Abstract
Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, ...non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of
Sphk2
suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC.
Differences between Earth’s global mean all-sky outgoing longwave radiation spectrum as observed in 1970 Interferometric Infrared Spectrometer (IRIS), 1997 Interferometric Monitor for Greenhouse ...Gases (IMG), and 2012 Infrared Atmospheric Sounding Instrument (IASI) are presented. These differences are evaluated to determine whether these are robust signals of multidecadal radiative forcing and hence whether there is the potential for evaluating feedback-type responses. IASI–IRIS differences range from +2K in the atmospheric window (800–1000 cm−1) to −5.5K in the 1304 cm−1 CH₄ band center. Corresponding IASI–IMG differences are much smaller, at 0.2 and −0.8 K, respectively. More noticeably, IASI–IRIS differences show a distinct step change across the 1042 cm−1 O₃ band that is not seen in IASI–IMG comparisons. This step change is a consequence of a difference in behavior when moving from colder to warmer scenes in the IRIS data compared to IASI and IMG. Matched simulations for the relevant periods using ERA reanalyses mimic the spectral behavior shown by IASI and IMG rather than by IRIS. These findings suggest that uncertainties in the spectral response of IRIS preclude the use of these data for quantitative assessments of forcing and feedback processes.
Abstract
In order to obtain the fracture and fragmentation of a cased charge under blast loading, the JWL equation of state of HMX-based PBX was fitted based on a cylinder test firstly, then the ...smooth particle hydrodynamics (SPH) method was used to perform a simulation of cased charge under interior blast loading, in the meantime, an blast test of cased charge was conducted. The results show that the parameters of JWL equation of state and the simulation method were reasonably. The simulated fragments velocities and calculated results from empirical formula agreed well with each other, the maximum error did not exceed 9.5%. Under the direct loading of the detonation wave, the fragments velocities increased to more than 1000m/s immediately within 5us, and then the fragments were continuously accelerated by detonation products and shock wave until the fragments reached the maximum velocities in the later 250us. Eventually, the shape of expansion contour of the casing tended to be ellipsoid. The method and results can provide references for the power design of the fragment warhead, as well as the protection design against the fragments.
Hepatocellular carcinoma (HCC) is a primary malignancy of liver. Nowadays HCC is one of the most common and aggressive malignancies worldwide. This study shows the aberrant up-regulation or ...down-regulation of miR-370correlates with the development and prognosis of different human malignancies including HCC.
The HCC cell lines were used as model cell lines and the anti-tumor effect of miR-370 in vitro were examined. The level of miR-370 in HCC cells was determined by qRT-PCR and restored in GC cells by using miR-370 mimic. Moreover, the target gene of miR-370 was then identified.
The expression of miR-370 in HCC cell lines was significantly lower than that in the other human liver cells. The miR-370 acted as a tumor suppressor in HCC. Moreover, it showed that miR-370 exerted anti-tumor effect by targeting PIM1 directly, a serine/threonine-specific kinase involved in the development and progression of HCC.
miR-370 acted as the tumor suppressor in HCC and was a potential therapeutic target for HCC treatment.
In the present work, the Doppler Shift Attenuation method (DSAM) was used to analyze the observed lineshapes of transitions from excited states in 45Sc, populated in the reaction 36Ar + 12C at a beam ...energy of 145 MeV. The interpretation and comparison of the experimental results have been performed with large-scale shell model calculations, involving different interactions like: GX1A, GX1J, FPD6, KB3 and ZBM2. KB3 and FPD6 (present work) interactions in the negative parity states, and in positive parity states ZBM2 are most pre-eminent in reproducing the results, due to the large configuration space describing strong collective effects. Furthermore, the present work also looks at the details of the shell model helping in improving the understanding for the occupancy of orbitals. The present investigation suggests the observation of stronger collectivity for positive parity states over negative parity states with predicted enhanced collectivity of states in 45Sc nucleus.
•The revised lifetime measurements based on Doppler Shift Attenuation Method in 45Sc populated with a non-standard C-target not only have verified the lifetimes with good accuracy but also the target’s effectiveness.•Reaction reported in the present work has suggested the highest cross section compared to the different reactions reported in the literature, and have confirmed better statistics to the results and thus the improved uncertainty.•Effect of side-feeding lifetime to the level of interest has been discussed.•Present investigation suggests the observation of stronger collectivity for positive-parity states with enhanced quadrupole coherence. The observed large collectivity and irregular energy-spacing may be considered as an evidence of either a level-crossing with consequent backbending, or alternatively as a break-down of collectivity with re-appearance of shell-model behavior.•The presented study will put forward the researchers for a better understanding of the occupancy of orbitals, and will lead to a more general but an effective shell model interaction matching the results near A∼45 mass region other than Sc and Ti nuclei.
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