Background: Pancreatic cancer is one of the most lethal types of cancer with extremely poor diagnosis and prognosis, and chemo-resistance remains a major challenge. The dynamic and reversible N 6-methyladenosine (m 6 A) RNA modification has emerged as a new layer of epigenetic gene regulation. Methods: qRT-PCR and IHC were applied to examine ALKBH5 levels in normal and pancreatic cancer tissues. Cancer cell proliferation and chemo-resistance were evaluated by clonogenic formation, chemosensitivity detection, and Western blotting assays. m 6 A-seq was performed to identify target genes. We evaluated the inhibitory effect of ALKBH5 in both in vivo and in vitro models. Results: Here, we show that m 6 A demethylase ALKBH5 is downregulated in gemcitabine-treated patient-derived xenograft (PDX) model and its overexpression sensitized pancreatic ductal adenocarcinoma (PDAC) cells to chemotherapy. Decreased ALKBH5 levels predicts poor clinical outcome in PDAC and multiple other cancers. Furthermore, silencing ALKBH5 remarkably increases PDAC cell proliferation, migration, and invasion both in vitro and in vivo, whereas its overexpression causes the opposite effects. Global m 6 A profile revealed altered expression of certain ALKBH5 target genes, including Wnt inhibitory factor 1 (WIF-1), which is correlated with WIF-1 transactivation and mediation of the Wnt pathway. Conclusions: Our work uncovers the tumor suppressive and chemo-sensitizing function for ALKBH5, which provides insight into critical roles of m 6 A methylation in PDAC.

Although attempts have been made to reveal the relationships between bacteria and human health, little is known about the species and function of the microbial community associated with oral diseases. In this study, we report the sequencing of 16 metagenomic samples collected from dental swabs and plaques representing four periodontal states. Insights into the microbial community structure and the metabolic variation associated with periodontal health and disease were obtained. We observed a strong correlation between community structure and disease status, and described a core disease-associated community. A number of functional genes and metabolic pathways including bacterial chemotaxis and glycan biosynthesis were over-represented in the microbiomes of periodontal disease. A significant amount of novel species and genes were identified in the metagenomic assemblies. Our study enriches the understanding of the oral microbiome and sheds light on the contribution of microorganisms to the formation and succession of dental plaques and oral diseases.

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High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians develop therapeutic strategies for pancreatic cancer patients.