Protein Kinase Cδ Suppresses Autophagy to Induce Kidney Cell Apoptosis in Cisplatin Nephrotoxicity

Nephrotoxicity is a major adverse effect in cisplatin chemotherapy, and renoprotective approaches are unavailable. Recent work unveiled a critical role of protein kinase Cδ (PKCδ) in cisplatin nephrotoxicity and further demonstrated that inhibition of PKCδ not only protects kidneys but enhances the chemotherapeutic effect of cisplatin in tumors; however, the underlying mechanisms remain elusive. Here, we show that cisplatin induced rapid activation of autophagy in cultured kidney tubular cells and in the kidneys of injected mice. Cisplatin also induced the phosphorylation of mammalian target of rapamycin (mTOR), p70S6 kinase downstream of mTOR, and serine/threonine-protein kinase ULK1, a component of the autophagy initiating complex. In vitro, pharmacologic inhibition of mTOR, directly or through inhibition of AKT, enhanced autophagy after cisplatin treatment. Notably, in both cells and kidneys, blockade of PKCδ suppressed the cisplatin-induced phosphorylation of AKT, mTOR, p70S6 kinase, and ULK1 resulting in upregulation of autophagy. Furthermore, constitutively active and inactive forms of PKCδ respectively enhanced and suppressed cisplatin-induced apoptosis in cultured cells. In mechanistic studies, we showed coimmunoprecipitation of PKCδ and AKT from lysates of cisplatin-treated cells and direct phosphorylation of AKT at serine-473 by PKCδin vitro Finally, administration of the PKCδ inhibitor rottlerin with cisplatin protected against cisplatin nephrotoxicity in wild-type mice, but not in renal autophagy-deficient mice. Together, these results reveal a pathway consisting of PKCδ, AKT, mTOR, and ULK1 that inhibits autophagy in cisplatin nephrotoxicity. PKCδ mediates cisplatin nephrotoxicity at least in part by suppressing autophagy, and accordingly, PKCδ inhibition protects kidneys by upregulating autophagy

Tacky Elastomers to Enable Tear-Resistant and Autonomous Self-Healing Semiconductor Composites

Mechanical failure of π-conjugated polymer thin films is unavoidable under cyclic loading conditions, due to intrinsic defects and poor resistance to crack propagation. Here, the first tear-resistant and room-temperature self-healable semiconducting composite is presented, consisting of conjugated polymers and butyl rubber elastomers. This new composite displays both a record-low elastic modulus

Tacky Elastomers to Enable Tear-Resistant and Autonomous Self-Healing Semiconductor Composites

Mechanical failure of π-conjugated polymer thin films is unavoidable under cyclic loading conditions, due to intrinsic defects and poor resistance to crack propagation. Here, the first tear-resistant and room-temperature self-healable semiconducting composite is presented, consisting of conjugated polymers and butyl rubber elastomers. This new composite displays both a record-low elastic modulus

Effects of sand burial on biomass, chlorophyll fluorescence and extracellular polysaccharides of man-made cyanobacterial crusts under experimental conditions

Soil cyanobacterial crusts occur throughout the world, especially in the semiarid and arid regions. It always encounters sand burial, which is an important feature of mobile sand dunes. A greenhouse 41 study was conducted to determine the effects of sand burial on biomass, chlorophyll fluorescence and extracellular polysaccharides of man-made cyanobacterial crusts in six periods of time (0, 5, 10, 15, 20 and 30 d after burying) and at five depths (0, 0.2, 0.5, 1 and 2cm). The results indicated that with the increase of the burial time and burial depth extracellular polysaccharides content and Fv/Fm decreased correspondingly and there were no significant differences between 20 and 30 burial days under different burial depths. The degradation of chlorophyll a content appeared only at 20 and 30 burial days and there was also no significant difference between them under different burial depths. It was also observed a simultaneous decrease of the values of the Fv/Fm and the content of extracellular polysaccharides happened in the crusted cyanobacterium Microcoleus vaginatus Gom. It may suggest that there exists a relationship between extracellular polysaccharides and recovery of the activity of photosystem II (PS II) after rehydration.Soil cyanobacterial crusts occur throughout the world, especially in the semiarid and arid regions. It always encounters sand burial, which is an important feature of mobile sand dunes. A greenhouse 41 study was conducted to determine the effects of sand burial on biomass, chlorophyll fluorescence and extracellular polysaccharides of man-made cyanobacterial crusts in six periods of time (0, 5, 10, 15, 20 and 30 d after burying) and at five depths (0, 0.2, 0.5, 1 and 2cm). The results indicated that with the increase of the burial time and burial depth extracellular polysaccharides content and Fv/Fm decreased correspondingly and there were no significant differences between 20 and 30 burial days under different burial depths. The degradation of chlorophyll a content appeared only at 20 and 30 burial days and there was also no significant difference between them under different burial depths. It was also observed a simultaneous decrease of the values of the Fv/Fm and the content of extracellular polysaccharides happened in the crusted cyanobacterium Microcoleus vaginatus Gom. It may suggest that there exists a relationship between extracellular polysaccharides and recovery of the activity of photosystem II (PS II) after rehydration

Body mass index and age at natural menopause: an international pooled analysis of 11 prospective studies

Current evidence on the association between body mass index (BMI) and age at menopause remains unclear. We investigated the relationship between BMI and age at menopause using data from 11 prospective studies. A total of 24,196 women who experienced menopause after recruitment was included. Baseline BMI was categorised according to the WHO criteria. Age at menopause, confirmed by natural cessation of menses for ≥ 12 months, was categorised as < 45 years (early menopause), 45–49, 50–51 (reference category), 52–53, 54–55, and ≥ 56 years (late age at menopause). We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CI) for the associations between BMI and age at menopause. The mean (standard deviation) age at menopause was 51.4 (3.3) years, with 2.5% of the women having early and 8.1% late menopause. Compared with those with normal BMI (18.5–24.9 kg/m2), underweight women were at a higher risk of early menopause (RRR 2.15, 95% CI 1.50–3.06), while overweight (1.52, 1.31–1.77) and obese women (1.54, 1.18–2.01) were at increased risk of late menopause. Overweight and obesity were also significantly associated with around 20% increased risk of menopause at ages 52–53 and 54–55 years. We observed no association between underweight and late menopause. The risk of early menopause was higher among obese women albeit not significant (1.23, 0.89–1.71). Underweight women had over twice the risk of experiencing early menopause, while overweight and obese women had over 50% higher risk of experiencing late menopause

Chemical-and mechanical-induced lubrication mechanisms during hot rolling of titanium alloys using a mixed graphene-incorporating lubricant

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Hot rolling of titanium alloy currently is carried out without lubrication because of the surface defects. In order to explore an effective lubrication scheme to reduce friction and wear during hot rolling of titanium alloy, a mixed graphene-incorporating lubricant has been proposed to study its lubrication performance and mechanism. The tribological experiments were carried out by ball-disk friction and wear tester under hot-rolling parameters. Scanning electron microscopy (SEM), X-ray energy spectrum analyzer (EDS), X-ray powder diffractometer (XRD) and Raman analysis were used to analyse the surface and cross-section of the wear marks on the samples after the tribological experiments. The results show that the friction coefficient decreases up to about 35% compared with tests under dry and lubricated conditions. The surface quality of the wear marks is improved significantly after applying the proposed lubricant. The graphene which is embedded in the phosphate film can be effectively applied as a lubricating material to strengthen the lubricating film with less combustion loss at high temperatures. A chemical-and mechanical-induced lubrication mechanism for the hot rolling of titanium sheets has been proposed due to the synergistic lubrication effect of the graphene, ZrO2 nano particles and phosphate. It is of great significance and potential value to apply this proposed lubricant as an effective way to reduce the wear, friction and oxidation during the hot-rolling process of titanium alloy