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g., YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3). Liver is the largest digestive and metabolic organ, and m6A modifications play unique roles in critical physiological hepatic functions and various liver diseases. This review focuses on the biological roles of m6A RNA methylation in lipid metabolism, viral hepatitis, nonalcoholic fatty liver disease, liver cancer, and tumor metastasis. In addition, we summarize the existing inhibitors targeting m6A regulators and discuss the potential of modulating m6A modifications as a therapeutic strategy. In the context of mechanically induced force transmission, the modification of the actin cytoskeleton through involvement of zyxin is an established concept. However, in cells of the periodontal ligament (PDL), which is physiologically subjected to intermittent mechanical forces, the force-responsive modulation of zyxin and the molecular key players, which orchestrate its cellular regulation, have not yet been elucidated. By employing indirect immunofluorescence and western blotting with different subcellular fractions, we show here in stretch force-exposed human PDL fibroblasts (hPDLFs) that (i) the zyxin protein is modulated, and (ii) its subcellular localization is altered. More importantly, using a pharmacological intervention approach, to inhibit the nuclear presence of the co-transcriptional activator yes-associated protein (YAP), we evidence for the first time that on the molecular level, the cellular abundance of zyxin, among the Thyrotrophic Embryonic Factor (TEF)-binding proteins, is regulated by YAP rather than TAZ. Our findings provide novel insights into the topic how cells of the periodontium and the periodontal ligament in particular respond and may adapt to mechanical forces, and first time identify YAP as the key player of the intracellular regulation of the mechano-sensor and mechano-transducer zyxin in hPDLFs. Moreover, the findings broaden the current knowledge on YAP, since so far, currently only very few YAP-regulated genes have been identified. The G12/13 subfamily of heterotrimeric guanine nucleotide binding proteins comprises the α subunits Gα12 and Gα13, which transduce signals for cell growth, cytoskeletal rearrangements, and oncogenic transformation. In an increasing range of cancers, overexpressed Gα12 or Gα13 are implicated in aberrant cell proliferation and/or metastatic invasion. Although Gα12 and Gα13 bind non-redundant sets of effector proteins and participate in unique signalling pathways, the structural features responsible for functional differences between these α subunits are largely unknown. Invertebrates encode a single G12/13 homolog that participates in cytoskeletal changes yet appears to lack signalling to SRF (serum response factor), a transcriptional activator stimulated by mammalian Gα12 and Gα13 to promote growth and tumorigenesis. Our previous studies identified an evolutionarily divergent region in Gα12 for which replacement by homologous sequence from Drosophila melanogaster abolished SRF signalling, whereas the same inver, our results identify key structural features near the C-terminus that evolved after the divergence of Gα12 and Gα13, and should aid the development of agents to selectively manipulate signalling by individual α subunits of the G12/13 subfamily. ATP-sensitive K+ (KATP) channels contribute to exercise-induced hyperemia in skeletal muscle either locally by vascular hyperpolarization or by sympathoinhibition and decreased sympathetic vasoconstriction. However, mean arterial pressure (MAP) regulation via baroreceptors and subsequent efferent activity may confound assessment of vascular versus neural KATP channel function. We hypothesized that systemic KATP channel inhibition via glibenclamide (GLI) would increase MAP without increasing sympathetic nerve discharge (SND). Lumbar and renal nerve SND were measured in anesthetized male rats with intact baroreceptors (n = 12) and sinoaortic denervated (SAD; n = 4) counterparts and blood flow (BF) and vascular conductance (VC) assessed in conscious rats (n = 6). GLI increased MAP (p  less then  0.05) and transiently decreased HR in intact (p  less then  0.05), but not SAD rats. Renal (-30%) and lumbar (-40%) ΔSND decreased in intact but increased in SAD rats (∼40% and 20%; p  less then  0.05). BF and VC decreased in kidneys and total hindlimb skeletal muscle (p  less then  0.05). Thus, because KATP inhibition decreases SND, GLI-induced reductions in blood flow cannot result from enhanced sympathetic activity. V.OBJECTIVES Fenestrated endografting for juxta- and para-renal abdominal aortic aneurysms (AAA) affords the ability to seal stent grafts in normal aorta at and above the renal arteries. The Zenith fenestrated graft (ZFEN, Cook Medical, Bloomington, IN) is custom-made to surgeon specification, subject to certain manufacturing limitations. The most common configuration in the pivotal trial and in post-approval commercial use has been a scallop for the superior mesenteric artery (SMA) and two small fenestrations for the renal arteries (configuration "A"). An alternative configuration to maximize seal zone length, consisting of a large fenestration for the SMA and two small fenestrations for the renals (configuration "B") has been routinely adopted at our institutions to potentially prevent type IA endoleak. METHODS This is a retrospective cohort study examining the 100 consecutive ZFEN grafts designed for patients at two university centers, from 2012 through 2019. see more The proximal seal length, from the top of the graZFEN with a large fenestration for the SMA and two small fenestrations for the renals. Whenever possible, surgeons should consider this configuration in order to maximize proximal seal length and potentially reduce the risk of proximal endoleak. An additional advantage of this approach is that stenting of the SMA to prevent shuttering is unnecessary or impossible, making the procedure more technically facile. OBJECTIVE Although endovascular repair (EVAR) for abdominal aortic aneurysm (AAA) significantly decreases perioperative mortality compared to open surgical repair (OSR), we have not concluded superiority between EVAR and OSR beyond the perioperative period. Our aim of this study was to compare phase-specific survival after EVAR versus OSR. METHODS The review was conducted according to PRISMA guideline. EMBASE and MEDLINE were searched up to November 2019 to identify randomized control trials (RCTs) and propensity-score matched (PSM) studies that investigated ≥2-year all-cause mortality (primary outcome) after EVAR versus OSR for intact infrarenal AAA. For each study, the hazard ratio (HR) with 95% confidence interval (CI) of mortality for EVAR versus OSR was calculated using survival curves for the following specific phases the early-term (0-2 years after repair), mid-term (2-6 years after repair), long-term (6-10 years after repair), and very long-term (≥10 years after repair) periods. The risk ratio (RR) in the perioperative (in-hospital or 30-day) period was also extracted.