Design, synthesis and evaluation of monoketene compounds as novel potential Parkinson's disease agents by suppressing ER stress via AKT.

Curcumin is identified that it has the potential to treat Parkinson's disease (PD), but its instability limits its further application in clinic. The mono-carbonyl analogs of curcumin (MACs) with diketene structure can effectively improve its stability, but it is highly toxic. In the present study, a less cytotoxic and more stable monoketene MACs skeleton S2 was obtained, and a series of monoketene MACs were synthesized by combining 4-hydroxy-3­methoxy groups of curcumin. In the 6-OHDA-induced PD's model in-vitro, some compounds exhibited significant neurotherapeutic effect. The quantitative structure-activity relationship (QSAR) model established by the random forest algorithm (RF) for the cell viability rate of above compounds showed that the statistical results are good (R2 = 0.883507), with strong reliability. Among all compounds, the most active compound A4 played an important role in neuroprotection in the PD models both in vitro and in vivo by activating AKT pathway, and then inhibiting the apoptosis of cells caused by endoplasmic reticulum (ER) stress. In the PD model in-vivo, compound A4 significantly improved survival of dopaminergic neurons and the contents of neurotransmitters. It also enhanced the retention of nigrostriatal function which was better than the effect in the mice treated by Madopar, a classical clinical drug for PD. In summary, we screened out the compound A4 with high stability, less cytotoxic monoketene compounds. And these founding provide evidence that the compound A4 can protect dopaminergic neurons via activating AKT and subsequently suppressing ER stress in PD.

Higher serum zinc levels may reduce the risk of cervical cancer in Asian women: A meta-analysis.

OBJECTIVE: This meta-analysis was conducted to examine the possible association between serum zinc concentration and cervical cancer risk. METHODS: PubMed, WanFang, China National Knowledge Infrastructure, and SinoMed databases were searched for relevant articles published between January 1980 and September 2017. Results were combined using a random-effects model, and pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare serum zinc levels in patients with cervical cancer versus controls. Publication bias was evaluated using Begg's funnel plot and Egger's regression asymmetry test. RESULTS: Twelve articles regarding serum zinc levels and cervical cancer were included in this meta-analysis. Combined results showed that serum zinc levels in cervical cancer cases were significantly lower than in controls without cervical cancer (summary SMD -1.379, 95% CI -1.527, -1.231), with high heterogeneity ( I2 = 98.8%). Analysis of data stratified by geographic location showed a significant association between serum zinc levels and cervical cancer risk in Asian populations (summary SMD -1.391, 95% CI -1.543, -1.239). CONCLUSIONS: Higher serum zinc levels may be a protective factor for cervical cancer in Asian women.

The response of tree growth to nitrogen and phosphorus additions in a tropical montane rainforest.

Rapid increase of global nitrogen (N) deposition has greatly altered carbon cycles and functioning of forest ecosystems. Previous studies have focused on changes in carbon dynamics of temperate and subtropical forests through N enrichment experiments; however, the effects of N deposition on tree growth remain inconsistent, especially in tropical forests. Here, we conducted a five-year N addition experiment (0 and 50kgNha-1yr-1) in a tropical montane rain forest in Hainan Island, China, to explore the effects of enhanced N deposition on growth of trees. We also set phosphorus (P) treatment (50kgPha-1yr-1) and N+P treatment (50kgNha-1yr-1+50kgPha-1yr-1) to examine potential P limitation driven by N deposition. Our results showed that N addition has not significantly influenced tree growth, while P addition significantly increased the relative growth rate of small (diameter at breast height, DBH≤10cm) and medium (10