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Glioblastoma is the most serious type of brain cancer with poor prognosis. Here, using the publicly available glioma database, we identified that USP30-AS1, an antisense lncRNA locating on the opposite strand of USP30 locus, is upregulated in human gliomas, particularly in high grade glioma. High level of USP30-AS1 is correlated with poor survival in both primary and recurrent glioma patients. USP30-AS1 regulates mitochondrial homeostasis and mitophagy in glioblastoma cells. Knockdown of USP30-AS1 decreases mitochondrial protein expression and mitochondrial mass, promotes mitochondrial uncoupler-induced mitophagy. However, USP30-AS1 does not regulate USP30 expression in a cis-regulatory manner. In summary, this study proposed that USP30-AS1 may serve as a valuable prognostic marker for gliomas. USP3-AS1 is a negative regulator of mitophagy and the regulatory effect is USP30-independent. USP30-AS1 mediated repression of mitophagy may contribute to the loss of mitochondrial homeostasis and tumor development in glioma.

In the mesosphere and lower thermosphere (MLT) region, residual circulations driven by gravity wave breaking and dissipation significantly impact constituent distribution and the height and temperature of the mesopause. The distribution of CO

The energetic particle precipitation (EPP) indirect effect (IE) refers to the downward transport of reactive odd nitrogen (NOx = NO + NO2) produced by EPP (EPP‐NOx) from the polar winter mesosphere and lower thermosphere to the stratosphere where it can destroy ozone. Previous studies of the EPP IE examined NOx descent averaged over the polar region, but the work presented here considers longitudinal variations. We report that the January 2009 split Arctic vortex in the stratosphere left an imprint on the distribution of NO near the mesopause, and that the magnitude of EPP‐NOx descent in the upper mesosphere depends strongly on the planetary wave (PW) phase. We focus on an 11‐day case study in late January immediately following the 2009 sudden stratospheric warming during which regional‐scale Lagrangian coherent structures (LCSs) formed atop the strengthening mesospheric vortex. The LCSs emerged over the north Atlantic in the vicinity of the trough of a 10‐day westward traveling planetary wave. Over the next week, the LCSs acted to confine NO‐rich air to polar latitudes, effectively prolonging its lifetime as it descended into the top of the polar vortex. Both a whole atmosphere data assimilation model and satellite observations show that the PW trough remained coincident in space and time with the NO‐rich air as both migrated westward over the Canadian Arctic. Estimates of descent rates indicate five times stronger descent inside the PW trough compared to other longitudes. This case serves to set the stage for future climatological analysis of NO transport via LCSs., Key Points First demonstration of the impact of the split Arctic vortex on the geographic distribution of nitric oxide at the winter mesopauseFirst evidence that a Lagrangian coherent structure inhibits horizontal transport of nitric oxide at the polar winter mesopauseDescent of nitric oxide is five times stronger between 80 and 90 km in a westward traveling planetary wave trough compared to the ridge

Lipotoxicity is an important factor in the development and progression of nonalcoholic steatohepatitis. Excessive accumulation of saturated fatty acids can increase the substrates of the mitochondrial electron transport chain in hepatocytes and cause the generation of reactive oxygen species, resulting in oxidative stress, mitochondrial dysfunction, loss of mitochondrial membrane potential, impaired triphosphate (ATP) production, and fracture and fragmentation of mitochondria, which ultimately leads to hepatocellular inflammatory injuries, apoptosis, and necrosis. In this study, we systematically investigated the effects and molecular mechanisms of empagliflozin on lipotoxicity in palmitic acid-treated LO2 cell lines. We found that empagliflozin protected hepatocytes and inhibited palmitic acid-induced lipotoxicity by reducing oxidative stress, improving mitochondrial functions, and attenuating apoptosis and inflammation responses. The mechanistic study indicated that empagliflozin significantly activated adenosine 5’-monophosphate (AMP)-activated protein kinase alpha (AMPKα) through Calcium/Calmodulin dependent protein kinase kinase beta (CAMKK2) instead of liver kinase B1 (LKB1) or TGF-beta activated kinase (TAK1). The activation of empagliflozin on AMPKα not only promoted FoxO3a phosphorylation and thus forkhead box O 3a (FoxO3a) nuclear translocation, but also promoted Nrf2 nuclear translocation. Furthermore, empagliflozin significantly upregulated the expressions of antioxidant enzymes superoxide dismutase (SOD) and HO-1. In addition, empagliflozin did not attenuate lipid accumulation at all. These results indicated that empagliflozin mitigated lipotoxicity in saturated fatty acid-induced hepatocytes, likely by promoting antioxidant defense instead of attenuating lipid accumulation through enhanced FoxO3a and Nrf2 nuclear translocation dependent on the CAMKK2/AMPKα pathway. The CAMKK2/AMPKα pathway might serve as a promising target in treatment of lipotoxicity in nonalcoholic steatohepatitis.

RNA-binding proteins are frequently dysregulated in human cancer and able to modulate tumor cell proliferation as well as tumor metastasis through post-transcriptional regulation on target genes. Abnormal DNA damage response and repair mechanism are closely related to genome instability and cell transformation. Here, we explore the function of the RNA-binding protein muscleblind-like splicing regulator 2 (MBNL2) on tumor cell proliferation and DNA damage response. Transcriptome and gene expression analysis show that the PI3K/AKT pathway is enriched in MBNL2-depleted cells, and the expression of cyclin-dependent kinase inhibitor 1A (p21CDKN1A) is significantly affected after MBNL2 depletion. MBNL2 modulates the mRNA and protein levels of p21, which is independent of its canonical transcription factor p53. Moreover, depletion of MBNL2 increases the phosphorylation levels of checkpoint kinase 1 (Chk1) serine 345 (S345) and DNA damage response, and the effect of MBNL2 on DNA damage response is p21-dependent. MBNL2 would further alter tumor cell fate after DNA damage, MBNL2 knockdown inhibiting DNA damage repair and DNA damage-induced senescence, but promoting DNA damage-induced apoptosis.

We show that inter-model variation due to under-constraint by observations impacts the ability to predict material transport in the lower thermosphere. Lagrangian coherent structures (LCSs), indicating regions of maximal separation (or convergence) in a time-varying flow, are derived in the lower thermosphere from models for several space shuttle water vapor plume events. We find that inter-model differences in thermospheric transport manifest in LCSs in a way that is more stringent than mean wind analyses. LCSs defined using horizontal flow fields from the Specified Dynamics version of the Whole Atmosphere Community Climate Model with thermosphere-ionosphere eXtension (SD-WACCMX) at 109 km altitude are compared to Global Ultraviolet Imager (GUVI) observations of the space shuttle main engine plume. In one case, SD-WACCMX predicts an LCS ridge to produce spreading not found in the observations. LCSs and tracer transport from SD-WACCMX and from data assimilative WACCMX (WACCMX + DART) are compared to each other and to GUVI observations. Differences in the modeled LCSs and tracer positions appear between SD-WACCMX and WACCMX + DART despite the similarity of mean winds. WACCMX + DART produces better tracer transport results for a July 2006 event, but it is unclear which model performs better in terms of LCS ridges. For a February 2010 event, when mean winds differ by up to 50 m/s between the models, differences in LCSs and tracer trajectories are even more severe. Low-pass filtering the winds up to zonal wavenumber 6 reduces but does not eliminate inter-model LCS differences. Inter-model alignment of LCSs improves at a lower 60 km altitude.