Artificial Intelligence (AI) coupled with promising machine learning (ML) techniques well known from computer science is broadly affecting many aspects of various fields including science and technology, industry, and even our day to day life. The ML techniques have been developed to analyze high-throughput data with a view to obtaining useful insights, categorizing, predicting and making evidence-based decisions in novel ways, which will promote the growth of novel applications and fuel the sustainable booming of AI. This paper undertakes performs a comprehensive survey on the development and application of AI in different aspects of fundamental sciences, including information science, mathematics, medical science, materials science, geoscience, life science, physics and chemistry. The challenges that each discipline of science meets, and the potentials of AI techniques to handle these challenges, are discussed in detail. Moreover, we shed light on new research trends entailing the integration of AI into each scientific discipline. The goal of this paper is to provide a broad research guideline on fundamental sciences with potential infusion of AI, to help motivate researchers to deeply understand the state-of-the-art applications of AI-based fundamental sciences, and thereby to help promote the continuous development of these fundamental sciences.

Artificial Intelligence: A Powerful Paradigm for Scientific Research

N6 methyladenosine (m6A) RNA methylation regulators play an important role in the development of tumors. However, their function in esophageal cancer (EC) has not been fully elucidated. Here, we analyzed the gene expression data of 24 major m6A RNA methylation regulators from 775 patients with EC from TCGA dataset. The present study showed the aberrations of m6A regulators in genome were correlated to prognosis in human ECs. Meanwhile, 17 m6A regulators showed increased expression in EC samples, including YTHDC1, IGF2BP2, FTO, METTL14, YTHDF3, RBM15, WTAP, HNRNPA2B1, HNRNPC, ALKBH5, YTHDF2, METTL16, IGF2BP3, VIRMA, RBM15B, YTHDF1, KIAA1429, HAKAI, and ZC3H13. Among them, we found HNRNPC, YTHDC2, WTAP, VIRMA, IGF2BP3, and HNRNPA2B1 were significantly correlated to worse outcomes and advanced stage in EC. Furthermore, we showed levels of m6A regulators is correlated with the expression of Immuno-regulators (Immunoinhibitors, Immunostimulators, and MHC molecules) and immune infiltration levels in EC. Bioinformatics further confirm m6A regulators were involved in regulating RNA splicing, RNA stability, and cell proliferation. Our study showed m6A regulators are promising targets and biomarkers for cancer immunotherapy in EC.

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m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

Epigenetic mark such as DNA methylation plays pivotal roles in regulating ripening of both climacteric and non-climacteric fruits. However, it remains unclear whether mRNA m6A methylation, which has been shown to regulate ripening of the tomato, a typical climacteric fruit, is functionally conserved for ripening control among different types of fruits. Here we show that m6A methylation displays a dramatic change at ripening onset of strawberry, a classical non-climacteric fruit. The m6A modification in coding sequence (CDS) regions appears to be ripening-specific and tends to stabilize the mRNAs, whereas m6A around the stop codons and within the 3′ untranslated regions is generally negatively correlated with the abundance of associated mRNAs. We identified thousands of transcripts with m6A hypermethylation in the CDS regions, including those of NCED5, ABAR, and AREB1 in the abscisic acid (ABA) biosynthesis and signaling pathway. We demonstrate that the methyltransferases MTA and MTB are indispensable for normal ripening of strawberry fruit, and MTA-mediated m6A modification promotes mRNA stability of NCED5 and AREB1, while facilitating translation of ABAR. Our findings uncover that m6A methylation regulates ripening of the non-climacteric strawberry fruit by targeting the ABA pathway, which is distinct from that in the climacteric tomato fruit.

/pdf/n6-methyladenosine-rna-modification-regulates-strawberry-37h0n19b7a.pdf

N6-methyladenosine RNA modification regulates strawberry fruit ripening in an ABA-dependent manner.

Summary The discovery that mutations in the EGFR gene are detected in up to 50% of lung adenocarcinoma patients, along with the development of highly efficacious epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has revolutionized the treatment of this frequently occurring lung malignancy Indeed, the clinical success of these TKIs constitutes a critical milestone in targeted cancer therapy Three generations of EGFR-TKIs are currently approved for the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) The first-generation TKIs include erlotinib, gefitinib, lapatinib, and icotinib; the second-generation ErbB family blockers include afatinib, neratinib, and dacomitinib; whereas osimertinib, approved by the FDA on 2015, is a third-generation TKI targeting EGFR harboring specific mutations Compared with the first- and second-generation TKIs, third-generation EGFR inhibitors display a significant advantage in terms of patient survival For example, the median overall survival in NSCLC patients receiving osimertinib reached 386 months Unfortunately, however, like other targeted therapies, new EGFR mutations, as well as additional drug-resistance mechanisms emerge rapidly after treatment, posing formidable obstacles to cancer therapeutics aimed at surmounting this chemoresistance In this review, we summarize the molecular mechanisms underlying resistance to third-generation EGFR inhibitors and the ongoing efforts to address and overcome this chemoresistance We also discuss the current status of fourth-generation EGFR inhibitors, which are of great value in overcoming resistance to EGFR inhibitors that appear to have greater therapeutic benefits in the clinic

Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors.

RNA methylation and cancer treatment.

N6-Methyladenosine (m6A) RNA modification brings a new dawn for RNA modification researches in recent years. This posttranscriptional RNA modification is dynamic and reversible, and is regulated by methylases ("writers"), demethylases ("erasers"), and proteins that preferentially recognize m6A modifications ("readers"). The change of RNA m6A modification regulates RNA metabolism in eucaryon, including translation, splicing, exporting, decay, and processing. Thereby the dysregulation of m6A may lead to tumorigenesis and progression. Given the tumorigenic role of abnormal m6A expression, m6A regulators may function as potential clinical therapeutic targets for cancers. In this review, we emphasize on the underlying mechanisms of m6A modifications in tumorigenesis and further introduce the potential m6A regulators-associated therapeutic targets for tumor therapy.

Zhengyu Huang

Papers

RNA m6A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications