The RNA N6-methyladenosine (m6A) writer methyltransferase-like 3 (METTL3) is upregulated in many types of cancer and promotes cancer progression by increasing expression of several oncogenes. Therefore, a better understanding of the mechanisms regulating METTL3 expression and the key targets of METTL3 in cancer cells could provide new therapeutic targets. In this study, we found that activated JNK signaling is associated with increased METTL3 expression in bladder cancer. Knockdown of JNK1 or administration of a JNK inhibitor impaired the binding of c-Jun with the METTL3 promoter, thereby decreasing the expression of METTL3 and global RNA m6A levels. Moreover, RNA m6A sequencing indicated enrichment of m6A in the 3′-UTR of immune checkpoint PD-L1 mRNA, which could be recognized by the m6A reader IGF2BP1 to mediate RNA stability and expression levels of PD-L1. Inhibition of JNK signaling suppressed m6A abundance in PD-L1 mRNA, leading to decreased PD-L1 expression. Functionally, METTL3 was essential for bladder cancer cells to resist the cytotoxicity of CD8+ T cells by regulating PD-L1 expression. Additionally, JNK signaling contributed to tumor immune escape in a METTL3-dependent manner both in vitro and in vivo. These data reveal the JNK/METTL3 axis as a mechanism of aberrant m6A modification and immune regulation in bladder cancer. Significance: The identification of a novel m6A-dependent mechanism underlying immune system evasion by bladder cancer cells reveals JNK signaling as a potential target for bladder cancer immunotherapy.

ObjectivesTo evaluate the risk factors for rupture of intracranial aneurysms (IAs) using high resolution MRI (HRMRI).Methods91 consecutive patients with 106 IAs were reviewed from February 2016 to April 2017. Patients and IAs were divided into ruptured and unruptured groups. In addition to the clinical characteristics of the patients, the features of IAs (eg, shape) were evaluated by CT angiography, whereas wall thickness, enhanced patterns, and enhancement ratio (ER) were evaluated by MRI. Multiple logistic regression analysis was used to identify independent risk factors associated with the rupture of IAs. Receiver operating characteristic curve analysis was performed on the final model, and the optimal thresholds were obtained.ResultsER (OR 6.638) and partial wall enhancement (PWE) (OR 6.710) were not markers of aneurysms more prone to rupture, but simply were more commonly found in the ruptured aneurysm cohort. The threshold value for ER was 61.5%.ConclusionsER (≥61.5%) and IAs with PWE are better predictors of rupture. Increased attentions should be paid to these factors during assessment of IA rupture.

Clear cell tumor of the lung is a rare and benign pulmonary tumor; only sporadic cases have been reported. Here, we report the case of a 38-year-old man with recurrent cough, blood-streaked sputum and left chest pain. A chest computed tomography scan showed a round, homogeneous pulmonary mass in the left lower lobe, which exhibited intense heterogeneous enhancement in the arterial phase and homogeneous in the delay phase after injecting a contrast agent. The patient underwent a fine-needle aspiration biopsy and was diagnosed as having a benign clear cell tumor of the lung. The clinical presentation and radiographic investigation of this tumor are summarized in this paper to recognize this rare disease. Interestingly, we found some differences with previously reported cases.

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Alzheimer's disease (AD) is a neurodegenerative process characterized by loss of neurons in the hippocampus and cerebral cortex, leading to progressive cognitive decline. Pathologically, the hallmark of AD is accumulation of "senile" plaques composed of amyloid-␤ (A␤) protein surrounding neurons in affected regions. Despite extensive research into AD pathogenesis and therapeutic targets, there remains no breakthroughs in its management. In recent years, there has been a spark of interest in the connection between the brain and gastrointestinal tract, referred to as the brain-gut axis, and its potential implications for both metabolic and neurologic disease. Moreover, the gastrointestinal flora, referred to as the microbiome, appears to exert significant influence over the brain-gut axis. With the need for expanded horizons in understanding and treating AD, many have turned to the brain-gut-microbiome axis for answers. Here we provide a review of the brain-gutmicrobiome axis and discuss the evidence supporting alterations of the axis in the pathogenesis of AD. Specifically, we highlight the role for the microbiome in disruption of A␤ metabolism/clearance, increased permeability of the blood-brain barrier and modulation of the neuroinflammatory response, and inhibition of hippocampal neurogenesis. The majority of the above described findings are the result of excellent, albeit basic and pre-clinical studies. Therefore, we conclude with a brief description of documented clinical support for brain-gut-microbiome axis alteration in AD, including potential microbiomebased therapeutics for AD. Collectively, these findings suggest that the brain-gut-microbiome axis may be a "lost link" in understanding and treating AD and call for future work.