However, none of the existing methods was suitable for Geoalkalibacter subterraneus, Geobacter pickeringii, and Mus musculus, thereby limiting their practical applicability. Model transferability to five species and non-transferability to three species are also discussed. The presented evaluation will assist researchers in selecting appropriate prediction tools that best suit their purpose and provide useful guidelines for the development of improved 4mC predictors in the future.The 5HT1B receptor (5HT1BR) contributes to the pathogenic effects of serotonin in pulmonary arterial hypertension. Here, we determine the effect of a microRNA96 (miR96) mimic delivered directly to the lungs on development of severe pulmonary hypertension in rats. Female rats were dosed with sugen (30 mg/kg) and subjected to 3 weeks of hypobaric hypoxia. GSK2578215A concentration In normoxia, rats were dosed with either a 5HT1BR antagonist SB216641 (7.5 mg/kg/day for 3 weeks), miR96, or scramble sequence (50 μg per rat), delivered by intratracheal (i.t) administration, once a week for 3 weeks. Cardiac hemodynamics were determined, pulmonary vascular remodeling was assessed, and gene expression was assessed by qRT-PCR, and in situ hybridization and protein expression were assessed by western blot and ELISA. miR96 expression was increased in pulmonary arteries and associated with a downregulation of the 5HT1BR protein in the lung. miR96 reduced progression of right ventricular systolic pressure, pulmonary arterial remodeling, right ventricular hypertrophy, and the occurrence of occlusive pulmonary lesions. Importantly, miR96 had no off-target effects and did not affect fibrotic markers of liver and kidney function. In conclusion, direct delivery of miR96 to the lungs was effective, reducing progression of sugen/hypoxia-induced pulmonary hypertension with no measured off-target effects. miR96 may be a novel therapy for pulmonary arterial hypertension, acting through downregulation of 5HT1BR.Long noncoding RNAs (lncRNAs), genomic “dark matter,” are deeply involved in diverse biological processes. The lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is a highly participatory lncRNA; however, its roles in gastric cancer (GC) remain largely unexplored. Here, we demonstrated that the expression of NEAT1 was significantly increased and negatively correlated with prognosis in GC. Subsequent experiments confirmed that KLF5 can induce NEAT1 expression by binding to the NEAT1 promoter region. Further experiments revealed that NEAT1 silencing significantly suppressed cell proliferation both in vitro and in vivo and induced apoptosis. We used mRNA sequencing (mRNA-seq) to identify the preferentially affected genes linked to cell proliferation in cells with NEAT1 knockdown. Mechanistically, NEAT1 bound BRG1 (SMARCA4) directly, modulating H3K27me3 and H3K4me3 in the GADD45A promoter to regulate GADD45A-dependent G2/M cell cycle progression. In addition, BRG1 was significantly upregulated and correlated with outcomes in GC; moreover, it promoted cell proliferation both in vitro and in vivo. Taken together, our data support the importance of NEAT1 in promoting GC tumorigenesis and indicate that NEAT1 might be a diagnostic and therapeutic target in GC.mRNA-lipoplex vaccines are currently being explored in phase II clinical trials for the treatment of patients with advanced solid tumors. Mechanistically, these mRNA-lipoplex vaccines are characterized by the induction of type I interferon (IFN) centered innate responses. Earlier studies have identified type I IFNs as major regulators of the T cell response instigated by mRNA-lipoplex vaccines. However, stimulatory or, in contrast, profound inhibitory effects of type I IFNs were described depending on the study. In this mouse study, we demonstrated that the opposing roles of type I IFN signaling on the magnitude of the vaccine-evoked T cell responses is dependent on the route of mRNA-lipoplex administration and is regulated at the level of the T cells rather than indirectly through modulation of dendritic cell function. This study helps to understand the double-edged sword character of type I IFN induction upon mRNA-based vaccine treatment and may contribute to a more rational design of mRNA vaccination regimens.Recent studies have increasingly shown that the chemical modification of mRNA plays an important role in the regulation of gene expression. N7-methylguanosine (m7G) is a type of positively-charged mRNA modification that plays an essential role for efficient gene expression and cell viability. However, the research on m7G has received little attention to date. Bioinformatics tools can be applied as auxiliary methods to identify m7G sites in transcriptomes. In this study, we develop a novel interpretable machine learning-based approach termed XG-m7G for the differentiation of m7G sites using the XGBoost algorithm and six different types of sequence-encoding schemes. Both 10-fold and jackknife cross-validation tests indicate that XG-m7G outperforms iRNA-m7G. Moreover, using the powerful SHAP algorithm, this new framework also provides desirable interpretations of the model performance and highlights the most important features for identifying m7G sites. XG-m7G is anticipated to serve as a useful tool and guide for researchers in their future studies of mRNA modification sites.Oral squamous cell carcinoma (OSCC) is a highly recurrent form of cancer arising from the oral epithelium, which is the result of mutational change due to etiological factors such as tobacco, smoking, chewing of areca nuts, and alcohol consumption. OSCC occurrence has been observed to be prevalent in different regions of Pacific countries and in most Asian countries. Despite the accessibility of the oral cavity, OSCC is diagnosed at an extremely late stage of pathogenic tumor node metastasis pTNM (III-IV), resulting in a poor prognosis for the individual. Therefore, it is important to make definitive, early, and efficient diagnoses. Owing to the development of omic-natured studies, the presence of proteins, transcribed elements, metabolic products, and even microflora detected in saliva helps us to select biomarkers, which is an especially exciting potential because of the availability and the non-invasive nature of sample collection. Since the discovery of circular RNA (circRNA) by Sanger sequencing, it has been reported to play a pivotal role in several human diseases, including cancer.