The angiotensin receptor neprilysin inhibitor LCZ696 attenuates renal fibrosis via ASK1/JNK/p38 MAPK-mediated apoptosis in unilateral ureteral obstruction.

The angiotensin receptor neprilysin inhibitor LCZ696 affords superior cardioprotection and renoprotection compared with renin-angiotensin blockade monotherapy, but the underlying mechanisms remain elusive. Herein, we evaluated whether LCZ696 attenuates renal fibrosis by inhibiting ASK1/JNK/p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Rats with UUO were treated daily for 7 days with LCZ696, valsartan, or the selective ATP competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1), GS-444217. The effects of LCZ696 on renal injury were examined by assessing the histopathology, oxidative stress, intracellular organelles, apoptotic cell death, and MAPK pathways. H2O2-exposed human kidney 2 (HK-2) cells were also examined. LCZ696 and valsartan treatment significantly attenuated renal fibrosis caused by UUO, and this was paralleled by downregulation of proinflammatory cytokines and decreased inflammatory cell influx. Intriguingly, LCZ696 had stronger effects on renal fibrosis and inflammation than valsartan. UUO-induced oxidative stress triggered mitochondrial destruction and endoplasmic reticulum stress, which resulted in apoptotic cell death; these effects were reversed by LCZ696. Both GS-444217 and LCZ696 hampered the expression of death-associated ASK1/JNK/p38 MAPKs. In H2O2-treated HK-2 cells, LCZ696 and GS-444217 increased cell viability but decreased the production of intracellular reactive oxygen species and MitoSOX and apoptotic cell death. Both agents also deactivated H2O2-stimulated activation of ASK1/JNK/p38 MAPKs. These findings suggest that LCZ696 protects against UUO-induced renal fibrosis by inhibiting ASK1/JNK/p38 MAPK-mediated apoptosis.

Caged polycyclic polyprenylated acylphloroglucinols as Cav3.2 low voltage-gated Ca2+ channel inhibitors from Hypericum curvisepalum.

Five caged polycyclic polyprenylated acylphloroglucinols including an unprecedented octahydro-2,5-methanoindene skeleton (1) were discovered from Hypericum curvisepalum. Biologically, 1 and 2 are potent Cav3.2 T-type Ca2+ channel inhibitors with negligible effect on the cardiovascular antitarget, the human ether-à-go-go-related gene potassium channel. Additionally, 2 indicates strong antinociception in the mouse acetic acid writhing test.

Diterpenoid Alkaloids from the Aerial Parts of Aconitum flavum Hand.-Mazz.

Sixteen diterpenoid alkaloids (DAs), including six aconitine-type alkaloids (5 and 9 - 13), seven 7,17-seco-aconitine-type alkaloids (1 - 4, 6 - 8), two napelline-type alkaloids (14 and 15) as well as one veatchine-type alkaloid (16), were isolated from the aerial parts of Aconitum flavum Hand.-Mazz. In which, flavumolines A - D (1 - 4) were four new ones, and flavumoline E (5) was reported as natural compound for the first time. Their chemical structures were elucidated by the analysis of extensive spectroscopic data. The inhibitory activities of these isolates on Cav3.1 low voltage-gated Ca2+ channel, NO production in LPS-activated RAW264.7cells, five human tumor cell lines, as well as acetylcholinesterase (AChE) were tested.

Isoprenylated Flavonoids as Cav3.1 Low Voltage-Gated Ca2+ Channel Inhibitors from Salvia digitaloides.

Saldigones A-C (1, 3, 4), three new isoprenylated flavonoids with diverse flavanone, pterocarpan, and isoflavanone architectures, were characterized from the roots of Salvia digitaloides, together with a known isoprenylated flavanone (2). Notably, it's the first report of isoprenylated flavonoids from Salvia species. The structures of these isolates were elucidated by extensive spectroscopic analysis. All of the compounds were evaluated for their activities on Cav3.1 low voltage-gated Ca2+ channel (LVGCC), of which 2 strongly and dose-dependently inhibited Cav3.1 peak current.

Carbon Nanomaterials: A New Sustainable Solution to Reduce the Emerging Environmental Pollution of Turbomachinery Noise and Vibration.

The vibration and noise that resulted from turbomachinery, such as fans, compressors, and centrifugal pumps, are known to bring considerable disturbance and pollution to the machine itself, the environment, and the operators. Hence, how to cope with the vibration and noise has become a recent research focus. With the advancement of materials science, more and more new nanomaterials have been applied in the field of noise and vibration reduction. To be specific, carbon-based nanomaterials, such as carbon fibers, carbon nanotubes, and graphenes, have achieved outstanding results. Carbon nanocomposites, such as carbon nanofibers, carbon nanotubes, and graphenes, are characterized by their low densities, high strengths, and high elastic moduli, all of which made carbon nanocomposites the most promising vibration and noise-reduction composites, thanks to their damping properties, compatibilities, noise and vibration absorption qualities, and wide wave-absorbing frequency bands. In light of this, this paper summarizes the progresses and application prospects of such carbon nanocomposites as carbon nanofibers, carbon nanotubes, and graphenes in the field of turbomachinery vibration and noise reduction.

[Effect of Junction Temperature on EL Spectra of GaN-Based White High Voltage LEDs].

High voltage light emitting diodes (HV-LEDs) have potential advantages on general lighting application for their special features. But as novel power LEDs, their optical, electrical and thermal characteristics still need to be further studied. In this paper, 6 and 9 V GaN-based HV-LEDs were packaged in the same package structure and process conditions. The optical characteristics of two samples were investigated under different temperatures range from 10 to 70 ℃ which were calibrated to junction temperatures using thermal impedance measurement. To ensure the same current density, working current was set to 150 mA for 6 V sample and 100 mA for 9 V sample respectively. Results show that the increasing junction temperature has a great effect on EL spectra of two samples, such as peak wavelength red-shifting, full width at half maximum (FWHM) broadening, luminous efficiency reducing and color rendering index (CRI) increasing. The junction temperature of 9V sample is lower than that of 6 V sample in the same platform temperature and injection power. With temperature increasing, the extended quantitative value of FWHM for 9 V sample is 1.3 nm less than that of 6 V sample, the reduced quantitative value of luminous efficiency is 1.13 lm·W(-1) less than that of 6 V sample, while the increased quantitative value of CRI is 0.28 less than that of 6 V sample. Those data suggest that EL spectra of HV-LEDs is less affected by junction temperature than traditional LEDs. It is because HV-LEDs perform better in current spreading and generate less heat. This conclusion has reference value for study, development and applications of GaN-based HV-LEDs. In addition, peak wavelength still has a good linear relationship with junction temperature and it can be a temperature-sensitive parameter when the spectra measurement accuracy is enough.