Objective To observe the effects of adiponectin (APN) on anxiety-and depression-like behaviors occurred in APP/PS1/tau triple transgenic Alzheimer's disease (3xTg-AD) model mice and investigate the possible mechanism.Methods The 9-month-old 3xTg-AD mice and wild type (WT) mice were randomly divided into four groups (n=8 for each group):WT+Saline,WT+APN,3xTg-AD+Saline and 3xTg-AD+APN groups.The mouse was chronically intracerebroventricular injection of APN or saline under free moving condition.Elevated plus maze task was used to evaluate the anxiety-like behaviors.Sucrose preference test and tail suspension test were used to evaluate the depression-like behaviors.Western blot was used to detect the protein expression levels of p-AMPK,AMPK,p-GSK-3β (Ser9),GSK-3β and SIRT1 in the hippocampus of each mouse.Results In the elevated plus maze test,the time percentage spent in open arms of 3xTg-AD+Saline mice was ((4.2±2.7) ％),which significantly lower than that in WT+Saline group ((10.1±4.1)％) (q=4.349,P＜0.01) and in 3xTg-AD+APN group ((9.7±3.3)％) (q=4.065,P＜0.01).In the sucrose preference test,the sucrose preference percentage in 3xTg-AD+Saline group((48.8±5.3) ％) was lower than that in WT+Saline group ((60.9±6.7) ％) (q=4.522,P＜0.01) and in 3xTg-AD+APN group ((59.3±6.2)％) (q=3.911,P＜0.05).As for tail suspension test,the immobility time percentage in 3xTg-AD+Saline group((40.7±9.9)％) was higher than that in WT+Saline group ((27.1±4.8)％) (q=5.257,P＜0.001) and in 3xTg-AD+APN group ((31.4±6.0)％) (q=3.624,P＜0.05).The result of Western blot showed that there was no significant difference in expression level of AMPK and GSK-3β among four groups.However,compared with that in WT+Saline group,the expression levels of p-AMPK (q=3.586,P＜0.05),p-GSK-3β (Ser9) (q=3.125,P＜0.05),and SIRT1 (q=3.044,P＜0.05) in 3xTg-AD+Saline group were significantly decreased.In addition,compared with that in 3xTg-AD+Saline group,the expression levels of p-AMPK (q=3.374,P＜0.05) and p-GSK-3β (Ser9) (q=3.063,P＜0.05) in 3xTg-AD+APN group were obviously up-regulated without affecting the SIRT1.Conclusion Adiponectin can effectively alleviate the anxiety-and depression-like behaviors of 9-month-old 3xTg-AD mice by up-regulating the protein expression of p-AMPK and p-GSK-3β (Ser9) in the hippocampus.

Objective To correlate the isokinetic strength of stroke survivors' trunk flexors and extensors with the kinematic parameters of their gait.Methods Thirty stroke survivors and 30 healthy counterparts formed an observation group and a control group.The strength of everyone's trunk flexors and extensors was measured isokinetically,including the flexor peak torque (FPT),extensor peak torque (EPT) and the ratio of the two (F/E).The test velocities were 30°/s,60°/s and 90°/s.And the kinematic parameters of their gait,including the step length,stride,velocity,frequency,width and cycle time were measured using a 3D gait analysis system,as well as the percentage of stance phase,swing phase,double support phase and single support phase.Results No significant differences were found between the average FPT,EPT or F/E of the two groups at any of the three test velocities.At the 30°/s test velocity the average FPT,EPT and F/E of the observation group were all positively correlated with the average step length,stride,velocity,steps/min,width and cycle time,as well as with the stance phase,swing phase,double support phase and single support phase percentages.The strongest correlation was between F/E and velocity (r=0.57),followed by frequency (r=0.54).Conclusion litating the walking ability of stroke survivors and correcting their gait should focus on strengthening the trunk muscles and optimizing their coordination.

Objective:To observe the effect of applying repetitive transcranial magnetic stimulation (rTMS) on swallowing function and auditory evoked potentials in the brain-stems of stroke survivors with dysphagia.Methods:Sixty stroke survivors with dysphagia were randomly assigned to an observation group and a control group, each of 30. Both groups were given 30 minutes of routine swallowing training 6 times a week for 5 weeks, while the observation group was additionally provided with two-second bursts of rTMS on the left and right brain hemispheres alternately for 20 minutes daily. The frequency was 3.0Hz and the strength was 80% of the resting motor threshold (RMT), with an interval of 10 seconds between bursts. Before and after the treatment, both groups′ swallowing was assessed using the functional communication measure (FCM) and the modified Mann swallowing capacity evaluation scale (MMASA). Brainstem auditory evoked potentials (BAEP) were recorded to detect any changes in the peak latency (PL) and inter-peak latency (IPL). The clinical efficacy was also observed.Results:After the treatment, the average FCM results of both groups had improved significantly, but the observation group had improved significantly more. The average MMASA total scores and the average scores on all the sub-items had improved significantly more in the observation group except for the expressive speech disorder and anarthria scores. After the treatment, improvement was observed in respiration, anarthria, range of motion of the tongue muscles, strength of the tongue muscles, gag reflex and soft palate movement compared with before the intervention. Peak and inter-peak latencies had also improved significantly more in the observation than in the control group, on average.Conclusions:rTMS combined with conventional swallowing training can significantly improve the swallowing of dysphagic stroke survivors, and shorten the PL of the BAEP so as to better regulate deglutition.

Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.

Glycosidases are widely used in food and pharmaceutical industries due to its ability to hydrolyze the glycosidic bonds of various sugar-containing compounds including glycosides, oligosaccharides and polysaccharides to generate derivatives with important physiological and pharmacological activity. While glycosidases often need to be used under high temperature to improve reaction efficiency and reduce contamination, most glycosidases are mesophilic enzymes with low activity under industrial production conditions. It is therefore critical to improve the thermo-stability of glycosidases. This review summarizes the recent advances achieved in engineering the thermo-stability of glycosidases using strategies such as directed evolution, rational design and semi-rational design. We also compared the pros and cons of various techniques and discussed the future prospects in this area.
Glycoside Hydrolases/genetics* ; Oligosaccharides ; Polysaccharides ; Protein Engineering

Proteins play a variety of functional roles in cellular activities and are indispensable for life. Understanding the functions of proteins is crucial in many fields such as medicine and drug development. In addition, the application of enzymes in green synthesis has been of great interest, but the high cost of obtaining specific functional enzymes as well as the variety of enzyme types and functions hamper their application. At present, the specific functions of proteins are mainly determined through tedious and time-consuming experimental characterization. With the rapid development of bioinformatics and sequencing technologies, the number of protein sequences that have been sequenced is much larger than those can be annotated, thus developing efficient methods for predicting protein functions becomes crucial. With the rapid development of computer technology, data-driven machine learning methods have become a promising solution to these challenges. This review provides an overview of protein function and its annotation methods as well as the development history and operation process of machine learning. In combination with the application of machine learning in the field of enzyme function prediction, we present an outlook on the future direction of efficient artificial intelligence-assisted protein function research.
Artificial Intelligence ; Machine Learning ; Proteins/genetics* ; Computational Biology/methods* ; Drug Development