Homocysteine-Induced Disturbances in DNA Methylation Contribute to Development of Stress-Associated Cognitive Decline in Rats

Chronic stress is generally accepted as the main risk factor in the development of cognitive decline;however,the underlying mechanisms remain unclear.Previous data have demonstrated that the levels of homocysteine(Hcy)are significantly elevated in the plasma of stressed animals,which suggests that Hcy is associated with stress and cognitive decline.To test this hypothesis,we analyzed the cognitive function,plasma concentrations of Hcy,and brain-derived neurotropic factor(BDNF)levels in rats undergoing chronic unpredicted mild stress(CUMS).The results showed that decreased cognitive behavioral performance and decreased BDNF transcription and protein expression were correlated with hyperhomocysteinemia(HHcy)levels in stressed rats.Diet-induced HHcy mimicked the cognitive decline and BDNF downregulation in the same manner as CUMS,while Hcy reduction(by means of vitamin B complex supplements)alleviated the cognitive deficits and BDNF reduction in CUMS rats.Furthermore,we also found that both stress and HHcy disturbed the DNA methylation process in the brain and induced DNA hypermethylation in the BDNF promoter.In contrast,control of Hcy blocked BDNF promoter methylation and upregulated BDNF levels in the brain.These results imply the possibility of a causal role of Hcy in stress-induced cognitive decline.We also used ten-eleven translocation(TET1),an enzyme that induces DNA demethylation,to verify the involvement of Hcy and DNA methylation in the regulation of BDNF expression and the development of stress-related cognitive decline.The data showed that TET1-expressing viral injection into the hippocampus inhibited BDNF promoter methylation and significantly mitigated the cognitive decline in HHcy rats.Taken together,novel evidence from the present study suggests that Hcy is likely involved in chronic stress-induced BDNF reduction and related cognitive deficits.In addition,the negative side-effects of HHcy may be associated with Hcy-induced DNA hypermethylation in the BDNF promoter.The results also suggest the possibility of Hcy as a target for therapy and the potential value of vitamin B intake in preventing stress-induced cognitive decline.

Prediction of Maximum Section Flattening of Thin-walled Circular Steel Tube in Continuous Rotary Straightening Process

Cross-sectional ovalization of thin-walled circular steel tube because of large plastic bending,also known as the Brazier effect,usually occurs during the initial stage of tube′s continuous rotary straightening process.The amount of ovalization,defined as maximal cross section flattening,is an important technical parameter in tube′s straightening process to control tube′s bending deformation and prevent buckling.However,for the lack of special analytical model,the maximal section flattening was determined in accordance with the specified charts developed by experienced operators on the basis of experimental data;thus,it was inevitable that the localized buckling might occur during some actual straightening operations.New normal strain component formulas were derived based on the thin shell theory.Then,strain energy of thin-walled tube（per unit length）was obtained using the elastic-plastic theory.A rational model for predicting the maximal section flattening of the thin-walled circular steel tube under its straightening process was presented by the principle of minimum potential energy.The new model was validated by experiments and numerical simulations.The results show that the new model agrees well with the experiments and the numerical simulations with error of less than 10%.This new model was expected to find its potential application in thin-walled steel tube straightening machine design.

Supervised Vessels Classification Based on Feature Selection

Arterial-venous classification of retinal blood vessels is important for the automatic detection of cardiovascular diseases such as hypertensive retinopathy and stroke. In this paper, we propose an arterial-venous classification （AVC） method, which focuses on feature extraction and selection from vessel centerline pixels. The vessel centerline is extracted after the preprocessing of vessel segmentation and optic disc （OD） localization. Then, a region of interest （ROI） is extracted around OD, and the most efficient features of each centerline pixel in ROI are selected from the local features, grey-level co-occurrence matrix （GLCM） features, and an adaptive local binary patten （A-LBP） feature by using a max-relevance and min-redundancy （mRMR） scheme. Finally, a feature-weighted K-nearest neighbor （FW-KNN） algorithm is used to classify the arterial-venous vessels. The experimental results on the DRIVE database and INSPIRE-AVR database achieve the high accuracy of 88.65% and 88.51% in ROI, respectively.

Performance of climate reanalyses in the determination of pan-Arctic terrestrial rain-on-snow events

Rain-on-snow(ROS)events can cause rapid snowmelt,leading to flooding and avalanches in the pan-Arctic and can also lead to starvation and the death of massive ungulates.Reanalysis products(e.g.,ERA-I,ERA5-land,JRA55,MERRA2)are the primary source data for the research about ROS events in the large-scale region.However,the accuracy and reliability of reanalyses have never been evaluated with respect to the determination of terrestrial ROS events.The present study aims to statistically evaluate the performance of reanalysis datasets in identifying ROS events with different criteria based on in-situ rainfall data and MODIS snow cover product.The results show that all reanalysis datasets exhibit poor performance(Recall≤0.16,Kappa coefficient≤0.26,F-score≤0.42,MCC≤0.33)in all criteria in the pan-Arctic,mainly due to the low accuracy of rainfall data(r≤0.56).Nevertheless,the spatial distribution pattern and hot spots of ROS from all reanalysis datasets are essentially close.The hot spots of ROS are mainly located on the coast of Alaska,Norway,and Greenland.All reanalyses demonstrate an increase in rainy days,but there is little overall change in ROS events due to the reduction in snow cover days.This work suggests that none of the current reanalyses are reliable in the determination of ROS events due to the poor representation of the rainfall parameterization scheme.The development of alternative strategies that can investigate ROS events at large-scale is urgently needed in a changing Arctic under rapid warming.

Zinc-based metal-organic frameworks as efficient carriers for anticancer drug to reduce toxicity and increase efficacy

The rational design of a specific co-drug delivery platform that can address the unavoidable resistance,toxic side effects and low targeting efficiency of traditional cancer treatments is of great meaningful.Herein,Zn-based MOF-zeolitic imidazole framework-90(ZIF-90)was selected as the drug delivery carrier,with the cancer therapeutic drug mercaptopurine(6-MP)and glucose oxidase(GOD)as the drug models,hyaluronic acid(HA)was used for protection and targeted delivery,which designed and fabricated an intelligent drug delivery platform(6-MP@ZIF-90@GOD@HA).This platform aims to reduce the toxic side effects of 6-MP and enhance its efficacy while improving the targeting ability of GOD,thereby further enhancing the treatment outcome.Notably,results from both in vitro and in vivo experiments demonstrate that the targeted synergistic chemo/reactive oxygen species(ROS)-mediated/starvation therapy inhibited the cancer cell growth while reducing the chemotherapy toxicity,which provides new possibilities for the development of more precise and effective treatment strategies.