Retro-BLEU: Quantifying Chemical Plausibility of Retrosynthesis Routes through Reaction Template Sequence Analysis

Computer-assisted methods have emerged as valuable tools for retrosynthesis analysis. However, quantifying the plausibility of generated retrosynthesis routes remains a challenging task. We introduce Retro-BLEU, a statistical metric adapted from the well-established BLEU score in machine translation, to evaluate the plausibility of retrosynthesis routes based on reaction template sequences analysis. We demonstrate the effectiveness of Retro-BLEU by applying it to a diverse set of retrosynthesis routes generated by state-of-the-art algorithms and compare the performance with other evaluation metrics. The results show that Retro-BLEU is capable of differentiating between plausible and implausible routes. Furthermore, we provide insights into the strengths and weaknesses of Retro-BLEU, paving the way for future developments and improvements in this field

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis

Leveraging Reaction-aware Substructures for Retrosynthesis Analysis

Retrosynthesis analysis is a critical task in organic chemistry central to many important industries. Previously, various machine learning approaches have achieved promising results on this task by representing output molecules as strings and autoregressively decoded token-by-token with generative models. Text generation or machine translation models in natural language processing were frequently utilized approaches. The token-by-token decoding approach is not intuitive from a chemistry perspective because some substructures are relatively stable and remain unchanged during reactions. In this paper, we propose a substructure-level decoding model, where the substructures are reaction-aware and can be automatically extracted with a fully data-driven approach. Our approach achieved improvement over previously reported models, and we find that the performance can be further boosted if the accuracy of substructure extraction is improved. The substructures extracted by our approach can provide users with better insights for decision-making compared to existing methods. We hope this work will generate interest in this fast growing and highly interdisciplinary area on retrosynthesis prediction and other related topics.Comment: Work in progres

An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma

<p>Abstract</p> <p>Background</p> <p>Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting.</p> <p>Results</p> <p>We identified <it>sphingosine kinase 1 (SPHK1) </it>as an invasion and metastasis-related gene of esophageal cancer. <it>SPHK1 </it>was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest <it>SPHK1 </it>mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (<it>P </it>< 0.0001) and lymph node metastasis (<it>P </it>= 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (<it>P </it>< 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. <it>SPHK1 </it>overexpression significantly increased the invasiveness of EC9706 cells <it>in vitro </it>and also increased EC9706 cell growth and spontaneous metastasis <it>in vivo</it>, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. <it>SPHK1 </it>expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR.</p> <p>Conclusion</p> <p>In summary, our data implicate <it>SPHK1 </it>in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.</p

ATP synthase ecto-α-subunit: a novel therapeutic target for breast cancer

<p>Abstract</p> <p>Background</p> <p>Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells <it>in vitro </it>and <it>in vivo</it>. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.</p> <p>Methods</p> <p>Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).</p> <p>Results</p> <p>Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (<it>P </it>< 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.</p> <p>Conclusions</p> <p>Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.</p

Research on Corn Ears’ Storage by Rectangle Small-scale Farm Bin with Steel Framework in Jizhou

The moisture of most newly harvested corn ears could be as high as 30% in Jizhou, and the method of air-drying on sides of roads, which is weather-sensitive, is mostly adopted in rural areas.Considering the small-scale farm bin has been used widely in the northeast of China, it is meaningful to explore its applicability and optimal thickness in Jizhou. In this study, JSWD-120 (4×1.5×2 m) is chosen and modified into tree small-scale bins with the thickness of 0.8 m, 1.0 m and 1.2 m. The newly harvest corn ears are stored from the middle October to early April and different quality index are analyzed timely. Results show that corn ears stored in the bin with the thickness of 1.2 m show good quality in terms of moisture of 14.05%±0.001%, lower fatty acid values of (51.59±0.007) mgKOH/100g, crude starch content of (68.66±0.171) g/100g and amylose content of 20.65%. Moreover, mycotoxins, such as deoxynivalenol and ochratoxin A, are not detected. Based on the experiment results, it is reasonable to consider wider utilization of JSWD farm bins to the south of Chin