Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Necrostatin-1 Mitigates Endoplasmic Reticulum Stress After Spinal Cord Injury.

Necrostatin-1 (Nec-1) has been shown to inhibit necroptosis and convey a significant protective effect after spinal cord injury (SCI). This small molecule inhibitor may reduce tissue damage and restore neurological function by lessening mitochondrial injury after SCI and preserving energy homeostasis. However, the effects of Nec-1 on endoplasmic reticulum stress (ERS)-an important pathological consequence of SCI-are still not clear. The present study investigates the relationship between necroptosis and ERS in a rat model of SCI. Electron microscopy was employed to observe ultra-structural changes in the endoplasmic reticulum and mitochondria after lesioning. Real-time quantitative PCR was used to measure the mRNA levels of ERS-related pro-apoptotic molecules such as C/EBP homologous protein (CHOP), immunoglobulin-binding protein (BiP/GRP78) and X box-binding protein-1 (XBP-1). Western blot and immunofluorescence were conducted to analyze CHOP, GRP78 and XBP-1 protein expression after lesioning. Results demonstrated that applying Nec-1 in SCI reduces ultra-structural damage to the endoplasmic reticulum and mitochondria and inhibits expression of ERS-related genes and proteins after lesioning. Immunofluorescence also shows ERS-related proteins mainly expressed in the cytoplasm of nerve cells. Taken together, these results demonstrate that Nec-1 has protective effect on the endoplasmic reticulum and mitochondria and alleviates ERS after SCI.

Enhanced electrocatalytic performance of TiO2 nanoparticles by Pd doping toward ammonia synthesis under ambient conditions.

The traditional Haber-Bosch process in industry to produce NH3 leads to excessive CO2 emissions and a large amount of energy consumption. Ambient electrochemical N2 reduction is emerging as a green and sustainable alternative method to convert N2 to NH3, but is in sore need of efficient and stable electrocatalysts. Herein, we propose using Pd-doped TiO2 nanoparticles as a high-efficiency electrocatalyst to synthesize NH3 under ambient conditions. The Pd-TiO2 catalyst delivers a large NH3 yield (17.4 µg h-1 mgcat.-1) and a high faradaic efficiency (12.7%) at -0.50 V versus reversible hydrogen electrode in a neutral electrolyte, outperforming most Pd- and Ti-based electrocatalysts recently reported for N2 reduction. Most importantly, it also demonstrates extraordinary long-term electrochemical stability.

Impacts of climate change and human activities on net primary productivity of grasslands in Inner Mongolia, China during 1982-2015.

We analyzed the impacts of climate change and human activities on the net primary productivity of grasslands in Inner Mongolia during 1982-2015. The results showed that the growth rates of actual net primary productivity (ANPP) were 1.08 and 1.36 g C · m-2 · a-1 in 1982-1998 and 1999-2015, respectively. Such changes were largely due to restoration, with restoration implementing in 81.6% and 76.3% of the total study area in 1982-1998 and 1999-2015, respectively. The area of degraded grasslands tends to increase. The effects of climate change and human activity varied across different types of grassland. Climate change was the main contributor to grassland restoration over the two periods, with the contribution rates being 79.3% and 94.1%, respectively. The ANPP was positively correlated with precipitation but not with temperature, indicating that precipitation was the main climate factor influencing grassland restoration. Human activities contributed most to grassland degradation over the two periods, with the contribute rate being 83.3% and 87.8%, respectively. Our results suggested that the climate change was the dominant contributor to grassland restoration, while human activities, such as increase in livestock numbers, cultivation and afforestation, accelerated grassland degradation.