determined by gene ontology (GO) and Genes and Genomes (KEGG), respectively. Finally, the expression level and biological function of STRIP2 in LUAD were determined by qPCR, CCK8, transwell, and wound healing assays. Results: This manuscript revealed a significantly increased expression of mRNA and protein of STRIP2 in lung adenocarcinoma compared with the adjacent normal tissues. GEO and Kaplan–Meier plotter databases showed higher STRIP2 expression levels were correlated with poor prognosis survival of LUAD. Moreover, Cox regression analysis suggested that a higher STRIP2 level served as an independent risk factor in predicting deteriorative overall survival (OS) for LUAD patients. SsGSEA results showed STRIP2 expression level was positively correlated with infiltrating levels of Th2 cells in LUAD. Lastly, GO analysis indicated the biological processes were enriched in nuclear division and positive regulation of the cell cycle. KEGG signaling pathway analysis showed STRIP2 was correlated with the MAPK signaling pathway and the TNF signaling pathway. The GSEA database showed that STRIP2 was positively associated with the epithelial–mesenchymal transition, cell cycle, and TNF signaling pathway. The QRT-PCR assay showed that STRIP2 was upregulated in LUAD cell lines. Cell proliferation and migration were inhibited in LUAD by knockdown of STRIP2. Moreover, we confirmed that the TMPO-AS1/let-7c-5p/STRIP2 network regulates STRIP2 overexpression in LUAD and is associated with poor prognosis. Conclusion: Our findings indicated that STRIP2 acted as a crucial oncogene in LUAD and was correlated with unfavorable survival and tumor infiltration inflation

Effect of Suture Lines on Lung Adenocarcinoma Cell in vitro

Background and objective The interaction of cell and medical biomaterial is one of the significant factors to affect clinical application of medical biomaterial. This research is to investigate three of suture lines how to affect the proliferation and cell cycle of Lung Adenocarcinoma cell A549. Methods Three of suture lines are respectively cultivated with Lung Adenocarcinoma cell A549, after of 72 hours, to detect absorptance of each groups by MTT method in order to reflect the proliferation of Lung Adenocarcinoma cell A549 and to detect percentage of G1 period cell and S period cell of each of groups by flow cytometry. Results Different of suture lines have effect differently on the proliferation and cell cycle of Lung Adenocarcinoma cell A549 (P < 0.05). The effect of absorbent suture line on the proliferation and cell cycle of Lung Adenocarcinoma cell A549 is strong, the effect of chorda serica chirurgicalis is medium, the effect of slide wire is poor. Different length of each suture line have effect differently on the proliferation and cell cycle of Lung Adenocarcinoma cell A549 (P < 0.05). Conclusion Three of suture line materials have different effect on the proliferation and cell cycle of Lung Adenocarcinoma cell A549, to reflect dose-effect relation

Molecular Conformer Search with Low-Energy Latent Space

Funding Information: X.G., L.F. and X.C. acknowledge the financial support from the Academy of Finland (project numbers 308647, 314298, 335571). X.G, Y.X. and W.D. acknowledge the financial support from the Basic Science Center Project of NSFC (grant no. 51788104), the National Science Fund for Distinguished Young Scholars (grant no. 12025405), the National Natural Science Foundation of China (grant no. 11874035), and the Beijing Advanced Innovation Center for Future Chip (ICFC), M.T. and P.R. have received funding from the Academy of Finland via the Artificial Intelligence for Microscopic Structure Search (AIMSS) project no. 316601 and the Flagship programme: Finnish Center for Artificial Intelligence FCAI. X.G. and X.C. Generous computational resources were provided by CSC – IT Center for Science, Finland, and the Aalto Science-IT project. L.F. also acknowledges financial support from the Chinese Scholarship Council (grant no. [2017]3109). Publisher Copyright: © 2022 The Authors. Published by American Chemical Society.Identifying low-energy conformers with quantum mechanical accuracy for molecules with many degrees of freedom is challenging. In this work, we use the molecular dihedral angles as features and explore the possibility of performing molecular conformer search in a latent space with a generative model named variational auto-encoder (VAE). We bias the VAE towards low-energy molecular configurations to generate more informative data. In this way, we can effectively build a reliable energy model for the low-energy potential energy surface. After the energy model has been built, we extract local-minimum conformations and refine them with structure optimization. We have tested and benchmarked our low-energy latent-space (LOLS) structure search method on organic molecules with 5-9 searching dimensions. Our results agree with previous studies.Peer reviewe

Research on Fast Track Surgery Application in Lung Cancer Surgery

Background and objective Fast track surgery (FTS) is a systematical method to accelerate the recovery of surgical patients by reducing the physical and mental trauma stress of them. The research is to investigate the feasibility of FTS application in lung cancer surgery. Methods A total of 80 cases of lung cancer patients with single leaf lobotomy resection were randomized into two groups. While the experimental group was treated with the conception of FTS, and the control group was treated with the traditional methods. The incident rate of post-operation pain degrees, telecasts, pleural effusion, the post-operation time stay in hospital time and the total cost during hospitalization in two groups were compared respectively. Results In FTS group: the VAS score of post-operation pain at 1 h, 6 h, 12 h, 24 h and 48 h all significantly decreased compared to the traditional therapy group. The incidence rate of telecast was 10.53%. The incidence rate of pleural effusion was 26.31%. The length of stay after operation was (4±1) d and the total cost was RMB 15 600±7 600. In the control group, the above values were 77.78%, 33.33%, 22.22%, (9±1) d, RMB 23 600±5 400, respectively. The post operation pain (VAS method) of FTS group was remarkablely below the control group. There has significant difference of the incident rate of telecasts, stay time in hospital and the total cast in two groups (P < 0.05). No significant difference was observed in the incident rate of pleural effusion. Conclusion The new methods of FTS can apparently accelerates recovery after lung cancer resection, reduces complications, shorten timestay in hospital and cut down the total cost

Therapeutic efficacy of Traditional Vein Chemotherapy and Bronchial Arterial Infusion Combining with CIKs on Ⅲ Stage Non-small Cell Lung Cancer

Background and objective The therapeutic efficacy of late lung-cancer was very poor, and cytokine-induced killer cells (CIK) were paid more attention to treat non-small cell lung cancer (NSCLC). The aim of this study is to get insight into the role of bronchial arterial infusion bronchial arterial infusion (BAI) plus CIK about NSCLC by comparing therapeutic efficacy among BAI, traditional vein chemotherapy and BAI plus CIK, for late NSCLC. Methods A total of 120 patients were enrolled in this study, dividing randomly into three groups: bronchial arterial infusion (BAI), traditional vein chemotherapy and BAI plus CIK. Clinical effects and side effects were estimated after two period of therapy. Results The effective rate (CR+PR%) of combined group is higher than the traditional vein chemotherapy group (66.67%, n=39) and there are significant differences (χ2=4.721, P=0.03); The side effect of rate of BAI plus CIK group is significantly lower than the traditional vein chemotherapy group, and so did the non-bone marrow inhibition side effects (P < 0.05). The tumor progression rate (PD%) of bronchial arterial infusion (BAI) group is higher than combined group (χ2=4.287, P=0.038). There was no difference between the traditional vein chemotherapy group and combined group (χ2=0.082, P=0.775). Conclusion Bronchial Artery Infusion combined with cytokine-induced killer cells is an ideal, safety, effective comprehensive treatment method for late stage lung cancer

TGFβ pathway is involved in the regulation of VEGF-C expression in TGFβ1 sensitive NSCLC lines.

<p><b>(A)</b> Real-time PCR showed that VEGFR3 mRNA expression levels were much higher in A549, NCI-H358 and NCI-H1993 cells than that in NCI-H1975, NCI-H1650 and HCC827 cells (fold expression as compared to control NCI-H1975, *** <i>P</i><0.001). <b>(B)</b> Immunoblotting showed that human recombinant VEGF-C 10 ng/ml treatment for 30 and 60 minutes activated ERK pathway in NCI-H1993 cells but not in NCI-H1975 cells. <b>(C)</b> Real-time PCR revealed that 2.5 ng/ml TGFβ1 treatment significantly increased the VEGF-C mRNA expression in NCI-H1993 cells. The presence of 0.1 μM LY2157299 significantly reduced TGFβ1-induced VEGF-C expression. <b>(D)</b> Similarly, siRNA targeting TGFβR1 significantly decreased TGFβ1-induced VEGF-C expression compared to scramble control (*** P<0.001).</p

TGFβ1 increases the gene expression of NSCLC stem-like cell markers and colony formation ability in TGFβ1 sensitive NSCLC lines.

<p><b>(A)</b> Real-time PCR showed that 2.5 ng/ml TGFβ1 treatment for two weeks significantly increased Oct4 and Sox2 mRNA expression in A549, NCI-H358 and NCI-H1993 cells compared to untreated cells (** <i>P</i><0.01, *** <i>P</i><0.001). <b>(B)</b> Oct4, Nanog and Sox2 expression remained same before and after TGFβ1 treatment. <b>(C)</b> 2.5 ng/ml TGFβ1 treatment for two weeks significantly enhanced anchorage-dependent colony formation ability of A549, NCI-H358 and NCI-H1993 cells but not for NCI-H1975, NCI-H1650 and HCC827 cells (* <i>P</i><0.05, ** <i>P</i><0.01).</p

The characteristics of ctDNA reveal the high complexity in matching the corresponding tumor tissues

Abstract Background Next-generation sequencing (NGS) is an efficient and sensitive method to detect mutations from ctDNA. Many features and clinical conditions could significantly affect the concordance between ctDNA and corresponding tumor tissues. Our goal was to systematically investigate the critical factors contributing to different concordance between ctDNA and corresponding tumor tissues. Methods We recruited two groups of IIIB or IV lung cancer patients: The standard group to evaluate the accuracy of our method and the concordance between ctDNA and tumor tissues, and the study group with various clinical conditions. We applied our unique identification (UID) indexed capturing-based sequencing (UC-Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR). Results Considering mutations detected from NGS of tumor tissues as golden standard, UC-Seq achieved overall 93.6% sensitivity for SNVs and Indels, and 0.8 Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long sampling date (more than 2 weeks) between tumor tissues and ctDNA and low concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the concordance between ctDNA and tumor tissues. About 84% mutations showed shorter mutant fragment length than that of wild-type fragments, and the AFs of mutations could be significantly enriched in small-size ctDNA. Conclusions In late-stage lung cancer patients, ctDNA generally has high concordance with tumor tissues. However it could be significantly affected by three clinical conditions which could dynamically change the content of ctDNA. Moreover, the detection limit could be further extended by enriching small-size ctDNA in the preparation of samples